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NAEEMAH LOGAN, CDC [00:12:11]
As noted earlier, most domestic cases of Shigellosis are caused by sonnei or flexneri. You can see that in 2015 most cases of shigellosis in the U.S. 91% were caused by sonnei. However, this changes, and since 2021, shigellosis in the U.S. is primarily driven by flexneri strains.
This challenges the conventional view that sonnei predominates in high income countries while flexneri dominates in low and middle income countries. The recent increase of flexneri in the U.S. demonstrates the incredible opportunistic ability of this pathogen to afflict vulnerable populations. And perhaps also urges us to reconsider previous views, where ever suitable living conditions and risk behaviors coexist, flexneri transmission can occur.
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NAEEMAH LOGAN, CDC [00:14:16]
The states with the highest XDR cases were highest in California, Colorado, Massachusetts and Texas. There are a few important things that we’d like to note with this slide. First, the figure represents case counts and infections as identified in Pulse Net by state, not incidence. Also, the extent of lab based surveillance may differ by state.
Some public health laboratories may not have the capacity to routinely perform whole genome sequencing on Shigella isolates. Therefore, case counts might not represent the full scope of excess Shigella infections in those states. Finally, duplicate records might exist in Pulse Net, but not enough to skew information presented in this report.
This chart shows XDR by demographic group for Shigella. On the x axis are years from 2015 to 2022, and on the y axis are the number of XDR shigella isolates. The orange bar corresponds to isolates from adult men.
You can see that overall, for each year, adult men have the greatest number of XDR shigella cases and, among adult men, that number increases each year from 0 in 2015 and 2016, to 130 in 2022. Compared to other demographic groups. Adult men also have the highest proportion of XDR at 2.3%. And this number increases to almost 85% when the denominator is restricted to XDR cases.
These trends are also consistent with recent increases in drug resistant shigellosis outbreaks among MSM.
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LOUISE FRANCOIS WATKINS, CDC [00:18:32]
The obvious challenge here is that emerging XDR Shigella strains are resistant to all of these recommended agents. Therefore, we’ll next turn to some agents that have been proposed as potential alternatives to recommended treatments. Again, this is not an exhaustive list.
This table shows some of the most common challenges in identifying a suitable alternative. I started with resistance because, although our working definition of XDR focuses on agents recommended for treatment, Shigella isolates are also commonly resistant to amoxicillin, chloramphenicol, nalidixic acid acid, and tetracyclines.
Some agents that work quite well for other types of diarrheal disease do not penetrate the intestinal mucosa well and therefore have limited clinical efficacy for Shigella specifically. These include first and second generation cephalosporins, amoxicillin, aminoglycosides like gentamicin and kanamycin, and nitrofurans.
And then some agents that have been shown to be effective against shigellosis are not available in the United States. We do not have access to oral formulations of chloramphenicol or pivmecillinam, for example, although you may see these agents recommended in some international guidelines.
Likewise, older penicillins such as temocillin and oral carbapenems like tebipenem are not currently available here.
Then some potential treatment agents have simply not been very well studied for Shigella. I’ve put fosfomycin and carbapenems such as meropenem in this category.
Although we do not currently have enough information to recommend either fosfomycin or meropenem for the treatment of XDR shigella, these agents are worth a closer look.
This table compares fosfomycin and meropenem on some of the metrics that are relevant to the treatment of shigellosis.
In terms of phenotypic resistance, CDC does not have data for fosfomycin because it is not included on our surveillance panel, but we have tested shigella isolates for susceptibility to meropenem since 2016 and found no resistance.
We have also screened all shigella isolates from U.S. surveillance isolates for genotypic resistance. Fosfomycin resistance genes have only very rarely been observed in shigella isolates, and we have never seen genotypic resistance for meropenem.
…
Neither fosfomycin nor meropenem has been extensively studied for the management of shigellosis, but there is some limited information from clinical trials available for fosfomycin. Much of it is older, was conducted outside of the United States or involved pathogens other than Shigella. Neither of these agents have an on label indication for use for shigellosis in the United States.
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LOUISE FRANCOIS WATKINS, CDC [00:24:33]
Clinicians should be aware that there is limited evidence based guidance for the best management of XDR Shigella infections. For this reason, CDC does not have official recommendations for antimicrobial management at this time.
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RACHEL JERVIS, CDPHE [00:36:01]
As of January 18th, there were 17 Colorado cases in this multistate XDR Shigella cluster with onset dates ranging from late July to late December. Next slide.
Each case receives a thorough public health interview to collect symptom information, collect exposure data, provide disease control guidance, and detect and solve outbreaks.
Through these case investigations and medical chart review, we learned that the median age of our cases was 40. All cases resided along the front range of Colorado. Almost half were hospitalized. 82% were male and 59% of them reported being a man who had sex with men. 24% were experiencing homelessness, 29% reported drug use, and 59% were immunocompromised.
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NAEEMAH LOGAN, CDC [00:58:42]
CDC surveillance data showing that kids younger than five years old tend not to have drug resistant infections. So susceptible infections are most common in that age group.
But drug resistant shigella infections are more common among adults within this very vulnerable group. And so we mentioned several of those. Those are MSM, those are people experiencing homelessness, those are people living with HIV, and international travelers.
FILIP DUBOVSKY, NOVAVAX [00:25:48]
When concerning variants emerge, they are placed into our variant development platform. Work begins with cloning the new sequence and evaluating spike proteins in vitro. The immune responses are evaluated in animal models, and monoclonal antibodies are developed for structure function analysis. Concurrently, we develop master virus seed that’s required for commercial manufacture, and we also manufacture monovalent vaccine bulk, which can be used for clinical evaluation or, if that variant is part of the selected future composition, it can be blended as a monovalent or bivalent vaccine and be available for initial commercial release.
Although we cannot be assured any of the variants we are working on will be selected for the future composition, this approach may shorten the time between strain selection and deployment of vaccine.
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JIM KELLY, NOVAVAX [00:31:24]
In our 10-K, you will see that we have added a going concern disclosure while our current business plan and cash flow forecast estimate that we have sufficient capital available to fund our operations for the next 12 months. We recognize that this plan is subject to significant uncertainty related primarily to future revenue funding from the U.S. government and our pending arbitration with GAVI. I’d like to first discuss these uncertainties and then share with you immediate actions we have taken to mitigate these concerns and improve our financial position.
Regarding our full year 2023 revenue, our performance will depend on our ability to deliver an updated version of our COVID-19 vaccine for the 2023 fall vaccination season. Key activities in support of this plan include our timely completion of the 311 study to demonstrate our strain change capabilities and delivering an updated COVID 19 vaccine consistent with public health recommendations for screen composition.
Regarding our U.S. government funding. In February 2023, the U.S. government indicated our existing agreement would not be extended past December 2023, which may place a portion of the remaining 460 million of funding at risk. We are proactively discussing mitigation options with the U.S. government in an effort to realize the full amount outstanding.
And finally, regarding GAVI, we recognize that the outcome of our pending arbitration is inherently uncertain. We are taking immediate actions as we seek to address these concerns with the intent of improving Novavax’s cash runway and best positioned the company to deliver near and long term value.
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JOHN JACOBS, NOVAVAX [00:42:06]
And obviously everyone knows that it takes a little bit longer to develop a protein based vaccine than an mRNA vaccine. But there are things we can do to speed up our timeline and we are taking decisive action with that intent in mind.
First and foremost, that’s partnering with the FDA very closely in conversations between our team and FDA senior leadership and FDA technical leadership to make sure that they understand what our requirements are and that we understand what their requirements are in a crystal clear fashion so we can move forward together with the goal of offering our protein based vaccine as an option for U.S. consumers.
In addition to that, we as an organization have a fully integrated capability set that allows us to bring forward multiple variants at the same time, and bring those variants to scale in our CMC process, so we can hedge your bets, if you will, ahead of the curve in anticipation of variants that may be selected.
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RICK CROWLEY, NOVAVAX [00:43:09]
As was said, we are actively producing variants of interest and we’re identifying those the public health authorities. And our discovery team is developing the variants that we are then moving on into the large scale manufacturing. And so we anticipate having a pool of inventory ready at the time of the decision being made.
And that allows us to, even though it still takes about six months to go from inception to commercial, we are getting a jump start on that by creating this inventory and putting this material in stock ready to be delivered in the fall.
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JOHN TRIZZINO, NOVAVAX [01:03:45]
I think it’s worth clarifying that the U.S., in particular the U.S. government’s action to suspend the public health emergency, will not affect our ability to sell under the emergency use authorization during the 2023 season. Of course, we’ll be filing our BLA in the second half of the year. And of course, we’ll have expectations of a BLA approval probably by late this year, or early next year. But there’s no, in conversations with FDA, there’s no concern at this point relative to operating under an emergency use authorization.
(1) Holly Janes = YES safety, YES effectiveness
(2) David Kim = YES safety, YES effectiveness
(3) Daniel Feikin = YES safety, YES effectiveness
(1) Marie Griffin = NO safety, YES effectiveness
(2) Hana El Sahly = NO safety, YES effectiveness
(3) James Hildreth = NO safety, YES effectiveness
(1) Jay Portnoy = YES safety, NO effectiveness
(2) Steven Pergam = YES safety, NO effectiveness
(3) Amanda Cohn = YES safety, NO effectiveness
(1) Henry Bernstein = NO safety, NO effectiveness
(1) Stanley Perlman = ABSTAIN safety, YES effectiveness
(2) Adam Berger = YES safety, ABSTAIN effectiveness
DAVID KASLOW, FDA [8:47 AM]
Welcome to this 179th convening of VRBPAC for a two day meeting in open session to discuss and make recommendations on the safety and effectiveness of actually two pioneering RSV vaccine candidates. Pioneering as they represent 21st science and technology over the shortcomings of previous efforts of a half century ago. Structural immunology and engineering over empiric vaccinology against a respiratory virus that causes life threatening disease in the youngest and oldest, particularly those with comorbidities.
The convening of VRBPAC focuses on respiratory syncytial virus disease in older adults as will be reviewed by presentations this morning. The committee will then consider two RSV candidates. One, a bivalent without adjuvant. The other a monovalent with an adjuvant. The particular product for consideration today is one submitted by the sponsor Pfizer in BLA 125769. The other for consideration tomorrow by the sponsor GSK in BLA 125775.
Let me conclude these brief welcome by thanking the committee members for their time today and tomorrow, by thanking those from the FDA who reviewed these submissions and helped organize this meeting, by thanking our presenters and by thanking those who joined this public open meeting virtually.
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NATALIE THORNBURG, CDC [00:13:58]
Now, I know we’re talking about adults today, but this is a pediatric network. We do have some other networks with that involve adults as well to be just be sort of a check to make sure what we see circulating in children is the same as what we’re seeing circulating in adults.
But there have been lots of community transmission studies that indicate that school age children tend to drive transmission in most communities. Additionally, children, whenever they’re experiencing their first or second infection, they tend to shed much higher titers of virus and therefore their specimens, we can recover much better sequences than we can from utilizing specimens from adult infection where they shed less virus because of probably previous infection.
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FIONA HAVERS, CDC [00:20:17]
This pyramid here shows a range of estimates for the burden of disease in adults 65 years and older. From the bottom of this pyramid up, RSV is estimated to cause approximately 0.9 to 1.4 million medical encounters, 60 to 160,000 hospitalizations, and 6 to 10,000 deaths per year.
Note the very large range for these estimates. There is substantial uncertainty in the published literature about the burden of disease in this age group and depending on the source of information, estimates for these three metrics vary considerably.
And there are studies that indicate that the disease burden is higher than what is indicated on this slide. But regardless of this source, however, we do know that the disease burden in older adults is substantial.
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FIONA HAVERS, CDC [00:20:59]
Next slide. Here’s the pyramid that was just shown, as well as comparable burden estimates associated with influenza and adults 65 years and older as estimate using estimates published by CDC.
The burden of disease varies annually for both RSV and influenza. Generally speaking, however, based on these estimates, the burden of RSV in older adults is lower than that of influenza. But in more severe seasons may approach the number of medical encounters and hospitalizations that we can see for influenza in some seasons.
There are a number of studies that show clinical outcomes among older adults with RSV are comparable to those with influenza. Note, of course, that influenza has a widely used vaccine, and without this vaccine, the burden of influenza would be much higher.
This graph shows estimates for rates of laboratory confirmed RSV associated hospitalizations over four pre-pandemic seasons from 2016 to 2020 by adult age groups. These data come from RSV-NET, a CDC population based hospitalization surveillance system in 12 sites. These rates are shown per 100,000 population.
As you can see, hospitalization rates in adults increase with increasing age, with hospitalization rates that are highest in those 80 years and older. However, please note that there is considerable uncertainty around these estimates. These are likely conservative rate estimates in other published studies that estimate the hospitalization rates higher.
As noted in a footnote, most of these data rely on PCR testing with nasopharyngeal slots, which is the most common clinical testing performed in hospitals. However, there is evidence from multiple studies that the use of acute and convalescent serology, saliva, oropharyngeal swabs and other testing modalities to identify additional cases that empty PCR testing is not as sensitive as previously thought, and some studies use large multipliers to account for this.
But regardless of how rates are determined, it is clear that rates of hospitalizations increase with increasing age and that those in their 70s and 80s are most affected by severe disease and severe RSV disease.
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FIONA HAVERS, CDC [00:33:07]
In conclusion. RSV is a frequent, often unrecognized cause of severe respiratory illnesses in older adults. There’s a high burden of severe disease with some variability across seasons. Hospitalization rates increase with increasing age. Adults with co-morbidities, including immunocompromised adults and also long term care facility residents are at risk for severe illness.
A high proportion of those hospitalised with RSV have severe severe outcomes, including ICU admission and death. And RSV illnesses can result in long term health consequences, including a decrease in functional status and independence.
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STANLEY PERLMAN, VRBPAC [00:36:09]
So we know from the COVID 19 evolution of the virus, SARS-CoV-2 evolution, we watched it evolve both for binding better to the receptor and in response to the immune response. And we also then went back and looked at the cold, common cold coronaviruses which were not thought to change like to 290 and found that they had changed as well over many years.
So is there any sense, doyou have enough information yet to know whether RSV is changing? Or is that still– we can see all these different genotypes, but is there any directed evolution that’s of interest?
NATALIE THORNBURG, CDC [00:36:42]
I don’t know. I don’t really think our sequencing data is deep enough to say with certainty.
Certainly we have very, very limited sequencing data from specimens collected before 2000. So we do see genotypes sort of emerge and then decrease in in prevalence. But again, the scale of that particular graph, first of all, it’s just absolute number of sequences, but it was like 185. And so when you look at that as comparison to the depth of our current coronavirus sequencing, it’s 10,000 sequences a week, just in the United States alone, and and not collected in any sort of systematic way through the last 20 years RSV sequences.
So I think it’s going to be several years. We can– we’re working on going back to 15-16 season to really start generating that data from systematically collected viruses. We just don’t have that data yet.
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HENRY BERNSTEIN, VRBPAC [00:39:08]
Dr. Havers, a lot of the epidemiology that you shared was for those older adults that are 65 and up. In today’s discussion, both both companies today and tomorrow, they’re studying for 60 and above. Is there– does the data apply for 60 to 64 year olds?
FIONA HAVERS, CDC [00:39:33]
Yeah, I know. That’s a great question. I don’t know if it’s possible to show slide six from my presentation?
We actually broke down the different age groups that show that the rates between hospitalization rates between 60 and 64 are as expected, somewhat intermediate, between those 50 to 59 and those 65 to 69.
I would say that we sort of see a bigger inflection point around 70, 75. Certainly adults, 60 to 64, are hospitalized for RSV, and they generally tend to be people that have underlying medical conditions, but they’re still in that age group compared to older adults– older, older adults, is lower.
But I mean, it does go up with increasing age, but hospitalization rates really kind of take a bigger jump when you get into the 70s and 80s.
So that is definitely a significant cause of hospitalization in the 60 to 64 age range. But it is the hospitalization rates are slightly lower than in those 65 or 75 or 85.
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KEIPP TALBOT, ACIP [01:06:53]
So the main takeaways that are incredibly important for this are that natural RSV infection does not provide durable or complete protection from reinfection.
Anti RSV antibodies returned to pre infection levels within six months after infection. And reinfection can occur as early as two months after the last infection.
Older adults have weaker interferon gamma responses to RSV than younger adults, likely making older adults more susceptible to infection and to severe infection.
Each of the authors summarize their papers and the discussion, talking about likely the need for annual immunization. They all responded that vaccines would provide some protection, but like natural infection would not be durable or complete, and that likely annual vaccination would be necessary.
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ALEJANDRA GURTMAN, PFIZER [00:01:03]
After more than 50 years of RSV research and vaccine development efforts, groundbreaking structural work by the National Institutes of Health elucidated that RSV F on the virus exists as an unstable prefusion form. As shown on the left of the cartoon, RSV F is anchored on the surface of the virus where it fuses the viral and host cell membranes during cell entry.
This fusion process is a result of a dynamic and irreversible change of F from metastable prefusion conformation to a stable postfusion conformation. Only the prefusion form on the virus can bind to human airway cells, resulting in the virus entering the cells where it can replicate causing illness. Antibodies specific to the prefusion form are most effective at blocking virus infection.
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ALEJANDRA GURTMAN, PFIZER [00:05:43]
In the study where we evaluated CPG aluminum, all RSVPreF vaccine candidates elicited robust serum neutralizing responses when administered with influenza vaccine, as you can see on the left graph of this slide. There was no notable difference in neutralizing response between the formulations, including those containing CPG aluminum, no difference in T-cell response between those levels or with and without CPG aluminum was observed one month after vaccination.
This study was important because our preclinical data with CPG was promising. But as I just showed you, in humans, the inclusion of CPG aluminum showed no substantial benefit in enhancing the immune response compared to RSVPreF formulations with aluminum at any of dose levels or compared to RSVPreF alone.
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ALEJANDRA GURTMAN, PFIZER [00:23:55]
In conclusion, the interim analysis for the RENOIR phase three pivotal trial demonstrated that RSVPreF was safe and well tolerated. Local and systemic events were mostly mild to moderate and short-lived. There were no difference in systemic events between those who receive RSVPreF and those who received placebo.
The adverse events profile did not suggest any safety concerns for the RSVPreF vaccination in adults 60 years of age and older. Considering that the vaccine was well-tolerated and there are no differences in adverse events between RSVPreF vaccine and placebo groups, these data should potentially encourage uptake once a vaccine is approved and recommended.
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ALEJANDRA GURTMAN, PFIZER [00:24:43]
I would like now to turn your attention to the efficacy results.
At this time, at this preplanned analysis, when looking at RSV associated LRTI defined by the least two symptoms, there were 11 cases in the vaccine group and 33 in the placebo. We then observe efficacy of 66.7% with a lower confidence interval of 28.8%.
For those who had at least three symptoms, there were two cases in the vaccine group and 14 in the placebo group, resulting in vaccine efficacy of 85.7%, with a lower confidence interval of 32%, indicating an even higher efficacy against those who have worse symptoms.
Both primary endpoints met licensure criteria.
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HANA EL SAHLY, VRBPAC [00:36:10] Can you help us understand further the interference with influenza vaccine responses? And why weren’t these data from the additional studies presented? And that would be sort of a safety question there?
ALEJANDRA GURTMAN, PFIZER [00:36:29] So thank you for the question. You are correct. In our phase one two studies, we did look at potential interference with flu vaccine, but the studies were not powered actually an inferiority studies. So it was just– it was a trend. And this is one of the reasons why we are now conducting a study in this age group with the high dose and adjuvanted flu vaccine, which as you mentioned, it has been fully enrolled and the results are going to be available very soon and we will be submitting this data to the FDA to hopefully be able to include coadministration in the label.
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SCOTT KELLY, PFIZER [00:48:48]
Thank you for your question. At Pfizer, we did conduct a review of the literature for the background rate. To note there is a lot of variability and heterogeneity for incidence of– incidence rates of GBS, which they vary by age group, gender, pre-existing conditions, region and temporality, as along with the case definition.
In general, the background rates range from about 1.8 to 7.8 events per 100,000 person years. I’ll stop there for the background rates. If there’s any questions there? I’ll move on to the observed versus expected results. Okay, I’ll proceed.
So whether using any of the various background rates in the range I provided, again, the ranges from the lower using a case definition where it’s neurologist confirmed studies and a systematic review by (unclear) in 2011 that included, I think, roughly 16 studies were on the lower end of that range, whereas additional newer data, that included administrative claims data as well as electronic health records, which again, the case definition varies, whether you’re using a more specific incidence rate, where the criteria requires that the primary position in the record signifies GBS as well as inpatient setting, those are more on the higher end of that range I suggested.
No matter which incidence rate is used from the studies, the observed versus expected is above one. However, there’s a lot of uncertainty in those estimates, which is exhibited by very wide confidence intervals.
While the trial was very large, proper assessment of any potential signal and refinement is best conducted in postmarketing studies with large databases, with millions of patients or more, to properly assess any potential signal for RSV in the settings.
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MARIE GRIFFIN, VRBPAC [00:51:27]
My question was also about the Guillain-Barre. I mean, it seems to me that, no matter what the background rates are, you have to think in terms of the rate within a few weeks rather than within a year. So that’s 1 to 7 per 100,000 person years. It’s much lower for within 3 to 4 weeks. So it seems to me that one case is a red flag. Two cases is very concerning. And it’s concerning to me that Pfizer doesn’t think that there are any safety concerns.
ALEJANDRA GURTMAN, PFIZER [00:52:15]
Thank you for that comment. I fully agree that, when used, for example, Brighton Collaboration to assess potential relatedness of a vaccine is the 42 days that has been widely accepted.
In these two particular cases, there were confounding factors. The Miller Fisher syndrome had had an infectious presentation a few days prior to the presentation and the Guillain-Barre syndrome had the myocardial infarction the day before he started with back pain.
So– and they’re both in an age group right where Guillain-Barre is already has a higher incidence. So we are going to be conducting a post-marketing study to assess actually Guillain-Barre and other potential demyelinating conditions. And that study is being currently discussed with the FDA.
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NADINE PEART AKINDELE, FDA [01:09:18]
Participants were enrolled and randomized one to one to receive either RSVPreF or placebo administered intramuscularly. Of note, the placebo used in this trial consisted of excipients matched to those used in the RSVPreF vaccine formulation minus the active ingredients. The physical appearance of the RSVPreF vaccine and placebo were similar.
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NADINE PEART AKINDELE, FDA [01:35:58]
Three SAEs, all of which were in the RSVPreF group, were considered to be possibly related to study vaccination by the FDA in agreement with the investigators assessment.
The first case was that of a 61 year old female who had experienced hypersensitivity of moderate severity beginning 8 hours after receit of RSVPreF. The participant developed shortness of breath and chest pain, had loss of consciousness and required hospitalization. She received a diagnosis of an allergic drug reaction, and her symptoms resolved five days after onset.
The second case was that of a 66 year old male with a past medical history of hypertension who developed Guillain-Barre syndrome or GBS, graded as life threatening in severity, with an onset seven days after receipt of RSVPreF. Prior to the onset of his symptoms, on day seven, the participant had experienced a non S.D. elevation myocardial infarction, not considered related to study vaccination. He was hospitalized from days 7 to 8 and underwent cardiac catheterization and angioplasty. On day eight, he developed lower back pain and on day 14 he developed bilateral lower extremity weakness and had a fall leading to his hospitalization.
Physical exam and laboratory findings were consistent with the diagnosis of GBS. He was treated with intravenous globulin and five sessions of plasma freezes. His symptoms improved, and the event of GBS was resolving at the time of the last available report, approximately six months after symptom onset.
The third case was that of a 66 year old female with a past medical history of type two diabetes mellitus developed Miller Fisher Syndrome, a variant of GBS, and was graded as severe with onset eight days after receipt of RSVPreF. The participant reported fatigue on day nine, sore throat on day ten, and ataxi on day 11. On day 19. She was hospitalized with severe fatigue and unstable movements and later diplopia, ataxi, and paresthesia of the bilateral palms and soles. Ophthalmoplegia was seen on exam. Her symptoms started to resolve on day 40 without treatment. On day 41, she was retrospectively diagnosed with Miller Fisher syndrome based on her clinical course. The participants symptoms resolved completely approximately three months after symptom onset.
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NADINE PEART AKINDELE, FDA [01:42:03]
To summarize the safety data. The study included 34,284 participants, including 17,215 who received RSVPreF.
Of these vaccinated participants, 77% have had at least six months of follow up. Solicited local and systemic reactions were generally mild to moderate and a short duration. The most frequently reported solicited reactions among RSVPreF recipients at a rate of over 10% were fatigue, headache, injection site pain and muscle pain.
Within one month after vaccination, a numerical balance was observed for events of atrial fibrillation. FDA review of these events is ongoing.
Serious adverse events were balanced between the RSVPreF and placebo groups. Three SAEs, including one case of GBS and one case of GBS variant, were assessed by the FDA as possibly related to the vaccine in agreement with the investigators assessments.
Finally, review of the safety data from five supportive clinical studies did not reveal any other safety signals, including additional cases of GBS or other immune mediated demyelinating conditions post-vaccination.
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NADINE PEART AKINDELE, FDA [01:48:19]
Thank you for your question. Yes, this was a very large study.
So although the proportion of participants 80 years of age and older does seem small, comparatively, the absolute number is reasonable. About 5,500 participants, 2,700 about which were vaccine recipients, were 75 years of age and older. And the numbers of participants in this age population are comparable with those that we’ve seen in studies for other vaccines that have been used in older adults.
Of course, if the vaccine is licensed, more data will then be more available on the age group and we would be able to access that through real world evidence.
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AMANDA COHN, CDC [00:46:22]
There’s available data here that we haven’t seen yet. And I feel like we– if this large outbreak hadn’t occurred last fall, I don’t know that we would be in a place where we’re being asked about this without the coadministration and other available data or data that will be available in the next several months. I think the timing feels rushed.
I don’t think that this is a viable vaccination program if we have to administer flu vaccine and this vaccine and maybe even COVID vaccine separately. So I, as you were saying that, it struck me that I agree this is a safety issue because it would be potentially interfering with the influenza vaccine effectiveness.
And it does seem like inevitably this vaccine will be coadministered if it is recommended and authorized. So it does feel like – and licensed – but it does feel like I would love to hear from the FDA like what would happen if we needed to wait for some of that additional data to be presented?
DAVID KASLOW, FDA [00:47:53]
No question. I just think that this discussion is absolutely essential in terms of our regulatory review process and incredibly helpful. And you’re delivering exactly what we wanted, which was a robust discussion around both the safety topics and the efficacy topics.
STANLEY PERLMAN, VRBPAC [00:48:33]
So I would just want to ask Dr. Kaslow if he can give a more definitive answer on whether we can postpone this and get more information?
DAVID KASLOW, FDA [00:48:53]
Again, I think we’re looking to the advisory committee to provide input to the FDA in terms of the timing of this of this approval. And these voting questions have been crafted specifically to ask that question. And so yeah, I think your input would be considered as will the vote.
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NADINE PEART AKINDELE, FDA [00:51:15]
That’s a great question.
So as is standard for all submissions, companies are required to meet specific criteria before they can submit to the FDA their applications. Once we receive their application, we then review their application. And the application submission is typically based off of predefined criteria that the company has established and has discussed with the FDA.
Now, the question of whether or not companies have come in previously with interim analyses, the answer is yes. There have been examples of vaccines in the past that have used case driven and interim analyses to meet their specific end points. And so that’s exactly what that’s Kaslow was mentioning, is that while this application has met criteria for submission and for our review, we really are eager to continue this discussion that the advisory committee is to help guide us in our decisions going forward.
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PETER MARKS, FDA [00:59:41]
I think, again, we have to judge this on its own and not– we are not in a position at this point to require a coadministration study. We have to essentially look at what we have in front of us and look at the benefits and risks for this particular vaccine, given a problem that, I think the issue here is that this goes back to the question about why are we talking about this now? It’s because obviously RSV is a pretty serious respiratory infection.
And so this was the reason for trying to, I think, where the sponsors tried to move forward with this, given the earlier part of this season, where there was a pretty big scare with RSV. So I think is there is some rationale of what’s going on in the background here for some urgency to having an RSV vaccine.
And the agency, based on your feedback, can use a variety of different tools, including different approval strategies as well as potentially requiring post-marketing studies to help clarify remaining uncertainties.
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ALEJANDRO GURTMAN, PFIZER [00:15:58]
We truly didn’t show interference. We just showed a trend in decreased responses in the flu vaccine in a study that was not powered to look at really non-inferiority and that’s why we are conducting and now completed a study with the with flu vaccine actually to see if there is interference or not. So the data is not available yet, but will be available very soon. And as I think I mentioned in the morning, we will be submitting the data to the FDA, with potential– for potential inclusion in the label.
In terms of coadministration with flu vaccine and RSV, in terms of detecting GBS in our pharmacovigilance, enhanced pharmacovigilance study, so our activities actually, we collect when the information is available but not always is available. But we make an effort to collect that concomitant administration once the vaccine will be approved and recommended.
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STEVEN PERGAM, VRBPAC
I’m concerned about the flu vaccine, at least what has been discussed, but without seeing data, I didn’t feel like I could include that as part of my discussion and my thought process.
I think in order to really get at the crux of the GBS question, it’s almost an impossibility without postmarketing data for the small number of cases that would be seen and even if we did another 40,000 patients with a study and we saw no cases, would that still mean there’s no potential risk? I think that’s a hard decision to make.
So I felt compelled that the data look safe, although clearly more work needs to be done in the postmarketing surveillance, which I think they outlined well and would work really closely with the FDA to accomplish.
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HENRY BERNSTEIN, VRBPAC
I voted no because I am concerned about the safety signal and if it was really just the safety signal I might have been convinced based on the data discussed today that we could have – that the safety data was adequate, but I am really concerned about the coadministration as well with flu vaccine and with coadministration with COVID vaccine.
These respiratory viruses we need as many of the public vaccinated as possible and I would not want to take two steps forward and three steps back, if there was a real problem with coadministration.
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JAY PORTNOY, VRBPAC [00:18:13]
I’m desperately eager to have a vaccine that works for RSV. This has been a terrible disease my whole career. I would love to see it. No doubt about it.
My concern is that so few patients were actually infected by RSV in this study that if just a few of the placebo patients, or I guess a few of the actively vaccinated patients, had actually developed RSV, the confidence interval would have gone past the 20% and this would have been statistically insignificant.
The numbers of patients are so small in this study that I just don’t have confidence in the statistics, even though they’re statistically significant. I’m very skeptical about that. I’m concerned that there could be a type one or two error or whatever kind of error that would be. And I think that it would be much better if this vaccine could be considered after the study was completely done, because I think more patients would have been included. There would have been time for a more complete analysis. It would have been more robust numbers. The confidence intervals might have been a little bit narrower, which would have given me more comfort that this vaccine actually works.
This is not an emergency use authorization. If we were in the middle of COVID and we needed a vaccine immediately or people are dying and I know that people are dying from RSV, but it’s not like COVID. It’s not an emergency use authorization. We can take the time to finish the studies and get the information we need before licensing this product going forward. And so I remain a little bit skeptical given the data that we have.
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STEVEN PERGAM, VRBPAC [00:58:01]
I voted no because I feel like there are too many lingering questions in this dataset. Yes, it did meet the primary endpoint for the letter of the law. But there is so much data that is just waiting on the other edge that I think will be informative.
I lean no only because of that information. But in terms of the data that’s presented, I’m very much interested in this being a yes. But I think with additional data that becomes an easier decision for me. I’m really struggling with this because of the importance of what this vaccine means to public health. But I really encourage the FDA to rethink how they develop this vaccine question, and this design of this trial, because what you hear from all of us is that this does not target the population of interest. And this was in some ways set up to be a population that was maybe a little bit easier to approach and easier to collect data from.
But the real importance is the population that is at risk. And I think there was a missed opportunity to develop and design this trial in a way that would be it would make this decision easier for us moving forward. And that’s unfortunate from my view, because I think there’s some real lingering questions that I think even with the additional data I can answers to and will lead to a lot of additional work in the post licensure period.
And then I just want to say, you’ll see where I am on the list of voting, that that’s how long it took me to think about this. And I think part of that is also because of what Amanda Cohn said, and I imagine she’ll probably feel the same, is this is a BLA. It’s very different. We’re approving this vaccine and that means it goes to production, it goes out to the public. And I think I want to be very cautious about how we do that. With the EUA and COVID vaccines, we were in a pandemic and a very different situation. I think we need to be cautious that we think through this. So that’s the reason that my vote was no.
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AMANDA COHN, CDC [01:00:15]
I also believe that had we had a little bit more time to see the data that is on the cusp, I would have been had been a confident yes but– and the data that was presented today, I do believe met the endpoint, as we all do.
But I feel like we– I think I voted no to try to take a step back and get into our sort of pre-pandemic approach towards vaccines. And I do know that we had a bad RSV season last year, but we’ve been waiting for these vaccines for decades. And I think the time we could have had to really be confident in this data and get the complete first season data and potentially even understand second season would really– it’s going to–
I feel like we’re going to get very stuck trying to sort through lots of post licensure data when, with a little bit more time, we may have understood the clinical trial data better.
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HANA EL SAHLY, VRBPAC [01:01:40]
As agreed upon with the agency and as agreed upon and the statistical analysis plan, the answer is yes.
However, I’m going to revisit COVID like some of my colleagues did when we were designing and implementing the COVID vaccine trials, we had to stop some of the enrollment for a while in order to allow for the at risk populations to be represented. Because when we do a clinical trial, invariably the healthier the non minorities, the ones living in certain areas, are the ones who are going to enroll, but they are not necessarily the the population in whom the vaccine needs to be implemented.
And we followed at the time actually FDA guidance that the trials have to mirror the populations at risk. And it does, for this particular trial, I think everyone here is an agreement that this did not take place and this should be taken into account as the analysis of of our discussion takes place at the level of the agency.
NATALIE THORNBURG, CDC [00:12:45]
Genomically XBB.1.5., we often see when a when a lineage reaches saturation, which XBB.1.5 is reaching saturation, we start seeing diversification. So we’ll see a couple of substitutions that may overtake. And so we are starting to see some diversification in XBB.1.5 viruses.
Now this increase in proportion has really been happening at the same time as that decline in cases that I showed you earlier. And so the total number of cases of caused by XBB.1.5 is not as large as some earlier lineages because that increase in proportion has been happening at the same time as the decrease in total cases.
Regionally speaking, XBB.1.5 really emerged in the Northeast. It has met saturation and has been at saturation for quite a while. So the Northeast continues to be the super dominant– predicted to be the super dominant leading edge of viruses circulating.
There was a delay moving across to the West Coast, although this is really the first week– or maybe it was last week, that XBB.1.5 was predicted to be the majority of circulating viruses in all regions. So it is now the majority of circulating viruses in all regions.
As far as growth rate goes, it is still the only lineage that is showing to be increasing in proportion. There are no other lineages that are increasing in proportions.
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JOHN BARNES, CDC [00:25:31]
CDC and state and local health departments actively are monitoring people exposed to infected birds and poultry for ten days after exposure. And so these are all poultry workers that are basically involved in these culling operations that have to happen when they find an exposed farm.
We’re actively monitoring those people and thusfar over 6,000 people who have been monitored in jurisdictions. Only 162 of those people were reported symptoms and just a single person tested positive, the one case from Colorado was actually that one.
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JOHN BARNES, CDC [00:26:22]
In the state and local public health laboratories, the CDC actively has developed and provides those states and local jurisdictions with H5 kits that they can actually use to diagnose the influenza H5 virus. And so these are all these kits are available there for use of them in the public health laboratories and are available for monitoring of the situation. So they’re available and 99 U.S. public laboratories in all 50 U.S. states and 129 international labs.
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JOHN BARNES, CDC [00:29:06]
The sequence analysis that we are doing currently indicates that most of these strains, our antiviral treatments would be very effective against them. And so over 99% of them would be a good candidate to be mitigated by antiviral treatments.
So– and then we have candidate vaccine viruses for this this strain, and it was added to manufacture and given to manufacturers in early 2022. The candidate vaccine virus, and then mink H5, are 100% identical for the part that matters HA1. And so so this this is a likely good candidate.
And CDC continues to analyze virus sequence data for any additional genetic markers that might be associated with severity, transmissibility, etc.. And so really have not seen anything in the outbreak that would indicate any additional risk.
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JOHN BARNES, CDC [00:30:14]
So our priorities at this point are really to be in a posture of readiness.
So we’re continuing our pandemic planning activities and should the situation change, we’ve got surveillance activities and monitoring of exposed individuals. We’re continuing our viral genomic analysis from the data that we’re getting from the outbreaks. We have pandemic vaccine risk mitigation, outlining for a potential H5 if we need to use that in a vaccine.
National testing capacity readiness is something that we’re working on. We’ve been engaging FDA and other interagency partners to see if they would be interested in making an H5 specific assay for use in their own platforms or own networks. And we’re exploring commercial interest for H5 assay development.
And so we’re continuing to look at vaccine effectiveness, safety and immunization systems.
ROCHELLE WALENSKY, CDC [00:12:18]
The pandemic has been the catalyst long overdue for building these capabilities. Today, public health must spend too much time negotiating data, use agreements, building interfaces, and establishing security. These are burdens on our limited public health resources, on those who provide the data and ultimately on the public.
The cost of our current way of operating both in time and in dollars is far too high. The long standing problems include siloed information caused by one off proprietary systems tracking multiple individual diseases. The heavy burden on health care providers who must share data with any number of systems in any number of ways. And older technologies at health departments that are not flexible don’t use cloud and aren’t scalable.
Legislation introduced by Senator Tim Kaine and Representative Lauren Underwood will provide a modern policy tool to create uniform data standards with secure access. My sincere thanks to them for engaging with us in this effort and understanding how important data is in the work we do every day for the people of this country.
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DYLAN GEORGE, CDC [00:53:43]
Similarly, we’ve been able to take over the responsibilities of doing the forecasts for COVID hospitalizations and deaths. And so if you type in CDC COVID hospitalization forecasts, they’ll pop up. It’s our team that is driving those now. We’ve taken over those responsibilities and they’ve been doing it exceptionally well, and they’ve been doing the unsexy work of refactoring it such that it’s not as much of a process of actually doing it in a manual way, but there’s a lot more automation associated with it as well. So not only have we taken it over, we’ve improved upon it going forward, which is very exciting as well.
The assessing– everybody was for a while there, everybody was wondering what was going to happen to COVID in China as the zero policies were lifted. We spent a lot of time trying to comb through, think through what are the different analytical capabilities that would be necessary or possible to help think that through at the White House level. We did a handful of that. That was much more internal, but it was very exciting.
Similarly, with what we did with Ebola, we developed a handful of risk assessments of understanding what was going on with Ebola in Uganda, and providing those not only to within the senior leadership, within CDC, but also to our colleagues in the White House going forward.
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DYLAN GEORGE, CDC [00:57:02]
The other thing that we did want to advance, similar to what Suzy was talking about in terms of the shared analytical zone, we are developing a pilot for what we refer to as the virtual analyst platform, and this is a platform that will help us have a common platform where people can actually it’ll be cloud enabled, similar to what the shared analytical zone is, it’ll be a cloud enabled sort of platform, where it will be using containerized workflows to help us understand how we’re actually using different modeling capabilities and try to make them as broadly available to people as we can.
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DYLAN GEORGE, CDC [00:58:12]
This is where we’re going forward. We are going to be developing a network for advanced outbreak analytics and we want to develop something in innovation, integration and implementation.
And so if you look at the link on the bottom, you will see that we’ve already forecasted this opportunity for people to learn more details about it.
But what we want to do is we want to fund a series of performers that will be developing innovation in outbreak analytics such that they can actually– we can think of different methodologies, different datasets, different sorts of capabilities that would improve our current existing capabilities going forward.
So we’re going to be funding a handful of folks to develop innovation. This is somewhat similar to like what you see in the weather forecasting environment of the National Center for Atmospheric Research. They develop new methodologies for forecasting climate and weather. This is what this group is going to be help us do going forward.
