Tag Archives: Covid

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.

[…]

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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 

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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. 

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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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FDA Promises Strong Safety Standards for Covid-19 Vaccines as It Convenes Advisory Panel

Thomas M. Burton, Wall Street Journal: October 23, 2020


SILVER SPRING, Md.—Food and Drug Administration officials gave fresh assurances Thursday that Covid-19 vaccines will undergo rigorous testing before being made widely available—a message they underscored in a meeting with outside medical experts aimed at bolstering the agency’s credibility.

“Only those vaccines that are demonstrated to be safe and effective” will be licensed by the FDA, said Marion F. Gruber, director of the FDA’s Office of Vaccines Research and Review. But some speakers and panel members raised concerns about whether the FDA’s vaccine guidelines for Covid-19 clinical trials are sufficiently rigorous.

These comments came at the first meeting of a 25-member panel of medical experts, including specialists in fields like virology, infectious diseases and biostatistics. The group, which met remotely via video-conferencing, was  established to make recommendations to the FDA on how best to assess the safety and effectiveness of vaccines.

“The FDA frequently convenes outside panels of medical experts for their advice on products,” said Peter Marks, director of the FDA’s center for biological products. “But normally panels about vaccines are watched by dozens of people. In this case, it’s watched by many thousands.”

[….]

President Trump has pushed to get a vaccine approved quickly, which has drawn concern from some public health experts and political opponents that the FDA would be under pressure to bypass usual precautions to rush a vaccine to market quickly.

FDA officials have vowed not to do so. In addition to convening the advisory panel, they have issued a set of guidelines to govern how vaccine clinical trials will be conducted and evaluated.

They also formulated a set of rigorous standards for the FDA to employ before granting what is known as an emergency-use authorization (EUA) for a vaccine. The EUA is the faster equivalent during the Covid-19 pandemic of a conventional approval by the agency.

[….]

Various speakers questioned whether the shorter EUA test period was sufficient.

“The vaccine trials have serious design flaws,” said Diana Zuckerman, president of the National Center for Health Research in Washington. In addition to the two-month period, she said FDA guidelines focus on measuring milder cases of the disease, and not the most serious cases.  

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