Tag Archives: covid vaccine

The Differences Between the Vaccines Matter

Hilda Bastian, The Atlantic: March 7, 2021


Public-health officials are enthusiastic about the new, single-shot COVID-19 vaccine from Johnson & Johnson, despite its having a somewhat lower efficacy at preventing symptomatic illness than other available options. Although clinical-trial data peg that rate at 72 percent in the United States, compared with 94 and 95 percent for the Moderna and Pfizer-BioNTech vaccines, many experts say we shouldn’t fixate on those numbers. Much more germane, they say, is the fact that the Johnson & Johnson shot, like the other two, is essentially perfect when it comes to preventing the gravest outcomes. “I’m super-pumped about this,” Virginia’s vaccine coordinator told The New York Times last weekend. “A hundred percent efficacy against deaths and hospitalizations? That’s all I need to hear.”

The same glowing message—that the COVID-19 vaccines are all equivalent, at least where it really counts—has been getting public-health officials and pundits super-pumped for weeks now. Its potential value for promoting vaccination couldn’t be more clear: We’ll all be better off, and this nightmare will be over sooner, if people know that the best vaccine of all is whichever one they can get the soonest. With that in mind, Vox has urged its readers to attend to “the most important vaccine statistic”—the fact that “there have been zero cases of hospitalization or death in clinical trials for all of these vaccines.” The physician and CNN medical analyst Leana Wen also made a point of noting that “all of the vaccines are essentially a hundred percent” in this regard. And half a dozen former members of President Joe Biden’s COVID-19 Advisory Board wrote in USA Today, “Varying ‘effectiveness’ rates miss the most important point: The vaccines were all 100% effective in the vaccine trials in stopping hospitalizations and death.”

There’s a problem here. It’s certainly true that all three of the FDA-authorized vaccines are very good—amazing, even—at protecting people’s health. No one should refrain from seeking vaccination on the theory that any might be second-rate. But it’s also true that the COVID-19 vaccines aren’t all the same: Some are more effective than others at preventing illness, for example; some cause fewer adverse reactions; some are more convenient; some were made using more familiar methods and technologies. As for the claim that the vaccines have proved perfectly and equally effective at preventing hospitalization and death? It’s just not right.

[….]

The data were indeed suggestive of an encouraging idea. Based on the numbers so far, we can expect the vaccines to provide extremely high levels of protection against the most dire outcomes. Still, we don’t know how high—and it’s clear they won’t uniformly cause hospitalizations and deaths from COVID-19 to disappear in vaccinated people.

The experts understand this, of course. Gandhi has been updating her table as more data come in, and now pegs Moderna’s efficacy on that front at 97 percent; Jha has since tweeted that “nothing is 100 percent … But these vaccines sure are close”; and Topol told The Atlantic that the numbers in his tweet are not a sufficient basis from which to draw “any determination of magnitude of effect,” though the fact that they all point in the same direction is “very encouraging.” Still, the message of perfection that their initial tables and tweets spawned—the gist, for many readers, of all those 100s and zeros—has since been picked up far and wide, and misinterpreted along the way.

For the AstraZeneca vaccine, one person in the control group had severe COVID-19, but eight people were hospitalized; for Johnson & Johnson, 34 people in the placebo group had severe COVID-19, but only five people were hospitalized. It’s true that zero vaccinated people were hospitalized in either study after the vaccines took effect. But with numbers that small, you can’t draw a reliable conclusion about how high efficacy may be for these outcomes. As Diana Zuckerman of the National Center for Health Research pointed out about the Johnson & Johnson trial, “It’s misleading to tell the public that nobody who was vaccinated was hospitalized unless you also tell them that only 5 people in the placebo group were hospitalized.” She’s right. And you can’t be confident about predicting effectiveness precisely in a wider population outside the trial, either. For example, some of the vaccine trials included relatively few people older than 60 as participants.