This middle group, this integrators group, is going to help us essentially develop a testbed to design, build and test some of those innovations in a modern day use case. And so here is where we want to work with a state and local jurisdiction to help us design, build and test with these. So these are going to be a set of performers that will actually be looking at those innovative approaches and then trying to see how they can actually be applied at a at a jurisdictional level and seeing what are the benefits and what are the disadvantages of using those different approaches.
And so we want to weld ourselves very closely with a handful of state, local, tribal or territorial jurisdictions to actually do that kind of work in a testbed environment. So we’re super excited about that.
Then this implementation group. So once something emerges from that testbed group that we find is really very effective, we want to be able to scale that to multiple different jurisdictions, as many jurisdictions as want to adopt that we want to figure out our function. So we’re going to be funding a handful of performers to do that sort of function.
Also, this will be a network that in a time of crisis, we can break glass and we can surge people from this network to help us on particular things. And we’ll figure out the rules of engagement and how to do that going forward. But that’s something that’s going to be really interesting.
So we want to be able to build this network to improve the speed, accuracy and use of data analytics in an emergency response. And so we’re super excited about how that’s going to we see this as a major step going forward to it to achieve our 100 X value proposition of working much more closely with the private sector and with the state and local jurisdictions to actually come up with much more broad use of different analytical capabilities. And so we’re excited about this.
You can, like I said, you can see it forecasted at grants dot gov right now. We’re going to have the actual funding opportunity come out in the next handful of weeks. So please stay aware of that. And I think we’ll probably have some more details coming out about that in the next little bit.
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JENNIFER LAYDEN, CDC [01:14:28]
So, absolutely, we are committed in our working with our non infectious disease partners.
So we look across our core data systems, the case data, the lab data, the vital statistics, syndromic, those all– certainly there’s an infectious disease heavy presence. But that data is used in chronic diseases.
So syndromic surveillance system is used very heavily by our opioid program. Vital statistics is critical data for for non infectious disease as well.
So as we’re continuing to modernize those systems, they benefit not just the infectious disease but also the chronic disease.
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DYLAN GEORGE, CDC [01:16:09]
So the other thing i would add to that thought was like clearly there’s there’s going to be a focus on chronic conditions as well. And so infectious diseases and chronic, just the way Jen has described it, but there’s also– we’re very keenly, within at least within CFA as well, we are keenly interested in the interaction of the two. And that’s where the social determinants and behavioral kind of components and trying to get a better understanding of what that variability looks like across the United States. And then how frequently do we have to update our understanding of that, because that’s critically important if we’re going to try to be able to provide services and understand who’s at risk when in a time of an infectious disease event, we need to understand what those co-morbidities look like.
And so there are opportunities for not only developing those capabilities within each program, but also synergies and interactions between them to meet our mission in a unique way as well.
MONA MARIN, CDC [01:45:49]
Historically, varicella was considered a disease of little consequence, a rite of passage during childhood, too mild to warrant prevention.
That misconception started to change after the first cases of fatal varicella were reported in mid 1950s in children treated with newly introduced immunosuppressive therapy that cured several serious diseases, that unmasked the lethal potential of the varicella zoster virus, or VZV.
Then in late 1960s through early 70s, immunosuppressive treatment was increasingly used as systemic steroids therapy for organ transplantation or childhood cancers. Leukemia, previously almost always fatal, was cured in about 80% of children, only to have many of them die of varicella before immune reconstitution.
Varicella thus no longer seemed too inconsequential to justify the development of a vaccine.
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MONA MARIN, CDC [01:47:54]
In 1995, the varicella vaccine was licensed and recommended in the United States, and the United States became the first country with a routine varicella vaccination program.
ACIP made the scientifically informed, yet bold, decision in recommending varicella vaccination. There was debate around the time of vaccine recommendations on whether the health burden of varicella justifies a vaccination program, whether the vaccine would be accepted by parents and providers, whether the varicella program would shift the burden of varicella from children who have milder disease to adults who have more severe presentations.
And there is also a risk during pregnancy and whether the program would increase herpes zoster incidence.
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MONA MARIN, CDC [01:50:46]
The varicella program implementation was highly successful. The graph on the left shows one dose coverage for children 19 to 35 months of age for varicella vaccine in blue, and as comparison MMR in gray. High coverage was attained among young children with 89% by the end of the one dose program in 2006, and remained around 90, 91% since then, with coverage levels similar to those of MMR, a more mature program.
The graph on the right shows the rapid uptake of the second dose after the two dose recommendation in 2007, coverage reaching a median of 93% by 2020 in six states with good immunization electronic records, again approaching the coverage of two dose MMR.
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MONA MARIN, CDC [01:54:24]
In this table, the second column presents the average annual hospitalizations in the pre-vaccine period. The third column presents the average annual hospitalizations in 2018 to 2019. In the last column, the percent declines in hospitalization rates.
We see dramatic declines in rates of over 94% in all age groups younger than 50, with the greatest declines in children and adolescents. Annually, more than 10,500 varicella hospitalizations are now prevented, including more than 1,250 among infants and more than 4,200 among 1 to 4 year olds.
We also saw large declines for deaths. The overall varicella mortality rate has declined 89% from the pre-vaccine period to 2017 to 2019. And most of this decline occurred during the one dose program.
Similarly to hospitalisations, the mortality rate declined in all age groups in persons younger than 50, which this graph presents. We have gone from an annual average of 84 deaths pre-vaccine with varicella as the underlying cause, to three deaths in 2018 to 2019, with deaths practically eliminated among younger those younger than 20, a 99.4% reduction in rates.
In five out of the last nine years, no deaths underlying or contributing were reported in this age group.
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MONA MARIN, CDC [01:56:15]
As I mentioned earlier, before the routine varicella vaccination program was adopted, there was concern by some experts that decreased circulation of VZV and therefore less external boosting would lead to an increase in herpes zoster in adults.
This graph presents herpes zoster trends in persons aged 30 years or older, born before the start of the varicella vaccination program. In this age group, herpes zoster incidence increased during the earlier study years, continuing a period of decades of increases, but with no acceleration following introduction of the varicella vaccine, and with deceleration in later years starting in 2007 with the oldest age groups.
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MONA MARIN, CDC [01:57:56]
High vaccine coverage was reached and maintained. The program prevented morbidity and mortality with large declines.
Approximately 91 million varicella cases, 238,000 hospitalizations, and 1,900 to 2,400 deaths have been prevented over the 25 years of the program. The program is highly cost saving, with $23.4 billion net societal savings to date.
And the U.S. data do not support prior predictions that the varicella vaccination program would increase herpes zoster incidence among adults.
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WILLIAM SCHAFFNER, NFID [02:03:01]
I would like to add my congratulations and thanks to Dr. Marin for a wonderful presentation.
I would like to give a little recognition, and perhaps even more than that, to all the people in all the states who got varicella vaccine included in school immunization laws. Those laws were very important in establishing those high immunization rates and maintaining them over the years.
True, not only for varicella, but many other vaccines also.
MEGAN WALLACE, CDC [00:13:09]
When we look at both the potential benefits and harms for adolescents together, using the hospitalization ranges from the sensitivity analyses, we see that per million doses we would expect to prevent between 31 and 136 hospitalizations, 9 to 40 ICU admissions, and one death. Based on the preliminary data on myocarditis following bivalent booster in VSD. We have seen zero myocarditis cases in nearly 50,000 males that have received a bivalent booster dose, and no cases in females with a similar number of doses. I want to again stress that these are small numbers of doses, and though they correspond to a point estimate of zero myocarditis cases per million doses, you can see in the footnote that the upper range of the 95% confidence interval runs from 0 to 62 cases per million doses. Next.
On this slide. We have taken the results from the previous slide and applied a correction to account for the potential incidental SARS-CoV-2 infections among hospitalized patients that Dr. Taylor discussed in the COVID NET presentation. After applying this correction, we estimate that per million doses over six months, we would expect to prevent between 17 and 75 hospitalizations, 5 to 22 ICU admissions, and potentially a death. Next.
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MEGAN WALLACE, CDC [00:16:53]
In summary, significant benefit is still seen for primary series vaccination in all age groups. The benefits of a bivalent booster dose vary by age, time since last dose, and COVID 19 incidence. The risk of myocarditis after COVID 19 vaccines is likely reduced by a longer interval since last dose. Additional data can better define risk after bivalent vaccines, but current data are encouraging. Changes in COVID 19 hospitalization rates would impact the benefit assessment.
There are additional benefits of COVID 19 vaccines unable to be quantified in the benefit risk assessment, including likely prevention of post-COVID conditions, possible reduction in transmission, and increased confidence in social interaction. The benefit risk assessment will continue to be monitored as new data are available. Receipt of primary series continues to be important in all ages. And boosters remain an important option to improve protection against severe COVID 19, especially for higher risk populations.
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MEGAN WALLACE, CDC [00:22:23]
We didn’t focus on them for the benefit risk comparison because the risk is primarily in those younger age groups, and that’s also the age group where the benefits are the smallest. But if we go to slide seven? We can see in the older age groups, 50 to 64, 65 plus, even depending on dosing interval, there’s still pretty substantial benefits. But particularly in that 65 plus age group, I mean, they’re pretty remarkable for even for the bivalent booster, just the incremental benefit we see, you know, 2,500 hospitalizations prevented, which is pretty substantial.
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SARA OLIVER, CDC [00:26:15]
So for this presentation will think through considerations for future planning for COVID vaccines. Next slide. So for planning purposes, we need to be aware and evaluate where we are now and then identify and discuss where we’re going. Next slide. And then obviously how we get there. Next slide.
So as we flesh that out, we’re going to review where we are now, including current recommendation vaccination rates and hospitalization rates for the program writ large. Then as we think through where we’re going, I think we’ve continued to say this today, but the goal is clear, simple recommendations. So as we think through how we get there, we have two questions we’re going to focus on today.
How frequently should people get a COVID vaccine? And are there groups or population who should potentially have more frequent COVID vaccines, such as more than one vaccine a year?
We’ll start first by reviewing where we are now. Next slide. These are our current recommendations for COVID vaccines. The point of this is not to review each individual recommendation, but that clearly the recommendations we have right now are complex.
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SARA OLIVER, CDC [00:35:47]
These data from the excellent University of Iowa colleagues who’ve been able to conduct rapid surveys around intent. We know that while vaccination rates remain low in these youngest age group, there are still parents with intent to vaccinate their young child.
For parents with an un or under-vaccinated child, 6 to 23 months and 2 to 4 years, for both, 38% said that they had an intent to get their child vaccinated in the next month or so
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SARA OLIVER, CDC [00:37:14]
So as we think through a population that may still need a primary series, children less than two years have higher COVID hospitalization rates than older children. Children less than four years are less likely to have both prior infection and prior vaccination. We also know that children have frequent visits to health care providers. The AAP’s recommended schedule for young children is on the right. And you can see that prior to three years of age, children are recommended to go to the pediatrician at least every six months, if not more, when they’re younger.
So the work group discussed continued primary series recommendations for young children, both ages six months through two years and six months through four years, were discussed without a clear consensus from the workgroup for either age cutoff. Without a clear cut off from the data, the workgroup thought feasibility could also be considered as we think through this.
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SARA OLIVER, CDC [00:39:42]
The work group discussed more frequent COVID 19 vaccine doses for older adults and at this time felt that the data were insufficient to determine a conclusion. The data weren’t conclusive to yet identify a need for frequent vaccines, and there was concern that it may not be feasible to implement a vaccine program in all adults 65 and over twice a year.
However, there was much discussion that these recommendations can be updated based on closely monitoring data in older adults, including hospitalization rates of older adults who received a bivalent booster, bivalent VE and patterns of waning in older adults, as well as SARS-CoV-2 virus evolution and the possibility of future immune escape variants.
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SARA OLIVER, CDC [00:43:49]
So as for the overall work group thoughts on considerations for future planning: simple recommendations are easier to communicate, which also may improve uptake. The work group was very supportive of simplified recommendations and planning for future of COVID vaccines, which could also include additional updates to COVID vaccines in the future, as was discussed at the recent VRBPAC meeting.
However, uncertainties remain for the ideal timing and populations for future booster doses, especially if new immune escape variants develop.
The work group was supportive of a fall or annual COVID vaccine program, at least for this year, with the flexibility to adjust based on new data, especially for populations at higher risk.
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SARA OLIVER, CDC [00:46:23]
The work group agreed with the concept that there is that population that’s going to continue to age in. There is likely to be an immune naive population that needs kind of still a prime boost.
What the work group, it didn’t feel like the data was completely clear, and would love to get ACIP’s thoughts on, is there a specific age group? So would we say for kids who’ve never had a COVID vaccine before, who are six months through two years of age, they need a primary series? And after that they could get, you know, an annual booster dose similar to flu, like there is a population for flu, if you’ve not had a flu shot before, where you get two vaccines in your first series because you need the prime boost?
So it’s specifically saying, is there a population that we would really want to say, if you’ve not had a COVID vaccine before, you need a primary series? And what population that would be? So six months to two, or six months to four.
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MATTHEW DALEY, ACIP [00:48:45]
I think the idea is that a 18 year old who’s never gotten the primary series, but has been infected, and then gets a single dose in the fall, probably has decent protection. We don’t know that as established fact, but I think that’s an assumption underlying this, that an 18 year old might just get a single dose, and the recommendation would not be get two doses and then get an annual dose.
So in other words, we’re at a pivot point. And for those of young adults who’ve never been vaccinated, probably they would just get a single annual dose and be considered up to date, quote unquote.
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SARA OLIVER, CDC [00:51:49]
I will say we have heard from some of our implementation minded colleagues that having vaccine recommendations that differ based on prior SARS-CoV-2 testing would be potentially be difficult to implement. I’m happy to hear from additional, if we think that that has changed. But I know that that has been a continued discussion, as we’ve discussed this on the work group.
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SARA OLIVER, CDC [00:52:12]
Then I specifically wanted to say something about your comment with pregnant individuals. I didn’t include that here because that’s we’ve not fundamentally had– this is more consistent with where we’ve kind of been with recommendations in the past, that would fundamentally be a little bit different. But I will say that that is one of the kind of top priorities for what we have for additional analyses to go moving forward, is to really do a deeper dive.
I think we’re getting emerging data on that and really look forward to kind of outlining all the available data we have to answer that question and to bring it to ACIP. So I think it it wasn’t included here because it’s– I think we need a separate, deeper dive on the data. But but that is up on the docket for things for us to tackle next.
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CAROL HAYES, ACNM [00:53:37]
I think I have some concerns and I would love to hear anybody else’s understanding of this.
But when we look at the bivalent vaccine and its ability to maintain a robust immune response, I’m thinking back to pertussis and whooping cough. And it was a vaccine that waned so quickly, we had to make that recommendation that every pregnant woman in every pregnancy get vaccinated. And we had a really hard time with uptake on that in the pregnant population.
So I feel like we need data that says that if you want to protect your newborn, and that’s really the message that we have to give, if you want to protect your newborn, you have to get vaccinated in every pregnancy. But we need a lot more data on what happens when you vaccinate a pregnant woman and how long does their immunity last.
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MICHAEL HOGUE, APHA [01:16:43]
I will just bring up a question that I think Dr. Sanchez asked earlier, but I didn’t hear the answer to, and that is where does the Novavax product fit into all of this? I know there are a lot of a lot of pharmacists and physicians who have been asking questions about that product. And could you briefly just tell us what where Novavax’s product fits into all of this?
SARA OLIVER, CDC [01:17:08]
Thanks. I will say we were just saying that we need to make sure, before we, at the end, we come back to that question. So happy to do it now.
I will say that for right now we were very intentional, especially in the last presentation, when we talked about the transition from monovalent to bivalent, for the primary series, those discussions were focused on the mRNA vaccines.
So for right now, no changes are anticipated. The primary series that is currently authorized and recommended for Novavax is monovalent, and it’s our understanding that that will continue to be available and recommended as is.
I know there were discussions moving forward for the future of bivalent vaccines kind of across all manufacturers, including the protein subunit for future doses. And for that I may turn– I think we have Novavax colleagues on the line, so I don’t know if they have a comment they want to make about planning for future as it relates to the Novavax vaccines.
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DENNY KIM, NOVAVAX [01:18:39]
I think you have that right, is that we’re in discussions with the FDA and I think the next two to three months will get a lot more clarity on sort of the future directions going forward, both for the fall and winter campaign for 2023, and future vaccination regimens. But I can’t offer much more clarity than that, other than that we are in active discussions with the FDA.
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JAMIE LOEHR, ACIP [01:34:44]
I’d like to respectfully disagree. If an 11 month old has had it, it seems that they probably don’t need a primary series. I think a fairly simple message would be if you’ve had documentation of a COVID illness, you don’t need a primary series, no matter what the age, and if you don’t have documentation, you would need a primary series. And I think that’s a fairly simple message in and of itself. So I would emphasize that reframing would be my suggestion.
PABLO SANCHEZ, ACIP [01:35:21]
I just want to say I agree with Jamie.
KATHERINE POEHLING, ACIP [01:35:26]
I would like to add that children, younger children, do not have this robust of immune response. And I would like to have some data before I made that decision. And I think we can obtain exactly that data, and that way we could follow the science.
CHRIS TAYLOR, CDC [00:12:03]
This figure shows the proportion of hospitalizations where COVID 19 is a likely reason for admission by age group and period of COVID variant predominance, for June 2020 through November 2022. Reason for admission is determined by trained COVID NET surveillance officers using an established algorithm. As a reminder, all COVID NET hospitalizations have a lab confirmed positive SARS-CoV-2 test during hospitalization or within 14 days before hospital admission.
Hospitalizations where the admission is noted as likely due to trauma, obstetrics or labor and delivery, psychiatric admissions requiring acute medical care, or inpatient surgery or procedures are categorized as such. Hospitalizations where the chief complete includes fever, respiratory illness, COVID like illness, or suspicion for COVID 19 are classified as having COVID 19 as a likely reason for admission. Hospitalizations, where the medical chart specifically indicates that COVID 19 was an incidental finding, or that the admission was likely not COVID related, were also categorized as such. For hospitalizations where another reason for admission is specified in free text, COVID NET clinicians examine the specified reasons and further classify.
The chart displays the proportion of COVID 19 associated hospitalizations, with COVID 19 as a likely reason for admission, among three pediatric and three adult age groups, as well as overall by periods of variant predominance. As indicated by the set of columns second from the left, about 80 to 90% of COVID 19 associated hospitalizations among children ages less than four years had COVID 19 as a likely reason for admission across all variant periods.
Older children, ages 5 to 11 years, range be between 70 to 95%. Adolescents, ages 12 to 17 years, had the lowest proportion of hospitalizations with COVID 19 as a likely reason for admission, between 50 and 60% for the Omicron predominant periods beginning in December 2021. Among this group, many admissions are psychiatric admissions requiring acute medical care, with more than 25 or 35% of hospitalizations in some months.
Adults ages 18 to 49 had a similarly low proportion of hospitalizations with COVID as a likely reason for admission. Between 50 and 70% during the Omicron period. Among this group, many admissions are due to labor and delivery, with more than 25 or 30% of hospitalizations attributed to that in some months.
Among adults ages 50 years and older, in the two rightmost set of columns, between 80 and 94% of hospitalizations have COVID as a likely reason for admission across all variant periods examined. Next slide.
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CHRIS TAYLOR, CDC [00:21:46]
So these data from this slide are posted publicly. The figure that I showed, again, for adults is age adjusted. I included that one because that one has the data on the bivalent booster dose.
We have a quality standard for the COVID-NET data where a certain proportion of the underlying COVID-NET catchment population has to reach a level of vaccination in order for our rates to be considered stable. In our most recent data that we have analyzed, the pediatric groups have not yet reached that standard for us to be able to include them. We were hoping– we hope with the data that we just received a few days ago, that we’ll be able to start displaying those data.
So the data that are posted, we have sort of the the pre updated booster dose categories of unvaccinated as well as vaccinated plus or minus a booster dose. But we aren’t– we have not yet been able to display the data showing the rates among those that have received the updated bivalent booster dose.
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AMADEA BRITTON, CDC [00:42:46]
This includes periods of both BA.5 related sub lineage predominance and of XBB and XBB.1.5 related sub lineage predominance because previously published work from this platform demonstrated that VE against symptomatic disease for these two groups was similar, we have combined these time periods.
And here are the results for relativity for children and adolescents aged 5 to 17. On the left I show age group and vaccine dosage pattern, including the reference group which received two or three monovalent doses and no bivalent dose. And then those who are two weeks to one month, 2 to 3 months, and for 12 to 17 year olds, 4 to 5 months since a bivalent booster dose.
What we see is that relative VE in the month after vaccination is 65% for 5 to 11 year olds, and 68% for 12 to 17 year olds, with an early indication of slight waning as was observed with the monovalent vaccine.
Please note that a Pfizer BioNTech bivalent booster was first authorized for adolescents 12 and older on September 1st and for children 5 to 11 on October 12th of 2022. Moderna was authorized for children and adolescents 6 to 17 on October 12th as well. This means that there is less follow up time for children aged 5 to 11 years, and we were therefore not able to estimate VE 4 to 5 months after the bivalent dose in the 5 to 11 year old age group.
This slide shows the same analysis. But for adult age groups with individuals that received a bivalent booster compared to individuals that only received 2 to 4 doses of monovalent vaccine. We observed similar waning patterns across age groups.
In the red box, I have highlighted the estimates among adults 65 and older, which appear slightly lower than in younger individuals. The pattern of waning against symptomatic infection is very similar to what was observed after monovalent booster doses, with VE against symptomatic infection decreasing to minimal protection by around 5 to 6 months.
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AMADEA BRITTON, CDC [00:46:41]
Now, on this slide, we show relative VE of the bivalent booster against ED UC visits and hospitalizations. The reference groups here are the individuals from the prior slide who received only monovalent doses with their last dose at least two months ago. Note again that most individuals in this group are almost a full year from their last dose. In the top red box are the ED UC estimates. Among these individuals, a bivalent booster offered an additional 50% protection against ED UC visits in the first 7 to 59 days after boosting, which declined to 36% after 60 days, with the median time since dose 76 days.
Relative VE against hospitalization shown in the lower red box was similar at 52% and 31% at 7 to 59 and 60 to 119 days respectively. Please note that although the relative trends are similar for both outcomes, residual protection prior to the booster was higher against hospitalization than for ED UC visits, and so likely total protection against hospitalization is also higher. There may also be some hospitalizations captured by the VISION platform that represent less severe COVID 19 disease, comparable to that of an ED or UC visit.
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AMADEA BRITTON, CDC [00:48:56]
And here we have the updated IVY results among adults age 65 and older. On the left hand side of this slide is the dosage pattern studied. We’ll start first with the upper section of the slide, which shows absolute VE against hospitalization for adults 65 and older, comparing people with at least two monovalent doses, but no bivalent dose, to unvaccinated people. This result is displayed in the upper red box and shows VE of 17% with a confidence interval crossing the null consistent with limited to no residual protection.
The second estimate displayed in the lower red box is relative VE of a bivalent booster, comparing individuals that received a bivalent booster with individuals with at least two monovalent doses but no booster. The additional protection offered by a bivalent booster is 52%. Note that the median time since last dose is almost a year, at 352 days.
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AMADEA BRITTON, CDC [00:49:53]
Lastly, I’m now displaying absolute bivalent VE at the bottom of the slide. This is comparing individuals that received a bivalent booster to unvaccinated individuals, i.e. people that never received even monovalent vaccine. This estimate is almost identical to the relative VE of the bivalent booster from the line above, which is consistent with the finding that the monovalent vaccine is providing limited to no protection after one year.
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AMADEA BRITTON, CDC [00:52:58]
In summary, current data from CDC vaccine effectiveness platforms demonstrates that bivalent booster doses provide added protection compared to earlier monovalent doses against symptomatic infection in children and adolescents aged 5 to 17 years and in adults 18 years and older, though there may be early evidence of waning, consistent with patterns previously observed for monovalent vaccines against symptomatic diseases.
Updates to VE of bivalent booster doses against ED UC visits and hospitalization in adults confirm that the bivalent vaccines are providing protection against ED UC visits and hospitalization compared to people who received two, three or four doses of the monovalent vaccine and no bivalent dose.
For most people who received monovalent doses and are eligible for a bivalent booster, more than a year has elapsed since their last monovalent dose and they may have limited remaining protection. All eligible people should stay up to date on COVID 19 vaccinations, including receiving a primary series and a bivalent dose if eligible.
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SARA OLIVER, CDC [01:11:04]
This slide shows representations for the number of mRNA COVID 19 vaccine products currently between monovalent and bivalent, as well as different doses and formulations by age. Next slide.
While the final number of products will ultimately depend on what is authorized, these are what is possible with transitioning from primary series to bivalent. We could be down to five total products, and importantly, it would eliminate lookalike vials for Pfizer and Moderna. Next slide.
So overall, a transition to a bivalent primary series could improve storage space. Providers have limited storage space, and as we move to the use of a VFC program in the future, it’s worth noting that VFC stock is required to be duplicate and separate.
It could also reduce errors again by eliminating lookalike vials, as well as currently, one of the most common administration errors reported right now is providers giving a bivalent vaccine as a primary series dose and error.
It would also allow for continued access to primary series, while the dates vary by product and age group. The majority of our current monovalent vaccine stock in the U.S. expires within the next few months. There would be a possibility that access to primary series could be more limited without transitioning to a bivalent option.
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GRACE LEE, ACIP [01:21:02]
If you’re able to comment on when you might anticipate it would be possible to transition to a BLA? And I ask because, you know, two options are in front of us. One is to continue to modify the authorizations for very special cases, or the second would be to allow clinicians to have the ability to prescribe as they think it makes clinical sense to do so. Dr. Kaslow, are you on the line?
DAVID KASLOW, FDA [01:21:30]
Yes. This is David Kaslow, office director here for vaccines research. Yes, we are working this topic very diligently and are trying to move towards this as quickly as as we can. But I probably can’t say any more than that at this time.
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PABLO SANCHEZ, ACIP [01:26:23]
As we harmonize the– will that– will the primary series with Pfizer continue to be three doses versus Moderna two? And so I like to see a little bit more concrete data, or what future recommendations may be?
SARA OLIVER, CDC [01:26:46]
Thanks, Dr. Sanchez. I will say we have colleagues from Pfizer on the line. Dr. (unclear), I don’t know if there’s others that from Pfizer who want to–
UNSPECIFIED, PFIZER [01:26:55]
Thank you, Dr. Oliver. We have a Dr. (unclear) from the RU, our research unit, to address that question. (unclear) are you connected?
UNSPECIFIED, PFIZER [01:27:06]
I am. Can you hear me? Perfect. Thank you. So I very much appreciate that question.
We are, as discussed at VRBPAC, currently enrolling in our dose finding portion of a primary bivalent series with the bivalent Omicron BA.4/5. We will have– we’re looking towards having data a little later in the fall. As you’ve noted in these discussions, there’s actually been low uptake, and we’re reflecting that also in our clinical trial as well, in terms of enrollment.
Regarding your question of the three dose primary series and a simplification, that would really require FDA guidance, and I would defer back to Dr. Kaslow on the next steps to allow for that.
PABLO SANCHEZ, ACIP [01:28:01]
Can you comment, though, with the current study that you’re doing, is it a three dose schedule?
UNSPECIFIED, PFIZER [01:28:07]
Of course. Thank you so much. Yes, we are working, as per the currently authorized vaccine, on a three dose primary series. The phase one includes children six months to less than two year olds, and the 2 to 5 year old age group, with 90 participants in both of those groups for a total of 180. And we’re dose finding with three, six and ten micrograms currently.
SARAH MEYER, CDC [00:11:30]
In terms of the vaccination program, much of the current COVID 19 vaccine program will remain unchanged after the PHE ends in May. The primary impact of the PHE ending on the vaccination program is the possibility of reduced submission of vaccine administration data from some jurisdictions. This is because the data use agreements, or DUAs, for COVID 19 vaccine administration were established with termination provisions that reference the PHE. However, state and territorial public health jurisdictions are being asked to extend this DUA through the end of 2023, and so far, the majority of jurisdictions have done so.
It is important to note that the end of the public health emergency does not equate to the end of the current national vaccine distribution program or the transition to commercialization. I think this has been one of the biggest points of confusion we have heard about, that the end of the PHE also means the end of the federal vaccine program, and that is not the case.
CDC has received many questions regarding commercializing COVID 19 vaccines. We continue to work with HHS on this process and are collecting questions to help ensure we address the needs of jurisdictions and partners as we move towards commercialization in the future. And we will share information with you all as soon as we are able to.
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TOM SHIMABUKURO, CDC [00:38:39]
There have been no unusual or unexpected reporting patterns observed and no evidence of a safety concern detected for ischemic stroke, with either bivalent boosters and VAERS, FDA monitoring, and CMS data, and VA monitoring in the VA system, have not detected any safety signals using the historical comparator designs. And surveillance conducted by international regulatory and public health partners has not detected a safety concern for ischemic stroke following bivalent booster vaccination.
There’s been no evidence of a safety signal for ischemic stroke in Pfizer’s global monitoring. And no safety signals were detected for a ischemic stroke for the primary series or monovalent boosters for Pfizer or Moderna vaccines in U.S. and global monitoring. Although these surveillance activities did not include analysis to evaluate the effect of simultaneous flu vaccination.
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VERONICA MCNALLY, ACIP [00:49:31]
At what point would this statistical signal be more widely publicized for clinicians to consider? So, for example, at what point would this issue maybe become something that would be noted, for example, in clinical guidance?
TOM SHIMABUKURO, CDC [00:49:54]
Well, we have we have made this information available through through a posting on the web, on the CDC website and presented this at the VRBPAC meeting and are presenting this today. And presumably this will be published soon.
I just want to be clear that the data that I’ve presented today are not sufficient to conclude that there is a safety problem with the Pfizer bivalent booster and ischemic stroke in the 65 year old age group, or a safety problem with the Pfizer bivalent booster and co-administration with with other high dose or adjuvanted influenza vaccines. We have a statistical signal and we are working through our signal assessment process.
other reasons besides vaccination which could be contributing to these findings, such as confounding, unmeasured confounding, potentially later arriving data. So we continue to monitor, we continue to do the work. But this– the data that I presented are not sufficient to conclude that there is a safety problem here with stroke.
And I think that Dr. Forshee’s presentation later on on this going to is going to further elaborate on that. And FDA also has a planned epidemiologic study to look at this and the recommendations for bivalent booster vaccination and flu vaccination vaccination have not changed. Everyone who’s eligible for a booster should get a booster and everyone eligible for a flu vaccine should get a flu vaccine.
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EVELYN TWENTYMAN, CDC [01:40:55]
We observed a high incidence of stroke following both COVID 19 and influenza diagnosis in the PCORnet data over the late Omicron period of 2022. You’ll see that the y axis ranges from 0 to 10,000 strokes per million. In the negative three days prior to COVID diagnosis to 28 days post diagnosis, we observe an incidence of approximately 8,800 incident strokes per million over these days. Although we do not have a current estimate of incident stroke in the United States, we are able, using this health care data to calculate average incidence of stroke in this population in this dataset over 32 days. And note that this comparison is visually striking.
I will note, however, that groups presented are of the same age category and adjusted time at risk. Crude incidence within these groups is not otherwise adjusted. Next slide, please.
This is the same slide you just saw presented. But now, with lines demonstrating the proportion of incidence of stroke within three days preceding or seven days following diagnosis of COVID 19 or influenza. Again, stroke appears to be an early complication of disease. Next slide, please.
As I move as we move to this slide, I want to alert you first to the change in the magnitude of the y axis. It’s no longer 0 to 10,000 strokes per million. It’s now 0 to 1,800 strokes per million. Average stroke incidence among adults aged 65 years and older and the overall Health Verity population over 32 days, sorry, 28 days is slightly less than 1,400 strokes per million over this time period. In contrast, you’ll see that we observe a very low incidence of stroke in the recently vaccinated population.
It’s important to underscore, again, though, that these are observations of crude incidence in these groups, which are within the same broad age category of 65 years and older and which are adjusted for time at risk but are not adjusted for any other potential confounders such as underlying medical conditions or older age groups. We are not presenting attributable risk. We are not assessing causality in any way. Nevertheless, these are helpful observations.
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EVELYN TWENTYMAN, CDC [01:35:53]
We know that those who develop stroke are more likely to be of older age, have more severe COVID 19 disease, and more likely to have hypertension, diabetes and coronary artery disease than those who do not develop stroke. In terms of who may be at lower risk, we have observed that COVID 19 vaccination is associated with a reduced risk of ischemic stroke after COVID 19, including for those ages 65 years and older. Next slide, please.
Now let’s turn to what we know about flu for a moment. An association between recent respiratory infection and increased stroke risk has been observed. And as is the case in COVID 19, disease, stroke appears to be an early complication. While two small randomized studies did not note a significant effect of influenza vaccination on stroke risk, decreased risk of stroke with influenza vaccination has been reported in several observational studies. Additionally, a benefit of influenza vaccination has been noted in some studies examining major cardiovascular outcomes, some including stroke, within composite outcomes.
We do hope to learn more about both COVID 19 and influenza, their relationship to stroke and to better understand potential protective effects of vaccination. Given the limitations reflected here and in our collective effort to interpret the safety signal discussed today, we were particularly interested in these outcomes within the population of people ages 65 years and older. Next slide, please.
We at CDC were able to initiate pursuit of these questions through two large health care data sources, which I will briefly describe here. The National Patient Centered Clinical Research Network, better known as PCORnet, is comprised of electronic health record data from ambulatory emergency department and inpatient settings. It covers all patients, in other words, with and without insurance, in participating health systems, or about 10% of the U.S. population, including those aged 65 years and above. There is almost no lag in this data because it comes directly from participating the PCORnet sites following structured inquiries and does not have external dependencies such as processing of claims. We used this data to rapidly assess incidence of stroke across this diverse population among those with recent COVID 19 or influenza and incidence overall in this population health.
Verity, on the right here, is a massive health care data source, including medical claims from closed payer systems related to ambulatory emergency and inpatient settings. The data is linked to vaccination data from the federal retail pharmacy program using Health Verity’s privacy preserving record linkage technology. It covers patients insured through Medicare Advantage, or about 25% of the U.S. population aged 65 years and above. There is an approximate three month lag in data when using closed claims. We use this data to assess incidence of stroke across the U.S.– sorry across the insured US population with recent COVID 19 or influenza vaccination and incidence overall in this population.
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EVELYN TWENTYMAN, CDC [01:39:15]
Methods used in each of these datasets were designed to capture incident strokes. Patients with a history of stroke were intentionally excluded to attempt avoiding overestimation of incidents. As a result, we may have under captured strokes as history of stroke and TIA is associated with risk of stroke. ICD 10 codes were generally chosen to align with the definitions of stroke used in Vaccine Safety Datalink.
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EVELYN TWENTYMAN, CDC [01:40:55]
We observed a high incidence of stroke following both COVID 19 and influenza diagnosis in the PCORnet data over the late Omicron period of 2022. You’ll see that the y axis ranges from 0 to 10,000 strokes per million. In the negative three days prior to COVID diagnosis to 28 days post diagnosis, we observe an incidence of approximately 8,800 incident strokes per million over these days. Although we do not have a current estimate of incident stroke in the United States, we are able, using this health care data to calculate average incidence of stroke in this population in this dataset over 32 days. And note that this comparison is visually striking.
I will note, however, that groups presented are of the same age category and adjusted time at risk. Crude incidence within these groups is not otherwise adjusted. Next slide, please.
This is the same slide you just saw presented. But now, with lines demonstrating the proportion of incidence of stroke within three days preceding or seven days following diagnosis of COVID 19 or influenza. Again, stroke appears to be an early complication of disease. Next slide, please.
As I move as we move to this slide, I want to alert you first to the change in the magnitude of the y axis. It’s no longer 0 to 10,000 strokes per million. It’s now 0 to 1,800 strokes per million. Average stroke incidence among adults aged 65 years and older and the overall Health Verity population over 32 days, sorry, 28 days is slightly less than 1,400 strokes per million over this time period. In contrast, you’ll see that we observe a very low incidence of stroke in the recently vaccinated population.
It’s important to underscore, again, though, that these are observations of crude incidence in these groups, which are within the same broad age category of 65 years and older and which are adjusted for time at risk but are not adjusted for any other potential confounders such as underlying medical conditions or older age groups. We are not presenting attributable risk. We are not assessing causality in any way. Nevertheless, these are helpful observations.
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EVELYN TWENTYMAN, CDC [01:44:13]
While the data pertaining to vaccine safety is reassuring, in contrast, the data pertaining to COVID 19 disease and influenza was not so reassuring. Based on the review of health care data demonstrating high incidence of stroke with COVID 19 or influenza, the priorities identified here include increasing awareness of the risk of stroke with COVID 19 disease and influenza, and continuing to encourage uptake of the bivalent COVID 19 boosters.
Next slide, please.
In summary, the COVID 19 ACIP work group remains confident in current COVID 19 vaccine recommendations and does not recommend any changes to current recommendations, including those regarding co-administration of vaccines. CDC and partners anticipate the opportunity to review and consider upcoming analyses prior to the 2023 2024 flu season.
RICHARD WEBBY, WHO [00:16:58]
We did make one recommendation to update the available candidate vaccine viruses for our H5, and this is really in response to the spread of H5, particularly through the Americas. And a little bit of the evolution of viruses associated with that spread. So we are putting another H5 candidate vaccine virus into production, and that will start soon.
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SYLVIE BRIAND, WHO [00:06:36]
Before we get to the influenza vaccine composition, I would like to briefly address the reports of human H5N1 infections in Cambodia. Cambodian authorities have informed us of two confirmed cases of avian influenza H5N1. Both member of the same family. One of the cases, an 11 year old girl, unfortunately passed away. We are in close communication with the Cambodian authorities to understand more about the outbreak. Field investigations are ongoing. The global H5N1 situation is worrying given the wide spread of the virus in birds around the world and the increasing reports of cases in mammals, including humans.
H5N1 influenza is a severe respiratory disease with a range of symptoms observed from mild to fatal. The mortality rate, among cases reported with H5N1 infection over the years, is over 50 percent. WHO takes the risk from this virus seriously and urges heightened vigilance from all countries.
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SYLVIE BRIAND, WHO [00:21:20]
This is a WHO-Cambodia call based on the IHR requirement, because, as you know, based on the international health regulations, we have a joint risk assessment with country’s authorities. And so this is currently what we are doing, discussing with Cambodian ministries of health to get the latest information on the risk assessment.
Regarding the case in the father. So the father was a contact and had symptoms. So that’s why he has been sampled. But so far, it’s too early to know if it’s a human to human transmission or exposure to the same environmental conditions. And so that’s why we need more investigation to clarify the mode of transmission.
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RICHARD WEBBY, WHO [00:31:55]
So when we do the updates of our candidate vaccine viruses, which you referred to, Todd Davis reported on or summarized this morning, we are really more focused on the finer details of these viruses. So we use serum that’s produced in ferrets, which is quite discriminatory. And the idea being we want to get sort of into the weeds of how different these viruses are. But what we’ve seen in the context of this, but also sometimes in the context of the seasonal decisions as well, sometimes the human response can be a little more broad than that ferret response.
So one is really more from a risk assessment, a finer detail analysis of what’s circulating, that the human response, I think, fortunately tends to be a little bit bigger. But I’ll say we need a whole lot more work like this to understand exactly how broad that response is. We’ve also got to keep in mind the study that I talked about that was came from a vaccine that was adjuvanted in humans, which again, gives a little broader response.
The work that Todd described this morning typically doesn’t include that type of reagent as well.
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RICHARD WEBBY, WHO [00:33:26]
I don’t think it changes timelines of anything per se. So many of these reagents that we produced, these updating of the candidate vaccine viruses, are really done for preparedness purposes. So they’re not necessarily pushed through to manufacture or even trial production immediately. So the impact on timelines in terms of response is limited.
If the question is coming from point of, well, if viruses represented by this new CVV start to take off tomorrow, then I guess we would still be four or five months– four or five weeks away from having that reagent developed.
But, you know, at the same time, the ones we have on the shelf now do a pretty good job against the circulating viruses as well.
