Category Archives: News Stories & Editorials

What Genentech is doing to fix biotech’s diversity problem

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Fortune Editors, Fortune: April 7, 2021

There’s a big problem with clinical trials: a lack of diversity. And that issue is ultimately detrimental to countless people’s lives and health.

Take, for example, breast cancer research. For a long time, the thinking in the health care world was that Black women didn’t develop breast cancer as often as white women, but when they did, they were more likely to die because of it.

“There was this assumption that it was an issue of access to care, the quality of care,” says Diana Zuckerman, president of the National Center for Health Research, a nonprofit think tank that analyzes the latest research and helps consumers and organizations put that information to work. But “if you looked at the research, you saw that the original major studies of breast cancer treatment were done on white women.”

That meant the research featured fewer women with triple-negative breast cancer, which Black women develop more often than white women. “Because [women with triple-negative breast cancer] weren’t studied,” Zuckerman continues, “[the researchers] didn’t realize that the treatments that they were studying would not work on those types of cancer.”

Zuckerman talks with Fortune’s Ellen McGirt on this week’s episode of Leadership Next, a podcast about the changing rules of business leadership. Also on the episode with McGirt and cohost Alan Murray is Alexander Hardy, who became CEO of biotech company Genentech two years ago.

Hardy has made it clear that he’s committed to boosting diversity within the biotech world and in clinical trials, and he was already doing so before the pandemic. But COVID-19 crystallized some of the issues in the U.S.

[….]

During the show, Hardy also discusses the ways the COVID-19 pandemic has changed the biotech industry, and how those changes could spill over into research on diseases such as Alzheimer’s, ALS, and cancer.

To read the entire article and listen to the podcast, click here.

The FDA Cut Off COVID Vaccine Testing. That Was a Really Bad Idea.

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Shannon Brownlee and Jeanne Lenzer, Washington Monthly: March 26, 2021

Not since the polio vaccine became available in April 1955 have Americans been so excited about getting a shot. After a year of isolation, fear, and death, most of us can hardly wait to get vaccinated against Covid-19.

[….]

From everything we know about the various Covid-19 vaccines, normal life, or some semblance of it, could return as early as late summer or fall in the United States. The first two vaccines, made by Pfizer and Moderna, appear to be more than 90 percent effective. The Johnson & Johnson vaccine also looks to be quite effective. Thus far, the side effects seem tolerable. If there’s a problem with the vaccines, it’s that production has not kept up with demand and rich countries are scooping up the majority of available doses, leaving poorer countries to fend for themselves.

But behind the scenes, there’s a lot we don’t know, especially about the vaccines made by Pfizer and Moderna, which employ a completely novel technology involving mRNA, a type of genetic material. The reason we don’t know it is because of a decision made back in December by the U.S. Food and Drug Administration (FDA). The agency allowed manufacturers to effectively stop their clinical trials as soon as they were authorized to market their vaccines. While the early results from the clinical trials look incredibly promising, we don’t actually know with any precision just how effective and safe they really are – and we probably never will. That might sound like the kind of hairsplitting that hardly matters when a pandemic is raging and people’s lives are at stake, but it does matter for future vaccination campaigns. It’s worth considering why the FDA did it and whether or not that’s how vaccines and other medical products should be regulated in the future.

[….]

Even before the first vaccine came out, there were worries the FDA would not hold the companies’ feet to the fire and make them finish the trials. In an editorial published on September 10, Howard Bauchner, the editor in chief of the Journal of the American Medical Association and colleagues wrote, “prematurely approving a vaccine could undermine Covid-19 vaccine efforts and erode confidence in vaccines more generally.”

Bauchner and others also predicted that once the shots were available to the public, study volunteers would leave the vaccine trials in droves in order to find out if they had gotten the real vaccine or a placebo (dummy shot) – so they could get the vaccine as soon as possible if they were on placebo. That would undermine the studies, effectively stopping them after just a median of two months of data had been collected. Once the studies were stopped and the vaccines were released to the general population, it would be very hard to track side effects and efficacy.