You can see how fragile these numbers are by looking at those compiled for severe disease. In the Pfizer trial, for example, just one vaccinated person developed severe COVID-19 versus three in the placebo group—which meant that a single bout of disease made the difference between a calculated efficacy rate of 66 percent and one of 100 percent. For the Novavax and Oxford-AstraZeneca trials, there were zero people with severe disease in the vaccinated group versus only one in the control group, so adding or subtracting one would have been even more dramatic. The problem is even greater for deaths. For that efficacy analysis, only two of the vaccine trials—for Moderna’s and Johnson & Johnson’s—reported any COVID-19 deaths at all in the control groups.

It’s also important to remember that these are early results: Some people who enrolled very late in the trials aren’t yet included in reported data, and analysis is still under way. Indeed, the FDA pointed out in December that one vaccinated person in the Moderna trial had been hospitalized with apparently severe COVID-19 two months after receiving a second dose. That person was in a group still awaiting final assessment by the researchers, and was not mentioned in Moderna’s formal readout of results.

[….]

 

“The idea that people can’t handle nuance,” Jha tweeted at the end of February, “it’s paternalistic. And untrue.” I couldn’t agree more. The principle of treating people like adults is fundamental. We don’t need to exaggerate. Talking about the trade-offs between different medicines and vaccines is often complicated, but we do it all the time—and we can do it with COVID-19 vaccines too.

To read the entire article, click here

J&J COVID-19 Vaccine Wins Unanimous Backing of FDA Panel

Kerry Dooley Young, Medscape Medical News: February 26, 2021


An FDA advisory panel lent their support today to a rapid clearance for Janssen/Johnson & Johnson’s COVID-19 vaccine.

The Food and Drug Administration (FDA) is expected to quickly provide an emergency use authorization (EUA) for the vaccine following the recommendation by the panel.

The FDA’s Vaccines and Related Biological Products Advisory Committee voted 22-0 on this question: Based on the totality of scientific evidence available, do the benefits of the Johnson & Johnson COVID-19 Vaccine outweigh its risks for use in individuals 18 years of age and older?

The Johnson & Johnson vaccine is expected to offer more convenient dosing and be easier to distribute than the two rival products already available in the United States. Janssen’s vaccine is intended to be given in a single dose. In December, the FDA granted EUAs for the Pfizer/BioNTech and Moderna COVID-19 vaccines, which are each two-dose regimens.

[….]

Weakened Standards?

Several researchers called on the FDA to maintain a critical attitude when assessing Johnson & Johnson’s application for the EUA, warning of a potential for a permanent erosion of agency rules due to hasty action on COVID vaccines.

They raised concerns about the FDA demanding too little in terms of follow-up studies on COVID vaccines and with persisting murkiness resulting in attempts to determine how well these treatments work beyond the initial study period.

“I worry about FDA lowering its approval standards,” said Peter Doshi, PhD, from The BMJ and a faculty member at the University of Maryland School of Medicine in Baltimore, during an open public hearing at the meeting.

“There’s a real urgency to stand back right now and look at the forest here, as well as the trees, and I urge the committee to consider the effects FDA decisions may have on the entire regulatory approval process,” Doshi said.

Doshi asked why Johnson & Johnson did not seek a standard full approval — a biologics license application (BLA) — instead of aiming for the lower bar of an EUA. The FDA already has allowed wide distribution of the Pfizer/BioNTech and Moderna vaccines through EUAs. That removes the sense of urgency that FDA faced last year in his view.

The FDA’s June 2020 guidance on the development of COVID vaccines had asked drug makers to plan on following participants in COVID vaccine trials for “ideally at least one to two years.” Yet people who got placebo in Moderna and Pfizer trials already are being vaccinated, Doshi said. And Johnson & Johnson said in its presentation to the FDA that if the Ad26.COV2.S vaccine were granted an EUA, the COV3001 study design would be amended to “facilitate cross-over of placebo participants in all participating countries to receive one dose of active study vaccine as fast as operationally feasible.”

“I’m nervous about the prospect of there never being a COVID vaccine that meets the FDA’s approval standard” for a BLA instead of the more limited EUA, Doshi said.

Diana Zuckerman, PhD, president of the nonprofit National Center for Health Research, noted that the FDA’s subsequent guidance tailored for EUAs for COVID vaccines “drastically shortened” the follow-up time to a median of 2 months. Zuckerman said that a crossover design would be “a reasonable compromise, but only if the placebo group has at least 6 months of data.” Zuckerman opened her remarks in the open public hearing by saying she had inherited Johnson & Johnson stock, so was speaking at the meeting against her own financial interest.