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DAVID WENTWORTH, CDC [00:41:05]
I think one of the things that I’m hearing in throughout these questions is really the ability to go to the library of vaccine viruses that already exist, eliminates six weeks to eight weeks from their creation. And so the pandemic preparedness or readiness efforts that the committee puts together on this are quite important. And so, for example, the clinical trials that Dr. Webby was pointing out, were to an H5, which is in this 2.3.4.4.b clade that has circulated for quite a while, but it was actually from nominated as a vaccine candidate many, many years ago. And then it had to go through these clinical trials.
Since then, another one was nominated. It was nominated a couple of years ago and that one is even more closely related when you use that fine grained ferret immunology to assess. And as Dr. Webby pointed out, humans tend to have a broader response. We also tend to have a lot of immunological memory, too many parts of the virus that help to protect us from disease, not just the key component of the vaccine, which is the virus attachment protein. And so I think when you started to talk about what the goals of the vaccine would be or what would be expected, a lot of it has to do with how, of the library of vaccines that we can pick from already, what could be used immediately and then start phasing in to what would be an optimal candidate as a potential outbreak unfolds.
And so that may not be a particular strain from the brand new one, but it might be unfolding a little bit later.
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SYLVIE BRIAND, WHO [00:04:15]
So it’s a very good question indeed, because it’s part of the vigilance we are having around human cases in general. So but so far, we have seen a lot of sporadic cases, meaning one case here and there. And so when you have only one case, you imagine that it’s because this case was exposed to animals, either alive or dead, and also or to the environment. So for us, it means that it’s a zoonotic transmission from animal to to human.
But when you see that there are a number of potential cases surrounding this initial case, you always wonder what has happened. Is it because maybe the initial case has transmitted the disease to other humans? And so we are really concerned about the potential human to human transmission coming from this initial spillover from animals.
And so this is currently the investigation that are ongoing in the contacts of this girl in in Cambodia. We are first trying to see if those contacts have H5N1 infection, and that’s why we are waiting for the laboratory confirmation of those cases. And secondly, once we have this confirmation, we will try to understand if those people have been exposed to animals or to a potential exposure to environment, contaminated environment, or if those people have been contaminated by the initial case.
And so this is a difficult investigation, requires really people going to the field and really assessing the situation. And so that’s why we are currently waiting for those results. So as we said, we think that currently the risk is not– the risk assessment is not changed. But we are really looking at this new information to see if we need to change the way we see things or not.
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DAVID WENTWORTH, CDC [00:08:33]
So that’s a good question, Helen. And I’m not the right person to address it. So I just wanted to make sure I commented that back to you, that I don’t have a good idea of what the production timelines for a particular H5 would be.
I would tell you, in some ways it’s quite similar to seasonal influenza virus. It would depend a bit on how well the yield of that particular antigen is. So with every different specific strain of influenza, you can have a different yield.
And you are correct. I think the anticipation is that it may need to have a prime and a boost, because people really haven’t been exposed to H5 for one reason, and in part because of the H5 immunogenicity. So you’re correct about that.
That is also why Dr. Webby mentioned the adjuvants, which would be dose sparing, so that you could potentially adjuvant the vaccine and not require as much to to boost it up. But to get to the specifics of how long it would take, there are going to be variables that would have to be considered. And then other parts of, for example, if it was, I think in specific countries, that would be different. And so I think they would have to address that specifically.
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SYLVIE BRIAND, WHO [00:09:45]
And also depends on the type of platform that are used for vaccine production. And currently most of the influenza vaccines are largely egg based production. So depends also on the availability of eggs. Of course.
But from 2019 estimates, we thought that and again, depending if we use adjuvant or not and lots of variables that we could have ten percent of the global production, could be in the range of 400 to 800 million doses of vaccine for the first year.
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DAVID WENTWORTH, CDC [00:01:50]
I think you’re all well aware of the power of mRNA technology to rapidly produce vaccine. And that was demonstrated by really good vaccines made against SARS-CoV-2 or COVID 19. There’s a lot of investigation by those same companies now and by others into how to adapt that technology for influenza, and for other any other pathogens of concern, but particularly those that could potentially be pandemic, in part because of the speed with which it can be produced and potentially the global dissemination of that vaccine, other countries being able to produce that on their own as well.
So I think there’s just a lot of effort in that space right now. There’s not a lot of– there’s hope that it would could reduce timelines and that can be particularly important for pandemic purposes. But I think, as Dr. Briand said, part of the influenza situation, which is quite specific to influenza, is because we have active vaccine production always happening, and the scale up capacity of the current vaccine manufacturers is quite great, that if the decision to switch is made, it can also be made rather rapidly.
It was about 100 days for the 2009 pandemic to have a vaccine. And so I think there is a variety of regulatory components that would have to be achieved for new technologies like mRNA or any other, like if it was DNA or other approaches. But I think everyone’s very hopeful that this will be a technology that can be applied to flu and will be able to determine its benefits or not.
TODD DAVIS, CDC [01:02:40]
As you can see, it’s sort of the beginning of December, as is expected from year to year, we typically see an increase in highly pathogenic strains detected and reported due to the circulation of those viruses and their appearance in migratory birds that are moving from northern climates to southern climates during this time period. And so we typically do see a slight increase during the colder months throughout the northern hemisphere.
As Dr. Briand mentioned, one of the intriguing findings from this reporting period is now detection of high path H5 viruses into Mexico, Central America, as well as South America, and also the sporadic detections, but increasing detections, in more than 12 different species of mammals around the world. And that includes even some of the recent detections, such as the sea lions that were detected in an outbreak in Peru. So, again, remaining quite vigilant both with veterinary health colleagues as well as public health colleagues to track the ongoing circulation and new incursions of this virus into new regions around the world.
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TODD DAVIS, CDC [01:03:53]
Looking at the activity in humans, as I said, there have been nine cases reported during this reporting period. Some of these viruses belong to both the H5N1 subtype, as well as three cases of H5N6 that were reported in China in this reporting period. And of those cases where sequence data has been obtained, all of them fall into the clade 2.3.4.4.b group of viruses, which we’ll talk a little bit more in detail.
But a case was recorded in Vietnam. Again, as Dr. Briand mentioned, the first case detected in South America was reported from Ecuador from a case that had illness onset in December of 2022, two cases that were asymptomatic, but also reported from Spain, from poultry workers, as well as the three cases of H5N1 from China and three from H5N6 in China.
I think the other thing I’ll mention is that while the outcome of each of these cases hasn’t been fully resolved through the IHR reporting system, many of these have recovered from infection. But I’ll note that some of these have also been severe, critically ill individuals, and several have resulted in fatal infections as well.
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TODD DAVIS, CDC [01:05:13]
Looking phylogeny of the clade 2.3.4.4.b viruses, another feature of this reporting period is again, as these viruses have expanded into new geographical regions, we’ve also seen some genetic clustering of these viruses, depending on where primarily migratory birds have been limited by their flyways.
And so what we’ve seen is that in North America, Central and South America, these viruses fall into a specific sub cluster of the clade two, three, four, four B’s. As you can see from the top of the screen, the case from Ecuador, as well as the previous case reported from the United States and Colorado, fall into this group of viruses. And most of the mammalian cases detected in both the U.S., Canada, as well as Central and South America, also fall into this group. Europe also has a group of viruses that are maintained among migratory birds, as well as from poultry outbreaks in those countries. The cases from Spain are shown in the following genetic tree as well. In Asia, also in particular in China, Vietnam, Laos and a few other countries also have a variety of two, three, four, four B’s that are genetically a bit different from what has been detected in other regions of the world. And finally, I’ve mentioned that in Africa there also remain some circulating viruses.
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TODD DAVIS, CDC [01:06:42]
The previous VCM, we did recommend a strain called the H Chicken Ghana 2021 that’s being developed as a CVV. And this has proven important, which I’ll talk about in a minute, but primarily just to say that the CVV is– it remains quite cross-reactive with viruses from Africa, as well as those that have been detected in Europe as well as in Asia.
But as these viruses have begun to cluster genetically based on their geographic region, we have noticed that there have been accumulation of amino acid substitutions, specifically in the protein of many of these viruses. And as you can see from this HI test, we have developed ferret antisera to several of the candidate vaccine viruses that have been developed by WHO collaborating centers and ERLs. One of those is called IDCDC-RG71A or the A Astrakhan 2020-like CVV. And this one has been used and has shown effective it cross reacting with many of the circulating strains around the world.
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TODD DAVIS, CDC [01:07:50]
But as viruses have again accumulated mutations in North American and Central and South American viruses, we have noticed a subtle reduction in the cross-reactive titers of viruses with the anti sera generated to the Astrakhan CVV. And while it’s not homogeneous across all of the viruses tested, we have noticed that about half of the strains tested from the United States are beginning to show a four fold reduction in heterologous titers and a few that have even dipped below eight fold relative to that ferret anti sera.
And so based on this finding, we’ve also generated ferret anti sera to circulating virus from the U.S., one of the first viruses detected in the U.S. in 2021 called the American wigeon in South Carolina in 2021 strain. And as you can see from the left hand side of this HI test, the cross-reactive titers are regained with ferret antisera here generated to the American wigeon, and so we see viruses now that only have as much as a two fold reduction relative to that ferret antiserum titer.
And so based on this data, we’ve decided to recommend the development of a new CVV antigenically like the American wigeon South Carolina 2021.
KATHERINE POEHLING, ACIP [00:29:04]
I’m trying to understand, when you look at all the various scenarios, what are those scenarios in which such a vaccine would be cost neutral or cost saving? Thank you.
DAVID HUTTON, UM [00:29:22]
That’s a good question. Actually, we didn’t find many scenarios where it would be would be cost saving. I think you’d have to find a scenario where several things were happening at the same time. So I think if you had I mean, even if you had higher incidence, or you had a much lower vaccine cost, that could cause things to be close to cost saving. We did look at a scenario with a three year time horizon and assuming that the the vaccine efficacy decays at an exponential rate rate, it is possible with higher incidence and over a longer time period that potentially it could be cost saving.
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ISMAEL ORTEGA-SANCHEZ, CDC [00:31:35]
Just to briefly say that there has been all the time discussions about what is a good threshold, and if there would be using a threshold or not. For many years, there have been use of $50,000 per QALY. Then that proved to be not substantiated either by theoretical principles or theoretical concepts or data. Then it was raised to $100,000 per QALY. That’s also something that was only inflated– it was corrected by inflation.
So to say that there is no specific threshold, that’s I think, the basic statement. There have been other thresholds that have been suggested by, for example, international organizations like the WHO, which will be three times the GDP per capita. In the case of United States, it would be approximately $180,000 per QALY, because we are talking about about $60,000 per GDP per capita. But that is only a suggestion. And CDC usually doesn’t adopt that kind of thresholds.
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ISMAEL ORTEGA-SANCHEZ, CDC [00:51:45]
In general, in the base case of the three models, we can say that vaccination will significantly reduce RSV disease burden in older adults. But the clinical trials data and the assumptions support the impact of disease reduction.
However, the economic value of the RSV vaccine appears to be costly and could be cost effective if some factors are taken into consideration, like RSV incidence, related health care costs, initial vaccine efficacy and duration, combined with reasonable vaccine price, will in fact determine the cost effectiveness of RSV vaccination.
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MICHAEL MELGAR, CDC [00:54:11]
I do want to acknowledge that surveillance for RSV disease has not been as robust, for example, as surveillance for influenza over the last 10 years or 20 years. And as we’ve seen from actually all three of the models that were presented by Dr. Ortega Sanchez, that the incidence of RSV hospitalization happens to be one of the most influential parameters that determines how cost effective it would be to vaccinate against RSV in this age group.
And as Dr. Ortega Sanchez showed, even within CDC derived estimates of RSV epidemiology, there is a tremendous amount of uncertainty in the per population incidence of RSV hospitalization. And I think you can see that reflected in in the charts that were showed showing the sensitivity of the incremental cost effectiveness ratio, by the model input of how many RSV hospitalizations are actually out there, year to year. And so, you know, CDC continues to work on its surveillance systems to update these estimates. And the uncertainty interval continues to be very wide. And I want acknowledge that.
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MICHAEL MELGAR, CDC [01:14:36]
Next, we’ll discuss the domain of values in which we’ll explore how the target population feels about the potential desirable and undesirable effects of vaccination. I’ll be drawing from unpublished results of an online survey developed by CDC in collaboration with the University of Iowa and the RAND Corporation. The survey was designed to assess vaccination intentions for a hypothetical RSV vaccine among U.S. adults 60 and older. The final sample consisted of 586 respondents.
Overall, 68% of respondents said they definitely or probably would choose to get vaccinated if a safe and effective FDA approved RSV vaccine was available. That proportion increased to 77% if it were recommended by a health care provider. Among those expressing hesitancy to accept the vaccine, the most common reasons included lack of knowledge about RSV and both long and short term safety concerns about the vaccine.
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MICHAEL MELGAR, CDC [01:18:05]
Now here is CDC’s older adult routine immunization schedule with the potential addition of a regularly scheduled COVID 19 vaccine, as was discussed at VRBPAC last month. The immunization schedule is becoming more complex, and vaccination is not the only age and risk based preventive health care that adult clinicians must provide. If an RSV vaccine is added, clinicians will likely face competing priorities at each patient appointment. Different age cutoffs may also add to the complexity. Harmonizing age recommendations with those of other older adult vaccines may improve feasibility and may increase uptake. At age 65, all adults are recommended to receive pneumococcal vaccination and there are specific influenza vaccine formulations licensed for adults 65 and older.
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MICHAEL MELGAR, CDC [01:24:54]
The work group notes pros and cons to the choice of age cutoff or an age based recommendation. If a recommendation is made for adults 65 and older, the target population would be at greater risk of severe RSV disease and therefore the balance of risks and benefits of vaccination would be more favorable. The work group was concerned about the possible risk of inflammatory neuropathy, particularly in light of the low observed RSV hospitalization rates in the trials impacting that balance.
It would also align with the age based cutoff for certain influenza vaccines and pneumococcal vaccination.
On the other hand, the selection would exclude adults 60 to 64, among whom certain racial and ethnic groups are impacted by RSV at earlier ages. If a recommendation is made for adults 60 and older, there’s the potential to prevent a greater total burden of RSV disease and it would increase access to persons 60 to 64 with medical risk factors for severe RSV illness.
On the other hand, persons 60 to 64 who are uninsured would have more difficulty obtaining vaccination, counteracting some of these potential gains in equity. As we’ve seen, clinicians may also be less willing to adopt a recommendation among adults younger than 65. And we’ve shown that such a recommendation would be a less efficient allocation of our collective societal resources.
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MICHAEL MELGAR, CDC [01:26:16]
I’ll now present the work of summary interpretation regarding GSK’s candidate vaccine.
For an age threshold of 65 and one of 60 years, the work group felt that the desirable consequences of a vaccine recommendation probably outweighed the undesirable consequences in most settings, however, when considering a recommendation at age 60, there were substantial minority opinions that the desirable and undesirable consequences were closely balanced, or that there was insufficient evidence to make a determination.
The majority opinion was in favor of recommending the GSK candidate vaccine for adults 65 years and older, but was not in favor of a broader recommendation for adults 60 years and older.
Saying that, there was a substantial minority opinion not to recommend this product based on currently available evidence. These work group members were concerned about the balance of risks and benefits, considering the single case of inflammatory neuropathy observed in a recipient of the investigational vaccine and the underrepresentation in the clinical trials of adults older than 80 who are at greatest risk of severe RSV illness. They felt that it’s imperative to demonstrate efficacy in this age group prior to making a recommendation. Further, they felt that a post implementation safety signal for inflammatory neuropathy, even if caught early, could undermine confidence in RSV vaccines and in vaccines more generally.
Among workgroup members who did support a recommendation among adults 65 and older, there was also a minority opinion to include a recommendation for individual adults age 60 to 64 years based on shared clinical decision making intended to facilitate access to the vaccine among adults with medical conditions, placing them at high risk of severe RSV disease.
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MICHAEL MELGAR, CDC [01:28:05]
Now moving on to the Pfizer candidate vaccine.
For an age threshold of 65 and one of 60 years, again, the worker felt that the desirable consequences of a vaccine recommendation probably outweighed the undesirable consequences in most settings.
However, when considering a recommendation of age 60, there were substantial minority opinions that the desirable and undesirable consequences were closely balanced, or that there was insufficient evidence to make a determination. The majority opinion was in favor of recommending the Pfizer candidate vaccine for adults 65 years and older, but was not in favor of a broader recommendation for adults 60 years and older.
However, as with the other candidate vaccine, there was a substantial minority opinion among worker members not to recommend this vaccine based on currently available evidence. Similar to the considerations for the other candidate vaccine, these work group members were concerned about the balance of risks and benefits, considering the two observed cases of inflammatory neuropathy and the underrepresentation of the very oldest adults in the clinical trials.
Among work group members who did support a recommendation among adults 65 and older, there again was a minority opinion to include a recommendation for individual adults 60 to 64 years based on shared clinical decision making intended to facilitate access to the vaccine among adults with medical conditions that place them at high risk of severe RSV disease.
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LEONARD FRIEDLAND, GSK [01:30:45]
RSV results in considerable clinical and economic burden in all adults aged 60 and older, including those age 60 to 64. GSK is cost effectiveness model, which uses burden of disease estimates that align to the current body of published scientific evidence, estimates that vaccinating 60 to 64 year olds would result in roughly 260,000 fewer symptomatic RSV cases in 60 to 64 year olds, including over 100,000 fewer outpatient visits and around 7,400 fewer hospitalizations each year. The model found that GSK’s RSV vaccine is cost effective across a range of price points, indicating that the vaccine would be considered a good public health value for adults 60 years of age and older.
In addition to reducing the burden of RSV, including 60 to 64 year olds in RSV, vaccine recommendations would also importantly have health equity benefits. Studies have demonstrated that certain racial and ethnic minority groups are more likely to have underlying risk factors for severe RSV outcomes, are more likely to be diagnosed with risk factors for severe RSV at younger ages, and are more likely to have undiagnosed risk factors, particularly in younger ages, before they are eligible for Medicare. Studies have also found that certain racial and ethnic minorities are more likely to have severe RSV related outcomes, including a study being presented by the CDC at the (inaudible) conference this week that demonstrates that a higher proportion of younger adults hospitalized for RSV were black, Hispanic or American Indian Alaska Native.
Excluding 60 to 64 year olds from age based routine recommendations would be detrimental to the racial and ethnic groups who develop risk factors for severe RSV at younger ages. Additionally, shared clinical decision making recommendations at any age would be detrimental to the racial and ethnic groups who have undiagnosed risk factors. Age based RSV vaccine recommendations for adults 60 years and older would ensure equitable access across all older adults.
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LEONARD FRIEDLAND, GSK [01:33:05]
Data on co-administration with high dose influenza and adjuvanted influenza vaccines and vaccine efficacy through two RSV seasons will become available in the second to third quarter of this year.
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MICHAEL MELGAR, CDC [01:37:55]
So the, in GSK’s case, the single case of Guillain-Barre syndrome, was observed in an open label trial phase three. It was randomized, but none of the arms included a placebo arm. And that’s why it was not included in GRADE. The intent of this trial was to evaluate different revaccination schedules, and that’s where the randomization took place.
There were a total of 1,650 adults aged 60 years and older that were enrolled. Among them, around 4% reported at least one serious adverse event. And one of those serious adverse events was a case of Guillain-Barre syndrome that occurred nine days after vaccination. It was reported as related to the investigational vaccine by the investigator. It was in a 78 year old female in Japan. The level of certainty of the diagnosis of Guillain-Barre syndrome was Brighton Collaboration level three. It led to hospitalization lasting 179 days, and the patient recovered.
So this was the one and only case of inflammatory neuropathy that occurred in GSK’s safety database that spans all of their clinical trials, in which there were a total of 15,000 approximately RSV vaccine recipients.
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MICHAEL MELGAR, CDC [01:39:05]
In Pfizer’s counts, so Pfizer’s two cases of Guillain-Barre syndrome or a variant thereof, one of them was diagnosed as Miller Fisher syndrome, both of them occurred in Pfizer’s pivotal phase three trial in which there was indeed a placebo arm. And you can see the numerators and denominators here.
But again, when you sum across all of Pfizer’s clinical trials, there were approximately 26,000 RSV PreF vaccine recipients and a total of two cases of inflammatory enteropathy.
So if you were to– so your summary of one in 13 to 15000 is correct for both investigational vaccines. Though, again, I would point out that one to two cases is very sparse to actually calculate a rate, which is why we did not attempt to do that.
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MICHAEL MELGAR, CDC [01:40:33]
We do know a little bit more about the two cases from the Pfizer phase three clinical trial.
Both occurred among patients in their 60s. One was in the United States and male one was in Japan and female. The patient in the U.S. initially suffered a non-STEMI after seven days after vaccination with the investigational vaccine. The day after, developed new onset weakness. There was a nerve conduction study that diagnosed acute mild demyelinating polyneuritis of the lower extremities. And this was diagnosed with certainty, Brighton Collaboration Level One as Guillain-Barre syndrome.
The other one was the Miller Fisher syndrome variant diagnosed retrospectively. The onset was 11 days after vaccination with the RSV vaccine and the certainty was Brighton Collaboration level four. And this is the level of detail that that was provided by the manufacturers.
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KEIPP TALBOT, ACIP [01:41:34]
I’m super excited about having an RSV vaccine and I’m looking forward to preventing hospitalizations in older adults and improving quality of life.
I do want to say, I would like some more data and I would like to kind of list the concerns and thoughts and needs that I would have.
One is, I am pretty sure if we prevent disease, we prevent hospitalizations. But in these trials, we saw hospitalizations for Guillain-Barré, but did not see the prevention of hospitalizations for RSV. And so we have to balance that risk benefit in the long run.
Two this vaccine will be given with COVID and flu. And we need co-administration data. We need co-administration data for all of these.
Along those lines, we’re removing COVID to Part B Medicare, and that will leave RSV as Part D, So the likelihood of them getting flu and COVID in their physician’s office and then later, maybe days later, going to get the RSV vaccine, or may not, is up in the air.
There is no data on VE in nursing home patients, and they have the highest morbidity and mortality from this disease, and we have no knowledge if it would even work in this population, nor do we know the side effects that would occur in this population.
Next, we don’t know the VE in those over 75 years of age where the highest morbidity and mortality is behind those that are in the nursing homes.
I think I’ll stop there. I have some other concerns, but I really I really want this vaccine to come to market, but I want it to come with good, solid safety data and good solid vaccine efficacy data so that when we introduce it, we have confidence in recommending it in our older adults, and that our older adults have confidence in the vaccine.
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MICHAEL MELGAR, CDC [01:56:04]
So regarding Guillain-Barre syndrome and inflammatory neuropathies in general. So yes, many patients who present with an illness compatible with the Guillain-Barre syndrome report having had an upper respiratory illness in the weeks preceding. We did a literature search regarding any association with RSV in particular there there’s very little and in the published literature linking those two. And in part that’s I think because very few adults are tested for RSV.
So there isn’t– I can’t offer you a rate of Guillain-Barre syndrome or other inflammatory neuropathies that results from infection with RSV. I can say that there are case reports in patients that’s that have had RSV and then present. But there’s there’s nothing I can offer in terms of a causative link or a rate.
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MICHAEL MELGAR, CDC [01:57:06]
And then finally, so that regarding the time horizon of protection and the question of revaccination, so we– the workgroup feels that there’s insufficient evidence right now to recommend a revaccination interval or revaccination at all, which is why the policy questions are phrased from a perspective of a one time dose.
That being said, both GSK and Pfizer are conducting multi-year phase three clinical trials, and what I presented today is limited to the first RSV season following a single vaccination, and in the coming months, the timeline would be very difficult for both manufacturers to present anything before June. But in the coming months, there will be a follow up, a second RSV season’s worth of follow up in both clinical trials.
So we will have some evidence regarding what the– whether the duration of protection extends beyond a single RSV season. But in the face of uncertainty, for that reason, the policy questions were phrased as a one time dose.
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CAMILLE KOTTON, ACIP [00:04:44]
I just wanted to say that in thinking this over and there’s so much information and it’s some of it’s conflicting and we wish we had more information about RSV. We wish we had more information about RSV and the potential Guillain-Barré syndrome from RSV, etc.
We actually– the reason we came down to sort of preferring the age 65 cutoff was we thought we might start with that, and then expand. But based on risk and benefit and multiple different factors. That’s why we sort of came to that conclusion in the work group.
Again, this was very challenging. I really appreciate all the work that Dr. Melgar and everyone from the CDC and others did, as well as everyone in the work group. It was it was a great amount of work. And I’m– we’re truly appreciative.
IONA MUNJAL, PFIZER [00:05:44]
So we do have two published trials that we conducted. And as I showed you the clinical development plan overall, we conducted a study characterizing coadministration with influenza in nonpregnant patients and then did an actually non-inferiority study looking at Tdap coadministration in women.
So regarding influenza coadministration, it was a descriptive, not a non-inferiority study. But in the nonpregnant participants in the lower age groups, there was a trend towards lower titers to influenza overall. And so we did not recommend coadministration in the phase three study.
There is this same vaccine, the 120 microgram RSV preF vaccine is actually being studied in the older adult population, as you well know. And there is a study ongoing that is assessing non-inferiority of administration in that older adult population.
But for the maternal population, there would be no additional clinical studies and we would actually analyze that in a larger post-marketing cohort.
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KATHERINE POEHLING, ACIP [00:09:07]
My other question is very similar to Dr. Talbot, and the question is, in the phase three trial, have you done a subanalysis where you look at breastfeeding and non-breastfed and look at the efficacy of the vaccine? Thank you.
IONA MUNJAL, PFIZER [00:09:25]
Yes. So that’s one of the things that we’re continuing to pursue. Again, we we collected– we collected data from the participants about whether or not they were breastfeeding, whether or not it was exclusive, and the duration of breastfeeding. So that is data that we look to analyze, but we do not have data on actual breast milk composition, or antibodies in breast milk in either of the studies.
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MATTHEW DALEY, ACIP [00:10:09]
I guess I was a little bit surprised that efficacy declined a fair bit by 360 days, because I would have thought that once you got through the season, you would then be– there wouldn’t be very much RSV disease happening after 180 days. So I wonder if you’ve looked at this as a time to event, and whether you’ve looked at it stratified by the time of year that a woman was vaccinated. Thank you.
IONA MUNJAL, PFIZER [00:10:38]
I’ll just reemphasize the study period that we conducted the trial in, because this may give you a little bit of context. So this study started in June of 2020 and we conducted the analysis in October of last year. So we undertook the study during a variable RSV seasonality period. And so some of the infants were exposed during their first six months. Some of the infants were exposed after their first six months. And some of the infants were exposed at both timepoints, we think, based on background epidemiology that we are conducting for collecting from the sites at the time contemporaneously. So what we see here may or may not be predictive of what you would see in a sort of typical peaked RSV season.
I’d also reflect on the fact that we continued to collect all the hospitalization and severe swabs throughout the study. But after six months, we did not systematically collect lower respiratory tract illness. So there’s a– the consistent swabs were done for hospitalization and severe.
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IONA MUNJAL, PFIZER [00:13:16]
So this is the fevers for the RSV preF in the placebo group. So if you look at the 39 to 40 group, there were six fevers, one was in RSV preF and five were in placebo. If you look at the fevers over 40 degrees, there were eight reported. Three were in RSV and five were in placebo.
Regarding developmental delay, when we looked back, we did not see consistent trends. I cannot speak to whether or not we specifically looked at fever. So I’ll have to get back to you on that. But we looked through all of those cases and did not see a consistent trend in any maternal reactogenicity and maternal adverse events, maternal history.
Largely those events of developmental delay are actually occurring in months or maybe even over a year, because some of the events that you may be thinking about as birth defects, would actually fall under the criteria of congenital anomalies.
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IONA MUNJAL, PFIZER [00:22:42]
For the infants who got RSV, were they more preterm, were they were more comorbid? And no, that doesn’t appear to be the case. So we– there are small numbers when you look at them going through. But case by case, we don’t see that and we don’t actually see when they do get these breakthrough infections, they’re not getting worse disease, enhanced disease. They’re getting disease that you would typically see in RSV infants or milder.
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KATHERINE FLEMING DUTRA, CDC [00:24:43]
The policy question being considered by the workgroup is should the Pfizer RSV bivalent prefusion-f vaccine be recommended for all pregnant people as a single dose given at 24 through 36 weeks gestation? This maternal vaccine is targeted prevention of RSV disease in infants and therefore, should this vaccine be licensed by FDA, this recommendation would be considered in the context of the current standard of care for prevention of RSV disease in infants at the time of an ACIP vote.
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KATHERINE FLEMING DUTRA, CDC [00:26:12]
Here’s the proposed tentative timeline of future ACIP presentations regarding this vaccine.
At the June 2023 ACIP meeting, we plan to present a summary of GRADE of the evidence, a cost effectiveness analysis, and the evidence to recommendations or ETR framework, and then an ACIP vote could be held in October 2023, if the product is licensed by this time.
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GRACE LEE, ACIP [00:27:20]
I could imagine a combined platform where we protect infants against RSV. And so just thinking through how to integrate this, if we discussed nirsevimab first and then this vaccine second, sort of when that comes through, if and when that comes through, how should we think about it from a decision making perspective and thinking about the relative benefits and risks?
And I can imagine, for example, there may be women who deliver quite early and never have an opportunity to get a vaccine– a pregnant person who delivers early, who might not have the opportunity to get a vaccine, and that might be where it would be really useful to have a monoclonal antibody available. So just, you know, thinking through those scenarios would be really helpful, although I recognize that’s a really complex.
MATTHEW DALEY, ACIP [00:28:11]
Well, and related to that, just understanding biologically the implications of of maternal vaccination followed by passive immunization in the infant. I mean, I think there’s biologic reasons to suspect that it’s not problematic from a safety standpoint, and would probably be additive from an effectiveness standpoint. But I want to make sure I’m not making too many assumptions.
DAVID HUTTON, UM [00:18:26]
Recall that the base case and cost ratio was about $100,000 per quality adjusted life year gained.
The light blue portion of the bar represents how the incremental cost benefit ratio would change if the parameter was lower, and the dark blue portion of the bar represents how the incremental cost effectiveness ratio would change if the parameter was higher.
As you look at the top bar, you can see how nirsevimab’s cost can change the results. If thenirsevimab costs were lower at $50 per dose, providing nirsevimab would be cost saving. However, if nirsevimab’s costs were higher at $600 per dose, then the incremental cost effectiveness ratio increases to $315,613 per quality adjusted life year gained.
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DAVID HUTTON, UM [00:25:53]
In summary, the cost effectiveness of nirsevimab depends on many factors, particularly the cost per dose that could cause the incremental cost effectiveness ratio to vary between being cost saving to over $300,000 for quality adjusted life years gained. Nirsevimab efficacy, particularly against upper respiratory tract infections, could cause the incremental cost effective ratio to vary between roughly 75 to $150,000 per quality adjusted life years gained.
And then finally, variations in the quality of life with RSV for both children and caregivers could cause the incremental cost effectiveness ratio to vary between 40,000 and $125,000 per quality adjusted life year gained. So under certain conditions nirsevimab may be cost effective, but under other conditions it might look less less favorable.
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JEFFERSON JONES, CDC [00:30:53]
Our understanding, while nothing is final, is that it’ll be an identical price for the lower dose and higher dose.
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ISMAEL ORTEGA-SANCHEZ, CDC [00:43:58]
The first take away from these two slides would be that both more or less agree that nirsevimab will be costly, but it will also prevent LRTI hospitalizations and save QALYs among infants and caregivers.
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ISMAEL ORTEGA-SANCHEZ, CDC [00:53:18]
In general, we can say that nirsevimab will significantly reduce the RSV disease burden in infants. Data from the clinical trials support the impact estimated on disease reduction. However, the economic value of using nirsevimab could be costly or cost effective, and reasonable price and ratio of protection, combined with careful design of seasonal interventions, will determine the cost effectiveness value of routine prophylaxis among infants less than seven months of age entering the first RSV season and those born during the RSV season.
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JEFFERSON JONES, CDC [00:55:50]
If the first infection was postponed until a child was later, it is presumed that their risk for severe disease or hospitalization would be considerably lower.
The second is that the manufacturer has told us verbally, but we haven’t been able to review the data, that for their randomized controlled trial data for breakthrough infections or those that received nirsevimab but were still infected, had similar level of antibodies against non-preF proteins as those who were infected that were received placebo. And they’ve interpreted that as there is still a robust response to the virus that could provide similar protection. And again, we have to review that data, but that is what we’ve been told.
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KEIPP TALBOT, ACIP [00:56:47]
Just so I’m clear, you said it’s presumed that it would be less severe, but we don’t have data to support that?
JEFFERSON JONES, CDC [00:56:53]
So in the context of when we look at risk of severe disease by age, it’s considerably less. And I’ll review that data in the next one or two presentations, the risk of RSV hospitalization by age. Now, that is in the context of people being exposed over time. But I think not everyone is infected. By the second year of life, nearly everyone is infected. The first year of life ranges around two thirds or so.
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JEFFERSON JONES, CDC [01:11:41]
In a survey conducted by the University of Iowa of 523 people who are actively pregnant or pregnant within the last 12 months, as shown in the red color, about one third of respondents thought their baby definitely or probably would get an RSV infection within one year after being born. And 70% of respondents, represented in blue, said they definitely or probably would get an RSV antibody injection for their baby, if safe and effective, licensed by FDA, and recommended by CDC.
63% of respondents said they were more worried, shown in light blue, or equally worried, shown in dark blue, about their baby experiencing side effects from an RSV antibody injection versus symptoms if sick with RSV. 38% of respondents believe that their baby would have no symptoms or mild symptoms if they got sick with RSV, and 24% expressed uncertainty about the disease severity or treatability if their baby got sick with RSV.
Despite being unsure perceiving RSV risk to be low, respondents were worried their baby would need to be hospitalised if they got sick with RSV, with the mean response, four out of five, with five being most worried.
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JEFFERSON JONES, CDC [01:15:24] Nirsevimab would be the first passive immunization product to be independently included in the CDC immunization schedule. Certain immune globulin products are already included, but are in conjunction with vaccines, for example, hepatitis B immune globulin and the hepatitis B vaccination.
One reason for this is that the proposed indication is for all infants and widespread use of nirsevimab would result in population level impact. It is unknown at this time if nirsevimab will be included in the Vaccines for Children program.
FDA has indicated they will likely classify nirsevimab as a drug.
Some related work group considerations include that certain types of health care workers, particularly medical assistance, can administer vaccines, but might not be able to administer a monoclonal antibody under current rules, which may require modification to enable administration of nirsevimab.
Adverse events would be reported to the FDA Adverse Event Reporting system rather than the Vaccine Adverse Event Reporting System or VAERS. Many providers are more familiar with VAERS and the methodologies to analyze these systems differ.
Billing and administration codes for nirsevimab have not been finalized and differ for vaccines versus drugs.
Some state immunization information systems might not be able to include products that are considered drugs and not vaccines.
The workgroup felt that year nirsevimab is probably feasible to implement. However, some members said this was dependent on inclusion in the VFC and others said they didn’t know or had concerns until more information on VFC was available.
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JEFFERSON JONES, CDC [01:17:16]
The next domain is resource use. Our primary source of data was the cost effectiveness analyses that were previously presented.
There’s a brief summary in the base case, with nirsevimab, for the CDC model at a cost of $300 per infant, the incremental cost effectiveness ratio was just over $100,000 per quality adjusted life year. And at $500 per infant, it was a little under $245,000 per quality adjusted life year. And you can refer to the full presentation for details.
The work group is concerned about the potential cost of nirsevimab and two polls were taken. At a cost of $300 per infant, the work group felt probably yes, with the minority stating yes, that use of nirsevimab would be a reasonable and efficient allocation of resources. At a cost of $500 per infant, approximately half of workgroup members said probably yes, while the remainder said no, probably no, or don’t know, if use of nirsevimab would be a reasonable and efficient allocation of resources.
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JEFFERSON JONES, CDC [01:31:52]
In summary, the work group recommends nirsevimab for all infants born during October to March at birth and, for all infants born during April to September, who are less than eight months of age when entering their first RSV season.
However, many members expressed concerns about feasibility and equity, particularly because inclusion in VFC is unknown. Some workgroup members expressed concern that, at higher prices, nirsevimab may not be reasonable and efficient allocation of resources. The work group would like more time to consider which infants and children would be sufficiently high risk to warrant nirsevimab in their second RSV season. There are limited efficacy and safety data available at this time, in this population, and there are little data to measure the risk of severe disease in the second RSV season by chronic disease, by chronic condition.
At this time, the work group recommends nirsevimab for those who are eligible for palivizumab in their second RSV season per AAP guidance. And because nirsevimab is assumed to cost less than palivizumab, and be of non-inferior efficacy, this was assumed to be cost effective. The workgroup will continue to evaluate other conditions.
So if licensed by FDA, the two questions we will ask ACIP to vote on are: One, should one dose of nirsevimab be recommended for all infants born during October to March at birth? And for all infants born during April through September, less than eight months of age entering their first RSV season? And two, should one dose of nirsevimab be recommended for children less than 20 months of age entering their second RSV season who are eligible for palivizumab in their second RSV season? The second question may have other conditions added.
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JEFFERSON JONES, CDC [01:35:41]
Only one dose of nirsevimab is recommended per season, even if given early in the season. So if the nirsevimab dose is given too early before the season, for example, May or June, during the peak of the RSV season, the infant could be beyond 150 days after the dose and have waning protection. Thus, nirsevimab administration should be timed to maximize protection during the RSV season, when infants are most at risk of exposure to RSV.
For infants born during October to March, just before the start of most RSV seasons and during the months with the highest RSV activity, the optimal timing of nirsevimab dosing is at birth. For infants born during April to September, in months typically with low RSV circulation, the ideal timing of nirsevimab dosing is just before or near the start of the RSV season. Typically this is mid-October to early December.
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JEFFERSON JONES, CDC [01:45:02]
So first on bundle payments, so CDC’s in discussion with multiple agencies. And as highlighted, there are many challenges. And we feel it’s really important that we address them, so that if nirsevimab is licensed, we have as smooth as possible a process going into the upcoming RSV season.
We’ve heard that bundle payments are updated. So while they may not have initial reimbursement, if nirsevimab is recommended and widely used, that those bundle payments would be updated to reflect the increased costs from its use.
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SARAH MEYER, CDC [01:46:31]
But as Dr. Jones pointed out, there are a lot of complexities with this being characterized as a therapeutic and not vaccine. Many of them he highlighted in his talk. This is another example of where there just– there are a few additional things to kind of work through. But those discussions are happening.
As Dr. Jones also mentioned, we are working closely with other federal agencies, including CMS, to explore all options to make sure that we can achieve equitable access of this product, if it should be approved and recommended. And I think we don’t have an update at today’s meeting about that. But as those discussions occur and as there are further updates, those will be shared with the work group and the committee as soon as possible.
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JEFFERSON JONES, CDC [01:48:13]
So the FDA Adverse Reporting System, FAERS, does differ from VAERS. And I believe you’re all quite familiar and many providers are with the VAERS system, which CDC is very familiar with. The FAERS system, I’m hoping we will be able to present more information on it at a future meeting.
Our CDER colleagues, rather than CBER, have been informing us about that system. It’s my understanding if an adverse event for nirsevimab should be reported to VAERS, it would be forwarded on to FAERS and the– how that system is analyzed and how ACIP members can be made aware of interim analyses, we hope to discuss that at a future meeting.
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VERONICA MCNALLY, ACIP [01:50:19]
So my second question is, for the benefit of parents, how is the CDC and the work group convinced that there is no negative impact to a child’s health in receiving this monoclonal antibody at the same time as other vaccines?
JEFFERSON JONES, CDC [01:50:42]
So we have discussed coadministration at the work group. The industry has sponsored a white paper that they published. The general consensus of the work group was that there is a lack of data on this, but the theoretical risk of adding a passive immunization to regular childhood vaccines poses a low risk.
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MATTHEW DALEY, ACIP [01:54:25]
I want to take a step back and say, this is incredible. And I know we’ve talked about this before, but this is transformative and I think we should recognize this. As a practicing pediatrician over the last 25 years, I’ve admitted more children for RSV bronchiolitis with hypoxia than anything else I’ve admitted children for by far. And so this is extraordinary. So that’s point one.
