Tag Archives: FDA

Biden chooses Robert Califf, former Obama FDA chief, as agency commissioner

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Laurie McGinley, Washington Post: November 12, 2021

President Biden is expected Friday to nominate former Food and Drug Administration commissioner Robert M. Califf to return as the agency’s head, ending a difficult, months-long search to find a leader for the sprawling bureaucracy on the front lines of the coronavirus pandemic.

The announcement is expected later in the day, according to people familiar with the decision who spoke on the condition of anonymity because they were not authorized to discuss the issue.

Califf, 70, a renowned cardiologist and researcher, is senior adviser for Verily, a research organization devoted to the life sciences, and Google Health. He served as FDA commissioner during the last year of the Obama administration. Before that, he had a long career at Duke University School of Medicine, where he founded the Duke Clinical Research Institute, one of the largest academic clinical trial operations in the world.

Many FDA experts see Califf as a safe choice — an experienced hand who is unlikely to make abrupt changes as the agency navigates a tumultuous period marked by high-pressure reviews of coronavirus vaccines and therapies and hot-button issues involving Alzheimer’s treatments, opioids and tobacco products. An expert on clinical trials and other types of health data, Califf is likely to press for better evidence in assessing drugs and devices.

But others hoping for fresh leadership see Califf’s nomination as a missed opportunity. Some are uncomfortable with his longtime relationships with the pharmaceutical industry.

[….]

“I think he would be terrific,” said Harlan Krumholz, a cardiologist at Yale School of Medicine. “It is critically important to have a commissioner who can step in and knows the job and knows how to make policy decisions.”

Even some of the agency’s toughest critics say Califf is acceptable.

“Rob Califf is a good choice,” said Aaron S. Kesselheim, a professor of medicine at Harvard Medical School who has faulted the FDA for approving drugs on what he considers flimsy evidence. “Califf certainly spent the vast majority of his early career working on clinical trials … and understands the value of rigorous data.”

But Califf’s longtime industry relationships have drawn criticism from some who argue the agency already is too close to the companies it regulates.

“Califf has a long history of extensive financial ties to Big Pharma, most significantly through pharmaceutical industry funding of the Duke Clinical Research Institute,” said Michael Carome, director of nonprofit Public Citizen’s Health Research Group, a consumer advocacy organization. “We need someone to tilt in the opposite direction and be more pro-public health and less pro-regulated industry.”

Some past critics, however, have softened their views of Califf. Diana Zuckerman, president of the National Center for Health Research, a nonprofit think tank, said that while she still considers Califf’s industry ties to be a shortcoming, “He has certain qualities that are very good for the position. He has experience at the FDA and a commitment to science. That’s very important.”

 [….]

 To read the entire article click here.

Breast Implants will now come with Black Box Warnings, List Risks

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Sara E. Teller, Legal Reader: November 9, 2021

In 2019, a Food and Drug Administration (FDA) panel heard from dozens of women asking the government agency to inform the public in a direct way about the debilitating and potentially life-threatening symptoms commonly referred to as “breast implant illness.”  Now, ten years after discovering a link between some implants and cancer, the FDA has ordered “black box” warnings be put on all boxes and a new checklist of risks to be provided to patients.

The warnings and checklist advise patients of the serious side effects, including the link to cancer of the immune system (anaplastic large cell lymphoma), as well as chronic medical conditions, including autoimmune diseases, joint pain, mental confusion, muscle aches and chronic fatigue.  The checklist even identifies which types of patients could be at higher risk for illness after breast implant surgery.  And this includes breast cancer patients who have had, or plan to have, chemotherapy or radiation treatments – the very same population of women who are commonly encouraged to seek implants for breast reconstruction.

The FDA is also requiring manufacturers to disclose the ingredients used to make implants, and these must be made public within thirty days.  However, one complication is that patients are unlikely to see a warning label on sterile medical device only a surgeon would have access to.  It’s also not clear how the new mechanisms will be reinforced, even though the FDA said all patients “must be given the opportunity to sign the checklist.”