“As soon as a vaccine is authorized, we start losing the placebo group. If FDA lets that happen, that’s a huge loss for public health and a huge loss of information about how we can all stay safe,” Zuckerman said.

Read the entire article here. 

Congressman calls for FDA to continue vaccine trials

D’Andre Henderson, ABC News: December 29, 2020.


WASHINGTON, D.C. (WRIC) — Americans are hopeful that the COVID-19 vaccines will make 2021 a better year than 2020. However, there are concerns that Pfizer and Moderna will stop their clinical trials and immediately treat everyone in their placebo group.

Some scientists, doctors and now a Congressman argues that can be dangerous because they said there is still so much unknown about the vaccines.

Rep. Llyod Doggett of Texas wrote a letter to the Food and Drug Administration (FDA) urging for the clinical trials to continue.

“the continuation of clinical trials is critical to our understanding of the efficacy and length of immunity the vaccines offer,” Doggett wrote.

In the letter, Doggett said while the initial results received from Pfizer and Moderna are showing positive results, it’s not definitive given the limited data.

[…]

“Clinical trials have suffered from a lack of diverse participant enrollment and evaluation of subpopulations,” Doggett said. “Including individuals with comorbidities, children, pregnant and breastfeeding patients, long-term care residents and individuals with diverse racial and ethnic backgrounds.”

Diana Zuckerman, President of the National Center for Health Research, a non-partisan think tank in Washington D.C., agrees that the clinical trials should continue. She said healthcare workers who volunteered for the clinical trials should have immediate access to the vaccine if they want it.

“Like most public health experts, I’ve been very concerned that Pfizer and Moderna told the FDA that they want to stop their clinical trials of the COVID vaccine and instead immediately inoculate everyone in their placebo groups,” Zuckerman said. “While I understand the desire to reward the clinical trial volunteers for their service, it would be a huge loss of information from a public health point of view. Losing the placebo group means we’d have no way to scientifically determine which of the vaccines – if any — have 95% efficacy rates that last more than 2 or 3 months. Or how long the vaccine works on people over 75.”

Zuckerman added the people who volunteer for the clinical trials shouldn’t be vaccinated before those in priority groups such as teachers, essential workers, etc.

“Since many of the study volunteers are young and healthy, it also seems unfair for them to “cut in line” for a vaccine while healthcare workers and others at high risk are still waiting their turn,” she said.

[…]

Read the full article here

Covid-19: Should vaccine trials be unblinded?

Jeanne Lenzer, BMJ: December 29, 2020.


The lack of planning for how to treat participants in covid-19 vaccine trials is a bad precedent, with the loss of potentially valuable safety and efficacy data, say research experts. Jeanne Lenzer reports:

 

In October the US Food and Drug Administration issued non-binding guidance to manufacturers of covid-19 vaccines urging them to devise a method to allow volunteers in their studies’ placebo arms to receive the vaccine while also maintaining the integrity of ongoing scientific data collection.1 Emergency use authorisation was not “grounds for stopping blinded follow-up,” said the agency.23

The companies say they have an ethical obligation to unblind volunteers so they can receive the vaccine. But some experts are concerned about a “disastrous” loss of critical information if volunteers on a trial’s placebo arm are unblinded.45

To try to tackle the problem the FDA invited Steven Goodman, associate dean of clinical and translational research at Stanford University, for a recommendation that could balance the right of volunteers to find out whether they were in the placebo arm and the simultaneous need to preserve scientific data.

Goodman recommended a study design endorsed by Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases: a blinded crossover study in which placebo recipients would be given the vaccine, and vice versa.235 That would ensure that all volunteers receive the vaccine but would be unaware of which shot they received at which time. This would allow ongoing surveillance of safety issues and more time to observe any waning effects of the vaccine and the possible need for booster doses.

But the companies said that the demands of a blinded crossover design were “onerous” and might not be feasible.6 And even before the FDA advisory committee meeting on Moderna’s vaccine on 17 December, the company notified volunteers that they could learn their status if they chose to receive the vaccine.