Point two is we can do this. Okay? I mean, by we, I mean practicing pediatricians and practicing family medicine physicians and hospitals. I mean, I think we can do this.
But, and here’s where we come to the but, we’ve spent 50 years building a system for coverage surveillance, safety surveillance, and immunization delivery. And that’s been 50 years that we’ve built that system that works pretty darn well. And I’m concerned that we will not use that system and everything in there, immunization information systems, vaccine safety surveillance. And frankly, just administration. To then achieve disease prevention that we want to achieve. And then we’re going to fall because of things that are really understandable but really more bureaucratic.
So, I mean, I have concern that we’re going to miss a lot of opportunities for disease prevention because we’re not going to use a system that we’ve built for the last 50 years
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TOM SHIMABUKURO, CDC [01:59:00]
Nirsevimab is regulated by CDER. So this is a CDER product and the safety monitoring system is the FDA Adverse Event Reporting System or FAERS. There are processes in place for the two systems VAERS and FAERS to redirect reports that are that are sent to essentially– missent to the wrong system. So if we do get reports into VAERS, we’ll have a process to identify those and to redirect those to FAERS, similar to how FAERS redirects vaccines reports to VAERS. And I think a lot of a lot of the monitoring issues there may be related to coordinating with FDA to make sure that we’re aware of safety findings.
We do plan to monitor nirsevimab in the Vaccine Safety Datalink. In fact, we’re in the process of planning to do that right now. So CDC will be monitoring the safety of nirsevimab, and that will be similar to how we do monitoring for routine vaccines or other vaccines. And we are able to capture co-administration of other vaccines in the Vaccine Safety Datalink. It’s challenging to monitor safety when you have multiple vaccines or multiple products being administered, but we will have the data to look at co-administration.
We also have another program at CDC called the Clinical Immunization Safety Assessment Project, which which will be able to do clinical case consultations for U.S. health care providers of complex adverse events associated with the product or when the product is given with other vaccines. So we’ll still be– that resource will still be available.
And we are also in the process of developing the next generation V Safe. So there would be other CDC systems which we could use to monitor the safety of this product. So I just just wanted to make those points.
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JOSE ROMERO, CDC [02:01:55]
We have experience with VAERS. We know how quickly you identify signals and move on them. Will we be able to get that data? Will the members of the ACIP get that data to vote, to see quickly, without lag?
TOM SHIMABUKURO, CDC [02:02:12]
Dr. Romero, I think we would have to have continued discussions with our CDER colleagues on the FAERS system. I’m aware of the FAERS system, but I’m not– I don’t know the details and the intricacies like I know for VAERS. But certainly having those conversations and ensuring that safety data could be made available to CDC on a timely basis is something that would be important to us. And I understand to ACIP as well.
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REBECCA COYLE, AIRA [02:03:09]
I just want to say that we know that there’s going to be challenges with implementing this using the routine systems. Not only will it be challenging from a clinical decision perspective, recognizing that your forecasting has to account for seasonality and locality as well as other considerations, but there are also even more significant issues in the background as to how the data would be sent to the IIS.
So not to overcomplicate things, but there are uniform code sets that every electronic health record system, every IIS uses. And because this is not considered a vaccine from a code set perspective, it will be cumbersome and costly to modify the systems using the existing pathways that we have now. So that’s cumbersome and costly for IIS and every EHR that’s out there.
So I also just want to recognize that we know our CDC and FDA colleagues out there are very aware of the issues, as are many of the other partners out there. And so I know that that folks are really trying to work through some of these challenges. But in terms of operationalizing sort of that send and receive feature that we’re so familiar with for all the other vaccines, this would not probably take effect when this product goes live.
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CAMILLE KOTTON, ACIP [02:05:06]
I think we’ve learned a lot from the experience with Evusheld, and I would ask for standardization as far as the ACIP and what we consider, and if we’re going to consider passive immunization, that we do it standardly rather than case based. It’s not clear to me why we’re reviewing this, but we didn’t review Evusheld.
And then I think we’ve learned a lot from the Evusheld experience. That information is not logged into immunization databases. It’s actually quite cumbersome, as we’ve heard. And so maybe we can look at some lessons learned from that experience, and think about how to implement this.
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SARAH LONG, ACIP [02:06:03]
I’m surprised that none of the ACIP members have questioned cost and resource utilization.
So when we asked the manufacturer how they would price this, when they presented the 500, we had assumed a lower cost and modeled the 300. I think the answer was, verbatim, by value afforded, which would allow a broad range of how you might price a drug. This would be for the first cohort, this would be a billion dollars cost of the immunization alone, and not even considering administration fee. And we learned just yesterday that the VFC budget is 4 million or 5 million? 5 million– billion, not million, so a little decimal for decimals. So it is extraordinary. And how states dish out their money is very different.
So the possibility is that other very important things could be dropped or lost or because it could not be afforded. So I think that it would be hard for the committee, the work group committee, to say that there is a recommendation regardless of cost. There was a sense that that at the cost of 200 to 300 dollars, this would be a go. And there was considerable trepidation for anything more than that.
So and the second thing is we felt that there really had to be a decision about VFC and how this was going to be provided for us to make as an ACIP any recommendation for the use of this product. At the time we make the recommendation, we must know that.
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PABLO SANCHEZ, ACIP [02:08:32]
It’s not a vaccine. We cannot say that it’s a vaccine, in the era of vaccine hesitancy. I am afraid that some parents will refuse this medication, in the name, because they don’t want to receive a vaccine. And we can do all the education about the vaccine, but it is not a vaccine. And I’ve been in that situation in the NICU where parents have refused vaccines, but they have accepted palivizumab. So it is not– we need the message needs to be clear and accurate.
But I really want to thank ACIP for taking this on, because any of us who’ve had to deal with palivizumab and the issues surrounding politics has become horrendous, not just at the AAP level, not at the industry level, but also even at the local level, where one hospital and one NICU has one recommendation and the next across town has another recommendation. So I really am very happy and really pleased because I think that this is groundbreaking, if it works, and if it gets approved, and we fully have it. It is a disease that we want to definitely be able to prevent.
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KATHERINE POEHLING, ACIP [02:12:38]
I did like keeping it very similar to what we have been doing for years. And I do see the possibility of improved equity with giving a single dose rather than monthly doses. My concern is insurance. Insurance can take a year before they pay for anything, and we are seeing that, I believe Dr. Loehr pointed out PCV 15 is not paid by several insurances, and this is commonly exceeded, and this continues to be a problem with the birth hospitalization, because I think it would be a year. That would decrease equity. And so my concern is that lag time as well.
SARAH KIDD, CDC [00:07:07]
I’d like to briefly summarize our work group deliberations on adult polio vaccination to date and present some proposed language for adult polio vaccination recommendations, in anticipation of an ACIP vote at the June meeting. We’d also like to solicit your feedback and identify areas where more data are needed prior to an ACIP vote.
As background, the most recent ACIP statement on adult polio vaccination was published in 2000. And it contains some ambiguous and outdated language. The 2000 statement states that vaccination is recommended for certain adults who are at greater risk for exposure to polio viruses than the general population. Unvaccinated adults who are at increased risk should receive a primary vaccination series with IPV and adults who have had a primary series of OPV or IPV already, and who are at increased risk, can receive another dose of IPV.
Multiple problems and questions with the recommendations came to light last year when the New York poliomyelitis case was identified.
First, the 2000 statement focused almost exclusively on adults who are at increased risk of exposure to polio virus, And it was unclear how how increased risk should be defined in the setting of circulating vaccine derived polio virus in the United States. In addition, the recommendations for unvaccinated adults who are not considered to be at increased risk of exposure were unclear. And the recommendation for vaccinated adults and when or if a booster was advised, was also unclear.
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SARAH KIDD, CDC [00:08:50]
So the first policy question the workgroup addressed was: should completion of a primary polio vaccination series with IPV be recommended for unvaccinated and incompletely vaccinated adults in the U.S.?
To be more precise, the population being considered was unvaccinated and incompletely vaccinated U.S. adults over the age of 18 years. The intervention is completion of a primary vaccination series with IPV.
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SARAH KIDD, CDC [00:13:12]
So there are no reliable data on vaccination coverage for people who are currently adults in 2023. So the best estimate of adults who are protected against paralytic polio comes from serosurveys. Serosurveys indicate that a large majority of Americans have protective antibodies to poliovirus. In this NHANES survey that was conducted in 2009 to 2010, seroprevalence varied by poliovirus serotype, but was high in all the age groups studied.
Seroprevalence for type three was consistently the lowest, but remained high even in the oldest age group studied.
The effectiveness of enhanced potency IPV has been established. The presence of detectable neutralizing antibody is an accepted correlative protection against paralytic disease. However, immunity against paralytic disease may be present even in the absence of detectable antibodies.
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SARAH KIDD, CDC [00:19:59]
Ultimately, the majority of the workgroup felt they believe the pros of uniform recommendation outweigh the cons and support a uniform recommendation. However, a substantial minority, about one third of the workgroup, favor maintaining a risk based recommendation.
For the majority, recommendation proposed language, the language would be as follows: adults who are known or suspected to be unvaccinated or incompletely vaccinated against polio should complete a primary vaccination series with IPV, and then the clinical considerations would have a statement along the lines of the following: in general, unless there are specific reasons to believe they were not vaccinated, most adults who are born and raised in the United States can assume they were vaccinated against polio as children.
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SARAH KIDD, CDC [00:20:52]
The second policy question addressed by the workgroup is: should a booster IPV dose be recommended for adults in the U.S. who have previously completed a primary polio vaccination series?
Again, the population being assessed are U.S. adults aged over 18 years who have completed a primary polio vaccination series with trivalent OPV, IPV, or a combination of both. The intervention would be booster– a booster dose of IPV, and the comparison group would be adults who completed a primary series, but did not receive a booster dose.
Again, the outcomes are the same as for the previous policy question. Prevention of paralytic polio. Serologic immunity to polio virus types. One, two and three serious adverse events following vaccination, and then also indirect effects such as community transmission and impact on health system.
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SARAH KIDD, CDC [00:21:47]
The current recommendation regarding adult boosters is that adults who have had a primary series of OPV or IPV and who are at increased risk can receive another dose of IPV. Available data do not indicate the need for more than a single lifetime booster dose with IPV for adults.
This has been a long standing recommendation, since trivalent OPV was used in routine immunization. However, the actual need for a supplementary dose has not been established, but it was thought that there is value ensuring protection against infection with wild polio viruses when exposure can reasonably be expected.
Of note, there have been at least two reported cases of paralytic polio in adult travelers who have completed a primary series with either Salk, IPV or trivalent OPV. However, further details on these cases are not available, and it’s not clear whether a booster dose would have prevented these cases.
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SARAH KIDD, CDC [00:22:55]
Showed Here again are the results of the NHANES serosurvey showing that the seroprevalence of neutralizing antibodies is high for all three serotypes in all the age groups studied.
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SARAH KIDD, CDC [00:23:45]
So the majority of the workgroup agree with the current recommendation for adult IPV boosters. This recommendation is risk based, and is based on shared clinical decision making.
The proposed language includes some slight edits to modernize the language, namely substituting the word may for can, from the previous from the 2000 statement, and it would read: adults who have received a primary series of trivalent OPV or IPV in any combination, and who are at increased risk of polio virus exposure, may receive another dose of IPV. Available data do not indicate the need for more than a single lifetime booster dose with IPV for adults.
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SARAH KIDD, CDC [00:26:18]
So that the Salk campaigns did target adults up to, I want to say– I want to say 20 or 30? So it was at least young adults. The coverage is not 100% for those. However, we do have data for estimated coverage for people born 1950 and later. I think when you get to that age group, the seroprevalence studies data is actually better than coverage. I think the coverage data is a little bit– it can be an underestimate. So the seroprevalence data indicate that a higher percent are actually protected.
Now, that could be from primary immunization. It also could be from secondary immunization, from exposure to somebody who received OPV. But the seroprevalence data indicate, again, high protection levels of protection in terms of neutralizing antibodies.
We do have some Salk vaccination coverage data for what that’s worth for people who were even children and adults during that. And that would indicate coverage a maximum of 50 to 60% in young adults. But so it wasn’t 100% at that time.
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SARAH KIDD, CDC [00:28:19]
We agree. And that’s why I think that clinical considerations statement is is so important to be reassuring, especially to the worried.
I think it is important to recognize that adults, the person who had paralytic polio in New York, was a young adult who knew they were unvaccinated. So there are definitely groups of young adults who were born 2000 and later those are adults now that are aware they were unvaccinated, or have reason to believe they’re unvaccinated. So I think those would be the target groups.
We want to be generally reassuring to the majority of Americans.
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SYBIL CINEAS, ACIP [00:29:02]
To follow up on Dr. Sanchez’s comment. In my practice, I also see a lot of patients who were not born in the United States who do not have vaccine records or who are refugee patients. So we will need clear guidance as to what to do with those patients, whether it would be to do a primary series versus a one time booster. So hopefully there will be clear guidance on that as well.
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KEIPP TALBOT, ACIP [00:37:20]
I wanted to touch base on an earlier comment. These were people who decided not to be vaccinated, yes, but actually, they were children and their parents decided not to vaccinate them. And many times we grew up and follow our parents footsteps, and many times we don’t.
And so this gives physicians a way to get these now adults who have decided to be vaccinated caught up. And so I think it’s a great opportunity.
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SARAH KIDD, CDC [00:38:38]
I do know that in New York City, when they did– they did expand, saying that all unvaccinated adults should be vaccinated in New York City, there was not a rush on adult IPV doses, that it was a manageable amount. So there is– there is an open question of how much public health messaging will create a demand or not.
We typically see Shigella cases peak in the summer months and decline in the fall and winter. However, Shigella activity increased in Fall 2022, and we are now seeing some antibiotic-resistant cases, which are confirmed via antibiotic susceptibility testing. CDPHE identified several outbreaks and clusters of cases that were related to each other. Cases have slowed so far in 2023, but we expect to see an increase in the number of cases in coming months, as is typical in summer months. We increased messaging to local public health partners and on social media to raise awareness and provide the public with general information about Shigella and guidance to help prevent transmission.
Coloradans can help protect themselves and their communities by following preventive guidance.
Carefully wash your hands with soap and water for at least 20 seconds during key times:
Before preparing food and eating.
After changing a diaper or helping to clean another person who has defecated.
Avoid swallowing water from ponds, lakes, or untreated swimming pools.
When traveling internationally, stick to safe eating and drinking habits, and wash hands often with soap and water.
If you care for a child in diapers who has a Shigella infection, promptly throw away the soiled diapers in a covered, lined garbage can. Wash your hands and the child’s hands carefully with soap and water right after changing the diapers. Clean up any leaks or spills of diaper contents immediately.
If your partner has been diagnosed with a Shigella infection, avoid having sex (vaginal, anal, and oral) for two weeks after they no longer have diarrhea. Because Shigella germs may be in stool for several weeks, follow safe sexual practices using barriers, such as condoms or dental dams, or ideally avoid having sex, for several weeks after your partner has recovered.
To date, we are not aware of any Colorado cases related to the Cabo Verde outbreak.
STEPHEN HOGE, MODERNA [00:11:57]
As you know, we shared the topline results from our Phase 3 RSV study in older adults earlier this year. And today we shared additional data that was presented this morning at RSVVW. The topline results we’ve seen are incredibly encouraging and we’re grateful to the FDA for breakthrough therapy designation for mRNA-1345, which further emphasizes the significant health impact of RSV in older adults and the high unmet need in.
In the top line data presented in January, mRNA-1345 demonstrated 83.7% vaccine efficacy in the primary endpoint of lower respiratory tract disease with two or more symptoms. 1345 was found to be generally well tolerated and there were no safety concerns identified by the Data and Safety Monitoring Board.
In the data presented today at RSVVW, we confirmed that 1345 was well tolerated and has an acceptable safety profile. Solicited adverse reactions were mostly grade one or grade two. And to date, most solicited adverse reactions were mild to moderate, with most common adverse reactions being injection site pain, headache, myalgia and elsewhere allergy. Vaccine efficacy was consistently high across all age groups and in participants with preexisting co-morbidities that are at highest risk.
Please refer to the scientific and medical meeting section of the Moderna investor relations website to see the full RSVVW presentation.
We’re very encouraged by these data and look to look forward to file a biologics license application with the FDA in the first half of 2023 if things proceed. With the option of using a priority review voucher, we might see regulatory action on this filing in late 2023 or early 2024.
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ARPA GARAY, MODERNA [00:20:46]
In the U.S. contracting discussions with commercial customers are ongoing, and we will provide visibility into expected U.S. sales at a future date after we complete these discussions. In our discussions with commercial customers in the U.S., it is clear to us that our customers recognise that COVID is still a substantial health burden. Throughout 2022, COVID continued to be a leading cause of hospitalizations and deaths.
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ARPA GARAY, MODERNA [00:23:04]
To ensure coverage of our vaccine. We are engaged in discussions with private customers as well as public entities such as the VA, CDC and the Department of Defense. We are increasing awareness and educating consumers as well as health care providers about the benefits of booster vaccinations in alignment with public health agencies such as CDC and the ACIP. We are reaching health care providers and consumers through innovative digital outreach programs. We have built the infrastructure needed to fulfill customer orders and shipments, and our commercial and medical organizations have been scaling to execute on this plan. And we are ready for the transition to a commercial market in the United States.
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ARPA GARAY, MODERNA [00:25:13]
In the U.S., we expect commercial market volumes to be approximately 100 million doses in 2023, and Moderna’s commercial organization is prepared for the transition to a commercial endemic market. Last but not least, we are committed to patient access in the United States.
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JAMEY MOCK, MODERNA [00:27:54]
A key driver of the increase in cost of sales as a percent of product sales was a catch up royalty payment to the National Institutes of Health or NIH of $400 million, representing 8% of product sales in the fourth quarter.
In December 2022, we entered into a nonexclusive patent license agreement with the National Institute of Allergy and Infectious Diseases, an institute or center of the NIH, to license certain patent rights concerning stabilizing prefusion coronavirus spike proteins and the resulting stabilized proteins for the use in COVID 19 vaccine products or 2P technology.
Pursuant to the agreement, we have agreed to pay low single digit royalties on future net sales of our COVID 19 vaccines.
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STEPHEN HOGE, MODERNA [00:44:47]
So first on superiority, you do not need to demonstrate superiority to get a flu vaccine approved. That’s well precedented. Non-inferior efficacy is the threshold. Our goal, though, over time is absolutely to develop a superior influenza vaccine. And so if we don’t see it with a first generation product, which is mRNA-1010, I would note that we have four other programs, flu programs in development, different stages of clinical trials that are looking to do even better than perhaps flu mRNA-1010. And our goal over time would be to demonstrate that we have a superior influenza vaccine.
But it’s not actually required for approval. Noninferiority should suffice.
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STEPHEN HOGE, MODERNA [01:03:17]
Now, as relates to age for approval. We’re currently studying mRNA-1010, only in older adults. And so as I said, the P301 was in 18 plus, P302 was in 50 plus. And that’s really where we see the broadest recommendations for seasonal influenza vaccine and where we have been most focused initially on building out our respiratory portfolio.
We will evaluate our influenza vaccine, in fact, many of our vaccines, in younger populations over time. But we’ll have to do age de-escalation dose finding and then bridge down from an immunogenicity perspective, very much like what we did with COVID. And so our initial filings for approval, if they proceed based on data, would be in adults and older adults principally, and then eventually we would follow on with pediatric populations.
And as I said a moment ago in response to Michael’s question, that may involve using updated B antigens to increase immunogenicity in that population. But again, that’s subsequent studies that we would do in children.
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STEPHEN HOGE, MODERNA [01:05:11]
We do not we have not yet had approved vaccines. And so what we don’t yet know is what the frequency of vaccination. Is it going to be seasonal every year, or is it going to be less than seasonal every every couple of few years? But what’s pretty clear, based from my perspective, based on the epidemiology of RSV infection, is that we do see RSV fairly regularly as adults. And unfortunately, over time, it breaks through more frequently. And so there probably will need to be repeated boosting to protect against RSV.
At the end of the day, the initial recommendations will come from ACIP as well as from regulators around that frequency, and we will have to defer to them on how they want to administer roll out the RSV vaccines, whether they want to follow a flu model, which would be annual to make sure that we get the broadest amount of protection, or that they want to initially rollout RSV vaccines and then follow over time for the durability of that efficacy.
At this point, none of us, none of the three products that have read out in phase three, have a clear answer on the durability of that efficacy, although we would expect it to wane as it does against natural RSV infection over time in older adults.
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STEPHEN HOGE, MODERNA [01:09:28]
I would note that it is well precedented. In fact, many of the currently approved influenza vaccines have in the past missed on non-inferiority for an influenza B strain endpoint here or there, and still have received full approval or accelerated approvals. And the reason for that is, as we’ve said sort of throughout, that at the end of the day, influenza B is not a primary driver of concern and it is known to be among the the different strains of influenza in the virus, in the vaccines, of lower import for disease in older adults. In fact, one of the four strains, there have been active debates about the B Yamagata strain, as to whether or not it’s gone extinct and even should be removed from quadrivalent vaccines in many of the recent WHO and other debates.
And so influenza B is a well trodden path for many of these vaccines, as well as now for mRNA-1010, where there is differential performance. And ultimately, there is there is precedent for moving forward, where you do not technically meet non-inferiority and immunogenicity or seroconversion endpoints, and still moving forward because of the lower concern about that disease in older adults.
JOSE ROMERO, CDC [00:04:01]
So this past fall and winter, as you all know, the United States saw high circulation of respiratory syncytial virus, RSV, influenza virus, and SARS-CoV-2. These put significant stress on our health care systems and our drug supply chain. After a brief and anticipated uptick of hospitalizations and cases over around the holidays, we are now seeing a continued decrease in COVID, influenza, and RSV cases and hospitalizations nationally.
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JOSE ROMERO, CDC [00:06:16]
Current national trends for RSV activity indicate that it has returned to baseline levels. For seasonal influenza, the activity continues to decline across the country. While influenza activity is declining, it remains possible that a second wave may occur later in the season, as it has in the past.
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JOSE ROMERO, CDC [00:13:51]
The percentage of uninsured children not vaccinated by their second birthday was recently found to be eight times that of privately insured children. And, you know, to me, the number itself is significant. But think about it in the context of having a VFC program, right? That program was was was created to deal with inequities in insurance and access and racial and ethnic barriers. And so if that is in place, and functioning as well as it has been pre-pandemic, and we have this eight times difference, there is a major problem.
And tomorrow, I’ll talk also about this. But this is particularly severe also, not just in those in poverty, but those in rural America, where data shows that we have lower rates of vaccination in that group. And whether it’s, and again with that with VFC, is that an access problem? Or is it another issue that we that we’re not addressing?
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JASON GOLDMAN, ACP [00:20:31]
Is it within the CDC’s purview or what can be done to handle certain state jurisdictions deliberately putting out disinformation regarding the safety and efficacy of the vaccines?
JOSE ROMERO, CDC [00:20:47]
Dr. Goldman, it’s good to hear from you again, and it’s always a pleasure to see you take the bull by the horns.
So CDC, as always, is engaged with educating the public and providing information that is scientifically correct and sound. It is not within the realm of CDC to actively involve itself within jurisdictions. So simply put, these are decisions made by the jurisdiction or jurisdictions involved. We are available to prevent to present the data, as it actually sits.
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MATTHEW DALEY, ACIP [00:30:36]
Do we know why? I mean, I realize that’s a hard question, but why influenza was so early this year? And I guess I’m asking in part for anticipating future years. And I realize it may be a little speculative.
LISA GROHSKOPF, CDC [00:30:49]
I think that’s always difficult to say. Flu seasons are unpredictable, and it’s not the first time we’ve had a season that early. There’s actually a good chart on the web pages that we have that cover about 39 flu seasons to date, and there were a couple that peaked as early as October. So, you know, some of it could be normal. Some of it could be that– hard to say, honestly.
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CAMILLE KOTTON, ACIP [00:31:19]
It’s interesting that the rate of hospitalization, although we had a brisk season, is still pretty low. Do we think that– I don’t know if you have any information on this, but do we think this is from better diagnostics? Better recognition of viral disease? Better use of therapeutics? Or maybe you can’t answer that from your perspective?
LISA GROHSKOPF, CDC [00:31:39]
We wouldn’t be able to discern that from the type of data we get in the system. But I mean, it would certainly be plausible to think, of course, people have, I think, a lower index of wanting to go get checked out perhaps by a medical provider if they’re not feeling well, given everything we’ve been through for the last couple of years. And it– that definitely could be something to do with it. It’s difficult to know for certain though, of course.
And also flu seasons do vary in severity. It is interesting to point out that H3N2 seasons are generally more severe than H1N1, and that’s what we’ve had the most of so far. But we also appear to have a reasonably good vaccine match this year. So as with flu, all things are variable.
MELINDA WHARTON, CDC [00:14:40]
In November 2021, ACIP unanimously voted in favor of Jynneos as an alternative to the other available vaccine for prevention of mpox in persons with certain occupational risks of exposure. Today ACIP is being asked to vote on an additional use of Jynneos vaccine for control of mpox outbreaks.
In 2022 a multinational outbreak of impacts began with more than 30,000 cases in the United States. In response to this outbreak, Jynneos has been successfully used in accordance with recommendations in CDC’s interim clinical considerations, and we’ve seen dramatic reduction in case counts.
Today’s vote will not change CDC’s recommendations for use of Jynneos in the current outbreak, but represents an update to ACIP’s recommendations, which were voted on in late 2021. And as you’ll hear in Dr. Sanchez’s introduction, we expect there will be additional decisions coming to ACIP for vote in future meetings.
The recent outbreak has highlighted again the risks that infectious diseases can present to our communities, the importance of a robust public health response at the state and local level, the value of engaged partners and communities in responding to public health threats and the impact that a vaccine can have in helping to bring an outbreak under control.
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PABLO SANCHEZ, ACIP [00:19:23]
In 2021, ACIP had made a recommendation, as well as an orthopoxvirus vaccine vote, where use of orthopoxvirus vaccine, the Jynneos that was licensed in 2019, for pre-exposure vaccination of people at occupational risk for orthopoxvirus exposures.
The Jynneos vaccine is a two dose series subcutaneous administration and recommendations were published in the MMWR in June 3rd, 2022.
Currently, there is no ACIP recommendation for the use of Jynneos during outbreaks.
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PABLO SANCHEZ, ACIP [00:22:21]
So the current tentative timeline for ACP discussions and votes is shown on this slide.
So in February 2023, currently right now, mpox, during the mpox outbreaks, we will be voting on the use of two dose Jynneos for persons aged 18 years of age or greater.
In June, we will be discussing the use of two dose Jynneos for persons age less than 18 years of age. And we’ll be presenting updates about vaccine effectiveness and safety.
And then in October of 2023, there will be consideration for a longer term vaccination strategy for the two dose Jynneos vaccine.
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SASCHA ELLINGTON, CDC [00:28:35]
Among cases with available data, more than half had rash reported on the genitals or perianal area, trunk or limbs, and head, face or mouth. And about a quarter had a rash on the palms or soles of the feet.
7.7% of people with mpox have been hospitalized and there have been 32 mpox associated deaths reported, representing 0.1% of cases. Deaths have occurred primarily in severely immunocompromised persons.
During the current outbreak and has been primarily spread through sexual or close intimate contact. Other routes of transmission have also been reported, including household transmission through injury with a contaminated sharp instrument in a clinical setting, through piercing and tattooing, and there have been a couple of cases of perinatal transmission from an infected mother to a infant around the time of delivery.
Current evidence suggests that some people can spread and mpox virus to others 1 to 4 days before they become symptomatic. However, there is no evidence that people who never develop symptoms have spread the virus to others.
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SASCHA ELLINGTON, CDC [00:34:47]
In another recent report of 83 cases in children from May to September of 2022, there were 16 cases in children aged 0 to 4 years, 12 cases in children aged 5 to 12, and 55 cases in children 13 to 17. Adolescents age 13 to 17 were overwhelmingly male and primarily had sexual exposures, mirroring the epidemiology of cases overall while in younger children, cases were more evenly divided by sex and were associated with household contact frequently from an infected caregiver.
While these findings are from a report analysing data through September, we have continued to investigate cases in children, particularly younger children, and findings have been similar.
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CAROL HAYES, ACNM [00:38:39]
Your slide indicated that there were 21 pregnant people who contracted the disease, but you only gave the outcome for three individuals. Do you have any data on the 18 others?
SASCHA ELLINGTON, CDC [00:38:52]
So at the time of the analysis, those 18 pregnant people were still pregnant. So there is continued follow up. There continue to be follow up, and outcomes will be reported as they become available, but they remain pregnant.
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LYNN BAHTA, ACIP [00:39:35]
You talked about none of the recently pregnant women receiving the Jynneos. Was that because it wasn’t indicated, in terms of– or it wasn’t licensed or authorized or was that refusal?
SASCHA ELLINGTON, CDC [00:39:52]
So we have documented cases of Jynneos being offered, and pregnant persons declining, but not in all circumstances. But it has been offered. But none of the none of the pregnant persons accepted or received the vaccine.
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GRACE LEE, ACIP [00:41:48]
Could you comment if any of the deaths we’re seeing observed in pediatric cases?
SASCHA ELLINGTON, CDC [00:41:54]
None of the deaths observed to date have been seen in pediatric cases.
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ANNA CHARD, CDC [00:52:21]
The multi-jurisdictional case control study is currently underway. This study examines vaccine effectiveness among men aged 18 to 49 who have sex with men and live in 12 U.S. jurisdictions. Cases are identified through the jurisdictions probable and confirmed mpox case lists. Controls are selected from health care settings, providing HIV PrEP, or from sexually transmitted infection clinics. Cases are frequency matched to controls based on time point within four weeks of clinic attendance and jurisdiction.
Jurisdiction staff members collect data on participants, demographics, exposure history and vaccination history using electronic surveys and vaccination status of enrolled participants is confirmed using state immunization registries. VE is estimated using multivariable logistic regression, with the random intercept for jurisdiction, and adjusted for a priori specified confounders. Next slide.
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ANNA CHARD, CDC [00:53:25]
Again, these are interim results as data collection is still underway.
Results indicate that vaccine effectiveness was 76% for full vaccination. Among those without immunocompromising conditions, vaccine effectiveness was 90% for full vaccination.
At this interim stage, there were few individuals with partial vaccination or with immunocompromising conditions. Therefore, data are not sufficiently powered to generate estimates for these strata.
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ANNA CHARD, CDC [00:53:58]
Lastly, I will share preliminary estimates from a case control study in New York State. Investigators linked case surveillance data to the immunization registry. Cases where adult male mpox cases diagnosed during July 24th to October 31st, 2022. Controls were adult male rectal, gonorrhea or primary syphilis cases during the same time period. Cases and controls were matched on week of diagnosis, and VE was estimated using conditional logistic regression.
VE was 68% for partial vaccination and 89% for full vaccination.
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ANNA CHARD, CDC [00:55:22]
Further research is needed to assess whether immunocompromised status modulates vaccine effectiveness. Due to small numbers in this population across studies, we were insufficiently powered to generate VE estimates among immunocompromised individuals.
Additionally, because of a decline in mpox cases and the limited follow up period from studies to date, further research is needed to assess the duration of protection conferred by Jynneos vaccination.
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ANNA CHARD, CDC [00:57:57]
So there are a very wide range in estimates for partial vaccination. And you can note that some of the confidence intervals are also very wide. And so they often kind of– they overlap.
The studies that investigated partial vaccination, they all have very different designs and varied– and they’re among very different populations. So I think that contributes to the range and VE estimates for partial vaccination.
But when you look at the the body of evidence in the studies that investigate both full and partial vaccination, across the board, we see that full vaccination provides higher protection than partial vaccination, when you’re comparing apples to apples.
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JONATHAN DUFFY, CDC [01:03:33]
An MMWR report about Jynneos vaccine safety monitoring was published that included data collected through October of 2022. Today’s presentation will include data through January of 2023. Next.
This presentation includes information collected using three surveillance systems. First is the Vaccine Adverse Event Reporting System, also called VAERS, which is the national passive reporting system. Second is the Vaccine Safety Datalink, which performs medical visit based active surveillance for prespecified adverse events of special interest in a population of more than 10 million people.
Third, V-Safe, which is a smartphone based system that uses text messaging to initiate web based survey monitoring for adverse events.
And then fourth, adverse event data was also collected as part of a single patient emergency Investigational New Drug procedures for persons aged less than 18 years vaccinated before the emergency use authorization was issued that allowed administration for that age group.
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JONATHAN DUFFY, CDC [01:08:56]
This slide shows the number of myocarditis cases and rates observed after Jynneos based on reports to VAERS and active surveillance in the Vaccine Safety Datalink.
In VAERS, there were 2 cases reported after dose 1, for a rate of 2.75 cases per million persons vaccinated. 3 cases were reported after dose 2 for a rate of 6.74 per million. In the Vaccine Safety Datalink population, there were 37,646 people who received at least 1 dose of Jynneos. There was one case of myocarditis observed after each dose. The VSD incident rate estimates have wide confidence intervals that range from about 1 to up to 250 cases per million. These confidence intervals overlap published historical population background rates, which range from 2.7 up to 21.6 cases per million persons during a 30 day period.
For context, the published historical rates after live replicating smallpox vaccines have ranged from 78 cases per million after Dryvax in a 2002 military cohort study up to 5,000 per million cases after ACAM 2000 in a 2018 military cohort study.
So in summary, the VAERS and Vaccine Safety Datalink data do not suggest an increased risk for myocarditis following Jynneos compared to these expected published background rates. But the possibility of a small risk cannot be excluded.
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JONATHAN DUFFY, CDC [01:11:27]
V Safe for mpox vaccines had 181 active participants, all of whom were adults and a majority male. Additional characteristics are shown on the slide. Next.
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JONATHAN DUFFY, CDC [01:13:27]
Jynneos was administered to 1,245 persons aged less than 18 years in the U.S. during the surveillance period and VAERS received 25 reports for this age group. Vaccinated persons ages range from 12 to 17 years. Reports of vaccine administration errors accounted for 84% of these reports, with the most common being intradermal administration instead of subcutaneous, which again is the authorized route for this age group.
The only adverse event reported was one person was syncope and there were no serious adverse events reported. Next slide.
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JONATHAN DUFFY, CDC [01:22:40]
I mean, the role of V Safe is really to compliment VAERS and VSD and provide different type of information, which is more focused around those injection site and systemic adverse events, which would provide that real world evidence similar to solicited adverse events collected in clinical trials.
And so in this mpox outbreak, I think part of the low participation was influenced by the timing of the availability of when the survey was rolled out. The survey didn’t become available until November. As you saw, I was after many of the vaccine doses administered.
But yeah, CDC plans to use V Safe in the future for other types of vaccines and in a non emergency response in a routine vaccination program. The expectation would be that that would be available at the launch or at the start early in the vaccination program.
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JONATHAN DUFFY, CDC [01:25:11]
So CDC is not aware of any persons who have received during pregnancy in the course of this outbreak. There have been no reports to VAERS
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JONATHAN DUFFY, CDC [01:27:13]
The V Safe for mpox collection will is scheduled to continue through March at this point. So we will be collecting additional data. But, you know, due to vaccine uptake, we may not have significant additional data in the future.
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ROSALIND CARTER, CDC [02:07:34]
There were many challenges, most notably the limited supply. At the peak of the outbreak in mid-July, when demand was highest, the intradermal route of administration was an important public health intervention in increasing our vaccine supply 300 to 500% when it was most needed.
Our ASPR colleagues handled the complex logistics of moving Jynneos vaccine from the federal Strategic National Stockpile to the jurisdictions. However, at the beginning, SNS was limited to only five shipments per week during the outbreak peak, leaving the jurisdictions to manage redistribution to providers in critical areas.
However, within about six weeks, ASPR was able to increase their shipping capacity to provide directly to providers.
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LYNN BAHTA, ACIP [02:10:37]
I think that the launch of this was really difficult because the system that the vaccine distribution system was totally different than what all of the public health immunization programs had been utilizing beforehand.
And not only that, in discussion of the issue of equity, the states were only allowed five sites to receive vaccine. And that was one of the reasons why there was such limited distribution of the vaccine.
And so I think that if we are going to use the national stockpile via ASPR, we need to think about the efficiency of that distribution system.
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ROSALIND CARTER, CDC [02:17:00]
To or the first part of that question, recommendation for health care workers working with potential patients with suspected mpox, we worked closely with our health care workers safety task force and our NIOSH colleagues who looked at this very carefully, and the conclusion was that PPE recommendations were provided adequate protection against risk of mpox transmission. And therefore we did not recommend Jynneos vaccine for health care workers.
I think the permissive attitude you may be referring to is we did have questions with the intradermal dosing. If there were doses left in a vial that were otherwise going to be wasted, could they be used for health care workers? That was left up to the jurisdictions to make those decisions.
But our overall stance was that health care workers could protect themselves with PPE and were not eligible for vaccine, that this was limited to the ACIP recommendations from for 2022 for occupational exposures.
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AGAM RAO, CDC [02:18:54]
So I’ll just say that it’s true that the number of of infections that we’ve heard of in people who are health care personnel that were exposed at work is very low. I think the last I heard, and it could be a little bit higher than this, but the last I heard, it was like 10 or less. So it was few. And they were predominantly sharps injuries. So people who were attempting to aspirate lesions or unroof lesions to get samples.
And we did come out on the CDC website and also on COCA calls explicitly saying that we do not recommend that that be done, that sharps, unroofing the lesions, are not necessary, that very good specimens are being obtained just from vigorous swabbing of the lesions. And so there really is not a need to unroof lesions and perhaps that’s cut down on the sharp– the risk for sharps injuries.
There have been a few cases, very few that that are unexplained, and that the individuals don’t have any personal risk factors that we’re aware of, and also cannot recall caring for a patient with mpox, and seem to have developed mpox. The good news is that those individuals had self-limited illness and recovered very quickly.
But we do offer post-exposure prophylaxis is something that should be considered whenever there is an exposure that is high risk or the individual is someone who is at high risk.
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MOLLY HOWELL, AIM [02:22:06]
One, I wanted to echo Lynn Bahta’s comments regarding the use of traditional systems in response to emergencies for vaccine ordering and management. These include immunization information systems and CDC’s vaccine ordering system Vtrcks.
It was very time intensive and difficult for states to implement a new system during the monkeypox response, and so it would have been appreciated to use the systems that we used successfully during the H1N1 response and COVID vaccine response.
And if new systems are going to be used in the future, we would appreciate any information on those systems now, so we can plan for their use and electronically connect our immunization information systems to those systems.
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AGAM RAO, CDC [02:48:07]
So the balance of consequences, after considering all of these responses, the workgroup felt that the desirable consequences clearly outweigh the undesirable consequences in most settings, and drafted the language on this slide for the consideration of ACIP.
So ACIP recommends the two dose Jynneos vaccine series for persons aged 18 years and older at risk of mpox during an mpox outbreak.
Clinical considerations is something that we could– we’d be certainly interested in hearing what ACIP members and others think about what should be included in an outbreak setting. The vaccine is ideally given pre-exposure, but may also be given as post-exposure prophylaxis. The complete two dose vaccine series should be given regardless of the timing of the exposure, and that is what we had planned to put into the clinical considerations. And if there are vaccine supply shortages, the intradermal or ID route of administration can be used.
We will be talking more about data for about the intradermal route of administration at the June ACIP meeting and of course the MMWR that consolidates the entire outbreak language from this meeting as well as the June meeting will be consolidated into one one MMWR after that. So ID data will be presented at that time.
And then just as a reminder of our plans, I mentioned that the February and the June meeting will be about this. So during the June meeting, we will provide updates about vaccine effectiveness and safety. And we will also have a separate vote for administration of the vaccine in people less than the age of 18 years.
We are focused today on greater than or equal to 18 years, partly because that is simply an expansion of the 2021– sorry, 2022 ACIP recommendations for persons at occupational risk. It’s the same age range. It’s just to a different group of people. In June, we will focus on individuals less than 18 years and updates.