Critics of the checklist have said that the language used is hard to understand and that patients may sign off without fully understanding what they’re signing. “It’s better than nothing, but it’s not as good as it could be,” said Diana Zuckerman, a scientist at the National Center for Health Research and member of the working group that advised the FDA on implant safety. “They say things like, ‘Breast implants are associated with lymphoma,’ but lymphoma is actually caused by the implants.  People understand it if you say, ‘Breast implants can cause lymphoma.’”

She also believes not every surgeon will take the time necessary to allow patients to digest the black box warning information and ask any questions. “What if a surgeon says, ‘Here’s a checklist.  I know it’s long, so it’s up to you if you want to read it or not’?” Dr. Zuckerman said. “Patient groups are very concerned that will happen.”

Dr. Mark Clemens, a professor at M.D. Anderson Cancer Center in Houston and a liaison to the FDA for the American Society of Plastic Surgeons Society, argued, “The black box warning and checklist represent a huge step forward for patient safety and implants.  But more high-quality data about long-term outcomes for women with implants is needed.”

[….]

To read entire article, click here.

Breast Implants will now come with Black Box Warnings, List Risks

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Sara E. Teller, Legal Reader: November 9, 2021

In 2019, a Food and Drug Administration (FDA) panel heard from dozens of women asking the government agency to inform the public in a direct way about the debilitating and potentially life-threatening symptoms commonly referred to as “breast implant illness.”  Now, ten years after discovering a link between some implants and cancer, the FDA has ordered “black box” warnings be put on all boxes and a new checklist of risks to be provided to patients.

The warnings and checklist advise patients of the serious side effects, including the link to cancer of the immune system (anaplastic large cell lymphoma), as well as chronic medical conditions, including autoimmune diseases, joint pain, mental confusion, muscle aches and chronic fatigue.  The checklist even identifies which types of patients could be at higher risk for illness after breast implant surgery.  And this includes breast cancer patients who have had, or plan to have, chemotherapy or radiation treatments – the very same population of women who are commonly encouraged to seek implants for breast reconstruction.

The FDA is also requiring manufacturers to disclose the ingredients used to make implants, and these must be made public within thirty days.  However, one complication is that patients are unlikely to see a warning label on sterile medical device only a surgeon would have access to.  It’s also not clear how the new mechanisms will be reinforced, even though the FDA said all patients “must be given the opportunity to sign the checklist.”

Critics of the checklist have said that the language used is hard to understand and that patients may sign off without fully understanding what they’re signing. “It’s better than nothing, but it’s not as good as it could be,” said Diana Zuckerman, a scientist at the National Center for Health Research and member of the working group that advised the FDA on implant safety. “They say things like, ‘Breast implants are associated with lymphoma,’ but lymphoma is actually caused by the implants.  People understand it if you say, ‘Breast implants can cause lymphoma.’”

She also believes not every surgeon will take the time necessary to allow patients to digest the black box warning information and ask any questions. “What if a surgeon says, ‘Here’s a checklist.  I know it’s long, so it’s up to you if you want to read it or not’?” Dr. Zuckerman said. “Patient groups are very concerned that will happen.”

Dr. Mark Clemens, a professor at M.D. Anderson Cancer Center in Houston and a liaison to the FDA for the American Society of Plastic Surgeons Society, argued, “The black box warning and checklist represent a huge step forward for patient safety and implants.  But more high-quality data about long-term outcomes for women with implants is needed.”

[….]

To read entire article, click here.

Patients Must Be Warned of Breast Implant Risks, F.D.A. Says

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Roni Caryn Rabin, The New York Times: October 27, 2021

Federal regulators on Wednesday placed so-called black box warnings on breast implant packaging and told manufacturers to sell the devices only to health providers who review the potential risks with patients before surgery.

Both the warnings and a new checklist that advises patients of the risks and side effects state that breast implants have been linked to a cancer of the immune system and to a host of other chronic medical conditions, including autoimmune diseases, joint pain, mental confusion, muscle aches and chronic fatigue.

Startlingly, the checklist identifies particular types of patients who are at higher risk for illness after breast implant surgery. The group includes breast cancer patients who have had, or plan to have, chemotherapy or radiation treatments.