Pfizer also sent a letter to its trial participants one week after its vaccine was authorised on 10 December.7 It told them that, on request, they could learn whether they were in the placebo arm so they could receive the vaccine as it became available and according to recommendations of the US Centers for Disease Control and Prevention.

Asked by The BMJ whether the FDA had set any baseline requirements for the companies regarding the removal of blinding, the agency declined to answer, referring the journal to the respective companies for their plans.

Pfizer told The BMJ that the “move from the placebo group to the vaccine group would be completely optional, and participants would be encouraged to remain blinded throughout the full study duration.” Moderna failed to respond to several requests for comment.

Loss of data

Diana Zuckerman, president of the National Center for Health Research, told The BMJ that the FDA could have demanded that companies use the blinded crossover design for them to win full approval for their vaccines. She said that failure to do that meant the loss of future reliable data, which is especially concerning given that preliminary data are insufficient to determine efficacy.

“I’m especially concerned that Pfizer’s vaccine trials included only five people aged 75 and older who were diagnosed with covid-19, with an unspecified number of those defined by Pfizer as severe cases,” she said. “That makes it impossible to determine how effective the vaccine is for frail elderly patients.”

Although the FDA has granted the vaccines emergency use authorisation, to get full licence approval two years of follow-up data are needed. The data are now likely to be scanty and less reliable given that the trials are effectively being unblinded.

Consumer representative Sheldon Toubman, a lawyer and FDA advisory panel member, said that Pfizer and BioNTech had not proved that their vaccine prevents severe covid-19. “The FDA says all we can do is suggest protection from severe covid disease; we need to know that it does that,” he said.

He countered claims, based on experience with other vaccines, six weeks of follow-up was long enough to detect safety signals. Six weeks may not be long enough for this entirely new type of “untested” [mRNA] vaccine, Toubman said.

Goodman wants all companies to be held to the same standard and says they should not be allowed to make up their own rules about unblinding. He told The BMJ that, while he was “very optimistic” about the vaccines, “blowing up the trials” by allowing unblinding “will set a de facto standard for all vaccine trials to come.” And that, he said, “is dangerous.”

Footnotes

  • Correction: On 30 December we amended the final paragraph to clarify Steven Goodman’s comment.

This article is made freely available for use in accordance with BMJ’s website terms and conditions for the duration of the covid-19 pandemic or until otherwise determined by BMJ. You may use, download and print the article for any lawful, non-commercial purpose (including text and data mining) provided that all copyright notices and trade marks are retained.

https://bmj.com/coronavirus/usage

References

  1. Food and Drug Administration. Emergency use authorization for vaccines to prevent covid-19: guidance for industry. 2020. https://www.fda.gov/media/142749/download.
  2. Food and Drug Administration. Vaccines and Related Biological Products Advisory Committee meeting December 10, 2020. 2020. https://www.fda.gov/media/144245/download.
  3. Food and Drug Administration. Vaccines and Related Biological Products Advisory Committee December 17, 2020 meeting briefing document. 2020 https://www.fda.gov/media/144434/download.
  4. WHO Ad Hoc Expert Group on the Next Steps for Covid-19 Vaccine Evaluation. Placebo-controlled trials of covid-19 vaccines—why we still need them. N Engl J Med2020. doi:10.1056/NEJMp2033538.
  5. Weiland CZ. Noah. Many trial volunteers got placebo vaccines. Do they now deserve the real ones? New York Times. 2 Dec 2020. https://www.nytimes.com/2020/12/02/health/covid-vaccine-placebo-group.html.
  6. Karlin-Smith S. Covid-19 vaccine sponsors want US FDA to find alternatives for control-arm data after first EUA. Pink Sheet. 2020. https://pink.pharmaintelligence.informa.com/PS143143/COVID-19-Vaccine-Sponsors-Want-US-FDA-To-Find-Alternatives-For-Control-Arm-Data-After-First-EUA.
  7. Tanne JHCovid-19: FDA panel votes to approve Pfizer BioNTech vaccine. BMJ2020;371:m4799.  doi:10.1136/bmj.m4799 pmid:33310748 FREE Full TextGoogle Scholar 

Read the full article here

NCHR Statement by Dr. Diana Zuckerman at FDA Covid Vaccine Advisory Committee

October 22, 2020


I’m Dr. Diana Zuckerman, president of the National Center for Health Research. Our center scrutinizes the safety and effectiveness of medical products, and we don’t accept funding from companies that make those products, although I’ve personally inherited stock in Johnson & Johnson. My expertise is based on post-doc training in epidemiology and as a faculty member and researcher at Vassar, Yale, at Harvard. I’ve also worked at HHS, the U.S. Congress and White House.