[….]

Back in September, Anthony Fauci, who was then head of President Trump’s Covid-19 task force and remains the chief of the National Institute of Allergy and Infectious Diseases, had already proposed a clever plan. He recommended a “blinded crossover design.” Volunteers who had been in the placebo group would be given the real vaccine, while vaccine recipients would receive placebo—without anybody being told which they had gotten first. In this way, all volunteers would receive the vaccine while allowing ongoing surveillance regarding long term safety and efficacy. When the FDA called in Steven Goodman, an expert in clinical trial design from Stanford, he too endorsed the blinded crossover design, which is commonly used in medical research.

The manufacturers were less than enthusiastic. They told the FDA that executing crossover studies would be “onerous.” In this case, that word translates to “expensive,” and there’s no doubt that continuing the trials would cost more money. Not to mention the fact that the longer the trials went, the more likely it would have been that the vaccines would look a little worse than they did at first, at least in some populations, like people with immune disorders. That’s precisely the kind of data the FDA needs to protect the public health. Nevertheless, with a solution offered by top experts on the one hand, and industry opposition on the other, FDA higher ups made their decision. Instead of insisting on the trials continuing, they asked the companies to “inform the agency” of their plans. Was it pressure from the Trump White House, members of Congress, or some other reason the FDA caved to industry, as often happens? We can’t be sure, but the testing design Fauci and Goodman endorsed would have let the wider public get the vaccine just as quickly.

This decision to cut the trials short could come back to haunt the FDA. For one thing, getting more data could have reassured millions of Americans who are currently “vaccine hesitant” that the agency is looking out for them.

[….]

Another reason longer trials would have been good policy: Public health officials and individual patients would probably like to know who is least likely to be protected by the vaccines and who is most vulnerable to their side effects. Diana Zuckerman, president of the non-profit National Center for Health Research, says, “I’m especially concerned that Pfizer’s vaccine trials included only five people aged 75 and older who were diagnosed with Covid-19.” She adds: “That makes it impossible to determine how effective the vaccine is for frail elderly patients.”

[….]

This episode in the annals of potentially wrongheaded FDA decisions bears directly on the Biden administration’s decision about who to nominate as FDA commissioner. The two top picks are Janet Woodcock, current acting commissioner and 35-year veteran at the agency versus Joshua Sharfstein, vice dean for public health practice at Johns Hopkins. Both are physicians and both have experience at the agency, and that’s pretty much where the similarity between them ends. Woodcock has presided over many of the most questionable drug approvals the FDA has made in recent memory. She sees industry as a “partner,” and she’s the preferred candidate of Pharma, device makers, and several patient groups, most of which receive industry funding – precisely because she has weakened the FDA’s oversight.

Sharfstein comes with a public health perspective and an acute awareness of the need to rebuild the agency’s reputation as independent from both politics and industry. As deputy commissioner of the FDA during the Obama presidency, he proved his mettle when he headed an internal investigation into the approval of an ineffective and harmful medical device.

[….]

Whoever the Biden administration chooses, whether it’s Sharfstein, Woodcock or someone else, Americans need to know the agency charged with protecting their health from dangerous medical products is, as the president often says, “following the science,” rather than the pleas of industry. We should be thankful that we have Covid-19 jabs that can help free us from this plague year. But we may never have the full story on them. The FDA can do a better job in the future.

To read the entire article, click here.

The Differences Between the Vaccines Matter

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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. 

Janet Woodcock revolutionized the way the FDA reviews cancer drugs, inspiring her supporters and raising concerns for detractors

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Nicholas Florko, STAT News: March 1, 2021

In 2000, the Food and Drug Administration approved just three cancer drugs. Last year, even with the agency laser-focused on the coronavirus pandemic, much of its staff teleworking, the agency still approved a record-breaking 17 different cancer therapies — more than in any other category. That’s the legacy of FDA drug center chief Janet Woodcock. Woodcock, a 36-year veteran of the agency, is infamous for pushing the FDA to loosen its standards for drugs for rare conditions like Duchenne muscular dystrophy. But Woodcock’s most lasting impact at the FDA is her transformation of the way the agency approaches cancer drug approvals….. Now the nation’s top cancer doctors are emerging as Woodcock’s most vocal backers in her campaign to become President Biden’s FDA commissioner.