That represents a large percentage of women who until now were encouraged to have breast reconstruction with implants following their treatment.

The Food and Drug Administration is also requiring manufacturers for the first time to disclose the ingredients used to make breast implants, information that patient advocates have long sought. The information must be made public in 30 days.

It is not clear how the new requirements will be enforced, and patients are highly unlikely to ever see a warning label on a packaged sterile medical device that is usually handled only by a surgeon. F.D.A. officials said in a statement that the patients “must be given the opportunity” to sign the checklist.

[….]

Reactions to the new requirements were mixed. While some doctors welcomed the new warning system, others worried that the potential risks and side effects would not be conveyed adequately by plastic surgeons who were eager to reassure patients the procedure is safe and that the new checklist would be handled in a dismissive manner.

Critics also said the checklist was overly long and written in obtuse language. “It’s better than nothing, but it’s not as good as it could be,” said Diana Zuckerman, a scientist who heads the National Center for Health Research and was a member of the working group that advised the F.D.A. on implant safety.

“They say things like, ‘Breast implants are associated with lymphoma,’ but lymphoma is actually caused by the implants,” Dr. Zuckerman said. “People understand it if you say, ‘Breast implants can cause lymphoma.’”

She worried that surgeons would not take the time to adequately review the information with patients.

“What if a surgeon says, ‘Here’s a checklist — I know it’s long, so it’s up to you if you want to read it or not’?” Dr. Zuckerman said. “Patient groups are very concerned that will happen.”

[….]

To read the entire article, click here.

Testimony of Diana Zuckerman, PhD, President of the National Center for Health Research at the FDA PDUFA Meeting, September 28, 2021

Policy, Testimony & Briefings,

I’m Dr. Diana Zuckerman, president of the National Center for Health Research, a patient-centered and consumer-oriented public health think tank.  Our Center is very involved in FDA issues pertaining to the safety and efficacy of medical products, and I appreciate the opportunity to share my views today. 

PDUFA performance measures have focused on speed, but in addition PDUFA performance measures should evaluate whether patients are protected from ineffective or unsafe products being approved!  As Commissioner, Peggy Hamburg said innovation needs to mean products are better, not just new.  The performance goals we’ve heard about today fall short, because they emphasize speed and ease of approval, not on the quality of the outcome of FDA reviews or of the outcome for the patients using these products.  

PDUFA have resulted in more and faster approvals, but not all those approvals have helped patients, and some have seriously harmed them.

Premarket performance should also include evaluations of the percentage of applications that were rejected or withdrawn because there was a lack of evidence proving safety or efficacy.  And the specific reasons why they were rejected or withdrawn.

When post-market surveillance works, it should sometimes result in FDA warnings, recalls, or withdrawals.  FDA should provide the percentage of these for 5 years post approval and the reasons for those actions.

Performance should also include the percentage of products approved based on at least two well-designed studies providing solid scientific evidence.  As someone trained in epidemiology, I love big data, but since most applications are for new products not yet on the market, clinical trials will still be the best data available.  We want to know how many approvals were based on at least two phase 3 randomized, controlled trials demonstrating robust evidence of safety and efficacy and favorable benefit-risk profiles.

Performance should also be based on the percentage of approved products for which FDA mandated post-marketing studies and the percentage where those obligations were fulfilled – started and ended on time, conducted as required, and whether they did or did not confirm safety and efficacy.  As you know, FDA recently had a meeting on widely used cancer drugs that were approved for certain indications through accelerated approval but failed to provide data confirming that they worked for those types of cancer.  And yet the indications remained approved for years after it was obvious they did not work.  Those delays are harmful to patients and should be considered a performance goal worthy of user fee support.  

A newly published study indicates that too often a rejected application is subsequently resubmitted and approved when FDA ignores their own criticisms of the original application, even when those criticisms remain valid.  The controversial approval of Aduhelm is just the most salient example of that.

 Specific Changes to Commitment Letter

I have a general concern about the Commitment letter, because it changes policies that should be publicly debated by Congress and should include input from patient, consumer and public health advocates as part of any negotiations. Policies should not be negotiated behind closed doors at meetings that exclude those important perspectives.  