We’ve heard today that the agencies are doing many things right, but the vaccine trials have serious design flaws. The standards set in FDA guidances and the study protocols make it likely that vaccines that will be authorized or approved won’t achieve what the public and policy makers expect. Instead, these vaccines will only be proven to reduce the risk of mild infections but not proven to reduce the risk of hospitalization, ICU use, or deaths.

The major flaws are as follows:

  • The FDA’s proposed primary endpoint is defined as symptomatic Covid-19 that can include only 1 very mild symptom, such as a mild cough or sore throat – as long as the person has tested positive.
  • FDA’s requirement of at least 2 months median follow-up after vaccination or placebo is too short to study efficacy.  Even if a person is exposed during that time, we don’t know the correlates of protection and so we need a longer follow-up to know how long an effective vaccine remains effective.  We can’t rely on post-market studies for that information, because once a vaccine is on the market, many people in the placebo control group will switch to a vaccine.
  • We don’t know whether diversity of study participants will be achieved in terms of age, race, or co-morbidities, especially for people who are exposed to the virus.
  • The requirement of at least 5 serious Covid-19 cases in the placebo group is completely inadequate for 2 reasons:
    • Serious Covid-19 cases are too loosely defined, and could include a case of mild Covid-19 if the patient has a blood oxygen saturation under 93%. But thousands of otherwise healthy Americans have levels below that.
  • Even if the definition were more stringent, such as requiring hospitalization or death, and even if there were no such cases among the vaccinated patients, the absolute difference in disease between 0 and 5 serious cases would not be clinically meaningful to individuals and could easily have occurred by chance.

The American public has been told for months that life can go back to normal when we have a vaccine.  It isn’t FDA’s job to achieve that overly optimistic goal for any vaccine, but it is FDA’s job to make sure that a vaccine has meaningful benefits for the health and lives of most Americans, and especially those most at risk.

Dr. Diana Zuckerman’s Testimony on Moderna’s COVID Vaccine Before the FDA Advisory Committee

December 17, 2020.


I’m Dr. Diana Zuckerman, president of the National Center for Health Research.  Thank you for the opportunity to speak today.

Our center scrutinizes the safety and effectiveness of medical products, and we don’t accept funding from companies that make those products. My expertise is based on post-doc training in epidemiology and as a previous faculty member and researcher at Vassar, Yale, and Harvard, and a fellow in bioethics at University of Pennsylvania.  I’ve also worked at HHS, the U.S. Congress and the White House.

Today I will focus on 3 major concerns:

#1:  The 2 month median follow-up is too short, so Moderna’s proposal to immediately unblind and offer to vaccinate the entire placebo group should be rejected.

#2:  Moderna made a good effort to include a diverse group of participants, but only 4 COVID cases were in Black patients, and there were even fewer in other racial groups.  We can’t assume that the vaccine was highly effective in demographic groups with so few cases because just 1 Covid case in the vaccinated group would have greatly reduced the efficacy rate.

The data on cases for participants with co-morbidities was slightly more substantial, with 24 placebo cases and only 1 vaccinated case

#3  I’m glad to see that unlike Pfizer, Moderna provided info on the total number of  participants who reported 1 or more adverse events.  That’s important.  Unfortunately, the total of severe systemic adverse events after the 2nd dose was over 17% for vaccinated group compared to 2% for the placebo group.

There are also too few severe cases to draw conclusions:

There were 30 severe cases after the 2nd dose, and none were in the vaccine group.  This is a strong finding.  However, only 9 of the severe cases required hospitalization; 12 involved the questionable criteria of at least slightly low blood oxygen saturation.