And then depending upon the epidemiology of this outbreak, if cases are continuing to occur and occur in large numbers, then during the October ACIP meeting, there will be more discussion and consideration for a longer term, even if it’s short term, vaccination strategy with the two dose Jynneos series.
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AGAM RAO, CDC [02:52:20]
I can partly answer this question. I think I guess– we think that the vaccines have had an impact, as have had behavioral changes. But it’s true that in countries where there is no vaccine available, case counts have also decreased in many of those countries. So perhaps this is a little bit more complicated, but vaccines certainly are having some– having a role.
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AGAM RAO, CDC [02:53:24]
We are collaborating with some other partners to try to do some immunogenicity sort of studies to try to understand the role of immunocompromise, and do plan on discussing that within the workgroup.
And we’ll certainly– we’ve had clinicians on our work group who have also brought up the same concern, because they care for patients with advanced HIV, but also with other reasons for immunocompromise, transplant patients and others who have been– who are at higher risk. And so we will certainly discuss it more and bring any new data to to the ACIP.
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AGAM RAO, CDC [00:00:00]
There will be at least two years. And the reason, we do not have data beyond two years.
So we do have a study that we are conducting in the Democratic Republic of Congo to try to understand booster doses beyond two years. It’s in progress, actually, where we administer boosters five years after to understand the immune response.
And we hope to have more information from that, as well as other collaborations over the coming years that will inform recommendations about booster doses.
ROBERT CALIFF, FDA [00:18:44]
And it’s well known that we’re looking closely at the labeling of chronic opioids at this point. I can’t say what we’re going to do or when we’re going to do it. I’m not allowed to do that.
But let’s just say the most recent CDC report once again said there is no evidence about the benefits of chronic use of opioids. Yet we have millions of Americans that are on chronic opioids. So I would point to that as an area where we need a lot more evidence.
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ROBERT CALIFF, FDA [00:19:16]
And then Dr. Volkow grabbed me already this morning and told me that we’re an impediment. She said it in a very nice one and very politically astute. That we’re an impediment to all these great new therapies that you’re developing on the HEAL network. So I’m very interested in hearing about that. And I would say the traditional pharma industry has been a failure in developing new non-addictive therapies for pain.
Maybe you all have the key, but I told Nora that a big part of my history in academia was telling academics that their ideas actually didn’t work because I did the clinical trials. So it’s great to have ideas, but we’re going to need hardcore evidence.
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ROBERT CALIFF, FDA [00:42:51]
We’re involved in intensive discussions. And I’d say there’s an openness at this point to a variety of alternatives signifying a better clinical state of an individual, whether that’s fewer symptoms or less use of things that are considered bad.
Now, a good part of my career was actually developing the substrate to change outcomes that were measured in different fields. And there’s a part of the statute that says adequate and well controlled trials in the opinion of experts in the field. And so if there really is a consensus and people feel strongly about it, not just one group comes out and then another group comes in and says something different, I would say there’s going to be a lot of openness to alternative end points. But to reach a consensus, you have to actually do the research and have the evidence that the measure matters.
And I throw in here that patient reported outcomes, I think is now having a resurgence at the FDA. So, again, it’s not just a matter of collecting a few, it’s a matter of rigorously doing the research, which I think this network is perfectly set out to do.
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ROBERT CALIFF, FDA [00:51:06]
And you know, what I’d say in general is, you know, people talk about the ratio, but it’s really a balance because the measurement of benefit and the measurement of risk often involve different numbers, different definitions of things. And of course, with drugs, you often have off target effects that cause risks that are not directly associated with the way you think about the target that you’re going after. And so you need a broad measurement during the early phase of development.
It’s also the case that Americans in general, for better or worse are risk takers, have spoken loudly that they would like access to treatments that might be effective earlier rather than later. Congress has passed laws that tell us as referees that our rulebook is different for these conditions. But part two of that, about which has been a lot of public discussion, is the rules for accelerated approvals based on preliminary evidence of benefit and risk with a biomarker used to get on the market have to be followed by definitive studies.
And CMS just recently floated the idea, which I love, that in those situations, maybe you’ll get paid less as the company selling the product until you get the definitive evidence in. Now, that’s not decided. The idea was just floated. I’m 100% in favor of that, I’ll say.
So those are all those are all considerations. It’s not one size fits all. Again, I come back to, if the experts in the field really have a consensus, it’s likely to happen. But theoretical benefits and risks are not the same as demonstrating benefits and risks.
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ROBERT CALIFF, FDA [01:00:17]
And when it comes to telehealth, I’ll just give the example that’s driving, between us, all of us right now, completely crazy, and it’s what not to do. And it’s an antidote to people who say, ‘just open it up for telehealth, it’s great.’ The thing not to do is to hire the lowest level provider, have them prescribe as much Adderall as possible, working for a company which is funded by hedge fund managers, to generate the most profit possible, with almost no follow up for who get prescribed. And that’s happening right now.
So as long as that’s happening, it’s very hard to say we’re not– we’re just going to open the floodgates on this. So you all need to be doing research on, okay, what are the appropriate ways to do this?
I personally had to defend telehealth in our program in Dayton before I came to FDA, when the state medical board tried to shut down the opportunity to give it. So I’m all for it, but we got to define the parameters better.
· A small number (3) of unopened bottles of EzriCare Artificial Tears were tested by CDC, and we did not recover bacteria from these. Our FDA partners are currently testing additional unopened bottles of EzriCare and Delsam Pharma Artificial Tears. They can provide the best information on timelines.
· The product was primarily available online, but we have received a report of a case patient purchasing the product in a Costco.
· Overall, at least 16 patients were newly hospitalized at least in part due to their Pseudomonas infection. Among the 11 patients with P. aeruginosa eye infections, at least 5 had permanent vision loss and 1 had enucleation. We are actively gathering more information about long term patient outcomes, particularly for patients with eye infections.
· There was a death in a Washington patient who had a bloodstream infection.
· Some patients were immunocompromised but this was not the majority of patients. Patients had a range of underlying conditions and health statuses. Most patients with eye infections had underlying eye disease, such as glaucoma or a history of cataract surgery with intraocular lens implant. Overall, about one-third of patients were very sick (e.g., receiving mechanical ventilation) at the time of P. aeruginosa identification.
· Isolates were not susceptible to any antibiotics routinely tested at public health laboratories. Three isolates that underwent additional susceptibility testing at clinical or public health laboratories and had results reported to CDC were susceptible to is a newer antibiotic called cefiderocol.
| · Updates will be posted weekly here: [Outbreak of Extensively Drug-resistant Pseudomonas aeruginosa Associated with Artificial Tears | HAI | CDC](https://urldefense.com/v3/https:/www.cdc.gov/hai/outbreaks/CRPA-artificial-tears.html;!!CxwJSw!KC-7ZTol6_Cp8EymtjnsUhnglimG1DG7WutpGsO869lbnmGMXThyXQK3M62McMPRYK9GQ2ZU9A$); |
Martha Sharan
Reporting adverse events to VAERS increased significantly across many, if not all, health jurisdictions after the availability of COVID-19 vaccines. However, it’s important to note that an increase in VAERS reports does not indicate that the COVID-19 vaccines are unsafe.
There are several key reasons reporting to VAERS after COVID-19 vaccination is higher than for other vaccines:
Mandatory reporting to VAERS. The reporting requirements to VAERS are more stringent for COVID-19 vaccines than for all other vaccines: The reporting requirements for healthcare providers who administer COVID-19 vaccines are listed at VAERS - FAQs hhs.gov. The reporting requirements for healthcare providers who administer other vaccines are listed at VAERS - FAQs (hhs.gov).
Mass Immunization. More than 670 million doses of COVID-19 vaccine have been administered in the United States (see https://covid.cdc.gov/covid-data-tracker/#vaccinations_vacc-people-booster-percent-total) since licensure or authorization; this accounts for more doses of COVID-19 being given than other vaccines.
Public Awareness. As part of heightened safety monitoring for COVID-19 vaccines, CDC and FDA have strongly engaged healthcare providers, public health jurisdictions and the public to report adverse events to VAERS. These reports include adverse events that occur after vaccination, regardless of whether it is known if the vaccine is the cause.
Media. VAERS has received wide media attention, which likely leads to increased reporting rates.
Please note, VAERS is CDC’s and FDA’s frontline vaccine monitoring system, and VAERS reports may be unverified. Anyone (healthcare professionals, manufacturers, general public) can send a report of adverse events into VAERS after vaccination, regardless of whether an adverse event is related to vaccination. Some of those adverse events may be true adverse reactions or they may be coincidental events and not related to vaccination. VAERS is not designed to determine if the vaccine caused the reported adverse event. VAERS is designed to be an early warning system. It looks for unusual patterns of rare and serious adverse events and alerts CDC and FDA experts to potential vaccine safety concerns, known as safety signals.
COVID-19 vaccines have undergone—and continue to undergo—the most intense vaccine safety monitoring in U.S. history. Clinical research has demonstrated the safety and effectiveness of the recommended COVID-19 primary series vaccines, as well as the recommended updated vaccines. CDC continues to encourage people to stay up to date with recommended COVID-19 vaccines, including an updated booster vaccine when eligible. This is particularly important for older adults and those with underlying conditions who are at higher risk.
LOVISA ROMANOFF, CDC
So why are we changing CDC’s model? I’m hoping everything that I shared on the previous slide with the common theme is starting to hint at why we are doing it. What we’re seeking to move away from is the volunteer based model that we’ve used historically which has resulted in spending time searching for staff to fill critical response roles, time that could really be spent in the response on activities and keeping routine CDC programs running.
…
MARK FRANK, CDC
So very broadly this is the vision and projected outcomes that we see with the CDC ready responder program. The goal ultimately is that CDC will be using its entire workforce to support our emergency response operations, and we are going to be using trained qualified and available staff who are assigned to response roles that align with everybody’s skills and expertise. When we ask people to serve in a response, we are really asking them to use the skills and expertise for which they came to CDC and they use on a day to day basis and apply those skills in an emergency response environment.
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MARK FRANK, CDC
So to start out the first element that we’re proposing as part of this program is what we’re calling our responder cadres. We’re talking about developing these discipline specific cadres to reflect key needs that we know are needed to response. So we intend to organize people in to these cadres, and these are largely areas of subject matter expertise. So whether vou’re thinking of epidemiology, laboratory functions, operational support, or the variety of other broad functions that we know are needed for response, we want to identify people and place them in to those cadres so that we can pull them in to a response as needed.
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MARK FRANK, CDC
We all recognize that responding to emergencies is both rewarding and very stressful at the same time. And we’re hoping that with broader participation from staff across the agency, we can really have a more sustainable response that is more manageable for everyone who participates. We also want to acknowledge and recognize that individual and family circumstances arise all the time. So you may say that you are available for deployment whenever, but we know those emergencies come up for you and your families. And we will take that in to consideration when considering specific response assignments. People have children, families, pets, partners, and their own situations to deal with, and we want to acknowledge that and recognize that in terms of response assignments.
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MARK FRANK, CDC
Robin has already signed a policy waiver to our emergency response staffing operational policy and in the coming months we expect to collaborate with many partners across the agency to revise that policy in full to reflect our program and how we’re going to implement that more fully. We are also working on assembling some of the initial cadres that I talked about, primarily with some of the experienced response leaders, health communicators, and operational support that we know we need in a response.
…
ROBIN BAILEY, CDC
We also would have an organization that has a workforce that is prepared for public health emergencies both infectious and non infectious that we are fully utilizing our highly skilled workforce by developing our workforce in their chosen profession to include response experience. That means what you came to CDC to do, but understanding how you will perform that role in a response atmosphere. Doing our part to be ready when called upon t o support So that means doing a l l the necessary training. That means making yourself available, participating in exercises so you’re fully confident in terms of how your current role plays out ni a response environment. That’s primarily what we’re talking about when we’re talking about a response ready agency culture.
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LOVISA ROMANOFF, CDC
Deploying to the field is going to be based on a voluntary nature. It’s really an opportunity, I think, to be able to see public health up front, but we are not picking people up from their homes and sending them out in the field. As it relates to response participation at the agency, I’d like to just sort of challenge everyone to think of yourself as a responder.
…
SPEAKER NOT SPECIFIED
I really just want to make sure that I emphasize that, no, we are not going to force anyone to go out in the field. We’re not going to force anyone to participate in a response serving in a role that they don’t have the right qualifications and training and support in order to do successfully.
…
SPEAKER NOT SPECIFIED
And I’ll also add to that just a couple things to take this just a little bit deeper. Specifically the questions that have come in have referenced the notion of turning CDC in to a military environment, forcing people to do things that they did not sign up to do. That is not what this is about at all. It’s really about the job that you did apply for and were selected for to come in to in CDC, helping you understand how you use those skill sets in a response.
…
SPEAKER NOT SPECIFIED
So we certainly want to make responses more manageable. It is unsustainable for our workforce to work 18 hours a day for 6 months at a time or a year at a time in some cases. That’s not good for our employees, and it’s not good for our agency. And so we are looking at efforts to make response work and participation more manageable. I do think in some cases being able to work remotely and have work at off hours really helps provide some of that flexibility, though not all of it.
…
SPEAKER NOT SPECIFIED
So linaudible] know that we’re going to have a scenario where if you’re saying no we’re going to say, “Yes. You are.” But just to be clear if it’s a part of your job we have a right to ask you to do that work. That doesn’t mean that we’re putting you on night shift. That doesn’t mean you’re necessarily if you’re working from home you’re going to have to come in. It’s just we’re going to ask you to do that work as a part of a response because again one CDC. We all have requirements. We’ve all been hired to do a job. And we’re going to make sure that piece of your job is fully explained and you understand what those requirements will be and you’ll have plenty of training associated with that. So if it were me, I wouldn’t be concerned about it in that way. You’ll have an opportunity to get really comfortable.
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SPEAKER NOT SPECIFIED
I would also say over the holidays don’t forget how enthusiastic you are about this because hope we can have your enthusiasm carry in to the new year. We’re very excited about this, and we hope you are as well. This is a great change for us, and it really will help us become more effective in the way we respond to public health emergencies.
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KEVIN GRIFFIS, CDC
The reorganization also created the Division of Communication Science and Services – run by Betsy Mitchell, which I believe will ultimately be an important asset for all of CDC communications – is the hub for our work and planning to counter mis and disinformation. And is a resource for the evidence-based, scientific practice of health communication. How can data inform how we talk about a topic that generates controversy - - such as mask wearing, for example - - so that people listen to the message as opposed to rejecting it out of hand.
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ABBIGAIL TUMPEY, CDC
So some of the structural issues Cate has already mentioned. So communication really being treated as a service feature versus a strategy feature. So we heard loud and clear from communicators, both during the strike team process and the PAT process, that sometimes communicators are not at the table or not involved early enough in the process to really make an impact.
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ABBIGAIL TUMPEY, CDC
Staffing issues. So there’s not enough communicators in some groups. So I’ll give you a key example of this that we’re looking into. Right now there’s no steady state FTEs in our JIC content team for responses. Which means that we end up burning through a lot of staff, really talented staff that we really need additional hands to do this work.
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ABBIGAIL TUMPEY, CDC
But I remember we were hosting a listening session, Cate and I , and Kevin was listening to communicators around the agency say this. And it was so surprising, I think, to you to hear this coming into the organization and hearing that communicators are getting things at the last minute and told, just put it up on the website or just make it pretty or just do X, Y, Z, and not really part of that whole process.
This was actually part of the reason that I asked Dr. Walensky the question in the last All Hands of whether you were sitting at the table so that other people around the agency could really hear that this is, at the OD level, communicators are part of the strategy table and really thinking through stuff early and really able to help in that decision-making process.
I think we have pockets around the agency that do include their communicators, and they ultimately have better products in the end. They have better, you know, thoughtful pieces that really align science, policy, and communications. And I think that’s our ideal model. This will definitely be a cultural shift.
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ABBIGAIL TUMPEY, CDC
I think the other issue we’re looking at at this point is, because we have multiple responses and then attempting to duplicate a JIC team for COVID, a JIC team for monkeypox, a JIC team for Ebola. That is just way too many staff that we do not have. So how can we actually think through a way that we’re a JIC that can pivot two different emergency responses? These are models that we have not, you know, completely done before or thought through before.
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SPEAKER NOT SPECIFIED
And I would just say just briefly that, you know, it’s clear, like the MMWR is a flagship communications tool for CDC. I do think there’s some sense outside the organization and maybe of some different parts of the organization that it tends to be very deliberate. But I really have been struck since I’ve been here about how quickly they work to try to get information out in a timely way so that it is relevant to, you know, a given outbreak or given, you know, issue that we’re dealing with. And I think it’s really a model for how communications can and sort of science publication can work across agency.
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SPEAKER NOT SPECIFIED
I mean, and obviously I think the challenge has perhaps gotten bigger because of some of the changes at one of the major social media platforms, Twitter. You know, we went from a situation where they were moderating content, perhaps imperfectly, but making an effort to do that. To now where they- -it is, there’s much less moderation.
And, you know, in terms of CDC even being able to even communicate with Twitter, you know, folks who we worked with previously, they’re simply no longer at the company, and they’re not being replaced. And ultimately, I think the vision there is that they’re hopeful that artificial intelligence is going to be able to do some of that content moderation, you know, on its own without having a human hand to guide it. But that’s not where we are right now. So I think the challenges that we have are real, and they’re not getting - -they’re not lessening.
I think what we’re hoping to do and Betsy Mitchell’s group is working on this, is figuring out how do we infuse the focus on misinformation and disinformation across all of our major rollouts? So how do we start thinking about that on the front end? What do we know that is likely to be taken out of context or misrepresented? And then , how do we position ourselves to, one, respond rapidly in that kind of situation? And then, two, I think, how do we also make sure that the folks who are in the sort of public health world with us who have important voices there, how do we make sure we arm them in advance so that they can be amplifying our messages, but also ensuring that they are working as well to help correct the record?
…
SPEAKER NOT SPECIFIED
How do you think you will change the institutional culture around scientists overruling communicators on final communication products and not just in emergency responses? Not sure who wants to take that one.
I can start it maybe, Abbigail. So, I mean, I think part of it is, you know, I need to ensure that I’m doing the best possible job that I can in advocating with our leaders across CDC to ensure that we have communications folks at the table early in the process.
Thanks for reaching out to CDC. What Florida was seeing in 2021 was seen across the country. Reporting adverse events to VAERS increased significantly across many, if not all, health jurisdictions after the availability of COVID-19 vaccines.
Below are several key reasons reporting to VAERS after COVID-19 vaccination is higher than for other vaccines:
Mandatory reporting to VAERS. The reporting requirements to VAERS are more stringent for COVID-19 vaccines than for all other vaccines: The reporting requirements for healthcare providers who administer COVID-19 vaccines are listed at VAERS - FAQs (hhs.gov). The reporting requirements for healthcare providers who administer other vaccines are listed at VAERS - FAQs (hhs.gov).
Mass Immunization. More than 670 million doses of COVID-19 vaccine have been administered in the United States (see https://covid.cdc.gov/covid-data-tracker/#vaccinations_vacc-people-booster-percent-total) since licensure or authorization; this accounts for more doses of COVID-19 being given than other vaccines.
Public Awareness. As part of heightened safety monitoring for COVID-19 vaccines, CDC and FDA have strongly engaged healthcare providers, public health jurisdictions and the public to report adverse events to VAERS. These reports include adverse events that occur after vaccination, regardless of whether it is known if the vaccine is the cause.
Media. VAERS has received wide media attention, which likely leads to increased reporting rates.
Please note, VAERS is CDC and FDAs frontline vaccine monitoring system. Anyone (healthcare professionals, manufacturers, general public) can send a report of adverse events into VAERS after vaccination. Some of those adverse events may be true adverse reactions or they may be coincidental events and not related to vaccination. VAERS is not designed to determine if the vaccine caused the reported adverse event. VAERS is designed to be an early warning system. It looks for unusual patterns of rare and serious adverse events and alerts CDC experts to potential vaccine safety concerns, known as safety signals.
COVID-19 vaccines have undergone—and continue to undergo—the most intense vaccine safety monitoring in U.S. history. Clinical research has demonstrated the safety and effectiveness of the recommended COVID-19 primary series vaccines, as well as the recommended updated vaccines. CDC continues to encourage people to stay up to date with recommended COVID-19 vaccines, including an updated booster vaccine when eligible. This is particularly important for older adults and those with underlying conditions who are at higher risk.
Nick Spinelli
| Date | Orders |
|---|---|
| 12/15/2022 | 5,488,929 |
| 12/16/2022 | 1,972,865 |
| 12/17/2022 | 682,677 |
| 12/18/2022 | 434,973 |
| 12/19/2022 | 516,587 |
| 12/20/2022 | 1,162,209 |
| 12/21/2022 | 477,752 |
| 12/22/2022 | 495,233 |
| 12/23/2022 | 249,818 |
| 12/24/2022 | 145,772 |
| 12/25/2022 | 112,662 |
| 12/26/2022 | 179,165 |
| 12/27/2022 | 208,761 |
| 12/28/2022 | 205,489 |
| 12/29/2022 | 185,666 |
| 12/30/2022 | 156,736 |
| 12/31/2022 | 114,520 |
| 1/1/2023 | 101,713 |
| 1/2/2023 | 145,757 |
| 1/3/2023 | 334,515 |
| 1/4/2023 | 162,774 |
| 1/5/2023 | 140,327 |
| 1/6/2023 | 145,035 |
| 1/7/2023 | 99,614 |
| 1/8/2023 | 89,393 |
| 1/9/2023 | 116,741 |
| 1/10/2023 | 203,950 |
| 1/11/2023 | 172,276 |
| 1/12/2023 | 85,612 |
| 1/13/2023 | 67,213 |
| 1/14/2023 | 52,436 |
| 1/15/2023 | 50,293 |
| 1/16/2023 | 60,080 |
| 1/17/2023 | 71,351 |
| 1/18/2023 | 68,388 |
Here is something on background that addresses a number of the issues raised.
The Big Picture: Approximately every 8 minutes, a person dies from an opioid overdose. Of the more than 107,000 overdose deaths in 2021, 75% involved opioids. These stats make clear how urgent and devastating this epidemic is and seeking to make NARCAN available over the counter is the next critical step in broadening access to this potentially life-saving treatment. It builds on the work Emergent and countless stakeholders across the country have done to increase access through naloxone access laws (standing order) and community distribution, to highlight a few.
Is it safe and effective? NARCAN Nasal Spray was approved by the FDA as a prescription opioid reversal treatment in 2015. We have more than 7 years of post-marketing data demonstrating the safety of NARCAN. To date, more than 44 million doses of NARCAN have been distributed in the U.S. and Canada. It’s important to note that naloxone has extensive literature support for safety and efficacy. It has been utilized in various routes of administration and since 2015 Narcan has been available as an intranasal formulation for community use. Since approval, NARCAN has had broad distribution and continued monitoring for both utilization and safety, and regardless of population, NARCAN is ready to use, reliable and has a well-established safety profile.
How much will it cost? It is premature to discuss details until the advisory committee has voted and the FDA has taken action on our application. Expanding awareness, helping to maintain affordability, and increasing accessibility to NARCAN continues to be at the forefront of our work with federal and state governments, healthcare providers, first responders, pharmacists, and insurers, principally in the U.S., but also in Canada. As addressed in our response to Congressional leaders regarding access to naloxone and in subsequent meeting with government officials, we continue to raise the importance of public and private insurance coverage for NARCAN. This is not an issue that Emergent can solve, and in many instances, requires government support.
When will it be available? The short answer: as soon as possible. However, production of NARCAN for the over-the-counter market will not begin until after the FDA approves our application (expected approval is March 29, 2023), so our anticipated timing is around late Summer of this year. We have been working on distribution plans with key stakeholders like retailers and government leaders. An important note: FDA approval for OTC status is not expected to immediately change Emergent’s NARCANDirect.com for public interest customers.
The last word: An overdose can happen anytime, anywhere and it often occurs outside of a medical setting where access to naloxone may not be readily available. A decision to make NARCAN available over the counter would expand access to more Americans and possibly help save more lives. Emergent is committed to working with the FDA to gain approval and continuing to work with stakeholders to enable accessibility, increase awareness and continue to offer our direct purchase and donations programs.
GEORGE AMEH, WHO [00:19:25]
The last information we got from the ministry is that in the last 48 hours, there has been no new suspicious case. That is the official information that we get. But as I said, we are scaling up the field epidemiology and surveillance interventions so that we have a firm grip on what is going on in the field.
…
MATTHEW DUCHARS, SABIN [00:35:43]
So Sabin has an adeno viral vectored vaccine, which has completed phase one and has some good data available for that already, has shown, good, safe, robust, durable response and is entering into phase two hopefully later this year. We have actually, just last year but halfway through last year, manufactured a small batch of drug product. Now, quite a lot of that product has already been used and is earmarked for further studies. So I’m being a little bit vague, but we’re at the moment trying to work out exactly how many vials would be available or could be made available very quickly for future use. But I’m not going to commit to a number right now because I think we still need to work through that with our sponsors as well.
And we have quite a reasonable amount of drug substance, which has also has been manufactured and is awaiting to be filled. And this probably up to about 20,000 doses could be filled from the bulk that is currently made. And we also have some manufacturing slots through the course of the first half of this year, which can be repurposed for filling that material, if that is in fact what we want to do.
So I think sort of briefly, in summary, the material that Sabin has is there’s a small amount– a small amount of already filled clinical materials ready to go, and a larger amount of drug substance is available.
…
DANIEL WOLFE, HHS [00:38:01]
There’s always been sort of a joint program that transitioned from the NIH to the Sabin vaccines through now under contract with us at BARDA. And the the word from the NIH team is that there are about 850 doses in vials, that are part of the existing stability programs, so not all of those would be available for use. They will need to continue to monitor stability to make sure that the product is still viable. But that’s kind of the short story there as far as any additional vials that could be available.
…
MATTHEW DUCHARS, SABIN [00:40:18]
So the fill that we completed last year was 2,000 vials, and at least half of those have now been used and are gone. And by, most of those vials are already committed to other studies. But what we need to do is look at whether we can release some of those vials to be able to, without sort of impairing the program completely. So I’m estimating that it’s somewhere between a hundred and a few hundred vials that can be made available potentially. But I’m not the person who’s able to commit that. So I can’t say for sure exactly the number that’s available.
…
DANIEL WOLFE, HHS [00:41:06]
The only thing I wanted to add was Phil, during the Sudan response, we were putting plans in place to fill all the remaining Sudan bulk that was the Sudan Ebola virus, chimp ad vaccine that was in existence. So basically we’re trying, between BARDA and Sabin, we’re trying to figure out if there is a way to expedite manufacturing and filling of the remaining Marburg bulk drug as quickly as possible. So hopefully we’ll have a better answer for that as soon as possible. But just trying to figure out exactly how quickly we can move on filling the remaining bulk.
…
ANDY KILIANSKI, IAVI [00:43:18]
We’ve advanced to clone into manufacturing. And right now we do not have any available bulk drug substance or field drug product. We have we had initially planned to do one to two more process development runs here over the next few months before moving into GMP manufacturing. We’re working on how to best accelerate that process, and we’ve also been supported by our DOD and HHS colleagues from the U.S. government on scaling that manufacturing process.
So long story short, we don’t have any drug product right now that’s available for use. We’re probably at least a few months out in terms of any vial drug product that can be used in Africa.
…
JOAN FUSCO, PHV [00:46:46]
And right now we do have vaccine supply in a small batch that is in unit dose vials, at approximately the target dose level of E7 pfu/ml. And we have 350 vials available and ready for use in the clinical setting.
At this time, we don’t have any GMP bulk supply and there is no active manufacturing ongoing. And at this time we are engaged with potential partners for initiating phase one clinical testing, which has not yet started, and are ready to proceed, having now received this regulatory greenlight from FDA for human testing and with vaccine ready in the vial.
Of course, this would be in concert with working with BARDA for use of these materials for that purpose, and any purpose that there may be, for use of these materials for this circumstance in Africa.
…
KAREN MARTINS, BARDA [01:21:00]
So right now it’s Terry mentioned we have a very limited number of doses, so it’s less than 30. And really again, this is material essentially leftover from the phase one study. So we’ve been working with Mapp really since the Sudan outbreak to try to establish outbreak response material. And we’re currently in the process of doing that with this product. Unfortunately, that means more material is still several months down the road. We should have more information in the next couple of weeks, but I’m just starting those conversations to see what we can do to expedite.
…
PHIL KRAUSE, WHO[01:56:14]
So this is just a summary of what I heard today. It’s a fairly brief– and so to the extent I say anything that doesn’t sound right, please let me know.
So Dr. Ryan opened by reminding us of the importance of global partnership in addressing these public health emergencies. And we heard from WHO that research is essential to assure ultimate availability of safe and effective diagnostics, drugs, and therapeutics for outbreaks, including for Marburg. This requires prioritization of funding for vaccines available in vials, trial platforms and protocols, legal insurance and liability framework, and funding for studies. And we actually have made substantial progress on all of these points for Marburg, even since last July, although we’re not perhaps not quite as far as we would like to be on all of this.
Index case was on the 7th of January. The ministry was notified on the 7th of February in Equatorial Guinea. It was officially notified to WHO on the 13th of February after a positive diagnosis at the Institut Pasteur in Dakar for Marburg virus. And we’ve heard that the sequence will be available very soon. So far there have been nine deaths, the epi links of which have been close family members, burial attendees. We have 16 people under quarantine and 15 additional asymptomatic contacts at home. The response so far has involved surge field epidemiological capacity and efforts of infection prevention and control and case management. And Equatorial Guinea is currently working on a 30 day response plan. And fortunately, we’ve heard that in the past 48 hours, there’ve been no new suspicious cases.
MARVAC is a WHO facilitated voluntary working group to foster development of vaccines and therapeutics and has focused a lot of its efforts on vaccines, animal models and assays. The landscape for vaccines includes vaccines that have protective efficacy in NHPs. And so most of these current efforts involve vector vaccines, which we heard from outside information from five of the developers from Sabin, phase one is complete with the ChAd3 vector vaccine. A small batch has been produced, but much of it has been used, and other doses are committed. But there is drug substance that’s awaiting filling. There’s also some additional doses at the VRC that are part of the stability program. The best estimate is that between a hundred to a few hundred vials could be available immediately for study in Equatorial Guinea.
IAVI is ready for phase one, but doesn’t have any doses available now. They’re still hoping to do some additional process development before producing the GMP lot. So they believe they’re a few months out. And that’s, of course, a VSV vector vaccine.
Another big vector vaccine is from PHV, which has an Angola antigen. Their preclinical testing is complete, has made and released a GMP lot where a few hundred doses could be made available. There is no active manufacturing going and there’s no bulk available that could be filled. But a phase one study is pending, with an active IND, where they have the go ahead to proceed.
Janssen has not had– does not have an active program ongoing, but is glad to support the situation with existing stock, where it seems like there are either 2,800 to 3,500 doses of Ad26 vector vaccines with corresponding MVA vectored vaccine, where however there is a need for some stability testing. Somewhat more acute on the Ad26 Marburg virus vaccine, all of them need stability testing fairly soon.
For oral, saw in the chat several people saying they don’t think the GMP lot is available, but Emergent also said in the chat that they’ll follow up to give us an accurate picture of what’s going on with that vaccine. But it may be that there are at least some of the indicators in the chat are correct, we may not have doses of oral that could be contemplated for use right now.
In therapeutics– sorry– there was a clinical trial protocol was discussed for vaccines, which involved ring vaccination, high risk populations. There are a lot of options there, including individual randomization and high risk and transmission clusters or cluster randomization within transmission clusters. For instance, rings for households. The primary endpoint would be virological confirmed disease and also obtained information on efficacy versus deaths. We did have some discussion about the primary hypothesis and sample size calculations, which could be discussed in the context of simplifying this protocol for use in the specific emergency that we have now, and drawing out of it the parts that are most relevant, which would likely be a cluster randomization comparing intermediate versus delayed vaccination of raise, possibly involving implementation across outbreaks while building on lessons learned from Sudan– the Sudan outbreak.
For therapeutics, Mapp Bio is in phase one. Remdesivir has doses available for off label use. The combination might be best, based on non-human primate studies, although we heard that there are not many regimens of Mapp Bio product available right now, with less than 30 leftover from phase one, but more material will be available in a few months.
Key principles for therapeutic studies are that it’s essential to establish the standard of care. Integration of research into the standard of care is essential and of course, to conduct trials where feasible. And the support that we’ve heard about includes build up of diagnostic capacity and this idea of standardized data collection and expanded access. And then study designs that we heard about include potentially placebo controls, factorial design, or comparisons versus A versus B versus A plus B, all of which also needs to be urgently discussed in the upcoming days.
Next steps, which was emphasized by many, need to be conducted with great alacrity, is to have the full sequence information and shared, perhaps do some modeling to predict epidemiology, because that may have implications for trials, to convene the prioritization committee to consider updated information from vaccine developers, to simplify the vaccine clinical trial protocol for potential use in Equatorial Guinea, to collect safety and immunogenicity data starting as soon as possible, and in therapeutics to establish the standard of care, identifying the appropriate context for antiviral use and data collection, including under (inaudible), followed by more formal collection of data using, for instance, factorial designs or other strategies.
Clearly, all decisions about what happens in Equatorial Guinea will be made by authorities in Equatorial Guinea. And the WHO and the international community is ready to support them in any way that can be done.
And the final note is that MARVAC is an open platform, so all within interests are invited to contribute and the contact Cesar if they would like to do that.
At this time Harris County Public Health (HCPH) has not received any reports of H5N1, or avian influenza, cases within its jurisdiction. The CDC considers the current risk to the public from the H5N1 bird flu outbreak in wild birds and poultry to be low. For information on the most recent bird flu developments specific to the United States, please visit the Current Situation Summary page. As always, HCPH continues to monitor communicable diseases to protect the health and wellbeing of our residents.
Thanks,
Maritza Vela
Communications Specialist
12:05:30 PM DEBRA HOURY, CDC: Today, we are releasing CDC’s Youth Risk Behavior Survey, or YRBS, Data Summary and Trends Report, which provides data on key behaviors and experiences among adolescents related to sexual behavior, substance use, experience of violence, mental health, and suicidality.
These data show a distressing picture. America’s teen girls are engulfed in a growing wave of sadness, violence and trauma. Over the past decade, teens, especially girls, have experienced dramatic increases in experiences of violence and poor mental health and suicide risk.
Findings also confirm ongoing trauma among lesbian, gay, bisexual and questioning youth. These data are hard to hear and should result in action.
…
12:07:42 PM KATHLEEN ETHIER, CDC: This nationally representative survey of U.S. high school students reveals the changing health risks our young people are facing.
Our findings from 2021 are the first national YRBS data that have been presented since the start of the COVID-19 pandemic. And while much attention has been given to the youth mental health crisis during the COVID-19 pandemic, YRBS data have shown that many measures were moving in the wrong direction before the pandemic. These data show the mental health crisis among young people continues.
In 2021, 42% of U.S. high school students experienced persistent sadness and hopelessness. Almost a third experienced poor mental health in the past month, and 10% attempted suicide in the last year.
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12:10:25 PM KATHLEEN ETHIER, CDC: When we look at findings by race and ethnicity, we see high and worsening levels of persistent sadness or hopelessness across all racial and ethnic groups. And that reported suicide attempts increased among black youth and white youth.
These data are clear. Our young people are in crisis, and schools are on the front lines of this crisis, and they must be equipped with the tools to support young people. This includes training for teachers to help them manage the mental health problems they’re seeing in their classrooms. Getting students out into communities and bringing mentors into schools to foster positive engagements and connections. And making sure that schools are safe places for our most vulnerable youth.
Schools should also connect youth to needed services and provide high quality health education that teaches skills like understanding sexual consent, managing emotions and communication. These are critical lifelines for students.
They are also part of CDC’s What Works in Schools program. And research has shown that schools that implement the program see significant benefits for their students and addresses many of the concerning trends we see in this data.
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12:23:39 PM KATHLEEN ETHIER CDC: This is the first YRBS, the regular YRBS survey, since the start of the pandemic. The data were collected in the fall of 2021.
We are releasing this first set of data today. We anticipate that the full survey data, as well as the state and local survey, will be available in April.
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12:27:16 PM QUESTION (LEIGH ANN WINICK): Wondering about resources in schools, since you talked about legislation required for youth mental health, there is currently a shortage of professionals and that can’t be addressed overnight. So are there alternative methods or training programs or para-professionals that CDC is investing in?
12:27:49 PM KATHLEEN ETHIER, CDC: Schools really are on the frontlines of the mental health crisis. We hear from educators all the time that they are dealing with mental health and behavioral health issues in their classrooms.
So a first line is to make sure that teachers have training in managing those mental health issues and behavioral health issues in their classroom, also called classroom management. That really prevents a whole host of problems. And rather than burdening schools with additional things to do, it can really alleviate the burden on teachers to know how to handle those issues.
DR ROBERT CALIFF, FDA [00:18:27]
I think advisory committees is an area where we need to do a lot of work. They’ve sort of– I’ve come to think of it, many things in government as sort of like artificial intelligence algorithms. If you develop one and you just leave it in place, it deteriorates over time and veers in directions you don’t expect and you need to be maintaining it.
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DR ROBERT CALIFF, FDA [00:22:29]
It was interesting that it came up in the hearing, I think on Wednesday, and I think– I think the comment that advisory committees are like democracy, they’re messy, is something that we really need to embrace because people will say, “well, you didn’t, FDA decided differently than the advisory committee or there were advisory committees that were unhappy.” You know, all those kind of things are going to happen. If you had advisory committees where everyone agreed and everybody was happy, you wouldn’t need to have a committee meeting. You should spend your time doing something else.
And so– but I think, I used to be a advisory committee chair back in what I call the good old days of advisory committees, and the amount of paperwork, the difficulty of dealing with potential conflicts that we think about rare diseases as an example, show me an expert in a rare disease who’s not spending time working on therapeutics for that disease. And then you automatically have what traditionally is a conflict.
And yet, if you look inside the FDA, what the main thing that FDA employees want out of advisory committees is expert opinion from the outside. There’s also value, of course, in the patient perspective and non-expert opinion, people that are general experts. But all these things need to be melded together, I think, in a much better way.
And I think evidence of the frustration was what’s pointed out in the two Reagan Udall reports. The food advisory committees were disbanded in somewhere around 2018 and TPSAC back for tobacco hadn’t met in two years. I think it’s essential in a public agency that you have public advisory committees.
To be fair, the food side started depending on the science board, but I would argue the science board is really constituted for a different reason than we need. So, we’re going to start back up the food advisory committee.
But across the FDA, we need to make it easy. We need to make it like a review group needs an advisory committee, it ought to be like the easiest thing they do, not the hardest thing they do because it is so important to get that interaction with people on the outside.
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DR ROBERT CALIFF, FDA [00:31:53]
I’ll regard the new authority as a start of what’s going to be a longer journey.
Obviously what’s happened to the cosmetics industry is dramatic. It’s an enormous growing industry. And the issues have so many variations from what happens with hair straightener to the skin is actually an organ, which I– we frequently have to remind people that when you put things on the skin, it’s actually configured to both block and absorb.
So the start is really being able to catalog what’s being sold and what’s in what’s being sold. But as all too often happens, we’ve got authority but no budget to go with it. So we’re going to do it.
And where cosmetics will reside is a frequently asked question. And the answer right now is we’re not sure, but it seems unlikely its final place will be in the foods area. But we’re going to make sure it gets the attention it deserves.
And then like a lot of things, as we get the program started and and the funding needs become obvious, we’ll have to make the sale that the funds need to be there. And there’s a good reason for them to be there.
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DR ROBERT CALIFF, FDA [00:39:58]
I’ve got a beautiful playbook from Dr Shuren and his CDRH colleagues that they’ve developed from the lessons learned as we have gone through several emergency needs for tests, of course, with COVID being the big one, but also the mpox situation.
And I think we know now that the basics of the playbook would be as develop a test as quickly as possible, make sure reagents are shared. And I think if we look at the societies that have done the best with rapid deployment of testing, the solution is not to have a hundred different entities developing their own tests, but to have a more limited number to develop scalable, reliable tests that can be distributed at a reasonable cost across the country.