Critics say Woodcock’s cancer crusade has come at a cost. With the speed has come an erosion of the agency’s high standards and an increasing willingness to greenlight drugs that haven’t actually been proven to extend a patient’s life. … Their complaint mostly revolves around Woodcock’s willingness to accept studies testing drugs based on so-called surrogate endpoints, measures like the shrinkage of a tumor, rather testing a drug based on how long it keeps a patient alive. ….It’s a view that even some former FDA officials hold; one described Woodcock as pushing “flexibility even at the expense of science.”

[.…]

“For many cancers there is an improvement in survival, the question is which drugs are responsible for that and which ones aren’t, that’s the big unknown and that’s what’s so frustrating,” said Diana Zuckerman, the president of the National Center for Health Research. The end result of this confusion, critics argue, is that doctors and patients are left guessing whether a drug is truly effective, or worth the money.

 [….]

Read the full article here.

What you need to know about J&J’s newly authorized one-shot COVID-19 vaccine

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Tina Hesman Saey, ScienceNews: February 27, 2021

And then there were three: A single-shot vaccine is the latest weapon to join the battle against COVID-19 in the United States.

On February 27, the U.S. Food and Drug Administration gave emergency use authorization for Johnson & Johnson’s vaccine against SARS-CoV-2, the coronavirus that causes COVID-19. South Africa is the only other country to OK Johnson & Johnson’s vaccine so far, though other countries are poised to follow suit.

The FDA determined that Johnson & Johnson’s vaccine meets the criteria for safety and effectiveness and that there is clear evidence that it may prevent COVID-19, the agency said in a statement.

“With today’s authorization, we are adding another vaccine in our medical toolbox to fight this virus,” said Peter Marks,  director of the FDA’s Center for Biologics Evaluation and Research.

Its authorization for emergency use in the United States – for people age 18 and older – follows similar authorizations in December for vaccines made by Moderna and by Pfizer and its German partner BioNTech.

[….]

As of February 25, more than 52,000 people were hospitalized in the United States fighting COVID-19, according to the COVID Tracking Project. That’s down from the record-setting daily peaks of more than 130,000 in early January and the lowest since early to mid-November. More than half a million people in the United States have now died from COVID-19.

In Johnson & Johnson’s clinical trial, two of the 19,514 people in the vaccine group were hospitalized with COVID-19 starting 14 days after vaccination. That compares with 29 hospitalizations among the 19,544 people in the placebo group. None of the vaccinated people died, but there were seven deaths related to COVID-19 in the placebo group. Those numbers are small and some researchers say the data aren’t clear-cut on the benefits.

“The data indicate that the vaccine is effective, but doesn’t prove that the vaccine is especially effective against moderate to severe COVID,” said Diana Zuckerman, president of the National Center for Health Research, a Washington, D.C.–based think tank that analyzes health research.

The data were also collected after only two months of follow-up. Normally, the FDA requires a year or more of data to fully approve a vaccine. Some questions about the vaccine can’t be answered with less than six months of data, Zuckerman said during a public comment period in the Feb. 26 advisory board hearing.  “Let’s be very honest with the public about what we do know and what we won’t know” for some time to come.

For all the vaccines, no one knows how long immunity will last. And what’s already authorized might need to be tweaked if resistant variants become widespread. Booster shots may be needed, Benjamin says.

[….]

To read the entire article, click here.

FDA blasts Merck’s Keytruda data for new breast cancer indication

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Ed Silverman, Stat News: February 5, 2021

Merck (MRK5 ) may have readily turned its Keytruda cancer drug into a medical and financial juggernaut, but its bid to win regulatory approval for at least one additional use may not come so easily, judging by documents from the Food and Drug Administration. The drug maker wants to sell the medicine to combat high-risk, early-stage triple-negative breast cancer along with chemotherapy before surgery, and then by itself after surgery.