Long-term care patients were not included in the study.  About 1300 people ages 75 and older were in the study, almost half of them vaccinated, but only 3 were cases (all of them placebo).  Only 15 cases were in patients over 65.

We want to save their lives, but with no data it’s not possible to provide useful informed consent to nursing home patients.  That puts a tremendous burden on those patients and their family members to decide whether or not to be vaccinated.

We need longer-term data to fully understand the benefits and risks for different types of patients.  The vaccine is clearly effective, but does that last 2 months, 4 months, or a year?  We need to know that, and that’s why it is essential that the blinded randomized controlled trial is continued.

In conclusion, EUA is not approval, and it should have more restrictions than approval would have.  The EUA should be targeted to priority populations, because if the EUA applies to all adults, celebrities and others who are well-connected will cut in line.  We’ve already seen that this week.

Other people could apply for the vaccine under FDA’s Expanded Access program.

We need at least 1 year of blinded, randomized, controlled data.  We agree with Dr. Goodman’s proposal that FDA should delay access to vaccines by members of the placebo group unless they are in priority populations.  Blinded crossover has limitations because it can’t control changes in the community spread of the virus, but it is better than not continuing a blinded controlled study, if continuing the current study is not possible.

FDA Panel Reviewing Pfizer Vaccine Leaves Out Some Experts Who Raised Concerns

David Hilzenrath, Project on Government Oversight: December 9, 2020.


When an FDA advisory committee meets tomorrow to review Pfizer’s coronavirus vaccine, the lineup of committee members will look different from the group that met in October to begin the committee’s discussion of coronavirus vaccines.

Four people who participated in the earlier meeting as temporary committee members, including experts who raised questions and expressed concerns about the testing process, do not appear on the “draft roster” of panelists the FDA has posted for tomorrow’s meeting.

Meanwhile, there will be new faces. The FDA has added 10 temporary committee members who did not participate in the earlier meeting.

The changes in the lineup raise concerns, Diana Zuckerman, president of the National Center for Health Research, said in answer to questions from the Project On Government Oversight (POGO).

Zuckerman said experts might have been excluded to avoid tough questions about Pfizer’s data.

“It is not unusual for temporary members of FDA Advisory Committees to change, but seems surprising since the issues they are considering at the Oct meeting and tomorrow are so similar,” Zuckerman said by email.

Zuckerman’s organization analyzes the safety and effectiveness of pharmaceuticals and other medical products.

POGO asked the FDA whether the disappearance of some people from the advisory committee lineup had anything to do with any questions, concerns, or opinions they have expressed. In response, an FDA spokesperson did not directly answer.

The FDA routinely supplements advisory committees with temporary voting members, including “scientists or medical personnel whose expertise may not be represented by the fixed voting membership,” the FDA spokesperson said by email. “Many times, committees need to invite experts who are unrelated to the knowledge and expertise spelled out in the committee charter if a medical product or topic for discussion calls for a specific need for a particular expert,” the spokesperson added.

That does not seem to explain why the FDA would drop temporary voting members it selected to participate in the October meeting. At that meeting, without evaluating any particular vaccine, the committee advised the FDA on how in general it should approach experimental coronavirus vaccines.

Dr. Luigi Notarangelo, an expert on clinical immunology at the National Institute of Allergy and Infectious Diseases, was not invited to participate in the December 10 FDA advisory committee meeting on Pfizer’s coronavirus vaccine. He served as a temporary committee member when the panel met in October and minced no words then as he expressed general concerns about the testing of coronavirus vaccines.

[….]

POGO recapped his commentary at the October meeting in a November 2 story, “FDA Whitewashes Warnings About Coronavirus Vaccine Trials.”

As POGO reported:

Dr. Luigi Notarangelo, a committee member who is a chief researcher at the National Institutes of Health, minced no words as he articulated several of the critiques.

Notarangelo said measures of vaccine effectiveness included in an FDA document the committee was asked to review have two problems.
“First of all, they really are biased—skewed towards mild disease,” he said. “Mild disease may not mean very much.”
“The other problem with those efficacy measures is that most of them are really subjective,” he said. “And I think that’s a major concern. I mean, we’re relying basically upon reporting from the subjects without any objective validation of what they’re reporting.”