Now, because you’ll be dealing with an unknown almost by definition in a outbreak pandemic type situation, of course you need multiple people working on it. So it’s not to cut out people, but we learned, I think, with COVID that initially it took– there are reasons for it, but took too long to get the testing out there to the country. But once the gates were open, a lot of bad tests got out there that probably shouldn’t have.
And so I think we’ve got a pretty good strategy now for how to operationalize a more efficient, effective testing system.
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DR ROBERT CALIFF, FDA [00:53:43]
What I’m proud of is that we’re taking on hard issues. And I’ve gotten entire lectures from people about how to kick the can down the road and not deal with it. I didn’t come back at age 71 to kick the can down the road as hard as it may be, and as much criticism as it may engender, we’re going to take on these issues.
I want to point to cannabis as an issue that we’re taking on. We’ve learned a lot in the last four years. But frankly, though, the briefing I got when I came in in 2022 was like almost identical to the one I got in 2016.
So it’s time to create a new regulatory pathway for the 30 something derivatives of a cannabis plant that end up in everything from animal feed to cookies. And we’ll deal with that.
DR GARY GIBBONS, NIH [00:12:00]
Toward that end, as we indicated before, an important operating principle was to be inclusive of a diverse population, reflective of the diversity of our country. And indeed, those who are affected most disproportionately by acute COVID would be represented in our long COVID studies as well.
And the consortium has been very successful, particularly with the adult cohort, which is actually nearing completion of its ambitious goal to enroll over 15,000 individuals in as short a time as 15 months. I actually believe that may be a new speed record for the NIH clinical study of this diversity and complexity and depth of characterization in near record time. And so we’ve been able to do that in a way that still is inclusive of these other populations.
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DR GARY GIBBONS, NIH [00:16:23]
We have a clinical enrolling cohort of about 15,000 adults. And that’s really giving us really in-depth characterization that will further characterize this clinical spectrum. And so we’re very excited by that. And in fact that we’re pretty much wrapping up that enrollment and have already begun an interim analyses that will be a key highlight of the next couple of months as we start to dig into that data set. As I say, the largest, most diverse cohort of deeply characterized long COVID patients. Should tell us a lot.
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DR GARY GIBBONS, NIH [00:18:42]
We are poised to start to roll out the master protocols that have been teed up that across about five different domains of viral persistence, immuno dysregulation, cardiopulmonary exercise, neurological cognitive dysfunction, autonomic dysfunction, etc. in those various symptom clusters informed by observational studies that really lend themselves to certain interventions designed to ameliorate those same endpoints, provide symptom relief, and hopefully change the natural history of this disorder.
And again, we would encourage you to stay tuned as those start to roll out over the next several months designed to actually treat long COVID.
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DR GARY GIBBONS, NIH [00:31:24]
Moreover, we can then take those individuals and do very deep characterization. So a lot of the studies that are out there are maybe online surveys that ask patients how they feel. But we have an opportunity to link not only those patient reported symptoms and outcomes to very in-depth clinical and diagnostic characterization, CT scans, echocardiogram, pulmonary function tests, etc. So really do a deep clinical characterization of these individuals.
And as I say to my awareness and our institute, there’s a lot of cohort studies. I’m not aware of an enrollment of 15,000 individuals with that kind of characterization, 15 months after master protocol. So something of this scale, scope, comprehensiveness, diversity has also been accomplished at unprecedented speed.
And so that’s where that perception is probably not accurate for those who understand how these studies are done. But recognizing that it’s probably response to the sense of urgency that all the patients feel as well as we feel that we can’t move fast enough to better understand this complex syndrome that’s real and to move as expeditiously as possible, to understand it, but see how we can both treat and prevent it, and that we’re pursuing with a sense of urgency to relieve the suffering of those patients.
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DR GARY GIBBONS, NIH [00:40:12]
And so each of those master protocols, those five would have different we would call arms or different interventions. It might be a drug, it may be a device, it may be a behavioral intervention, etc. And so that’s that’s what the master protocols are being developed.
And we anticipate this will be iterative. Part of the structure is to be adapted, to be nimble and to try a variety of things that we think not only be safe but effective and doing it in a systematic way. And by doing it with these master protocol strategies, we probably can be even more cost time efficient with a higher throughput of attempts to test different hypotheses and again, move with a sense of urgency to find out what works and what doesn’t work as soon as we can again.
And some of it’s leveraging what we learned in the pandemic in which we didn’t want to do a whole series of very small studies that really would not yield definitive results or would not be generalizable. That’s why it was important to develop these master protocols, all of which often have a core of common we call data elements that are capturing similar data.
We have similar clinical endpoints that we’re measuring across those protocols so that they’re actually informing each other. So we’ll be learning about what is relieving these symptoms, how stable are they, how do they do relative to the placebo controlled comparator and in each will inform the others in that way.
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DR GARY GIBBONS, NIH [00:42:02]
We anticipate that a lot of the participants in the clinical trial interventions will come from the broader community of patients suffering from long COVID. And so, in fact, there has been enough interest already that there are over 20,000 individuals in contact to RECOVER and have suggested some interest in participating in clinical trials.
So we’re formulating a registry where we can have individuals interested in participating in these clinical trials sign up as they start to be launched in the next several months. So we look forward to that being a very large pool of individuals who are willing to participate in these studies to help us understand what we can help relieve their suffering.
Update: Our department checked with all local hospitals and none report an avian flu case.
Thanks
Porfirio Villarreal
Public Information Officer & City Council Liaison
Houston Health Department
HHS OFFICIAL 1 [00:01:08]
I’ll start off with what actually happened today, which is that the secretary sent a letter to the governors advising that, as of February 11th, he’s renewing the COVID-19 public health emergency for 90 days.
This action is based on some of the most recent COVID-19 trends. He also advised them that he intends for this to be the final renewal of this PHE, meaning that this renewal would expire on May 11th, 2023.
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HHS OFFICIAL 1 [00:13:42]
As we’ve been doing the prep for this call and these materials for today, we’ve gotten a ton of incoming on the CMS questions. And so in response and again, this goes back to my point that we’ll be continuing the conversation, we’ll plan to – CMS plans to put out a fact sheet or more information, probably early next week, to get more in depth into some of these questions. So a little bit more than the two bullets in the roadmap, and maybe a little less than the hundreds of pages on the roadmap. Everything for is already out there in the public domain. But we need we know we need something more digestible. So they’re working on that now.
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QUESTION [00:14:23]
First, can you clarify something about the fact sheet? I see there’s like a reference in here to the resources for the USPS testking kit program and then obviously ICATT. What do the resources look like now? And is it realistic to expect that to continue, say, through the end of this year?
HHS OFFICIAL 1 [00:14:40]
I think we’re continually assessing the status of those programs.
I think the point there, and I want to underscore this, is that although some of the Medicare coverage for OTC tests is going to end with the end of the year, there are other programs that will buffer this.
There’s going to be no cliff for the access that Americans have to tests and those are two examples, but those are subject to ongoing appropriations and ongoing resource needs. And we’ll try to stack up and see where those are as we go here.
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QUESTION [00:15:10]
One separate question. Can you clarify whether you expect the COVID vaccination requirements for, both on the Medicare side as well as for international travel, is that something that can extend beyond the May 11 deadline? Or is that tied to those authorities in some way? Thanks.
HHS OFFICIAL 1 [00:15:26]
I’m going to defer on the legal ramifications of that. I will only say that, as we stated in the the administration statement of position on the bill that was on the floor yesterday, I think this is another piece that we’ll be reexamining as we head towards the end of the PHE. And so this is under active discussion.
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HHS OFFICIAL 4 [00:16:20]
So lab data for COVID 19 come to CDC through the states. There’s a mandate through the CARES Act that says, while the public health emergency is in place, individual labs that are performing COVID tests must report those tests to the state. And then the state sends those data to CDC.
Once the public health emergency is no longer in place, there’s no longer implementation of that part of the CARES Act, which means that those data from independent labs do not– they’re not mandated to go to the states.
They can still choose to voluntarily send it to the states, and the states are then required to send it to CDC. So we will continue to receive any data that are voluntarily sent from labs to states, so that we can report on positive lab tests and negative lab tests.
But unfortunately, we won’t know which labs are and are not doing this voluntarily, and we won’t know if they’re sending everything that they’re receiving or part of what they’re receiving. So it makes it challenging for us to use a metric such as percent positivity after the end of the public health emergency.
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HHS OFFICIAL 4 [00:29:27]
Right now at CDC, the majority of our metrics that we use to understand what the COVID 19 community level is in each county across the country should rely on data that we will continue to receive after the end of the public health emergency. So COVID 19 community levels are based on cases in an individual community, which we’ll continue to receive from local public health through case report forms. They’re also based on hospitalizations, both overall hospitalizations for COVID 19 and new admissions for COVID 19. And those are data that will continue to be reported through CMS to CDC, so that we can continue to report COVID 19 community levels.
We also have other metrics at CDC. Community transmission is a metric that we used previously to help understand how COVID was impacting various communities, and we continue to use to help inform infection prevention and control measures within hospitals. Community transmission relies on cases which we’ll continue to receive, but also on percent positivity, which requires knowing both positive and negative tests in an individual community.
So we at CDC are doing the work right now to understand where we are using community transmission, what other metrics might be useful for hospitals as they think about infection prevention and control, and how we can make sure we’re leveraging the data we do receive to inform communities as to what they need to do to protect themselves from COVID 19.
There were 28 cases of invasive group A strep in children under the age of 18 years old reported in Colorado during 2022, but official and final case numbers may change as additional information is collected. A majority of the cases in 2022 were reported during November and December. We continued to see some cases reported during January 2023, but far fewer than in previous months, possibly due to the decrease in respiratory illnesses like COVID-19, flu, and RSV that can contribute to group A strep infections.
| Prior to the COVID-19 pandemic, around 150-160 invasive group A streptococcal, or iGAS, infections in children were reported each year from the 10 sites participating in CDC’s [Active Bacterial Core Surveillance System (ABCs) | CDC](https://urldefense.com/v3/https://www.cdc.gov/abcs/index.html;!!CxwJSw!IBjqCEOEhgzQUBIlUHImC7nvu9VDE6wYowkY_iFJNGrNAtI8DPVwq6tyTgaUoIwsGpYXoUlUWw$). Given that the population covered by ABCs for group A strep surveillance is around 10 percent of the total U.S. population, this corresponds to approximately 1,500-1,600 iGAS infections in children nationwide each year. The majority of these infections pre-pandemic were consistently reported between January and June each year. |
Starting in April 2020, the number of reported pediatric iGAS infections in ABCs areas decreased to less than half of pre-pandemic numbers and remained lower than normal every month until September 2022. Preliminary data from ABCs for 2022 indicate that over the entire year, less than 100 pediatric iGAS infections have been reported. However, >80 percent of the cases reported in 2022 were between July to December, which represents an approximately 40 percent overall increase in cases for this time period compared to pre-pandemic years. However, substantial variation was noted between areas, with some locations not seeing any increase in cases during the second half of 2022.
Data from emergency department visits for less severe group A strep infections from CDC’s National Syndromic Surveillance Program (NSSP) show a similar pattern, with cases decreasing dramatically in the first half of 2020 and remaining substantially lower than normal until September 2022, when they increased to levels similar to those seen during seasonal peaks pre-pandemic.
Influenza strains of pandemic potential change over time and multiple new strains circulate in animals every year without leading to sustained human-to-human transmission, making stockpiling of hundreds of millions of doses of vaccine against each circulating strain impractical. Therefore, the U.S. government has a preparedness program that enables a rapid response to influenza strains as the strains evolve. As part of this program, the Biomedical Advanced Research and Development Authority (BARDA) works with private industry partners to make and test small quantities of updated vaccines that match new strains of influenza viruses with pandemic potential as they emerge in case any of them drive sustained human-to-human transmission, while at the same time, supporting manufacturing capacity to allow for large-scale vaccine production when needed.
DAVID SWAYNE, CONSULTANT [00:00:54]
So I’m a poultry veterinarian and trained in infectious diseases for the past 28 years. I was the director at the U.S. Department of Agriculture’s Agricultural Research Service, Southeast Poultry Research Lab, which was and continues to be USDA’s high biocontainment research facility that’s in-house for working on highly pathogenic avian influenza and other very dangerous, I guess very dangerous and non-endemic viruses that we don’t necessarily have in the U.S. But research is done there to do it safely, so that preventative strategies can be developed.
Since then, I’ve retired, only a month I’ve been retired. That was the end of December. Great career at USDA. So now I’m just trying to do a little bit of consulting, and doing a little bit of having fun around the house with my wife. Looks like bird flu is taking my priority.
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DAVID SWAYNE, CONSULTANT [00:02:37]
We can say there are multiple technologies of avian influenza vaccines that are available and used around the world as part of control programs for poultry.
And it depends on the country, because globally every individual country licenses their own vaccine. So there’s not a global entity that does the licensing. It’s done in each individual country, by their usually ministry of agriculture or department of agriculture, and they decide if they are sufficiently and scientifically, rigorously tested to be licensed and registered. Then that country would have a second task, which would be to decide if they could be used and how they could be used in their country.
So yes, there are available vaccines that are used in some countries around the world, and they can be done. They can be used properly and be a tool that helps in control, prevention of highly pathogenic or other types of avian influenza in poultry.
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DAVID SWAYNE, CONSULTANT [00:04:32]
So two siloed process. The first process is a vaccine technology would have to be licensed by a company through USDA, and that would require them to submit a dossier showing how the vaccine against a virus challenge, and showing the purity of the vaccine, etc., that would all be required to be registered or have a license. And that means the company has the legal authority to manufacture that product because it’s safe and effective.
The second part of that is that they couldn’t just start manufacturing and selling it. You would have to, because highly pathogenic avian influenza is a controlled disease, it’s an exotic disease to the U.S., then use of vaccine would have to be determined by the U.S. Department of Agriculture, would have to make a declaration that it could be used, and they would only do that in consultation with multiple partners. For example, the state government. And there’s a veterinarian that is responsible for the health of the animals in their state, the state veterinarian. And then they also would consult with the poultry production industry, whichever piece of the industry they’re talking to, whether it’s broilers chickens, whether it’s turkeys, or it’s breeders, or it’s egg-layers, so they would talk to them.
Now, there are several vaccines that are registered in the United States by several different companies, so they are available if a declaration was made to use in by the Department of Agriculture. And some of those technologies are what we would call non replicating, meaning they’re not a live vaccine, meaning you’re injecting really a product it’s just the proteins with the nucleic acids and then that product, the body of the animal, will produce protective antibodies that would then hopefully protect against a disease.
So those products can actually be changed pretty quickly to update the vaccine, either the strain of the vaccine or the genetic code of the vaccine, or the proteins within that vaccine, as the field viruses might change that potentially could be exposed. So those can be done very easily in just a few months.
And so, for future of the U.S. right now, vaccination is not allowed, but it’s being discussed. And I’m, of course, involved in those discussions anymore because I’m not an employee, but I understand those are still ongoing between the federal government, the state government and the different parts of the industry.
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DAVID SWAYNE, CONSULTANT [00:08:03]
It’s a very complex issue and every country has to make that decision based upon the facts.
And, for us in the United States, we are a major global producer of poultry products. It is a major export throughout the world. Multiple countries buy our poultry products, mainly chicken meat, but also turkey meat and some eggs and egg products. So we have a very large global market and we have to make sure that our partners understand that we have this same type of concern about food safety and food security for our partners that we do for ourselves.
So we look at vaccines as maybe a tool, but we want to make sure our partners understand that, if we use them, we’re going to use them in the right the right manner so that they can feel secure and safe, that the products they buy are not products that might contain, say, a highly pathogenic avian influenza virus. That we can be able to tell that there is that virus in there or not. And we would not, as part of our country regulations, that we do not put into the food chain poultry or poultry products that are– that contain the high path AI virus. And we have to make that same sure to our trading partners.
So that makes that vaccination a little more complex because then you have to have some extra criteria and testing to, you know, show those partners that you are not doing something that is not within your regulations. And just as far as poultry in general, we have vaccination of poultry, a process that’s used all over the U.S. for other poultry diseases. And there are several viral diseases, for example, infectious bronchitis is a very common viral disease of chickens. And so most chickens that are grown in the U.S. are vaccinated.
So chickens, just like people are vaccinated from the diseases that they commonly come in contact with. And so vaccination for influenza is not done currently for poultry in the United States. But there are other diseases, vaccination by itself is not something new. It’s used to promote the health of our poultry to keep them healthy. It’s just a different type of disease than we usually vaccinate for.
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DAVID SWAYNE, CONSULTANT [00:11:06]
So the primary issue is going to be the trade. So it’s a trade issue.
Saying that, there are 182 countries that belong to an intergovernmental agent organization called the World Organization for Animal Health. And that organization is the origin and the standards used by the World Trade Organization. So to say, okay, we’re going to let these 182 countries agree to trade fairly poultry and poultry products, and here are the rules.
And so when you look at those rules, they do not prohibit trade in poultry and poultry products if you vaccinate for avian influenza. It says you can’t just say because you vaccinate you prohibit.
But what it says there’s a technical issue, and the technical issue is that you have to have adequate surveillance or high path AI. And if you have if you have adequate surveillance, then you can trade.
So that’s – trade is the big issue, and that’s a global trade issue. But there is a little bit of technical part, that we don’t have all the pieces worked out, and that’s kind of what many countries are working on right now, is what kind of surveillance and how do you do that? So you can then assure the World Organization for Animal Health and all the member countries that you are vaccinating, that you can vaccinate for high path AI, and at the same time you have surveillance to assure them that anything that leaves your country as poultry or poultry products does not contain a highly pathogenic avian influenza virus.
So that’s a little technical issue that is in the works with multiple countries looking at how would they do that. And I think USDA is also looking at how we do surveillance, if we did vaccination. So this is a combination of there is a little technical issue. And then there’s also, of course, the trade issue, which, of course, is individual countries. There may be some political views on that. But we have to assure them that we are not going to allow infection of avian influenza in our vaccinated poultry.
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DAVID SWAYNE, CONSULTANT [00:13:44]
There are several different ways to do this. So, for example, you mentioned sentinel chickens, and I a sentinel chicken or turkey or whatever species you’re looking at would be a non vaccinated bird that somehow marks, you could identify them in a flock, and then they would be highly susceptible to avian influenza because they’re not vaccinated. And so if the idea is if you get a virus into the flock, then they would be affected and you could identify them and they would become very sick or possibly could even die. So that’s your sentinel, that’s the sentinel program.
And you could look at those birds, look for antibodies, but of course, high path AI in chickens doesn’t– they don’t survive. So there’s no antibodies in the survivors. But you could look for the virus. So that’s kind of one way that surveillance program could be done. Sentinel chickens looking for antibodies, which is not going to work for high path or looking for the actual virus.
And so the other way is you’d vaccinate everybody in the flock. But when you do that, and you have a flock of, say, 20,000 chickens, you’re going to have a few birds in there that are going to be missed in the vaccination process. So somebody picks a bird up, and they start to inject it and they forget to pull the trigger, and they let it go, something like that, or they put the needle into the bird. But instead of going into the skin or the skin, it may go all the way through the skin, inject the vaccine outside so you have some birds in that flock that are essentially, unintentionally, not producing a protective immune response. And so those are sort of your naturally built in sentinel birds. You’re not putting in sentinels. And so they’re the susceptible ones. And so what you would do is you would look at the flock, in a flock of 30,000 chickens, you will have maybe ten birds that may die from natural causes within that within each week. And you would then take those birds and you would sample them looking for the virus. And so we would call that targeted surveillance, looking for the virus.
And in the United States, as well as most countries around the world, we use a real time PCR molecular test. And that would tell us, at a very sensitive level if, the bird might have died from a high path AI virus. So it’s looking for the virus and it’s looking for it in that daily mortality.
Another way that it can be done, and this is part of the exploration, part of the science, is looking at are there ways you can test environmentally to find the virus. And so back in 2015, I think there were some studies done by colleagues at the University of Minnesota, and they were looking at the water containers that turkeys have called water jugs. And they would look at the biofilm, which is the films on the inside of the water container where the turkeys are out in the house. And they could find the virus there very quickly. And they didn’t have to go look at individual turkeys. They could just take a swab and look. So those are the kind of things.
Now, the other way that some people propose is to look for antibodies in vaccinated birds, that are different types of antibodies produced by different types of influenza viruses. And that can be done. It’s much more rigor– it’s a much more difficult process to look for those because you have to get lucky, you have to pick up live birds. You have to handle them, you know, bleed them, take the blood back to a lab, centrifuge it, pull off the the serum and then run a test. So it’s a lot more complex. And then you’re looking for antibodies to the field virus. And the vaccines must be different in the field. So there’s– it’s a much more complex process. And in the end, it’s really not about the antibodies. It’s about is the virus there? And that’s why most surveillance talks about surveillance looking for the virus.
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DAVID SWAYNE, CONSULTANT [00:18:23]
It is feasible to produce a vaccine strain that would protect against an outbreak virus. If you start vaccinating over time, of course, the field virus does not stand still. The field virus is changing. So you would have to build into any kind of vaccination program, a monitoring program to monitor the virus in the field, to make sure that that virus is not moving away from the vaccine strain. That is, it’s becoming antigenically different so that the vaccines would protect against it.
And we already have in place a great program. It’s very analogous to what we would do in agriculture, and that is the human influenza program. And it’s based upon surveying around the globe of human influenza infections. And then twice a year, the World Health Organization gets together and they look at that data to say, you know, are the field or good viruses causing outbreaks in humans. This would be for H1A3 human influenza. You know, are they moving away from the official vaccine strains? And if they are, then they would change the vaccine strain.
And it would be a same kind of process we would do in agriculture. And we already have some countries that have been vaccinated for influenza in poultry that have been doing that kind of program and with good success. An example, would be, Indonesia has been vaccinating poultry for H5 influenza since 2004, I believe, and they have a program in place to monitor the viruses in the field. And if they find that the virus is moving away from the vaccine, they will update the vaccine. And there are other countries that do the same thing.
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DAVID SWAYNE, CONSULTANT [00:20:40]
And so Indonesia is the example that has been vaccinating Vietnam is another example, Egypt, Bangladesh, that’s probably the three major ones. And then you have transition countries, and there’s a couple of those that do. China is one, and they’re one of the largest users of vaccine in poultry. You also have Mexico, which is a very large user of vaccine in poultry. So those are probably the major examples.
And we don’t have right now a example of a high income country like the United States or equivalent that is doing vaccination, but there are multiple countries, as you probably know, in the European Union that are studying the same issue, and they’re having the same problems as we are with the current outbreaks of high path AI. It’s just it’s been going on in Europe for a little over a year, longer than it has with us. So they’ve been they’re starting their third year of high path AI outbreaks.
So there are several countries in Europe that are examining the vaccine question and they they have plans to further along to ours, as far as looking at maybe potentially targeted vaccination come the fall if the virus continues to circulate in the countries.
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DAVID SWAYNE, CONSULTANT [00:22:23]
With the current strain that’s circulating and the genetic name is going to be 2.3.4.4b, it’s a Eurasian virus. There is, I’ll say, some loose seasonality in that you have increased numbers of outbreaks and declining outbreaks depending on the timing of wild bird migration through an area that contains poultry or, depending upon infection of possible resident aquatic birds in that population.
So for us in North America, and just speaking about this past year, of course, the cases increased in the winter of 2022 through mid-spring, and then they started declining in the summer. The case numbers were down.
So the decline in the summer of 2022 and the reasoning behind that is, is that the wild birds, these are quite migratory bird species that were the major source of the virus and spreading the virus, they moved northward into their summer breeding grounds in Canada and Alaska, some parts of the northern part of the United States. And so therefore that central part of the U.S., southern part, didn’t have as much virus available. There was some still present in some of the resident birds, but because of the movement of so many of the migratory species that the numbers were decreased.
And on top of that, in the summer, of course, is warmer time. The viruses survive as well in the environment, so it doesn’t hang around as well environment to transmit as well. So that probably contributes to it. And then as the migratory birds, the dabbling ducks, move from their summer breeding grounds in the northern part of the northern hemisphere southward, then you start seeing increase in the number of outbreaks. And that’s what we have seen in the in the curves of outbreaks for the United States this past fall.
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DAVID SWAYNE, CONSULTANT [00:25:30]
I think the other final thing to emphasize is that the vaccine by itself is not the solution. That we have to continue in our poultry producers into practicing the high level biosecurity to shield their birds against exposure to wild birds that could carry the virus, or being careful in movement of people and equipment from a contaminated environment like the outside inside, to make sure they don’t carry the virus in. And so biosecurity really is the first line of defense, and any vaccination that might be done is only sort of another layer of protection, sort of an insurance policy.
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DAVID SWAYNE, CONSULTANT [00:27:00]
I think the word is trigger points. What is the trigger point of when you might use vaccination? And that’s what they’re looking at. Is it so many birds in a poultry farms in an area getting infected? Or is it a certain amount of economic loss? Or is it because a neighboring state has the virus in poultry, and you’re concerned? So there’s those are really the tough, tough questions, which I cannot answer for sure. But those are the trigger points.
ERIN SPACKMAN, USDA [00:00:52]
My training is in virology and specifically I’ve worked on poultry health. So viruses that affect poultry and avian species. And within that, vaccines are a fairly important control measure for a lot of poultry diseases. So I’ve been involved in research with avian influenza vaccines for about 20 years.
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ERIN SPACKMAN, USDA [00:01:46]
So there are vaccines that have been created or have been designed that should be able to be used. But most of them haven’t been tested yet against the current strains in the U.S. and what actual vaccine stocks are available, that would be a question for the manufacturers.
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ERIN SPACKMAN, USDA [00:02:31]
Based on what’s been used historically in vaccines that we test in our lab for other outbreaks, there is an inactivated vaccine.
So it’s an inactivated vaccine, and it’s similar to the human seasonal flu vaccine. There are some differences, but it’s the same kind of idea. Just killed virus.
And then there are some vaccines in different platforms where they’re vectored in other viruses. And those kind of vary what’s available, and how much they’ve been tested. They’re used for other viruses regularly, I should say that. So the question would be just developing those specifically for the avian influenza strains currently in the U.S.
There are some other experimental platforms out there. People looked at something called virus like particles, which is well, it’s very similar to the inactivated vaccine, there are just some technical differences. It behaves like a killed vaccine.
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ERIN SPACKMAN, USDA [00:04:07]
Not yet. So not for a couple of years.
We do testing again, and that’s one thing our lab is fairly heavily involved in is testing the vaccines. We just haven’t been able to test them yet against the current strains that are here. That’s forthcoming.
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ERIN SPACKMAN, USDA [00:04:45]
There are a lot of moving parts to this kind of testing. And some of it is just pure logistics of getting everything in place to do the testing, getting the vaccines that are updated, getting things from parties that are involved, different manufacturers, that kind of thing. So it’s really kind of a logistical question.
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ERIN SPACKMAN, USDA [00:05:34]
They are challenge studies that are okay. It’d be kind of similar to human trials, in the sense that we’re actually vaccinating animals and seeing if they’re protected.
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ERIN SPACKMAN, USDA [00:06:12]
So the actual, because we have to vaccinate and then wait for immunity to develop, and then process all the samples and collect the data afterwards, from end to end, we’re talking 2 to 3 months.
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ERIN SPACKMAN, USDA [00:07:18]
And there’s a lot of examples of that. And most of these diseases will probably not be familiar to you, but one would be infectious bronchitis virus, Newcastle disease virus, infectious bursal disease virus. There’s a lot of them that are routinely vaccinated for in the U.S.
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ERIN SPACKMAN, USDA [00:08:16]
So we provide the data to whoever supplied the vaccine and our stakeholders, our regulators, whoever needs the data, and eventually it’s published in peer reviewed publications. So our goal is to produce that data and share it with whoever’s interested.
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ERIN SPACKMAN, USDA [00:09:15]
We are actually not in that line of licensing and registration. We’re outside of the regulatory. So our goals are really to look at the scientific side of does it work. Within USDA, there’s a group called the Center for Veterinary Biologics, and that’s the group that is sort of the FDA analog. And they work directly with the vaccine manufacturers for all the licensing process, that whole process. Our data doesn’t really inform that.
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ERIN SPACKMAN, USDA [00:10:31]
And I think part of what makes it a little bit difficult is the whole process can happen without what our lab does, kind of providing an independent evaluation that’s kind of outside of the manufacturer or outside of that process and just purely scientific.
If we do this process, is this vaccine going to work under these conditions?
The actual time from, and whether you go from development to putting it in a flock, that’s really variable because many of the processes for different vaccines– so I mentioned inactivated vaccines, that timeline would be different from one of the vaccines that’s put into a vectored system. So there’s a lot of variability there.
And I think what you’re kind of getting at is, okay, if we wanted to use the vaccine, what would that timeline be? And that’s– it’s really kind of hard to say because, one thing, if we don’t plug into that and it’s going to vary. There are a lot of kind of factors that go into it depending on the type of vaccine and where it is in the. How long does it take to manufacture those kinds of things?
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ERIN SPACKMAN, USDA [00:13:00]
So it’s one of those things that is in the pipeline. But it hasn’t been– we haven’t done– the testing hasn’t been completed, but it is getting on the calendar, if that makes any sense.
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ERIN SPACKMAN, USDA [00:16:14]
This is kind of another area where we were kind of looking at the different variants, and how vaccines might affect them. And there are differences between different lineages of virus in different parts of the world. So the viruses in the U.S. and the viruses in Europe, they are very close cousins. So they’re not the same, but they’re pretty closely related.
QUESTION [00:16:43]
And you said that the virus that is here in the United States for this outbreak is substantially different than the ones that previous vaccines have been– that your lab has tested against. Is that right?
ERIN SPACKMAN, USDA [00:16:57]
Yeah. It’s different enough that we feel that we need to test it again, that we need to test against the modern isolates.
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ERIN SPACKMAN, USDA [00:17:48]
So the overall lineage is called Goose Guangdong 1996. And within that lineage have branched off since 1996. Kind of the descendants of that lineage have gone down into what we’re calling different clades.
So that would be somewhat like the different SARS-CoV-2 variants. You know, it’s an imperfect analogy, but what’s in the U.S. is currently called clade 2.3.4.4b. What was in the U.S. years ago was related to that. And they are cousins way back somewhere, clade 2.3.4.4c. So believe it or not, just that little bit, is just a little bit of change and how the virus evolved over the years and different parts of the world.
Within that clade 2.3.4.4 throughout the world, I think we have got A through F now or maybe up to A through G or H at this point. And those are just kind of how the sub clades are labeled.
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ERIN SPACKMAN, USDA [00:19:35]
And that’s actually testing I did myself. So what we do is we do a test that compares the antibody response, how well the antibodies react to a specific virus. And so we took antibodies to the older virus and the new virus, and checked how they cross reacted with each other, kind of in a matrix. And so by doing that, we can see that the amount of reactivity between the virus in 2014-2015 and now is reduced.
On the test, it’s a twofold reduction, but that makes it sound a lot closer related than it is. In vaccine-speak, it means it’s starting to drift away. So we wouldn’t have as good protection. But how much protection, whether or not– I guess I should put it this way. It’s far enough that we feel like we need to that we need to retest the vaccines.
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ERIN SPACKMAN, USDA [00:21:06]
So the vaccines in 2014-2015, the vaccines that were, what we call well-matched, so that the immune system saw them. So in SARS-CoV-2 speak, it’d looking at like the original virus versus a far variant, that the original viruses and vaccines were well-matched. So they protected well.
So there was good protection back then. So, they were efficacious back then.
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ERIN SPACKMAN, USDA [00:24:08]
Almost all of them are just direct shots.
QUESTION [00:24:11]
Okay. Does it go into the wing? Or like where where in the chicken does it go into?
ERIN SPACKMAN, USDA [00:24:19]
Yeah. So depending on the shot, it either goes like subcutaneously, and that’ll often go either in the nape of the neck or sometimes in kind of loose skin around the breast muscle. Or they can be intramuscular, and kind of like us, it will go into the thigh.
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ERIN SPACKMAN, USDA [00:25:36]
People that people may say there are vaccines available, and the confusion will that be, well we get back to the, the vaccines were made many years ago. So we have them technically either available, technically either licensed, but it gets back to that vaccine match issue. And that’s kind of the– I think so that’s the big question. If you kind of hear different things about why we’re at different stages and why I’m hemming and hawing, that’s why. Because historically there are vaccines available. But there’s a question about whether or not they would actually have any positive effects or how much. It’s a gradient, it’s not black and white.
“Boehringer Ingelheim is monitoring discussions in the United States regarding avian influenza vaccination. As U.S. officials determine the best path forward, our industry experts continue to actively support the poultry industry in its ongoing efforts to enhance biosecurity and prevent additional avian influenza occurrences.”
10:04:33 AM REP MORGAN GRIFFITH: The NIH has been reluctant to answer our inquiries on issues such as EcoHealth withholding data, potentially double billing the federal government, and missing laboratory notebooks and electronic files that were supposed to be delivered to the NIH by EcoHealth.
This process does not have to be confrontational. Republican leaders have sent a similar letter to entities such as Boston University about an experiment involving a hybrid COVID virus that attracted press attention. Boston University fully cooperated, sending a written response letter directly addressing the questions, producing about 2000 pages of documents and providing a briefing to bipartisan staff.
In contrast, the NIH has not provided a satisfactory or complete response. This is not acceptable. Let me be clear. It is not acceptable to stonewall any member of Congress with oversight authority, whether that member be a Democrat or be a Republican, whether that member be in the minority or in the majority. The people of America entrust us to find the answers and to provide oversight of the federal government.
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10:20:51 AM REP CATHY MCMORRIS RODGERS: Director Walensky and the Centers for Disease Control and Prevention. Your guidance was used by the federal government to justify mandates that have more parents questioning routine vaccination. Your guidance, influenced by teachers unions, kept schools closed. Your guidance, using unreliable studies, was used to justify mask mandates on our on our kids.
We know these weren’t decisions based upon best science and data from around the world. And now our children are paying the price. Academically, they’ve been set back for years. Emotionally, they’re living– we are living through the most severe youth mental health crisis we’ve seen. And physically cases of type two diabetes and obesity in children has surged.
Dr. Walensky, the CDC does not need more authority. It needs robust oversight. It’s always operated without a congressional authorization. And it’s going to change.
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10:22:01 AM REP CATHY MCMORRIS RODGERS: Finally, regarding Assistant Secretary Dawn O’Connell’s absence. I understand why she’s not here today, and I extend my deepest sympathies, condolences to her and her family.
However, the Administration for Strategic Preparedness and Response is the top official in public health emergencies. ASPR’s job is to be prepared. So it’s unacceptable that another leader from the administration wasn’t prepared to be here today in the assistant secretary’s place. There are no excuses, especially given the enormous amounts of resources and responsibilities we’ve allocated to ASPR over the years.
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10:34:42 AM DR LAWRENCE TABAK, NIH: RECOVER is following a large cohort of children and adults at various stages of recovery from SARS-CoV-2 infection over time, to gather data that will help us fill knowledge gaps such as understanding what makes some people but not others, vulnerable to long COVID.
The program will also launch clinical trials in the coming months to evaluate whether certain interventions help improve outcomes for people with various long COVID symptoms.
The information gained from this initiative will help those whose lives have been upended by the lingering effects of COVID 19.
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10:36:18 AM DR ROCHELLE WALENSKY, CDC: Thanks to 670 million vaccines administered in the United States and the work of those at CDC and thousands of federal, state, local and private sector partners, and because of the more than 100 million infections, Americans have endured and survived. We have built a wall of immunity and expanded the tools available to decrease the risk of severe disease and death from COVID 19.
This past week, hospital admissions and deaths are down both nearly 9% from the previous week. Though we have made remarkable progress, we also had nearly 3,500 deaths from COVID 19 in the last week. These are our family members, our neighbors and friends and colleagues. Their deaths are tragic and make it clear that we have more work ahead.
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10:38:12 AM DR ROCHELLE WALENSKY, CDC: Two weeks ago, I announced a reorganization to reduce bureaucracy, break down silos, promote public health capabilities, and increase accountability. This strengthens the foundation of the agency to tackle our focus areas.
But we know that moving boxes around alone will not modernize CDC. We are equally focused on how we do our work on our systems and processes internally.
For example, we reduced internal scientific review times by 50% and are publishing our science and data faster. We were the first in the world to produce and share data showing real world performance of the Jynneos vaccine against mpox.
We’re investing in accessibility and communications, fostering clearer public health communications by rebooting the front door to CDC, streamlining content to make it easier for American people to find what they need.
And we’ve established a CDC ready responder program to better prepare CDC’s workforce to engage at a moment’s notice to future health threats, no matter where they work at CDC, and to sustain that engagement throughout a response.
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10:46:08 AM REP MORGAN GRIFFITH: We received responses from other agencies, such as the CDC, to our letters. It appears there was a standing policy at the NIH to disregard letters from the minority members of this committee. Is that true? Yes or no?
DR LAWRENCE TABAK, NIH: No.
REP MORGAN GRIFFITH: So it’s just incompetence that caused 14 letters to go basically unanswered? I’ll take that as a given.
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10:47:58 AM REP MORGAN GRIFFITH: Even though the NIH suspended EcoHealth’s grants in July of 2020, before our COVID 19 inquiries began over grant noncompliance concerns, and later it was found that EcoHealth did not follow important grant terms, the NIH subsequently gave a new grant to EcoHealth in September 2022.
Why would you allow a company who breached their contract with the NIH and failed to comply with some important reporting requirements to get more of the American taxpayer dollars?
DR LAWRENCE TABAK, NIH: We follow process. They were put under advisement of these deficiencies. They have been working with us to correct them, and that’s why we proceeded.
REP MORGAN GRIFFITH: But they can’t correct the information that they didn’t require their partners at the Wuhan lab to give them to give you three years later.
So we don’t have the information that we learned last week was important in determining both the origins and how to treat those origins at an early date. They failed in a major respect. How can that possibly now comply with your processes?
DR LAWRENCE TABAK, NIH: And we have corrected with them their administrative shortfalls and continue to work with them. We are unable to disbar an organization that–
REP MORGAN GRIFFITH: So do you want authority from Congress to be able to disbar an organization that breaches their contract and fails to get us information from a subcontractor that may have had vital information in helping us to respond to the COVID 19 outbreak?
DR LAWRENCE TABAK, NIH: The shortcomings of the Wuhan Institute of Virology have been noted in the GAO report, as you know.
REP MORGAN GRIFFITH: I know.
DR LAWRENCE TABAK, NIH: And they recommend that disbarment be considered. And this is something that, you know, we will of course–
REP MORGAN GRIFFITH: Do you need new authority from us to disbar?
DR LAWRENCE TABAK, NIH: We do not disbar that. The disbarment official sits in HHS.
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11:04:44 AM REP ANNA ESHOO: The Congress appropriated a billion dollars to NIH to study Long COVID. Patients have been waiting, and they’ve been more than patient since December of 2019. And I think the effort is called RECOVER, and it’s to research potential treatments.
Where is that? How close are you to coming out with what’s needed for those that have been waiting a long time?
DR LAWRENCE TABAK, NIH: We have put together a national cohort of patients at different stages of infection with COVID 19 and those who have already reported that they suffer from long COVID–
REP ANNA ESHOO: I’m familiar with that. And I want to know how close you are–
DR LAWRENCE TABAK, NIH: We’re within the next few months to launch the first interventional trials. The reason it has taken the time it has is because we wanted to build a large enough cohort of patients so that we would actually get actionable answers.
REP ANNA ESHOO: So it took from 2019 to now to get the cohort?
DR LAWRENCE TABAK, NIH: And indeed it has, because–
REP ANNA ESHOO: How many are in it? How many are participating in it?
DR LAWRENCE TABAK, NIH: I’d have to get back to you with specific numbers, but please appreciate that as the virus evolved, so too has long COVID.
REP ANNA ESHOO: Exactly. That’s why I’m asking–
DR LAWRENCE TABAK, NIH: And that’s why we need to continue to build a cohort that’s representative of the disease so that the answers that we get with our interventional trials will have some actionable.
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11:05:39 AM REP ANNA ESHOO I think the public and certainly members of Congress became all too familiar with advisory committees during it, and that impacts your work. But I think that it also added to the confusion of the American people.