I have time to recommend 5 specific changes to the Commitment letter:

  1.   I was glad to hear about FDA’s new efforts to include patient preferences and involvement. The Commitment letter should specify that these activities should always include harmed patients, not just patients recruited by industry, who are often patients desperate for treatment.  All patient perspectives are important, we all are concerned about patients who urgently need a treatment that works, but harmed patients have too often been excluded from FDA meetings and committees.
  2.   Voluntary REMS strategies are rarely proven to work. The REMS program needs a complete overhaul or REMS should be avoided. Instead, most safety concerns should be resolved before products are approved. A good example is the REMS for prescription opioids, which FDA learned was not working. Few doctors took the voluntary training, fewer finished the voluntary training, and even those who were trained did not learn all the important issues that were included.
  3.   The letter should implement the National Academies’ public health framework for regulatory oversight of opioids.
  4.   In-person manufacturing inspections remain the most effective way to determine problems. We all understand that remote inspections were needed during the pandemic, but the Commitment letter should specify that remote inspections should be the exception.
  5.   User fees should fund independent, objective studies to assess and quantify the harms that resulted or were avoided due to approval decisions.

And I will just add one other issue, since enhancements to the Sentinel program were discussed earlier in this meeting.  I have been a strong supporter of the Sentinel post-market surveillance program, but it has been in place for years and cost an enormous amount of money.  So, it was distressing to hear this morning that the FDA is still trying to figure out how to use those data so that they can provide usable information about safety and efficacy.

In conclusion, those of us who respect and admire the FDA know how important it is as a public health agency. We must make sure that industry user fees do not interfere with that essential mission. When performance goals and the Commitment letter are made behind closed doors, it is difficult for the public to have confidence that the FDA is a public health agency.

How Fauci and the NIH Got Ahead of the FDA and CDC in Backing Boosters

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Sarah Jane Tribble and Arthur Allen, KHN: September 16, 2021

In January — long before the first jabs of covid-19 vaccine were even available to most Americans — scientists working under Dr. Anthony Fauci at the National Institute of Allergy and Infectious Diseases were already thinking about potential booster shots.

A month later, they organized an international group of epidemiologists, virologists and biostatisticians to track and sequence covid variants. They called the elite group SAVE, or SARS-Cov-2 Variant Testing Pipeline. And by the end of March, the scientists at NIAID were experimenting with monkeys and reviewing early data from humans showing that booster shots provided a rapid increase in protective antibodies — even against dangerous variants.

Fauci, whose team has closely tracked research from Israel, the United Kingdom and elsewhere, said in an exclusive interview with KHN on Wednesday that “there’s very little doubt that the boosters will be beneficial.” But, he emphasized, the official process, which includes reviews by scientists at the Food and Drug Administration and the Centers for Disease Control and Prevention, needs to take place first.

“If they say, ‘We don’t think there’s enough data to do a booster,’ then so be it,” Fauci said. “I think that would be a mistake, to be honest with you.”

The support for an extra dose of covid vaccine clearly emerged, at least in part, from an NIH research dynamo, built by Fauci, that for months has been getting intricate real-time data about covid variants and how they respond to vaccine-produced immunity. The FDA and CDC were seeing much of the same data, but as regulatory agencies, they were more cautious. The FDA, in particular, won’t rule on a product until the company making it submits extensive data. And its officials are gimlet-eyed reviewers of such studies.

On boosters, Americans have heard conflicting messages from various parts of the U.S. government. Yet, Fauci said, “there is less disagreement and conflicts than seem to get out into the tweetosphere.” He ticked off a number of prominent scientists in the field — including Surgeon General Vivek Murthy, acting FDA Commissioner Janet Woodcock and covid vaccine inventor Barney Graham — who were on board with his position. All but Graham are members of the White House covid task force.

Another task force member, CDC Director Rochelle Walensky, said her agency was tracking vaccine effectiveness and “we’re starting to see some waning in terms of infections that foreshadows what we may be seeing soon in regard to hospitalizations and severe disease.” As to when so-called boosters should start, she told PBS NewsHour on Tuesday, “I’m not going to get ahead of the FDA’s process.”