At the time, Notarangelo was not commenting specifically on Pfizer’s data.

Another person who served as a temporary member on October 22 but does not appear on the roster for tomorrow is Kathryn Holmes, a professor emerita in the Department of Immunology & Microbiology at the University of Colorado School of Medicine.

“One of the things I have not heard much about during this conversation is infection,” Holmes said at the October meeting. “I’d like to see how we could actually be measuring infection rather than just mild disease. … We should be looking to see what can prevent infection because that is the rubric which would prevent spread through the community most effectively and that is what would protect our elderly as well.”

Holmes could not be reached for comment for this story.

Another person who participated in the October meeting but is not slated to participate tomorrow is Dr. Michael Nelson, president of the American Board of Allergy and Immunology and a physician at Walter Reed Army National Military Medical Center.

At the October meeting, Nelson said “more real-time data might be needed.”

Nelson also noted that, when the acting chair of the committee summarized members’ comments, he omitted “a lot of concern” about an aspect of how vaccine effectiveness was being measured—whether it was focused inordinately on preventing milder cases.

Read the full article here

Public Comments Regarding ACIP Meeting on December 1, 2020

Diana Zuckerman, Ph.D., on behalf of the National Center for Health Research


Thank you for the opportunity to express my views on behalf of the National Center for Health Research regarding the priorities for allocation of initial supplies of the COVID-19 vaccines. Our center is a nonprofit think tank that scrutinizes the safety and effectiveness of medical products, and we do not accept funding from companies that make those products. My expertise is based on post-doctoral training in epidemiology and public health and more than 30 years of health policy expertise, including my previous employment at the U.S. Department of Health and Human Services, the U.S. Congress, and the White House.

If a COVID-19 vaccine is authorized through an EUA or approved by the FDA, we support prioritizing allocation to healthcare workers, paid and unpaid, and especially those in contact with patients. We agree that people working at long-term care facilities should be included with other healthcare workers. We also support the sub-prioritization considerations for healthcare workers that were specified by Dr. Sara Oliver at the December 1 meeting.

We support prioritizing healthcare workers because they are at clear risk of infection and also have the knowledge to make an informed decision about whether to be vaccinated. Protecting them against infection also protects their patients. We emphasize that healthcare workers should have the choice of whether or not to get the vaccine; it should not be required for a vaccine that is authorized rather than approved by the FDA.

Although we agree that people living in long-term care facilities are clearly at the greatest risk of severe reactions to COVID-19, including death, we are concerned about the lack of data on those types of patients, or any patients over 65 years of age. According to the Reactogenicity chart presented by Dr. Oliver, data are available for only 10 community-dwelling patients in that age group in the Moderna study and only 12 patients in the Pfizer study. It is not clear whether these are the total number of individuals who were vaccinated in those age groups, or the total number in studies published so far. Either way, that is not enough information for older adults living in long-term care facilities to make an informed decision about whether or not to get the vaccine, or for family members or physicians to help make that decision. It is essential that more patients over 65, and preferably more frail elderly patients, be carefully studied in the randomized clinical trials prior to a massive vaccination distribution to tens of thousands of patients. Such data should not take more than a few months to add to existing studies.

Patients in these facilities should not be pressured to be vaccinated.  They should make an informed decision influenced by their personal preference and specific risk of infection.  We are especially concerned that the vaccine might be less effective for older patients and that the pain and fatigue that was reported in the reactogenicity data for younger and older patients could be especially debilitating to long-term care patients, many of whom would not be at high risk of exposure if the employees at their facility have been vaccinated.  

HEALTH CARE BRIEFING: FDA Vaccine Rules Challenged as Weak

Brandon Lee and Alex Ruoff, Bloomberg Government: October 23, 2020


U.S. vaccine advisers questioned whether safety and efficacy standards set by Food and Drug Administration officials were high enough to warrant emergency authorization of a shot.

About two dozen outside advisers to the FDA with expertise in infectious diseases met yesterday to weigh in on agency standards that require a vaccine to work in at least 50% of people and for drugmakers to collect two months of safety data on at least half of clinical trial volunteers.