[…]

Given the FDA review, though, the likelihood of a recommendation next week is not high, according to Ira Loss of Washington Analysis, who tracks pharmaceutical regulatory and legislative matters for investors. “The agency believes, and we think the (FDA expert) committee will agree, that further data from the trial are needed to make an informed decision,” he wrote to investors.

Another FDA watcher was even more blunt. “It’s important to have good treatment because this disproportionately occurs among Black women,” said Diana Zuckerman, who heads the National Center for Health Research, a nonprofit think tank. “But they’re saying this may not be needed, may not work and may be harmful – that’s pretty damning. And there are some real safety issues that can have terrible impact on patients… This is one of the most negative reviews I’ve ever seen.”

[….]

Read the full article here

Patients Continue to Be Inadequately Informed of Risk for Breast Implant-Associated ALCL

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Christina Bennet, MS, Cancer Therapy Advisor: February 8, 2021

Although the risk for breast implant-associated anaplastic large-cell lymphoma (BIA-ALCL) has been well-documented, patients considering breast implants continue to be inadequately informed of the propensity for disease development. Awareness of BIA-ALCL has risen since 2020, but adequate safeguards have not yet been put in place, according to experts in the field.

“There have been efforts made [to ensure patients are informed], but they have not been successful,” Diana Zuckerman, PhD, president of the National Center for Health Research (NCHR), said in an interview with Cancer Therapy Advisor.

The most recent effort to more frontally disclose the risk for BIA-ALCL is a final guidance document released by the FDA on September 28, 2020.1 The guidance, which applies to all breast implants, advised breast implant manufacturers to add a black box warning that mentions the risks associated with breast implants such as BIA-ALCL. In the guidance, the FDA also encouraged manufacturers to incorporate a patient decision checklist in the labeling to “better ensure certain information is received and understood by patients.”1,2 Manufacturers, however, are not required to follow these recommendations.

Zuckerman, who is a member of the Breast Implant Working Group, said she was surprised by the FDA’s decision to recommend rather than require these facets of the guidance. “We don’t have the answer to that question other than we have talked to FDA officials who said that at least some of this will at some point be a requirement, but we don’t know when that is,” she said.

With no mandates in place to ensure that patients receive information about the risks for BIA-ALCL—among other breast implant-associated complications—upfront, the industry is left to educate—and this does not seem to be working.

Patient advocates Terri McGregor and Jennifer Cook, both of whom have received a BIA-ALCL diagnosis, discussed a misleading patient brochure that has further contributed to the misinformation about breast implant-associated cancer risk. Sold online by the American Society of Plastic Surgeons (ASPS), the brochure featured the symbol for breast reconstruction awareness—a modified pink ribbon—and the slogan “Closing the loop on breast cancer.”3

The brochure was sponsored by several companies, including 2 prominent breast implant manufacturers, Allergan and Mentor. Though the document was promoted on Twitter by the ASPS and users were encouraged users to “stock up now” ahead of Breast Reconstruction Day,3,4  it notably made no mention of BIA-ALCL—not even on the page that describes the risks and safety issues associated with breast implants.

Conflicts of Interest Cloud Risk Disclosure

[…]

Eric Swanson, MD, a plastic surgeon at the Swanson Center for Cosmetic Surgery in Leawood, Kansas, told Cancer Therapy Advisor that plastic surgeons’ financial ties to breast implant manufacturers are part of the reason why they have been slow to respond to the issue of BIA-ALCL. “There’s a big problem with conflict of interest in plastic surgery. Once [a person has] taken funds from a company, it is very rare for the taker to be critical of that company,” Swanson said.

[….]

Zuckerman described the ASPS brochure as “terribly” out of date. “The Institute of Medicine report is more than 20 years old, and there has been a great deal of research since then,” she said.

[….]

The ASPS Brochure: Current Status

When Cancer Therapy Advisor inquired about the content of the brochure, an ASPS representative agreed that the information was “outdated” and removed the brochure from sale on its website.