Differences in the scientific community are likely to be voiced Friday when the FDA’s vaccine advisory board meets to review Pfizer-BioNTech’s request for approval of a third shot. Indeed, even the FDA’s official briefing paper before the meeting expressed skepticism. “Overall,” agency officials noted, “data indicate that currently US-licensed or authorized COVID-19 vaccines still afford protection against severe COVID-19 disease and death.” The agency also stated that it’s unclear whether an additional shot might increase the risk of myocarditis, which has been reported, particularly in young men, following the second Pfizer and Moderna shots.

Part of the disagreement arose because President Joe Biden had announced that Americans could get a booster as soon as Sept. 20, a date Fauci and colleagues had suggested to him as practical and optimal in one of their frequent meetings just days before — though he cautioned that boosters would need CDC and FDA approval.

Now it appears that that decision and the timing rest with the FDA, which is the normal procedure for new uses of vaccines or drugs. And Fauci said he respects that process — but he thinks it should come as quickly as possible. “If you’re doing it because you want to prevent people from getting sick, then the sooner you do it, the better,” Fauci said.

Researchers at the NIH typically focus on early-stage drug development, asking how a virus infects and testing ways to treat the infection. The job of reviewing and approving a drug or vaccine for public use is “just not how the NIH was set up. NIH does relatively little research on actual products,” said Diana Zuckerman, a former senior adviser to Hillary Clinton and president of the nonprofit National Center for Health Research in Washington, D.C.

“It’s no secret that FDA doesn’t have the disease experts in the way that the NIH does,” Zuckerman said. “And it’s no secret that the NIH doesn’t have the experts in analyzing industry data.”

‘Data in Spades’

Yet no other infectious disease expert in any branch of the U.S. government has Fauci’s influence. And while other scientific leaders support boosters, many scientists believe Fauci and his colleagues at the NIAID — some of the world’s leaders in immunology and vaccinology, men and women in daily contact with their foreign peers and their research findings — are leading the charge.

Fauci was hard-pressed to give exact dates for when his thinking turned on the need for boosters. The past 18 months are a blur, he said. But “there’s very little doubt that the boosters will be beneficial. The Israelis already have that data in spades. They boost, they get an increase by tenfold in the protection against infection and severe disease.”

In July, Israel, which started vaccinating its population early and used only the Pfizer-BioNTech vaccine, began reporting severe breakthrough cases in previously vaccinated elderly people. Israel’s Ministry of Health announced boosters July 29. Fauci noted that Israel and — to a lesser extent — the U.K. were about a month and a half ahead of the U.S. at every stage of dealing with covid.

And once Israel had boosted its population, the Israeli scientists showed their NIH counterparts, hospitalizations of previously vaccinated people, which had been rising, dropped dramatically. Emerging evidence suggests boosters make people far less likely to transmit the virus to others, an important added benefit.

To be sure, members of the White House covid response team — including Fauci and former FDA Commissioner David Kessler — had begun preparing a timeline for boosters months earlier. Kessler, speaking to Congress in May, said that it was unclear then whether the boosters would be needed but that the U.S. had the money to purchase them and ensure they were free.

Fauci explained that “practically speaking, the earliest we could do it would be the third week in September. Hence the date of the week of September the 20th was chosen.” The hope was that would give regulators enough time. The FDA’s advisory board meeting Friday is set to be followed next week by a gathering of the CDC’s immunization advisory committee, which offers recommendations for vaccine use that can lead to legal mandates.

[….]

Real-Time Science

Scientists tracking the coronavirus are swimming in data. Hundreds of covid studies are published or released onto pre-publication servers every day. Scientists also share their findings on group email lists and in Zoom meetings every week — and on Twitter and in news interviews.

Kessler, chief science officer of the White House covid response team, said the case for boosters is “rooted in NIH science” but includes data from Israel, the Mayo Clinic, the pharmaceutical companies and elsewhere.

As Fauci put it: “Every 15 minutes, a pre-print server comes out with something I don’t know.”