“They haven’t gone far enough” in terms of safety, said Hayley Altman-Gans, a panel member and pediatrics professor at Stanford University Medical Center.

Many panel members and outside researchers who commented during the hearing worried that if a vaccine is rushed out that later turns out to have safety problems or to be less effective than promised, it could backfire in a big way, undermining public confidence in Covid-19 vaccines for years to come.

Several panel members expressed concern that the two-month safety follow-up the FDA is calling for before a vaccine gets an emergency authorization is simply not enough. In addition to safety, it means that doctors won’t know whether a vaccine’s efficacy could fade after just a few months.

Diana Zuckerman of the National Center for Health Research told the committee the vaccine trials “have serious design flaws.”

The trials are too geared to preventing mild infections, and may not show whether they prevent severe infections and hospitalizations, she said. Longer follow up may be especially important because some of the first vaccines, including messenger RNA vaccines from Pfizer and Moderna, are based on new technologies that have never been used in an approved product. 

Read the full article here

FDA Panel To Lay Regulatory Groundwork For COVID-19 Vaccine


Noel King and Sydney Lupkin, NPR: October 22, 2020


NOEL KING, HOST:

There are several COVID-19 vaccines in development. But before they are approved, they have to be safe. It’s the FDA’s job to ensure that. Today an FDA advisory panel is meeting for the first time about the coronavirus vaccine. It’ll be making recommendations based not on politically motivated timetables, but on data.

Sydney Lupkin covers the pharmaceutical industry for NPR. Good morning, Sydney.

SYDNEY LUPKIN, BYLINE: Good morning.

KING: So what is the deal with this FDA panel? Who’s on it? What are they going to be doing?

LUPKIN: Well, the FDA regularly turns to committees of outside advisers for guidance. Most often, these panels are asked to evaluate specific drugs or health products, and that helps the agency to decide whether to approve these products. Today’s meeting of the committee that looks at vaccines is going to be a little different.

KING: How?

LUPKIN: Like everything else in this pandemic, it’s a bit unusual. The big difference is that the committee isn’t going to be sifting through data for a specific coronavirus vaccine like it normally would. The meeting will be a broader discussion of how the agency should think about safety and effectiveness of these new kinds of vaccines, particularly safety. Dr. Paul Offit is a committee member who works at the Children’s Hospital of Philadelphia.

PAUL OFFIT: How robust should safety data be? How long, for example, after the first or second dose should patients be followed or participants be followed for any possible safety issue?

LUPKIN: They’ll be discussing FDA’s existing guidance to companies, which includes some of that information. They’ll also discuss how studies should continue after the first vaccine is given the green light. What do you do for patients who got a placebo once a vaccine is widely available? Of course, the FDA usually heeds the advice of these committees, but it doesn’t have to.

KING: So since there’s no vaccine to review, I would think that in ordinary times, we would not know about this meeting. It would not be news at all. It’s very clear that the FDA wants to make public that this is happening. Why do they want to do that?

LUPKIN: Well, I mean, it gives the American public a window into the process. There’s been so much discussion around whether the FDA will put politics ahead of science. So it’s important to see what’s going on. And the FDA has questions that it wants answers to. Here’s Dr. Miles Braun, a former FDA epidemiologist.

MILES BRAUN: There is a level of humility that the FDA is coming to its advisers with. And I think that’s a good thing. And if they find out they’ve missed some important things, they’ll address those.

LUPKIN: Committee members will hear presentations from scientists at the FDA, the Centers for Disease Control and Prevention and the Biomedical Advanced Research and Development Authority. The public will also have an opportunity to weigh in. Diana Zuckerman is the president of the National Center for Health Research, an advocacy group slated to speak.

DIANA ZUCKERMAN: We’ve seen the guidance of what they’re telling companies they’re supposed to be studying. Frankly, they’re not very stringent, so we are concerned about them.

LUPKIN: She hopes the meeting will delve into making sure the clinical trials are diverse, for example. She also questions whether the study approach the FDA suggested to manufacturers is long enough to assess vaccine safety.

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