Advisory is exactly that. It’s advisory. And I have to say that I found it troubling. It seemed to me that there was a lack of balance between the ultimate decision maker and an advisory committee.
So can you, first of all, do you think that there should be some streamlining of these advisory committees? And really make them more practical?
DR ROBERT CALIFF, FDA: Thank you for that question. I actually chaired an FDA advisory committee for some period of time back in the good old days.
REP ANNA ESHOO: There you go.
DR ROBERT CALIFF, FDA: I think advisory– it’s like democracy. It’s messy. And I think advisory committees are critical. The FDA full time staff need to interact with outside experts in a structured manner.
But you’re right, they are advisory. They’re not decision making. Our regulatory decisions are made by full time civil servants who don’t have a conflict of interest financially and whose mission is preserving and protecting public health. We are looking across the FDA right now at what we can do.
Streamline is one word. I would say to optimize the use of advisory committees. They’re so important, whether it’s food, tobacco or rare diseases, for example, we need to have that kind of input. So it’s critical. We need to make it better.
DR ROCHELLE WALENSKY, CDC: I don’t have much to add to that except to say that there is incredible value in the independent expert opinion of non-governmental officials who are very well recognized across the country in their field of vaccine that we have, and our Advisory Committee on Immunization Practices.
I agree they are messy. They have been challenging during this–
REP ANNA ESHOO: So are you looking to change anything?
DR ROCHELLE WALENSKY, CDC: We are reviewing the advisory committee processes. Yes.
However, I do think that there is an important component of our Advisory Committee on Immunization Practices that has been steadfast through all of vaccines. Certainly, it’s been in the spotlight during COVID 19 vaccines. But there are many pediatric vaccines that have been reviewed carefully through this committee.
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11:12:54 AM REP CATHY MCMORRIS RODGERS: I continue to hear concerns about the FDA having virtual meetings. And especially for innovators and others that have some amazing breakthroughs, being told by the FDA that you can only meet through us through Zoom, or not even through Zoom. I had one. Can we meet through Zoom? You have to be– have written correspondence. You know, this slows down approvals for everything from flu tests to novel vaccines.
So I would just like to ask when is everybody going to be back to work, or what percentage of employees are back to work, five days a week? What percentage of meetings are via Zoom?
DR ROBERT CALIFF, FDA: Hundred percent of our employees have been at work every day since the beginning of the pandemic and will continue to do so, in fact, working in the.
REP CATHY MCMORRIS RODGERS: In the office?
DR ROBERT CALIFF, FDA: Many of our employees aren’t in the office to begin with. We have inspectors. We have people reviewing data. We have 200 locations around the country.
I would also add we have now added back in-person meetings. They are being scheduled. Interestingly, when I’ve said, would you like all in-person meetings, the industry by and large has said we sort of like both, because the ability to have a meeting on the spot via Zoom is superior to trying to get a bunch of people to Silver Spring.
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11:16:39 AM DR LAWRENCE TABAK, NIH: The specific effects on us are modest. We will have to work with our grant community for the slight changes that they will have to address when the PHE is over.
DR ROBERT CALIFF, FDA: Our effects are also a little modest because our EUAs are independent of the public health emergency, so we can keep them going as long as we need to. We’ve been preparing the industry since day one to be ready for the transition. We’ll put a federal register notice out about exactly how to make the transition, as these products go to routine use, and no longer used on an emergency basis.
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11:17:16 AM DR ROCHELLE WALENSKY, CDC: I’d like to be clear that we plan to address this emergency and work towards the safety and security of all Americans 24/7, regardless of whether there’s a public health emergency in place.
It is the case that when the public health emergency comes down, we lose some of our ability to see the data. We will lose testing data that we have, as part of the public health emergency. We will lose other data as well.
And we’re actively working right now to set up data use agreements so that we will have the data that we need in the absence of those authorities so that we can see the data and be able to present them back to the American people.
Finally, we do not in this country have a Vaccines for Adults program. We don’t have a vaccine program for the uninsured adult as we do for children. And so it would be really helpful, and we’re working now, to see how we can ensure that uninsured adults will get vaccinated.
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11:22:08 AM REP MICHAEL BURGESS: I do have a couple of questions. You know, we got a big OIG report the other day, and it generated a lot of interest. Some questions have come up from that. Let me just ask you, roughly, how many awards does the National Institute of Health issue every year?
DR LAWRENCE TABAK, NIH: About 55,000.
REP MICHAEL BURGESS: So that’s a lot.
In the report, in the OIG report, they obviously discuss there the potential risk associated with research being performed under EcoHealth awards. NIH did not effectively monitor or take timely action to address EcoHealth’s compliance with some requirements.
These costs included salaries exceeding the NIH salary cap, employee bonuses, travel costs, tuition costs, indirect costs. This audit covered all three NIH awards to EcoHealth between 2014 2021 and found $89,171 in allowable costs. That’s in one grant. And you just said, how many grants do you administer?
DR LAWRENCE TABAK, NIH: We– about 55,000 a year.
REP MICHAEL BURGESS: So 89,000 multiplied by 55,000 is a lot. Are you taking steps to tighten this process up so we don’t have 55,000 OIG reports down the road?
DR LAWRENCE TABAK, NIH: So certainly this is an outlier and the–
REP MICHAEL BURGESS: Dr Tabak, with all due respect, we’re not sure because we didn’t know about the outlier status of the current OIG report.
DR LAWRENCE TABAK, NIH: I take your point. We accepted all of the OIG recommendations and we are working to redress each of them. We now have modified our systems to prevent some of these missteps from occurring.
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11:45:49 AM DR ROBERT CALIFF, FDA: I appreciate your bringing this up. I couldn’t agree with you more that there’s a lot of work to do on the supply chain. So I’d also point out it’s not just an FDA issue. It’s really an interaction of FDA and industry and other parts of government. And in addition, we are thanks to the omnibus bill, now we have additional hiring authority in these areas to bring on more people. And we’re hard at work in doing it.
Our numbers of inspections are growing daily now, and we’re catching up to what was lost during the pandemic, and particularly in China. As you know, this has been a big issue because of lack of access to entry into China until very recently.
So we’re glad to provide you with the numbers. And also we’ll have a lot to discuss about how to make this better. It is a global supply chain. It’s fragile. The only industry where we’re not seeing supply chain problems is tobacco, as far as I know, which is not exactly the way I’d like to see it.
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11:53:02 AM REP BILL JOHNSON: In the American Rescue Plan passed almost unilaterally by our Democrat colleagues, it included a staggering $47.8 billion of new spending for, quote, activities to detect, diagnose, trace and monitor SARS-CoV-2 and COVID 19 infections and related strategies to mitigate the spread of COVID 19.
In addition, that law provided CDC one billion for, quote, vaccine confidence activities.
Would you say the one billion for vaccine confidence activities was successful in building confidence in the vaccines?
DR ROCHELLE WALENSKY, CDC: Thank you for that question. I think that what we don’t know is what would have happened in the absence of those–
REP BILL JOHNSON: I know, but do you think it helped in instilling confidence?
DR ROCHELLE WALENSKY, CDC: I absolutely know that we have been using those resources to–
REP BILL JOHNSON: But did you– did it improve the confidence level of the public? That’s what I’m asking you.
DR ROCHELLE WALENSKY, CDC: Compared to where it otherwise would have been in the absence of it. Yes.
REP BILL JOHNSON: Okay. Well I’m not sure that we got our money’s worth, because in my district, people tell me not only are they losing confidence in the COVID vaccines, but now, other more proven vaccines as well. We’re going backwards.
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11:56:14 AM REP BILL JOHNSON: Is it fair to say that the CDC has, through grants, technical assistance and research, spent billions of dollars over the course of the COVID 19 pandemic on supporting contact tracing activities?
DR ROCHELLE WALENSKY, CDC: Again, I don’t know the specific number off the top of my head, but I would– what I would say is it’s contact tracing, mitigation, testing, outreach–
REP BILL JOHNSON: That’s been allocated, though, right? Contact tracing billions has been allocated and approved to the CDC for that purpose.
DR ROCHELLE WALENSKY, CDC: I would need to get back to you specifically on the line item–
REP BILL JOHNSON: What is your contact tracing staff doing now?
DR ROCHELLE WALENSKY, CDC: Well, I’m not sure that we have contact tracing specific staff.
REP BILL JOHNSON: That answers my next question.
DR ROCHELLE WALENSKY, CDC: I do want to say, though, that we had 25 people deployed– 2,500 people deployed who had into our response, who had–
REP BILL JOHNSON: Well, you kind of answered my my next question. I asked this because I was surprised to find out that as of last Friday, the CDC’s contact tracing website hasn’t been updated since February of 2022, during the Omicron surge.
The CDC has not changed or updated its guidance in a year. Adding insult to injury, there is a notice on the contact tracing web page stating that, quote, CDC is reviewing this page to align with updated guidance. This notice has been on the website since August 11th, 2022. This means the CDC contact tracing guidance has been undergoing alignment for 181 days.
And, Mr. Chairman, I would ask unanimous consent to put these website documents into the record.
So when we talk about CDC losing its credibility, it’s things like this. CDC and its supporters argued as recently as December 2022 that it needed billions of dollars for, among other activities, contact tracing. But the CDC can’t even be bothered to update its public facing guidance in a timely fashion.
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12:07:42 PM REP LARRY BUCSHON: So on the last question, with that information, why does it currently we still recommend mandates?
DR ROCHELLE WALENSKY, CDC: You know, my job at the CDC is to provide the scientific data that demonstrates the safety efficacy of these vaccines in preventing serious–
REP LARRY BUCSHON: Okay. Fair enough–
DR ROCHELLE WALENSKY, CDC: –piece of a larger policy puzzle.
REP LARRY BUCSHON: And I saw it’s basically policy driven, probably from the White House. And, the White House says their executive order requiring COVID 19 vaccination for travelers to the U.S. is based on CDC’s advice.
But what you’re telling me that you’ve given them advice, and they’re quoting you in saying that that they’re maintaining this vaccine for people to come in, even though we’ve just now discussed the fact that we know that it doesn’t prevent transmission, it’ll prevent the individual from getting really sick. But there’s no– it doesn’t prevent the risk of someone coming into the country and spreading it to other people–
DR ROCHELLE WALENSKY, CDC: – as well. So it does prevent severe disease and death. It doesn’t prevent transmission as well as it did for prior variants, but it does still prevent some. I’d like to offer–
REP LARRY BUCSHON: So I just I’m out of time, but we need to lift this mandate on travelers. It has a big impact on our on our tourism industry and most other countries are doing it.
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12:09:06 PM REP DEBBIE DINGELL: I want to thank all of our panelists for all of their work that you’ve been doing under not the easiest of circumstances, and I have a lot of questions, so I need to get to them.
But I need to say that we are going backwards on vaccines, and we are building– we are– I hope our hearings do not contribute to the lack of public trust.
I look at measles, which has been in my community because people are afraid to get it. And I say this is as someone who got (inaudible) from the swine flu shot and was more afraid of anybody in the Congress of the COVID flu shot.
But I did my research. I got it. I didn’t die and I got every other one. So we need to make sure that we understand vaccinations save lives in all kinds of things, as we are doing these hearings, we can ask questions, but let’s not contribute to the lack of trust in the community.
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12:17:03 PM DR LAWRENCE TABAK, NIH: And we currently are not funding that type of research. We have nothing in that category.
The NSABB, which is an advisory committee to the USG, just provided a set of draft recommendations which will presumably tighten our approach to this type of research.
Once the report is finalized, which we expect will occur very shortly, I will send a memorandum to the secretary of HHS and he, in turn, I presume, will reach out to the NSC and to the OSTP, will convene a government wide effort to update the framework with which we work in these.
REP BUDDY CARTER: I want more than that. I want to hear more than just the effort. This has to be done. So what you’re telling me is that it has been done and it has been done immediately? And I’ll accept your limited definition of gain of function research.
DR LAWRENCE TABAK, NIH: That is the definition.
REP BUDDY CARTER: Then it goes on to say that in the in the 2023 omnibus that we banned the funding of pandemic potential research in foreign countries of concern, and we defined foreign countries of concern as China, North Korea, Russia and Iran. Can you tell me, has that been done?
DR LAWRENCE TABAK, NIH: There is no funding of ePPP research in any foreign country today that is sponsored by NIH.
DR LAWRENCE TABAK, NIH: Has there been in the past?
DR LAWRENCE TABAK, NIH: No.
REP BUDDY CARTER: There has not been in the past?
DR LAWRENCE TABAK, NIH: There has not been in the past, funded by NIH related to the SARS-CoV-2 virus. Many years ago there was ePPP research conducted in the Netherlands, and that was in influenza.
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12:38:53 PM DR LAWRENCE TABAK, NIH: So, in fact, we are having conversations now through our ACTIV consortium, which is a public private partnership, federal agencies and industry, to do just that, to look at T-cell read out. And so we are working towards that goal.
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12:47:12 PM REP DEBBIE LESKO: Given the failure of an NIH grantee to get lab records, there could be other cases where NIH can’t get the lab records. Isn’t that right?
DR LAWRENCE TABAK, NIH: It’s possible. As you know, that sub award is now been terminated. They are no longer funded by NIH to do anything.
REP DEBBIE LESKO: So how can you state– how can the NIH know for sure that it hasn’t funded ePPP when NIH can’t be sure it can get the lab records of experiments funded by NIH?
DR LAWRENCE TABAK, NIH: As as a result of them failing to provide us with the adequate documentation, they no longer have any funding from NIH. The NIH funding, we approve what they are to do from their progress reports and from their publications. They have done what they said they would do. The work was commensurate with the modest sums of money that we provided to them. I don’t know what other work they’re conducting.
REP DEBBIE LESKO: I guess what I’m saying is that if we couldn’t get the research, the reports accurately, how can you definitively say that there was no funding of this?
So anyway, I have another question for you.
As the vice chair of the Oversight and Investigation Subcommittee and a member of the Select Committee on the Coronavirus Pandemic, I can’t stress how inexplicable the failure I believe of NIH oversight on the EcoHealth Alliance grant is to me.
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12:49:32 PM DR LAWRENCE TABAK, NIH: The most important point to appreciate here is that the viruses that were under study in that sub project bear no relationship to SARS-CoV-2. They are genetically distinct. They are absolutely unrelated to SARS-CoV-2. That’s the most important thing to understand, as far as the administrative–
REP DEBBIE LESKO: And how do you know that for sure, sir?
DR LAWRENCE TABAK, NIH: By looking at the phylogeny of– by looking at the genetic sequence. It would be equivalent to saying that a human is equivalent to a cow. That’s how distant the sequences of the bat viruses that they were using in this work were to the actual SARS-CoV-2.
Now, the administrative overla– the administrative issues, we concur with that. We concurred with the oversight report. We have taken steps to redress those administrative issues.
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1:07:30 PM REP DIANA HARSHBARGER: According to Twitter files reported by David Zweig on December 23rd, the Biden administration was working with Twitter to flag anything that conflicted or differed from CDC guidance as misinformation.
Dr. Walensky, were you or your staff in meetings, phone calls, or virtual meetings with the Biden White House administration officials and Twitter? And that’s a yes or no.
ROCHELLE WALENSKY, CDC: I’m thank you for the question. There’s pending litigation on that. So I’m not going to get into the specifics on that today. Thank you.
REP DIANA HARSHBARGER: What about Facebook and Instagram?
ROCHELLE WALENSKY, CDC: Similar.
REP DIANA HARSHBARGER: Giving given reporting that CDC was consulted frequently, and at times daily, and then given recommendations on what content to flag as fake or misleading on Twitter, Facebook and Instagram. How many staff did you have dedicated to working with technology companies?
ROCHELLE WALENSKY, CDC: Again, there’s pending litigation on that. So I’m not free to comment right now.
REP DIANA HARSHBARGER: Was there any centralized guidance from you about what staff should relay is fake or misleading.
ROCHELLE WALENSKY, CDC: Pending litigation, regrets.
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1:18:19 PM REP MARIANNETTE MILLER-MEEKS: Dr. Walensky, you and I have had the opportunity and the pleasure, if you will, to receive testimony before and ask questions.
I’m a physician. I’m also a former director of the Iowa Department of Public Health. And when it comes to trust in our agencies, if you’ve lost me, that means there is a lot that has to be answered for, and oversight that has to be taken care of.
I vaccinated ,individuals all 24 of my counties in my district, I was vaccinated. But even now there still persists this non-recognition of infection acquired immunity, of herd immunity, of immunity that exists. And the purpose of a vaccine is to do what? It is to confer immunity.
So the failures of the CDC and the FDA and I won’t get into the NIH were both administrations.
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1:29:25 PM REP KAT CAMMACK: Do you believe that Stanford Medical School, Oxford, and Harvard hire, quote, fringe medical professors?
DR LAWRENCE TABAK, NIH: It depends on the individual professor.
REP KAT CAMMACK: Okay. Well, the reason that I ask is because on October 8th of 2020, you were CC’d on an email from the then head of NIH, Dr. Francis Collins, to Dr. Anthony Fauci. Now, I’m going to refresh your memory on the contents of this email. It says, Hi, Tony and Cliff. This proposal, citing the Great Barrington Declaration from the three fringe epidemiologists who met with the secretary, seemed to be getting a lot of attention and even a co-signature from Nobel Prize winner Mike Leavitt at Stanford. There needs to be a quick and devastating published takedown of its premises. I don’t see anything like that online yet. Is it underway? Signed, Francis. Again, you were CC’d on this email. Yes or no, Dr. Tabak, did you communicate with Dr. Collins with you about these doctors or the Great Barrington Declaration, other than when emailing Dr. Fauci?
DR. LAWRENCE TABAK, NIH: I have no recollection of speaking to him about that.
REP KAT CAMMACK: Yes or no? Are you aware of other instances where either Dr. Collins or Dr. Fauci planned to have the media publish articles to discredit other scientists or doctors during the COVID 19 pandemic?
REP KAT CAMMACK: I’m not aware of any such instance.
REP KAT CAMMACK: Of course.
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1:32:16 PM REP KAT CAMMACK: Just a few months after that, Twitter was directed by the Biden administration to deplatform multiple scientific accounts: doctors, Nobel Prize winners. They went so far as on March 14th, 2021, in internal communications between top Twitter executives and the Biden administration to say, we are very angry. The Biden administration needs a push to deplatform these multiple accounts.
These de-platforming of accounts were, of course, related to the Great Barrington Declaration, and they said, according to the Biden administration, to Twitter, that not enough had been done to silence these doctors.
Dr Tabak, did you provide Dr. Collins with any ethical counsel or advice on this matter?
DR. LAWRENCE TABAK, NIH: This is a subject of ongoing litigation, and I can’t comment on anything related to the social platform.
REP KAT CAMMACK: Who else at NIH did you talk to about the Great Barrington Declaration and its authors?
DR. LAWRENCE TAAK: I don’t recall speaking to anybody about that.
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1:33:38 PM REP KAT CAMMACK: But contrary to the comments of some of my colleagues today, actually just now, apologizing to you all for appearing before this committee, saying that we’re taking you away from your primary responsibility.
You have a responsibility to appear before this committee, just as we have a constitutional responsibility for oversight. That is our duty to the American people.
If I were you, I would clear your schedule. This will come to light.
I appreciate you all being here today. Thank you.
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1:40:50 PM REP GARY PALMER: And you’re also then aware that the study basically said that it really didn’t make much difference, even if you wore an N95, whether for influenza or COVID?
ROCHELLE WALENSKY, CDC: I would love to address that Cochrane Review. I know it well.
So Cochrane Review looked at randomized controlled trials related to COVID 19, but other respiratory viruses. Of course, COVID 19 is different because it has pre-symptomatic transmission rather than post-symptomatic transmission– not rather than alone post-symptomatic transmission.
One of the limitations of that that study, in addition to the fact that it included randomized trials from before COVID 19, was that, and it stated in the study, is that people actually had limited uptake of using masks. So of course randomized trials that look at mask use, but people are not wearing them, are going to have–
REP GARY PALMER: For the record, it was nine studies in over 276,000 people. That’s–
ROCHELLE WALENSKY, CDC: If they don’t take uptake the intervention, then it is not going to prove working. It is also the case that our masking guidance was very much related on cohort studies and many other studies.
Randomization, as you can imagine, of a mask versus no mask approach during the height of the COVID 19 pandemic would have been a challenge.
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1:42:31 PM REP GARY PALMER: And it kind of surprises me that the NIH, CDC didn’t do any follow up testing even while this was going on, to determine the effectiveness of this, and the impact it was going to have on kids.
ROCHELLE WALENSKY, CDC: Yeah, I appreciate– in order to do a randomized clinical trial, you need to actually have equipoise in the question. And ultimately, what would happen– what happened is that there were so many studies that demonstrated time and time again, in the height of COVID transmission, that masks were working to prevent transmission that I’m not sure anybody would have proposed a clinical trial because, in fact, there wasn’t equipoise to the question anymore.
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1:43:55 PM REP GARY PALMER: You said that the teachers did not need to be vaccinated to reopen the schools. The teacher unions pushed back. And Jen Psaki first said that you were talking in your personal capacity, is is that true?
ROCHELLE WALENSKY, CDC: I was very motivated as I came in to get our schools open, and I think that’s very clear and I was very successful in our efforts. I’ve been working in the front lines of of health care, and had seen that we were able to safely bring health care workers into the hospital treating COVID patients. So I did say that–
REP GARY PALMER: Speaking in your personal capacity? How do you differentiate between your personal capacity and your professional capacity?
ROCHELLE WALENSKY, CDC: As I said that, which I believe was on February 3rd, I said it from an official CDC capacity, and I believe Jen Psaki– Jen Psaki, I can’t speak to her comments. But I was definitely in my CDC capacity when the comments were made. And in fact, we reopened schools.
We do expect to continue running COVID hospitalization and likely death forecasts too for perhaps at least another year. Case forecasts I’m not as sure about. The expiration of the public health emergency declaration is not (at this point) impacting our ongoing modeling/forecasting work. I suppose we might reconsider that if some states started reporting less data, but the hospitalization data at least is mandated by HHS to be reported through April 2024 I think.
There were 28 cases of invasive group A strep in children under the age of 18 years old reported in Colorado during 2022, but official and final case numbers may change as additional information is collected. A majority of the cases in 2022 were reported during November and December. We continued to see some cases reported during January 2023, but far fewer than in previous months, possibly due to the decrease in respiratory illnesses like COVID-19, flu, and RSV that can contribute to group A strep infections.
Here is our response, on background, attributable to the Centers for Medicare & Medicaid Services (CMS) or a CMS spokesperson:
Nursing home COVID-19 vaccination reporting requirements for residents and staff will continue until any additional regulatory action is taken to change it. All of the other non-vaccine reporting requirements are in effect through December 2024. Regardless of the COVID-19 public health emergency (PHE), nursing homes are still required to have an effective infection prevention and control program, which is a longstanding requirement to follow national standards to prevent the transmission of infectious diseases (including COVID-19).
Under the August 1, 2022, Fiscal Year 2023 Medicare Hospital Inpatient Prospective Payment System (IPPS) and Long-Term Care Hospital Prospective Payment System (LTCH PPS) final rule, CMS revised the hospital and critical access hospitals (CAHs) infection prevention and control Condition of Participation so that hospitals and CAHs will continue to report on a reduced number of COVID-19 data elements after the conclusion of the COVID-19 PHE until April 30, 2024, unless the Secretary establishes an earlier ending date.
For additional background:
While the response to COVID-19 is not over, because of the Biden-Harris Administration’s whole-of-government approach since day one, we are in a position where we can effectively start to lift the PHE and the national emergency-related authorities.
For over a year, CMS has been working alongside states, public health departments, and stakeholders for a smooth transition out of the PHE. CMS has also developed a roadmap for the eventual end of the COVID-19 PHE waivers and flexibilities, and is sharing information on what health care facilities and providers can do to prepare for future events. CMS also released provider-specific fact sheets that will help the health care sector transition to non-emergency operations when the PHE ends.
Additionally, we are offering technical assistance to states and engaging in public education about the necessary steps to prepare for the end of the PHE. For additional information, visit CMS.gov.
DR ROCHELLE WALENSKY, CDC (ACD 1) [00:09:37]
The organizational changes you’ve seen were developed by CDC senior leaders with extensive staff input through ten strike teams focused on public health data, global health, advancing equity, science, policy, laboratories and more. So taking their input into consideration, we have submitted a proposed organizational structure to HHS and the prior structure and the proposed new structure are in that printout that you have received. Ultimately, the proposed changes for our processes are about eliminating reporting layers, breaking down silos within the agency, putting our foundational public health capabilities, and facilitating bi-directional communication and accountability.
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DR ROCHELLE WALENSKY, CDC (ACD 1) [00:18:08]
But what I, what I will just generally say is, in the before flow chart, there is this layer of offices called the communities of practice. We are generally moving away from that extra layer. Part of that is because it didn’t offer a full visibility, full line of sight, as well as accountability, reporting into the immediate office of the director. And then also, if you sort of look at how that is built, it created silos between our infectious side of the house and our noninfectious side of the house. And I really felt like those silos were not productive, because we really would like them working more closely together. And if anything, COVID showed us that in spades. So we are moving away from that structure of communities of practice.
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DR ROCHELLE WALENSKY, CDC (ACD 1) [00:23:05] Maybe I’ll start with the organizational pieces. And those organizational pieces are– I anticipate that by the end of this month, we will be fully functioning in this new organizational structure.
Now, what we have said, and I think is really important, is under this new organizational structure, there may be further organizational things that need to happen at the center level. And so we have asked individual centers to do that work now. This was going to be the one sort of centralized piece, but we wanted to– we understand, in sort of CDC Moving Forward, that to accomplish those structural missions, people within those processes and procedure missions, people within the centers may have other changes that they’d like to make. So those are currently ongoing right now within the centers, they’re doing that evaluative work right now.
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DR ROCHELLE WALENSKY, CDC (ACD 1) [00:24:47]
What I will say is that, for example, in the communications area, one of the things that we really wanted to do was look at our website. People now, Americans, are now coming to our website in ways that they hadn’t before. And when I arrived, I believe we had about 200,000 webpages of content on the CDC website. So we are doing a project called Clean Slate, where we are looking at our website, all of our components of our website, seeing what needs to be archived, what can be archived, what is not yet in plain language and accessible. And that is work that’s probably going to take close to a year.
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DR ROCHELLE WALENSKY, CDC (ACD 1) [00:43:47]
One related to our data authorities. We receive data currently in a non standardized fashion that is voluntarily reported. I still don’t know who is vaccinated in hospitals, and that is with a public health emergency in place. We are not confident that we will get immunization data from every state at the end of a public health emergency. We’re working through that now, and that is with COVID. And so when you get a sense of all of the other data that we– it took us 2 to 3 months to work out data use agreements on getting vaccination data for the Jynneos vaccine.
When you’re in the precipice of a public health emergency, you really don’t want to be in that position to try and be working on data use agreements. So again, to be very clear, we want to have it privacy protected. We are looking to do this from a public health vantage point and not just at CDC. We want your you to know the neighboring counties, so you know what is happening around you as well. So county to county across the states, state to state, standardize that data reporting and have it accessible so people know what’s happening.
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DR ROCHELLE WALENSKY, CDC (ACD 1) [00:54:57]
High on my radar. We’ve already been in touch with our teams as to where we are with both surveillance and detection, as well as our USDA colleagues and the detection in the avian population as well. In fact, I know I have a I have a hearing tomorrow and a briefing the next day on exactly that issue.
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DR JULIE MORITA, ACD (ACD 2) [00:00:16]
I wanted to update you on what the what happened to the ACD recommendations that we all submitted to HHS. They were approved and accepted by HHS. So that’s exciting to hear.
And I, just as a reminder, so you all remember what it is that we all approved last time we met, was that there were three priority areas to improve essential data exchange between health care and public health systems.
And the first was really focused on defining the minimal data set necessary for core public health data sources. The second was to establish public health data system standards and certification. And the third was really, as it relates to as Dr. Walensky mentioned earlier, how there are limitations in terms of the authorities that CDC has. We made a recommendation regarding establishing data use agreements and frameworks that could be put in place, even though there isn’t a whole lot of authority that CDC actually has. Next slide, please.
So just to get a little bit deeper into each of the recommendations, I thought I would just provide you with a little bit more detail about each one of them, and then we’ll ask Jen Layden, I think she’s joined us as well to give a little update on what happens next.
But first, in terms of defining the minimal data necessary for core public health data sources, it was really– our recommendations is CDC in consultation with the states, tribal, local, and territorial partners and with input from health care and federal agency partners that they should actually develop and regularly update a list of data elements that constitute the minimal data necessary for disclosure to CDC for public health activities. And then also, there was a follow up recommendation to work with states to develop a list of data elements that would be reportable to the STLTs as well. So it didn’t just stop at the CDC level, but it went on to the state, local or tribal territorial level as well. Next slide, please.
The second was really establishing public health data, system standards and certification. So the recommendation was for CDC in collaboration with STLT partners and the Office of the National Coordinator for Health Information Technology, or ONC, and that they should develop and implement a coordinated, phased approach to certification, which to start with expanded guidance for public health criteria, moved to requirements, and ultimately advance to certification. So as has been done for health care system, public electronic health record systems, this is a certification process that would be done for public health data systems as well. Next slide.
And then the third was to establish data use agreements and frameworks, recognizing that CDC doesn’t necessarily have the authority that they need. The feeling was that CDC, in coordination was STLT partners, could actually establish a proactive approach for data use agreements and to streamline the process. So we’re really looking at umbrella kind of an approach that would standardize language, provide standardized language for core components of data use agreements, to address the common challenges. And then looking at ways to leverage sharing data expectations through federal funds, through some of the assistance program mechanisms like grants and cooperative agreement. So that’s what that second– the third recommendation actually entails.
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DR JENNIFER LAYDEN, CDC (ACD 2)[00:03:46]
Really excited to see the both the endorsement as well as the approval by HHS for these recommendations. I think these were felt to be really strong and important steps that we take to promote the sharing and exchange of data across the public health ecosystem.
Now that the approval is in place, the next steps are to really lay out an implementation plan. We’re excited to move forward with this. There is some ongoing work already that is occurring around minimal data sets, particularly for case data, both as part of the case surveillance system as well as looking at some response standpoint.
In doing this, we will need to work very closely with our partners, state and local partners, to develop some of the language and get to a consensus on some of these critical aspects around DUAs, as well as the minimal data necessary, and identify some of the challenges and barriers as we lay out the implementation plan for standards and certification.
So a lot of work to come, both within CDC to bring the team together for these three recommendations, but also doing it really closely with our partners.
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DR JENNIFER LAYDEN, CDC (ACD 2) [00:13:21]
So there’s been some really good estimates, both CSTE and HIMSS, on the cost of DMI modernization. And the costs that are projected are much higher than certainly funds that are available.
If there’s continued effort to continue to update those, to be as to reflect the reality of the situation, we do hear, I would say quite often, from states and locals, the concern of of investing in something not knowing their ability to sustain that long term. So that is a challenge that we hear and recognize to be a real challenge for states and locals, and at the federal level.
For CDC, as we are standing up the proposed new Office of Public Health Data Surveillance and Technology, one aspect of that work and function of that office is to define a public health data strategy. In doing so, one of the things that we think is critical is to outline the priority work for the next couple of years, recognizing that the funds as well as the bandwidth, our personnel and resources and time, don’t enable us to do everything right at once. And so to really articulate from a public health response readiness, and to support those core missions across public health, what do we want to prioritize for the next couple of years?
As we’re standing up the new office, our goal is to disseminate that and also work very closely with our partners to support the alignment on that, recognizing, when we’re talking about some of this core priority work in the core data systems, the exchange of the data occurs across the ecosystems we have to– the more we can be aligned on that to better.
So there’s effort there to the sustained funding. One of the things that we need to start looking at is what that sustained funding model looks like, as more and more jurisdictions are going to cloud migration. The reality of that is the costs are quite high. And how do we support that in a way that enables the sustained functions, and not have to take a step backward to some of the progress that has been made across the jurisdictions?
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DEB HOURY, CDC (ACD 3) [00:02:15]
I just want to mention fiscal year 2022, Congress directed the Secretary of Health and Human Services to establish a task force that included participation from outside stakeholders and subject matter experts to evaluate what contributed to the shortcomings of the first COVID 19 test and what policies, practices, and systems should be established to address these issues in the future.
Through an agreement with HHS and Congress, the Advisory Committee to the Director, through the laboratory work group, has served as the task force requested by Congress. CDC welcomed the in-depth review of the work conducted of its laboratory policies, practices, and systems, under the direction of co-chairs, Dr. Jill Taylor and Jeff Sharfstein, and we look forward to hearing the presentation of their work over the past six months. I truly want to thank them, as well as the CDC staff that provided a lot of time and input, and the lab work group of what I believe will be a comprehensive review of action steps and discussion.
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JOSHUA SHARFSTEIN, ACD (ACD 3) [00:14:09]
What we found in our document requests in interviews is that there was not a plan for how CDC could develop and scale a test in this circumstance of a pandemic rapidly. So it just– there was no such plan. There was no in case of emergency, break class, inside is the plan.
Instead, what CDC was really relying on was something called a graduated response framework, which was a document that was supposed to support responses that were too big for just one office to do, but too small for agency wide activation, and for really the key weeks of test development, CDC was operating under a graduated response framework. The overall incident command had not been activated.
You know, at that time it wasn’t really clear what was happening with the COVID. And so it was a less than full agency activation, and there was no clear plan for how to develop a test in that in that circumstance.
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JOSHUA SHARFSTEIN, ACD (ACD 3)[00:15:53]
Here’s an example of what it means to not have a plan. The same lab had to be relied upon for both the primers and probes, as well as the positive control. So it’s obviously a risk when you are in manufacturing the positive control in the same lab that you’re doing the actual probes, and that created a risk of contamination. But the CDC felt like it had no reasonable alternative approach.
Now, I should be clear, it’s known actually, in fact, the CDC’s conclusion was that it wasn’t actually in the lab where it was manufactured that the contamination occurred. But nonetheless, everybody saw it as suboptimal to have to manufacture these things in the same place. But there was no plan for what to do when you didn’t have the virus itself, and you had to actually manufacture the positive control, and so they wound up having to do it in the same lab.
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JOSHUA SHARFSTEIN, ACD (ACD 3) [00:18:05]
So the second major issue is ineffective governance. So there were three different labs at CDC that were involved in manufacturing the tests, but they were not led by someone whose job it was to oversee that whole process. That just did not happen. The labs were just engaging based on their job descriptions. There was no point in coordination responsibility across these labs. If you were to say who’s responsible, who’s empowered to make this test the right way across all these different labs that are participating, there wasn’t someone in that role. There was no clear governance like that.
And that’s true prior to the emergency. It was also true during the graduated response, and it was even true during the incident management mobilization, because one of the labs was not included as part of the incident management structure. So it was really a big gap in governance that everybody was sort of doing their job, handing it off to the next lab, or just doing what the other lab asked for, without somebody thinking like, is this a good idea? And that created the potential for additional problems.
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JOSHUA SHARFSTEIN, ACD (ACD 3) [00:19:13]
Here’s an example of this. There are few examples of the consequences of ineffective governance, but one example is that it caused delays in understanding the scale and cause of test issues. There wasn’t anyone who was empowered and responsible for seeing these issues across the different labs. In addition to the fact that one lab made the positive control and the probes in the same place, there was another lab which was storing the positive control near where some of the tests were. And it’s thought that that could have been where the contamination occurred.
In addition, once problems started happening, the incident management leadership, which in a crisis is really responsible for the development of the tests and for everything to happen, was not even made aware of the performance issues. The flow of information was not effective. So even when you had, somebody who is nominally in charge of the tests, they were very frustrated that they couldn’t get information about what was happening and were learning about it kind of after the fact. They did not know, for example, that the tests had failed the quality control step.
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JOSHUA SHARFSTEIN, ACD (ACD 3) [00:21:24]
So the third major area of the causes of the causes were inadequate quality control, quality assurance, and regulatory oversight.
One of the challenges that CDC has is that research and clinical lab spaces intermingled and that creates different risks because there’s not a clear quality management system for the clinical space. CLIA is a law that we’ll talk about on the next slide, I believe, but it’s a law that’s supposed to assure quality in labs, but it is really for tests that are done at the lab. So it does not apply for the test made for the state and locals. And CDC did not rely on its CLIA office for oversight. So you didn’t have a clear quality system coming in from CLIA.
And then you might wonder, well, what about the FDA, which was reviewing the specs on the test? The failed quality control came actually after the CDC application to FDA. FDA is looking more at some of the design issues, not so much the quality control. And so that also was not able to catch the problem.
The biggest overall issue is that there was not a clear quality assurance system to oversee the test development. And one thing that I learned in this process, not being a lab specialist myself, as we talked to people in the work group who do this for a living, is that having a clear quality system for a lab is like is like the air they breathe and really understanding what each step what, what a test has to do at each step to proceed to the next step through the quality system, is really important. And that was missing for this test and that level of clarity.
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JILL TAYLOR, ACD (ACD 3) [00:23:23]
The research and clinical space were intermingled. We also told that a scientist in the lab might be doing clinical testing in the morning and then research in the afternoon, and that’s to us, a vulnerability, especially in emergency situations where time is of the essence, you’re moving very quickly. You really need to know what system you are working under.
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JOSHUA SHARFSTEIN, ACD (ACD 3) [00:26:43]
Typically when a new test is developed, there are sort of a series of gates that the test goes through. There are people who will review the test to make sure that it’s right. It’s not all on one person to make all the decisions and then put the test out. And during that process, there may be certain steps that you go through, including using computer models to predict design failure. And in fact, when CDC went back and used a computer model on that N3 probe, it predicted design failure. It’s unclear whether that was ever done in that control process.
The other thing that a test design process would do is specify the criteria for releasing the test at the end. And so when the test was released, even after a failure, it indicated that something was off in the design process. So that was another fundamental cause of the more proximate failures.
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JOSHUA SHARFSTEIN, ACD (ACD 3)[00:35:09]
I should say that just to be clear, while it may read like a mystery that we’re unfolding, the CDC helped us unfold this, And so we were learning from people at CDC, who spent a lot of time thinking about what what went wrong, in order to put this assessment together. This is not sort of figured out around CDC, this is figured out with CDC.
And I just want to add to that there is absolutely no gotcha aspect to this report. And the CDC were incredibly. Forthcoming and honest. And so the whole tone of the group was very much. How can we help?
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JOSHUA SHARFSTEIN, ACD (ACD 3) [00:38:01]
We heard from Dr. Walensky that there will now be a senior laboratory leader reporting directly to the immediate office. So that that is a major step for the agency in this regard.
The second thing I would say is that there are a lot of issues that we didn’t focus on like the difficulties scaling the tests. What was the problem with the gaps in all those supply chain issues. Big issues in testing that happened that really weren’t part of the CDC is making this first test.
But the the workgroup felt like it be great for the person who is the lab leader at CDC to also be related to all those problems out there, that what CDC– CDC is part of a lab development system for the country, not just focused on this one discrete task of creating the first test. And it’s really important for CDC to fit into that system. And there needs to be leadership coming from CDC, convening people where necessary, to get to those bigger issues. So having someone at a very, very high level, it’s both to assure quality and other things that we’ll get into within the agency, but also for this critically important role nationally intersecting with the private sector, with FDA and with CMS and with others.
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DEB HOURY, CDC (ACD 3)[01:31:33]
The one piece of housekeeping, I’ll just say while I have the floor, as you know, as you review the workgroup report and if approved, then the report will be transmitted to HHS and that takes about 30 days to review and respond from HHS. That will then be published to the website. So for folks that are tuning in or workgroup members that want to revisit or share, it’ll be about six weeks before the report will be publicly available on our website.
We’re committed to working closely with the federal government, states, manufacturers and private insurers to ensure consistent access and care for all individuals as the federal government adjusts the public health emergency related to the COVID-19 pandemic. As a convenient partner and trusted resource for all health and wellness needs, Walgreens pharmacy teams will continue to provide our patients with the services they rely on to keep them safe and healthy – including COVID-19 vaccinations, tests and treatments.
Yes, we plan to continue offering FDA authorized OTC Covid-19 tests, lab testing performed at the drive-thru and rapid-result testing following the expiration of the PHE.