The SAVE group, active since February, was organized by NIH officials who in normal times track influenza epidemics. The 60 to 70 scientists are mostly from U.S. agencies such as the NIH, CDC, FDA and Biomedical Advanced Research and Development Authority, but also from other countries, including Israel and the Netherlands.

“This is very much the basic scientists who are in the weeds trying to figure things out,” said Dr. Daniel Douek, chief of the human immunology section within NIAID.

[….]

Dr. Robert Seder, an NIH senior investigator, was in a group testing the booster theory long before America’s “Summer of Delta.” The researchers injected rhesus macaque monkeys with the Moderna vaccine for the “express purpose of looking at the immune responses over a long period of time.”

“Are they durable? And would you need to boost?” Seder said.

Matthew Frieman, a participant and associate professor of microbiology at the University of Maryland School of Medicine, said the data makes it clear that the time for boosters is approaching. Biden’s booster announcement “may have gotten ahead of the game, but the trajectory is pointing toward the need for boosters,” Frieman said. “The level of antibody you need to protect against delta is higher because it replicates faster.”

[….]

Monday, an international group of scientists led by Dr. Philip Krause, deputy chief of the FDA’s vaccine regulation office, and including his boss, Dr. Marion Gruber, published an essay in The Lancet that questioned the need for widespread booster shots at this time.

Krause and Gruber had announced their retirements from the FDA on Aug. 30 — at least partly in response to the booster announcement, according to four scientists who know them. Gruber, who will remain at the agency until later this fall, is listed as a participant in Friday’s meeting.

The Lancet paper argues that vaccine-based protection against severe covid is still strong, while evidence is lacking that booster shots will be safe and effective. University of Florida biostatistician Ira Longini, a co-author on the Lancet paper, said it would be “immoral” to begin widespread boosters before the rest of the world was better vaccinated. As the disease continues its global spread, he noted, it is likely to develop deadlier and more vaccine-evasive mutants.

Longini was also skeptical of an August study, which Israeli scientists are to present to the FDA on Friday, that NIH officials had touted as strong evidence in support of boosters. …That study found that people receiving a third dose of the Pfizer-BioNTech vaccine were 11 times more likely to be protected from covid infection than those who had gotten only two doses. But the study observed people for less than two weeks after their booster vaccinations kicked in. Biostatisticians felt it had irregularities that raised questions about its worth.

[….]

Fauci emphasized that no single study or piece of data led Biden or the members of the White House covid response team to conclude that boosting was necessary. The compilation of evidence of waning immunity combined with reams of research was a factor. Now the crucial decisions are in the hands of the regulators, awaiting the FDA and CDC’s judgment on how the nation should proceed.

“It isn’t as if,” Fauci said, “one day we’re sitting in the Oval Office saying, ‘You know, Mr. President, I think we need to boost.’ And he says, ‘Tony, go ahead and do it.’ You can’t do it that way. You’ve got to go through the process.”

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Covid-19: FDA set to grant full approval to Pfizer vaccine without public discussion of data

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Gareth Iacobucci, BMJ: August 20, 2021

Transparency advocates have criticised the US Food and Drug Administration’s (FDA) decision not to hold a formal advisory committee meeting to discuss Pfizer’s application for full approval of its covid-19 vaccine.

Last year the FDA said it was “committed to use an advisory committee composed of independent experts to ensure deliberations about authorisation or licensure are transparent for the public.”1 But in a statement, the FDA told The BMJ that it did not believe a meeting was necessary ahead of the expected granting of full approval.

“The FDA has held numerous meetings of its Vaccines and Related Biological Products Advisory Committee (VRBPAC) related to covid-19 vaccines, including a 22 October 20202 meeting to discuss, in general, the development, authorisation, and licensure of covid-19 vaccines,” an FDA spokesperson said.

“The FDA also has held meetings of the VRBPAC on all three covid-19 vaccines authorised for emergency use and does not believe a meeting is needed related to this biologics license application.”

The spokesperson added, “The Pfizer BioNTech covid-19 vaccine was discussed at the VRBPAC meeting on 10 December 2020.3 If the agency had any questions or concerns that required input from the advisory committee members we would have scheduled a meeting to discuss.”