Enclosed in the ASPS brochure was a list of websites that included breastimplantsafety.org, which—despites its domain name—did not include any safety information about breast implants. Instead, the domain redirected users to a different domain, smartbeautyguide.com, the patient site for The Aesthetic Society, a professional organization for plastic surgeons. A representative for The Aesthetic Society told Cancer Therapy Advisor that breastimplantsafety.org was active until 2015, when it migrated to their patient site, Smart Beauty Guide.

“We have been developing and will launch our new Aesthetic Society website that will include a dedicated section for patient education,” the representative wrote in an email. Within days of being contacted by Cancer Therapy Advisor, The Aesthetic Society updated the breastimplantsafety.org domain name to direct users to an existing page that provides resources about breast implants, including information about BIA-ALCL and breast implant illness, a systemic condition characterized by a wide range of symptoms that is currently under FDA investigation.18

Read the full article here

Congressman calls for FDA to continue vaccine trials

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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?

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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.
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How Effective Is the Mask You’re Wearing? You May Know Soon

News Stories & Editorials, We're In the News,

A CDC division is working with an industry standards group to develop filtration standards — and products that meet them will be able to carry labels saying so.

Sheila Kaplan, The New York Times: December 16, 2020

More than 100,000 varieties of face masks are currently for sale. They come in silk, cotton and synthetics; with filters and without; over-the-head and over-the-ears. They have sparkles and sunflowers; friendly greetings and insults; cartoon characters and teeny reindeer.

What they don’t have is a label that shows how well they block infectious particles, an omission that has frustrated public health officials during the coronavirus pandemic. Those experts note that there is a big range in the effectiveness of various designs, and some barely filter out particles at all.

“The most fundamental, basic question is, What is the safest mask and how do I assure that I have that, and my family members and children have that?” said Fran Phillips, who stepped down in August from her post as deputy health secretary of Maryland. “It’s so startling that we are here in this moment and we don’t have that information.”

That may change soon. A division of the Centers for Disease Control and Prevention is working to develop minimum filter efficiency standards, and labels showing which products meet them, for the vast and bewildering marketplace for masks and other face coverings.

The National Institute for Occupational Safety and Health, a division of the C.D.C. known as NIOSH, has been quietly writing guidelines with an industry standard-setting organization, ASTM International (formerly the American Society for Testing and Materials), that are expected to be made public next month.

“By having a standard in place you will be able to know what level of protection is being achieved and you’ll have a consistent way of evaluating these products,” said Maryann D’Alessandro, director of the NIOSH National Personal Protective Technology Laboratory.

Since the pandemic began, there has been little federal oversight of masks and other face coverings. Both the Food and Drug Administration and the C.D.C. have some authority over the industry. The F.D.A., which regulates medical devices, shares authority with NIOSH for oversight of N95 respirators, which are the most protective devices available. But most of the masks the general public wears are just pieces of cloth and don’t come under any regulatory oversight.

Sales of masks took off after the F.D.A. issued an emergency measure in April that said in part that the agency would not take action against companies selling them to the general public. At the same time, however, the F.D.A. also noted that these products “may or may not meet fluid barrier or filtration efficiency levels.” That warning didn’t hurt the market, and some critics now blame the F.D.A. for the poor quality of many of the products being sold.

“There were many things the F.D.A. could have done to improve the situation, especially after research started coming out about which masks worked and which didn’t,” said Diana Zuckerman, president of the National Center for Health Research, a nonprofit health policy group. “F.D.A. could have issued a guidance that masks should be fitted, at least two layers of cloth, not made of stretchy materials, etc. Instead, there was a free-for-all.”

The effectiveness of masks can range “from 0 to 80 percent, depending on material composition, number of layers and layering bonding,” said Dale Pfriem, president of Protective Equipment Consulting Services and a member of the standards development working group addressing mask guidelines.

[…]

Read the full article here https://www.nytimes.com/2020/12/16/health/covid-masks-effectiveness.html