It is important to note that one of the most effective ways to prevent avian flu outbreak at farms is strong biosecurity measures.
Our current portfolio consists of vaccines for the H5 and H9 strains. We test each vaccine against local strains on a case-by-case basis in a particular market, and the effectiveness of the vaccine depends on the specific field strain. Even if the field strains look similar, we are obligated to test to each one to ensure the vaccines meet stringent efficacy requirements before they can be used.
At Merck Animal Health we do not disclose our pipeline, but we can share that we have an extensive, ongoing research program that is focused on discovering and developing vaccines that are DIVA (differentiating infected from vaccinated) and address the holistic issues associated with avian influenza, including clinical efficacy and the prevention of viral shedding.
Currently, the United States has not authorized the use of highly pathogenic avian influenza (HPAI) vaccination but there are several avian influenza vaccines that are licensed by USDA Animal and Plant Health Inspection Service (APHIS) Center for Veterinary Biologics (CVB). However, the efficacy of these vaccines against the prevailing HPAI strain is unknown and they are currently not being used in the United States.
The animal vaccine approval process entails 20 discrete stages that begin with feasibility work by the manufacturer and culminates with product label submission and review. General timeframes are 2.5-3 years, however in emergency situations manufacturers may expedite development, resulting in a shortened timeframe to licensure. It is important to note that for live, genetically modified organisms, National Environmental Policy Act requirements can add from 9 months to 1 year to the approval process timeline.
APHIS believes we must consider as many approaches as possible to protect against and respond to HPAI, including vaccination of vulnerable bird populations. The decision to proceed with vaccination is complex, and many factors must be considered before implementing a vaccination strategy. APHIS has initiated discussions with and are soliciting input from many different industry stakeholders that would be impacted by a vaccination strategy for U.S. poultry.
APHIS also continues to coordinate with CDC on matters related to human health.
[00;52] STEVEN PEARSON, ICER: So we’re an independent non-partisan review institute, and we look at the evidence on the clinical effectiveness and the cost effectiveness of treatments, drugs, and other things. And our methods help us kind of identify what would be a fair price, as it aligns with the benefits that are provided to patients.
So something that provides a big benefit would merit a high price. Something that just provides a smaller benefits merits something smaller.
ANd we put these out into the public domain with without any governmental requirement that they be used, but because I think they come from an independent group whose work has been trusted, our work is used by the VA, by private insurers, by Medicaid, and others as well.
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[01;53] STEVEN PEARSON, ICER: That’s a question, because technically, they don’t– the government doesn’t have any power, after it moves outside of the initial contract. The VA can negotiate, and Medicaid can kind of negotiate, but they all have to cover it because there really aren’t a lot of good options for patients who are in the outpatient setting, who are at high risk.
So they don’t have that much leverage. They can’t walk away from the table. But they do use our reports to often give them a kind of a benchmark against which to consider what a fair price would be. And then they go into the negotiating room with Pfizer and something happens.
And in this case, it is hard to know what will happen because it’s expected that the price will be higher than what they received from the government’s contract and the question is how much higher.
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[04;01] STEVEN PEARSON, ICER: And what changes through time is what that risk is, because when Delta was around, more people who got it ended up in the hospital with a higher risk of dying than we’re seeing now with Omicron and its variants.
So in a sense, the relative value of taking Paxlovid is reduced today, compared to what it was back then, and you’re never 100% sure which direction it will be in five or six months.
But the other thing that’s changed is more Americans have had the vaccine and have had an infection– and/or have had an infection. So in a sense they’re also kind of more protected, at the same time that the variant is a little bit less serious.
So when we initially said what a fair price would be for Paxlovid, linked to its benefits, we said it was in the neighborhood of $3,500 which is a fair amount for something that you only need to take for a few days, but the risk was pretty serious. And it’s still serious but it’s reduced. So now when we redid our calculations, it came out more in the range of around, $500 to 900.
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[08;28] STEVEN PEARSON, ICER: We’ve been doing this now for about seven years and over the entire range of drugs we’ve looked at, about 25 to 30 percent of the time, we find that the drugs in the market is in the range that we would consider to be a fair value-based price. And that means it’s 75 percent of the time, it’s not. And sometimes it’s close and sometimes it’s miles away where you would need an 80 to 90 percent discount to get close to a value-based price.
So our system really isn’t, in some ways, really set up well to get the price aligned to the value, given the distortions in our drug pricing system. But, still sometimes that we do find that price aligns well.
Interestingly, the price that the government paid during the last couple years for Paxlovid is right basically at the bottom end, actually, with the range that we today, say, would be fair.
So the government’s price through those years has been $530 for a course of treatment. And our finding, I think you know from our report, was $563 to 906 to be precise, but you can see that it’s pretty close.
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[09;44] STEVEN PEARSON, ICER: There’s been talk that the vaccine that you know Pfizer makes and that Moderna makes, that they’ve talked about increasing that price four times or five times from what they’ve charged the government.
So people have been wondering, what will happen with the price of Paxlovid? Will it be four to five times higher? And again, our most recent update suggests that it shouldn’t be. It could be a little bit higher but certainly not four to five times.
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[10;51] STEVEN PEARSON, ICER: They’re in an interesting position. They have almost a monopoly. There’s another drug called molnupiravir, but it’s not as effective. And so in a way, they have a monopoly, certainly on the most effective treatment option. And that gives them a lot of negotiating power.
How do they want to use that? Will the health plans, private ones, be able to walk away from the table if Pfizer wants 5,000, 10,000 dollars? Would they be able to say no?
The way our system generally works is that, what the health plans would do is to say, well, if you’re going to charge a lot more than we think is fair, we’re basically going to try to reduce its use by creating tough criteria that patients have to get through in order to get a prescription covered. So they might create some hurdles that doctors and patients would have to go through.
So, in some ways, we really don’t want that, we want people to be able to get rapid access if they are at high risk and really can benefit from this treatment. So, everybody would hope to shoot for a price that is both a value, but also in the near term affordable.
I don’t know how that dynamic will play out, but that’s I think one of the things that you should in your article, obviously this is a good time to talk about it, because it’s negotiations are ongoing right now, they’re doing it in advance of this happening later this year, so we will know relatively soon.
But the dynamic– most of the cards are in Pfizer’s hands, and the question is, how will they play it so that patients, do have great access to this drug?
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[12;38] STEVEN PEARSON, ICER: One of the interesting things is that this kind of issue, where we think about a private insurance company sitting down with a drug maker and the drug maker has a drug that everybody wants to have available through insurance, this happens every single day with every single drug basically.
And so the dynamics that we’re witnessing around the power struggle, if you will, over the pricing and availability plays out in cancer drugs, and asthma drugs, diabetes drugs. And so, this is something that we, as a country, should realize happens every day and the same problems and opportunities, perhaps apply.
But it’s obviously a great importance with the pandemic, but it’s important to patients every single day.
[01;01] ANNE ZINK, ASTHO: I’m Dr. Anne Zink. I am the chief medical officer for the state of Alaska. I’ve been serving in this role since prior to the pandemic. So I started in July of 2019 and have been in the role throughout the pandemic and then had the honor of taking the job as the president of ASTHO. So I represent all the states and territories to partners, to federal agencies, and others since September of 2022.
And then currently serving the role. And just for a little bit of background, I also clinically practice emergency medicine still. So I continue to see patients regularly, which does inform some of my perspective.
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[03;07] ANNE ZINK, ASTHO: There continues to be a lot of conversation with us as well as many federal agencies on how we can make sure that Americans still have access to vaccines treatments and testing moving forward.
I do not suspect an immediate cliff with the kind of quote unwinding of the public health emergency, and I think that’s important for people to know and I think it’s important for people to follow the best guidance for themselves regarding things like vaccinations. So if they’re eligible to get a COVID-19 booster, I would get a COVID-19 booster. I wouldn’t, worry about you know, well what if i get it now? And what’s going to happen in the fall? We still have a lot of COVID circulating. That’s still a great time to get it.
And then we’re continuing to work with the federal government, what that looks like. But there’s a lot of details in that that need to be sorted out. So I think that provides a lot of anxiety for the states as our planning can be– it can take a while for states to pivot in the way that we do things. And so that’s part of the reason why we have to have really close communication with the federal government in this space, it’s critically important.
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[04;33] ANNE ZINK, ASTHO: From a public health perspective, my teams are very much thinking about: how do we make sure that people who are uninsured still have access to testing? How are we going to make sure that they still have access to treatment? How do we communicate effectively about the risk benefit? How can we make sure that data that has been shared during the public health emergency continues to be shared?
CMS has made some changes already regarding hospital data but there’s other data sharing agreements that are tied to the public health emergency and making sure that that continues, so that we can give situational awareness to our hospitals and to communities and individuals about what this.
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[05;10] ANNE ZINK, ASTHO: So for Medicaid, for example, the continuous eligibility that has been ongoing during the public health– during the COVID pandemic, that process of unwinding that and redetermining eligibility has begun. Every state is working on a plan on what that looks like.
And there’s a real risk that many Americans who are currently insured with Medicaid may lose their coverage, just in the churning of this redetermination process. So making sure that there’s really clear communication between beneficiaries, those who support them, states and then things like the private marketplace.
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[07;54] ANNE ZINK, ASTHO: So a lot happened in the background under the public health emergency that states and the federal government are having to find ways to unwind and take lessons learned. Build those into the regular parts of the system, but then also just trying to be really cognizant and mindful of not having people fall between the gaps, not losing coverage, not having access, and I think that’s where all of our concern is with this much change in the system. There’s real risk of potentially people losing that coverage or access to services.
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[09;28] ANNE ZINK, ASTHO: I think the reality is that the authorities to share data really relies within the states, not within the federal government and the current structure. And so, there are not mechanisms to force or to employ that data sharing without it potentially being tied to funding. And state health departments are tired, and they’re exhausted. And we’re all looking at fairly large financial cliffs, at the end of the 2023-2024 budget cycle as a lot of the COVID funding has and will be wrapping up, without having been able to rebuild a lot of the systems that we would hope to have in place so that people could have the information that they hope to have that, they need to have, regarding COVID or other infectious diseases.
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[11;22] ANNE ZINK, ASTHO: I think there’s a lot of talk about it. And we just need to action as many of those things as possible. And I think the impetus from the public health emergency just increases that need to solidify and formalize some more of these data sharing agreements now, before the public health emergency ends, or as soon as possible.
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[11;59] ANNE ZINK, ASTHO: So for things like syndromic surveillance, depending on the states agreement with CDC, they may be sharing what showing up in the emergency departments, or they may not be sharing what’s happening in the emergency departments with the CDC.
So if we start to have a lot of hospitals being very overwhelmed, it can be very helpful to understand why that’s happening. And to provide information to a community.
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[13;29] ANNE ZINK, ASTHO: I’ve got our state’s syndromic surveillance data but if I don’t have the other states also reporting their data to the CDC in that space, it limits me and my ability to learn from the other states, and provide my learning to them as well, so that we can best collaborate together.
I think that’s one of the beauties of our democracy is that all of these states do do things slightly differently but they get to learn from and share that. But if we don’t have a mechanism to share that learning and information, as well as kind of what is that overall burden, it becomes very hard to learn.
So just the hospital data would be an example recently that we were very much relying on other states sharing their syndromic data to make programmatic changes for what we were doing in a state level.
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[14;35] ANNE ZINK, ASTHO: Most states have a children’s vaccine program that they have a degree of a template for, but most states that is related just children. So that makes COVID harder particularly because we see COVID hitting adults more than it hits kids. And so our vaccine for children programs don’t perfectly apply there.
Some states have adult programs or some states have taken their children’s program and extended it beyond that to try to better meet the needs of adults needing vaccines, including flu, and there’s a lot of conversation about what does that look like from a state perspective.
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[16;08] ANNE ZINK, ASTHO: We’re trying to figure out what that means for COVID, but not knowing how much it will cost, when it’s going to be on the private market, those details matter in our systems to being able to respond to this.
So unfortunately, states tend to have a very limited window to be able to ask for funds or to change the way the programs are set up, and that’s right now during the legislative session and so not knowing how much is this going to cost, when is this exactly, when are we going to run out, what is it going to look like for the fall, is going to make planning for this harder. And under the public health emergency, we didn’t have to worry about that because we got free vaccine from the federal government and then we could just roll it out. But if we have to switch to the private marketplace, we really have to switch our purchasing, our distribution, and that takes a long time, from a state perspective. That takes like a year or sometimes more. And so, what does that look like from the fall? I think that it’s– the lead time and path that it takes a public entity to pivot is really, really hard and it’s because we are using public dollars and we owe it to the public to be very clear and transparent where those are spent, but the legislation decides how that’s spent.
But I can’t even tell the legislature right now who’s meeting what I might need for the fall because it’s unclear what that’s going to look like in the marketplace. So those are those are the things that keep me up at night. It’s like, I don’t know how to plan for our system now, because I’m not sure what the private sector is going to look like come the fall, because we know that the public health emergency is changing but what the private market is going to do is still unclear still.
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[18;22] ANNE ZINK, ASTHO: I think that this public health emergency, COVID, has just really highlighted the need for really good public health response, rapid public health response, and really good increased surveillance of what is happening for the population health.
And I’m hopeful that we can build that into our normal health care systems so that we don’t have to rely so much on all of these changes that happen during the public health emergency, so our next challenge, we’ve got systems built to be able to respond, rather than having to all these exceptions that we had to do during this last public health emergency.
The U.S. Government has purchased PAXLOVID from Pfizer and it is currently making it available under Emergency Use Authorization to patients at no charge.
We’ll share updates when we have them, but to date we have not set a list price for PAXLOVID in the U.S.
“Fortunately, we understand that the 564 declaration which includes the EUA pathway at FDA is remaining at least for now.
“The other change that may have an impact is changes to insurance coverage for both home tests and potentially for lab-based tests (with private insurers). This may lead to some shifting of where individuals seek testing and, in some cases, which labs offer testing.
“There was also a relaxation in some rules around CLIA certification of laboratories and which labs could perform testing. I am not clear on how many labs took advantage of the relaxation in those rules or if those labs are still being used. If there is an impact, I don’t think it would be very large.”
There are currently no planned changes to how COVID-19 mortality data are collected or reported.
Regards,
Bert Kelly
The PHE may be ending, but there is more work to do to address the challenges spurred by the pandemic. Long term care is now facing a historic labor and economic crisis, and we need meaningful, supportive solutions that will help us rebuild. We look forward to working with the Administration and Congress to develop solutions that will invest in our caregivers and protect access to care for vulnerable seniors.
The safety and wellbeing of the traveling public and employees is the top priority of U.S. airlines, and we continuously rely on science and data to guide decisions. More than 2 million people each day are choosing to fly. Science has routinely demonstrated that the air on an airplane is as clean as – if not cleaner than – restaurants, grocery stores and even some hospitals.
While the country may be entering a new phase of the fight against COVID-19, hospitals and their caregivers continue to navigate a host of weighty challenges including workforce shortages and financial pressures, cost increases for equipment and drugs, disrupted supply chains and sicker patients. These issues will require continued attention and investment from the federal government.
The decision to sunset the PHE is a testament to the progress we have made, but that progress should not end with the PHE. We should preserve many of the best care innovations that served us well during the pandemic, like expanded use of telehealth and the development of hospital at home programs. We will work with the Administration to build on the lessons learned from the COVID-19 pandemic, beginning with our strong urging that many of the COVID-19 PHE flexibilities be made permanent.
We just got corrected information from our partners - the person who died was a Snohomish County resident, not King County, an adult male. The person tested positive for Pseudomonas aeruginosa, and had used artificial tears, but public health investigators have not confirmed that he used the EzriCare drops. Because of privacy laws, we can’t share more details about the case.
Roberto Bonaccorso
12:48:00 PM TOM VILSACK, USDA: As I outlined, the four critical areas: on milk, essentially providing options for consideration in terms of access to no fat, unflavored, and flavored milk, and low fat flavored milk. On sodium, gradual reduction in both breakfast and lunch offerings phased in over a period of time, using small reductions, multiple times, which is consistent with the FDA’s guidelines and guidance.
On sugar, for the first time, focusing on a standard on added sugars. Phasing in that approach as well. Importantly, building on what already exists in the marketplace, products that are currently being used in our child and adult care food programs, so that we can encourage participation in this.
Whole grains, basically prioritizing and continuing to prioritize whole grains, with some flexibility as well for nonwhite grain options. Obviously, we’ll continue to promote fruits and vegetables in nutrition– nutritious eating.
Also in this rule is that is a acknowledgment of the important role of developing a greater connection between local and regional providers and the schools that they can potentially serve. We have a local and regional food purchasing agreement system in place, 77 agreements across the country, where we are trying to work out ways in which we can encourage more local and regional suppliers. We think that’s an important consideration and certainly something that we’re going to continue to look at ways that– where we can be supportive.
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12:56:01 PM STACY DEAN, USDA: With respect to the added sugars, as of starting in school year 25-26, we have a phase in here. So phase one is we’re proposing to setting product specific added sugar limits in foods, the foods that we know to be the leading sources of added sugar, and that would include grain based desserts, breakfast cereals, yogurt, flavored milk.
These are also food items where we know there are a lot there’s a lot of choice with respect to the product and added sugar. And the standards that we’re putting forward are similar or akin to what we’ve already done in the child and adult care feeding program where they’ve been able to adapt. So we know there’s a lot of ability to move there.
Then another two years later, in school year 27-28, the rule proposes to limit added sugars to school meals to be no more than 10% of the calories per week on average. School lunch is pretty close to that right now. So just want to offer a minor correction to what you said, is that we think that’s around 11%. School breakfast is a little higher. And so that’s where we’ll probably see most of the change.
And this is just one of the areas we got overwhelming input from pediatricians and public health professionals out of concern that there’s just too much sugar in kids diets. And of course, it’s one of the big changes off of the last dietary guidelines.
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12:57:26 PM TOM VILSACK, USDA: An important point that I want to emphasize, as Stacy just mentioned, is it’s not as if the people who work for the Food and Nutrition Service at USDA are in a room and are sort of concocting these standards based on what they individually think might work.
This is really based on what the experts, the people that understand nutrition, understand diet, understand the correlation between what we eat and some of the challenges that many of us face in terms of of weight-related chronic diseases and so forth, these experts have come up with a set of dietary guidelines and recommendations relative to the meals that our youngsters should have. And based on that information, and then basically looking at ways in which those recommendations can be phased in in a way that is acceptable, is how we come up with these standards. And I think it’s important for people to understand the foundation of these standards is what the experts in this particular field say it ought to be.
And then number two, I want to really, really enforce the notion that this is, in some cases, not necessarily new product development. These products already exist in market. They’re already being made available to consumers, and they’re already being utilized in some of our nutrition programs.
To the extent that it does require potential reformulation, we’re sensitive to that, which is why the second component of the Healthy Meals Initiative, we launched the first, and announced the first component today with the grants to small schools and so forth. The second component is basically providing resources for those who say give us some resources so we can work on reformulation. So we are trying to respond to the need for additional resources in that space.
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1:01:18 PM TOM VILSACK, USDA: Let’s back up and just basically remind folks that these don’t start until after we get comments under the proposed rule that is being announced today, make whatever changes or modifications may result as a result of those– that input, and then they don’t go into effect until the beginning of the 24-25 school year. So we’re talking about a bit of a distance here before we even begin this process.
And when we begin it, we don’t necessarily begin and require compliance with every standard on that during that school year. So in terms of product availability, the expectation is and will be, that over a period of time products will continue to be available, products will expand in terms of their availability, and new products will be developed. So that’s number one.
Number two, the reason why we have the grant program is to give those small schools and rural schools, who believe that they may be faced with a problem or today are faced with a problem, a little breathing room to be able to to deal with being able to access or additional costs that may be associated.
In addition to the resources that we’re making available, I just want to remind folks that there are a tremendous amount of unspent dollars that were provided to states and their educational accounts as a result of the pandemic that are unspent. And the Department of Education has given permission for those unspent state dollars to be utilized by school nutrition officials for the purpose of continuing to improve school nutrition. So if it’s cost, that’s an issue, I would strongly encourage the school districts that are concerned to make sure that they’re checking on the availability of those resources because they may find that they’re leaving money on the table here.
That’s number three, is the Healthy Meals initiative, which I mentioned earlier, which is the Department of Agriculture basically providing tens of millions of dollars on the table to say, hey, if you need additional resources to reformulate to come up with new products, we want to be a partner with you. We want to help. So there are multiple ways in which we think we can be of assistance.
We have also pointed out that that as issues arise, the Department of Agriculture has been willing to work as a as a good partner, a solid partner in the utilization of resources that we have to be able to purchase certain items through the Commodity Credit Corporation. We’ve done $2 billion of purchases during the recent last couple of years to assist school districts. So there are a lot of options here.
But I think we want to make sure that we that folks recognize this doesn’t go into effect tomorrow. It doesn’t go into effect this year. It’s going to be a while before it goes into effect, and then it’s going to be several years before the full impact of it goes into effect.
And, you know, frankly, there will be some folks, I suspect, who will say, gosh, you need to accelerate this. All right? And so the way I’ve explained it to many people is, well, it’s like Goldilocks. Some people are going to say it’s too hot. Some people are going to say it’s too cold. And the challenge is to make sure that we’re complying with dietary guidelines and the science, and at the same time trying to be helpful on the real world implications of all this.
But at the end of the day, it’s about 15.3 million kids eating school breakfast that needs to be nutritious and 29.6 million children do have to have a decent lunch. And the fact is that we are faced with some serious issues from health care, national security, economic competitiveness, educational achievement and equity that need to be addressed.
DR MYSHEIKA ROBERTS, COLUMBUS PUBLIC HEALTH [00:54:05]
So as I told you, a lot of our cases were on the younger side. So you see here the age breakdown of our cases, as well as the sex and gender breakdown. A little more than half were male, but 72% of our cases were under the age of two. But what’s most notable is 71% of our cases were age eligible– were age eligible for the vaccine, yet they had not been vaccinated.
And that takes me to the next slide, where you will see that the vaccination rates, to no surprise to many of you, that the majority of our cases were unvaccinated or had received one dose. In one case, we have yet to be able to confirm the vaccine status. So that basically means that the parents said I think my child was vaccinated, at least got one dose maybe, but we haven’t been able to verify that through the vaccine registry in the state of Ohio or any medical records.
So 94% of our cases were unvaccinated, and that’s pretty concerning.
I mentioned earlier about the hospitalization, and I also want to tell you that about 52% of our cases, even though the hospitalization rate was 43%, 52% of our cases had some complications from measles. So that would include otitis media, diarrhea or pneumonia.
…
DR MYSHEIKA ROBERTS, COLUMBUS PUBLIC HEALTH [00:56:53]
So this just shows you the rash onset date. And the good news, as we stand right now, there have been no confirmed cases with a rash onset onset date since Christmas Eve. So December 24th was the last noted rash onset. So that’s really good news. And I’ll take the next slide.
Again, just reiterating that the last rash onset date was December 24th. So as of today, and this slide was made a few days ago, as of today, we are 40 days since the last rash onset and we need to go two incubation periods for measles, which is 21 days, we need to do that twice before we can say that this community wide outbreak is over.
So that if that stands true, February 4th, which is Saturday, if we get to the end of Saturday and have no more cases, we have gone two incubation periods and we can say that this outbreak is over, per CDC guidelines of meeting the end of an outbreak. So we’re holding tight and hoping that that stands true.
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DR MYSHEIKA ROBERTS, COLUMBUS PUBLIC HEALTH [01:01:31]
If you recall, when this first case was reported to us in November that was community acquired, we were also nationally, as well as right here in Columbus, having a significant RSV increase or outbreak. And so some of our initial cases, we believe, were misclassified. So we were able to go back.
Many of our pediatricians or providers had never seen measles. I myself have never seen measles, except for in a textbook. And so a lot of education to providers as well as what to look for and to raise the red flag that this is now happening in our community, and we need to be more critical about who, what we’re doing, and what we’re seeing.
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DR MYSHEIKA ROBERTS, COLUMBUS PUBLIC HEALTH [01:03:32]
So we have the second largest Somali population here in central Ohio, second to Minneapolis. And we know, we’ve had experience with that community, that they are very reluctant about the MMR vaccine because of misinformation that they have been given. So that’s why you saw one of our flyers, we did go to an Islamic temple to provide some education. And we have been working with the imams and trying to make sure that we get the correct information to this community.
We also have a group of anti-vaxxers. I believe strongly this has nothing to do with COVID 19. There’s a lot of question and concern that, did we see an increase of unvaccinated individuals with MMR because of the pandemic and people not being able to get in to get vaccinated?
I really don’t think that the pandemic had anything to do with our vaccine coverage or low vaccine coverage for MMR. I really think it was the thought and beliefs of certain populations, pre-pandemic, that continued on to the post pandemic phase.
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DR MYSHEIKA ROBERTS, COLUMBUS PUBLIC HEALTH [01:04:45]
Sure, absolutely. We have been and I– ICS since the beginning of this– since the beginning of this outbreak, and the last reported number is we’ve spent about $250,000 on response.
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DR MYSHEIKA ROBERTS, COLUMBUS PUBLIC HEALTH [01:05:37]
What we were able to identify, particularly with the help of the epi-aid team, is that the majority of our cases were concentrated in one geographic region of our community. And others who were– became cases were exposed, usually in a health care setting or in a child care setting. So we did have some individuals who did not live in that geographic region who became cases because they were exposed in a health care setting.
So working with our state health department and with the CDC, we were trying to be as strategic as possible to not say that everyone in our community should get their second dose early or even get their first dose early. But really trying to concentrate it into that geographic region of our community.
And so, again, we worked with health care providers in that part of town to really try to educate them. But we did finally make a decision probably in early December that, if a parent came in and wanted to get their child, their 11 month old vaccinated, they could get it done early. Or if they wanted to get their child vaccinated with a second dose after they’d already received a first dose, they could.
But per CDC guidance, that was an additional dose that would not count as the first dose. It would count as a pre-dose, so to speak. And so they would still need another dose. When they became one years of age, they would still need a second dose between 4 to 6 years of age. So we had to explain that to not only the providers but also the parents.
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DR MYSHEIKA ROBERTS, COLUMBUS PUBLIC HEALTH [01:09:16]
I remember and I can’t remember what year it was, but a few years ago when Minneapolis had a significant measles outbreak and we were bracing ourselves here and providing education, and the anti-vaxxers were, as the same time we were providing education to the Somali community, the anti-vaxxers were providing their information to the Somali community.
In protecting public health, it is not uncommon for more vaccine doses to be made available than are ultimately used before reaching their expiration date. This is the case during the COVID-19 pandemic, which by its nature, has been unpredictable. Novavax’ COVID-19 vaccine, adjuvanted has a 9-month shelf life at the time of manufacture, which is comparable to other COVID-19 vaccines.
We are in active conversations with the government to ensure continuity of access to our vaccine. In the meantime, as with all vaccines, doses already in market are available for administration until the date of expiry. To find locations where the Novavax vaccine is currently available, visit vaccines.gov.
Novavax’ protein-based COVID-19 vaccine is an important part of the public health strategy to provide a diverse vaccine portfolio. We are committed to continuing to deliver our vaccine and collaborating with local, regional and global officials to ensure vaccines are available when and where they’re needed.
ASHISH JHA, WHITE HOUSE [00:12:06]
The public health emergency created a whole bunch of, we sort of talk about as flexibilities, another way of saying waivers, regulation, sub regulations, a bunch of things.
And I’ll give you an example. For instance, under normal circumstances, if a hospital says we’re going to go set up beds in our parking lot and take care of Medicare patients, usually Medicare doesn’t look super favorably on that. Right? And they’re like, okay, you really got to justify what you’re doing here. But in April of 2020, if you did that, or May of 2020, you did that, we wanted that to be super easy for people, because you were doing in the middle of a crisis. You needed to be able to set up those beds in a parking lot. And so that was a flexibility that Medicare gave hospitals.
The question is, do we want to give that flexibility forever? So like in 2025, a hospital says we’re going to set up some beds in the parking lot, maybe not. There is a time when you want to say, okay, that flexibility needs to go away if you want to set up beds in a parking lot, you’ve got to come back and justify it a little bit more than you did in the middle of the of the worst days of the pandemic.
So there are a whole lot of these, and there are literally dozens and dozens of rules on paperwork to what kinds of how doctors and nurses can cross state lines, so those things we– again, the feeling inside this administration was like, those are not things we need to continue forever. There were some flexibilities that turned out to be great like a lot of the telemedicine stuff, and nobody has any interest in going back to 2019 and undoing those.
So the idea was, we want to keep some of these things, and some of these things, we want to go back to normal ways of functioning. So the public health emergency had to end. But we wanted to make sure that some of the stuff got preserved.
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ASHISH JHA, WHITE HOUSE [00:20:24]
Now, Congress hasn’t funded COVID for over a year. You’ve heard me complain about that. It has made our job much, much harder. It means that we’re going to stock out at some point. That we’re going to run out of of vaccines and treatments and we have to move towards a more kind of regular way of delivering vaccines and treatments.
And when is that going to happen? And that is going to depend on our stocks, it’s working with all the payers and providers. All I can say, because I literally don’t know, we don’t have the specific dates, is that it’s going to happen sometime over the summer into early fall. And you’ll see that transition and we’ll kind of give people as much notice as we can possibly give.
What happens then? So let’s say it’s November of 23. By that time, both vaccines and treatments should be in the kind of regular health care market. Remember the Affordable Care Act, preventive services are free, vaccines are preventive services. Anybody with insurance, public or private, is going to get vaccines for free.
I can come back and talk about the uninsured in a second.
Treatments are going to go through like the way people get them, the way they get other medicines. We’re really committed. I’m personally super committed, to making sure that there are relatively low– as low as possible out-of-pocket costs for consumers. I think that’s really, really important. And we’re going to do a bunch of things to try to really limit those costs for consumers. I think that’s important.
And then we are creating a whole separate set of efforts for the uninsured, because the uninsured, of course, will not be able to get vaccines for free and treatments for free under the regular insurance system, by definition. Right? They’re uninsured. And so we’re we’re working on a plan on that.
But none of that needs to be implemented like next month, because first the PHE doesn’t until May. But even after that, this stuff will be available for the uninsured and for everybody else for a while. So at some point over the summer into fall, you’ll see that transition.
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ASHISH JHA, WHITE HOUSE [00:22:15]
Let’s talk about testing, because it’s a bit more complicated. Obviously, there are free at home tests that we’ve been sending out through the USPS. We had a rule that through the public health emergency, everybody could go buy a test per person per month. That does come to an end with a public health emergency.
And I will tell you that it is my hope that every insurance company will continue to cover COVID tests. Beyond that, we can’t compel them. We could compel them during a public health emergency, but we can’t compel them. But these are relatively small costs. I think it’s really important for people to be able to access COVID tests. So there’s a lot of work going there.
But my very strong hope, it’s the right thing to do, that insurance companies will just continue covering it. And so people will continue to have access. But there’s a lot of work to be done to to make sure that happens.
QUESTION [00:23:05]
It sounds like (crosstalk) no, I actually just– your ability to use sort of the bully pulpit you mentioned, we want the cost to the consumer of Paxlovid, for example, not to all of a sudden get jacked up to something that’s unaffordable. And sort of a similar thing about the testing, after the PHE ends. What levers do you have other than just that, you’re a very persuasive guy, but what what levers do you have to make Aetna do something or to make Pfizer do something?
ASHISH JHA, WHITE HOUSE [00:23:34]
You don’t think my charm alone will do it?
QUESTION [00:23:36]
I think it’d probably gets you 80% of the way there.
ASHISH JHA, WHITE HOUSE [00:23:40]
Look, we’re we’re really exploring a lot of that. Like, there is obviously, there are kind of generally levers. But I think like PHE for testing was very clear. We could– we could just put in a rule and people would just do that.
So this is one where it’s going to be working with insurance companies, working with payers, providers, reminding people that for the last two years the U.S. government has paid for all of this with taxpayer money. And that has been a boon for insurance companies that haven’t had to pay for any of this stuff. And it’s also about talking to the manufacturers about prices. So there’s just a lot of work ahead.
But let me just be very clear that we’re very committed to making sure that, when it comes to for consumers, the costs are low. And that is the goal, that is the value. And there’s a lot of work we’re going to do to try to make that happen.
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ASHISH JHA, WHITE HOUSE [00:35:52]
We need better therapeutics that are more long lasting. Like the monoclonal antibodies have been amazing, but they keep running out every few months, because the virus changes. The science behind monoclonal antibodies that really target more conserved regions of the virus, that are going to give you kind of longer term play, is getting better and better, and we think that needs to develop. And then the two types of vaccines, both mucosal and pan-sarbecovirus vaccines, are really important areas of investment.
Frustrating that Congress did not come through on that. We have been talking internally, the president is very committed to moving this agenda forward. So we are now looking at across the administration saying, where do we have resources, what can we pull together?
We have got to do this. I just feel like it’s unacceptable for us not to get moving on this, but it is just made dramatically harder by the fact that Congress continues to not fund it.
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ASHISH JHA, WHITE HOUSE [00:42:52]
So I can talk a little bit about what we do here at the White House. We’ve lean pretty heavily in on testing. I end up getting tested, maybe not every day, but majority of the days. Kind of simple rapid antigen tests. I have to get a test before I see any of the principals, the president, the vice president, first lady and gentlemen.
We have done– we’ve had a lot of large gatherings, a lot of celebrations, a lot of events at the White House over the holidays in January. Everybody gets a test before those large gatherings, so they can be pretty packed. And we have done pretty careful tracking, have not seen outbreaks come out of those large gatherings.
And so I have become really convinced. I was pretty convinced beforehand, but feel even more confident, that testing before large gatherings are very powerful way of making sure that you don’t get big superspreader events. Not perfect, but very, very good.
So that sort of– kind of– and so my testing regime is a little bit odd by the fact that we just do a lot of testing here. And I think it’s great, by the way, that like– I think testing should be widely available and certainly right now, like people can still go out and get eight tests per person per month. And as I said, so testing availability is and continues to be an important thing.
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ASHISH JHA, WHITE HOUSE [00:44:12]
On a personal level, what do I do? Do I dine? I do indoor dining. I’ve gone out to dinner with my wife on weekends and kids. I travel back and forth to Boston every weekend and I will put on a mask when I get to the airport, certainly as I’m boarding and on the airplane. And that’s just because the jetways are pretty packed. There’s a lot of people getting on and off. And people, you know it’s interesting, because people ask, I get people who don’t want to wear a mask. And I’m like, this– I have not gotten COVID so far. I didn’t get the flu this winter. I feel very lucky. And maybe some of the stuff I’m doing is helping.
I did end up getting a cold earlier. Yeah, I was kind of miserable for a few days. I feel like if I can avoid respiratory infections, I’m happy to avoid them. And if I have to, like if I put on a mask traveling, it just does not feel like a particular burden to me. So I do that.
But I feel like I live my life pretty close to normal to where I was in 2019, with some modest modifications.
Global Pharma is fully cooperating with US Federal authorities, and is continuing to investigate this matter, but thus far we have not determined whether our manufacturing facility is the source of the contamination. Nevertheless, out of an abundance of caution, we are recalling the products at issue
| Date | Cumulative | Increase | % Change |
|---|---|---|---|
| 29-Jan-23 | 7,819,232 | 211,302 | 80% |
| 22-Jan-23 | 7,607,930 | 117,419 | -34% |
| 15-Jan-23 | 7,490,511 | 178,547 | -18% |
| 8-Jan-23 | 7,311,964 | 217,363 | -12% |
| 1-Jan-23 | 7,094,601 | 246,039 | 4% |
| 25-Dec-22 | 6,848,562 | 236,255 | |
| 18-Dec-22 | 6,612,307 |
Eye drops were obtained through Amazon and Walmart; some patients received eye drops while inpatient or during outpatient care visits.
CDC is now aware that at least 5 of the 11 patients with eye infection had vision loss.
Martha Sharan
NICOLE NEMETH, UNIVERSITY OF GEORGIA [00:21:05]
The last kind of interesting scenario I wanted to show you is these black vultures, which more– so more in the eastern U.S. but black vultures had been dying in the hundreds and thousands probably.
And they– something interesting happened with them, because they were probably consuming dead waterfowl at the beginning, but they’re in these roosts with hundreds of birds, and once the vultures themselves started getting it from waterfowl consumption, they started dying and eating each other, because they’re not very discriminatory in that regard.
And they just maintained this cycle that perpetuated, without really any outside influence or force, or virus introduction into these roosts or these groups of vultures.
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NICOLE NEMETH, UNIVERSITY OF GEORGIA [00:22:25]
I just wanted to mention Florida Wildlife Commission’s efforts. And they have tried to remove carcasses. It became logistically unfeasible, because there were so many. They also educated people, put a lot of messaging out, limit access to these affected areas. They cordoned off areas, as you can see in the top picture. They warned people not to handle live or dead birds.
The human aspect was really difficult there, because people wanted to help these sick birds, so they wanted to pick them, bring them into their houses. So that was tough. And they had to say, please don’t, let nature to take their course so to speak. And they asked rehabilitators to euthanize upon arrival any suspects. So they came to conclusion that really information sharing is key. The lower picture is an incinerator, right on site, trying to keep up with the carcasses.
But suffice to say, so many efforts have gone in to try to figure out what we can do about managing it in the environment. And that is very difficult, if not impossible.
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NICOLE NEMETH, UNIVERSITY OF GEORGIA [00:49:43]
One thing I would suggest is in order to know, you know, if there are where these birds are dying off and if it’s due to high path, you know, I would probably if you’re going to be out more remote or quiet environment the time, contact your state wildlife agency possibly to get that information. And I mean–
On a practical standpoint, I know this kind of goes without saying, but if I was in an area where I saw multiple birds, dead and dying, I probably myself would avoid contact with the water where you’re submerging yourself and it’s in contact with your mucous membranes.
But in general, I would tell you, the avian influenza experts I have talked to have said, pretty emphatically, that water doesn’t as much– the environmental kind of exposure route doesn’t pose as much as a risk to humans as it is more a risk to poultry or wild birds, who may be in contact with water. And that may be a matter of kind of duration and extent of contact.
WALTER KOROSHETZ, NINDS [00:31:20]
I want to talk a little bit about a problem that occurred at the neuroscience research center. As those who may know, it’s fantastic institute here on the NIH campus, home for 85 laboratories, 800 scientists, all in this– in these buildings that cross-collaboration. But just before Christmas, we had two catastrophic floods.
These are just some of the horrible pictures, the water came pouring down from the really the roof of the building and top areas of the building and flooded all the laboratories below, causing really catastrophic damage to supplies, equipment. The labs that were badly affected are still not open.
A lot of work going on in terms of remediation of the flood damage and then developing a sense of the equipment and supply damages that NINDS will have to reimburse. 18 of the labs that were damaged were NINDS labs.
KENA SWANSON, PFIZER [03:51:14]
Though evaluation of the primary series is ongoing, today I am pleased to share initial data in children younger than five years of age for the booster dose. Shown here is the design for the booster study that includes BNT162b2 experienced children, six months to less than five years of age, who received the three dose primary series of the original vaccine at the three microgram dose level. Safety and immunogenicity has been assessed in a subset of 60 participants, where the bivalent booster was administered a median of approximately six and a half months following dose three of BNT162b2. The booster dose was administered in the fall of 2022.
A descriptive analysis was performed assessing responses following the bivalent fourth dose booster compared to a control group that received three doses of the original vaccine. Here, the bivalent vaccine group is shown on the left in purple and the original vaccine on the right and blue. Vaccine groups were matched by age, baseline infection status, and interval from prior vaccine dose. In participants six months to less than five years of age, the Omicron BA.4/5 responses were substantially higher in the bivalent vaccine group after the fourth dose compared to the control original vaccine group after the third dose, with a GMT of 1,700 versus 600.
Now shown for the whole group and divided by age subgroups, responses were similar for children six months to under two years and children two to less than five years of age. These data provide further support and assurance of the improved immune responses with the bivalent vaccine for all ages. Evaluation of the bivalent BA.4/5 vaccine as a primary series is ongoing within this pediatric study, in children six months to five years of age, and results are anticipated in the coming months.