The vaccine has already been rolled out to millions of Americans through an emergency use authorisation. Companies typically apply for full approval after a longer period has elapsed so that more data are available for review.

But with the US government indicating this week that it plans to start making booster shots widely available next month, experts said the decision not to meet to discuss the data was politically driven.

Data scrutiny

 Kim Witczak, a drug safety advocate who serves as a consumer representative on the FDA’s Psychopharmacologic Drugs Advisory Committee,4 said the decision removed an important mechanism for scrutinising the data.

“These public meetings are imperative in building trust and confidence especially when the vaccines came to market at lightning speed under emergency use authorisation,” she said. “The public deserves a transparent process, especially as the call for boosters and mandates are rapidly increasing. These meetings offer a platform where questions can be raised, problems tackled, and data scrutinised in advance of an approval.”

[….]

Public discussion

Diana Zuckerman, president of the National Center for Health Research, who has also spoken at recent VRBPAC meetings, told The BMJ, “It’s obvious that the FDA has no intention of hearing anyone else’s opinion. But if you make decisions behind closed doors it can feed into hesitancy. It’s important to have a public discussion about what kind of data are there and what the limitations are. As we think about risk versus benefit, we need to know.”

Joshua Sharfstein, vice dean for public health practice and community engagement at the Johns Hopkins Bloomberg School of Public Health and former FDA deputy commissioner during the Obama administration, said that advisory committee meetings were more than just a way of receiving scientific input from outside experts. “It’s also an opportunity to educate the public about the important work that the FDA has done reviewing an enormous amount of data about a product,” he told The BMJ. “It’s a chance for questions to be asked and answered, building public confidence. If there are no advisory committee meetings prior to licensure, the FDA should consider taking extra steps to explain the basis of its decisions to the public.”

[….]

To read the entire article, click here https://www.bmj.com/content/374/bmj.n2086

Biden yet to nominate new FDA chief even as delta surges

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Justine Coleman and Alex Gangitano, The Hill, August 8, 2021

President Biden has yet to nominate a permanent head of the Food and Drug Administration (FDA) at a time when the government is navigating a surge in COVID-19 cases from the delta variant.

It’s unclear why the post remains vacant more than six months into Biden’s presidency, but some experts suggest politics may be getting in the way.

Some Democratic senators are pushing back on the prospects of acting Commissioner Janet Woodcock being named to the permanent role, but health care experts are warning that the administration needs to fill the position immediately.

[…]

Biden selected Woodcock, a longtime FDA regulator, to serve as the acting commissioner in January but has since received pushback, including from senators and anti-opioid advocates on that move.

Several Democratic senators have voiced opposition to Woodcock, citing her time at the FDA when opioid painkillers were approved, later contributing to an epidemic that has left many Americans dead.

“I continue to have concerns about Dr. Woodcock as a potential permanent FDA Commissioner, especially given the role she played in approving and labeling opioid-based medications,” Sen. Maggie Hassan (D-N.H.), a member of the Senate Health, Education, Labor and Pensions Committee, said in a statement. “That’s why I’ve called on President Biden to put forward an FDA commissioner who will act independently from the industry that he or she regulates.”

Sen. Joe Manchin (D-W.Va.), a centrist, has also called on the administration to prioritize nominating a different commissioner, citing concerns about the opioid epidemic and the FDA’s controversial approval of the Alzheimer’s drug Aduhelm.

“Dr. Woodcock is not the right person to lead the FDA,” he wrote in a June letter to Biden.

Two months earlier, Sen. Catherine Cortez Masto (D-Nev.) vowed to oppose a potential Woodcock nomination.

Her prospects have not improved over the summer.

In a statement, Sen. Ed Markey (D-Mass.) called for a “permanent, qualified, trusted” commissioner to address the pandemic and opioid epidemic. Without specifically mentioning Woodcock, he said, “The FDA needs a leader who will learn from the agency’s past mistakes to ensure it never makes them again.”

Other names floated for commissioner include Zeke Emanuel, former health policy adviser in the Obama administration and an architect of the 2010 Affordable Care Act; Michelle McMurry-Heath, CEO of the Biotechnology Innovation Organization; Katherine Luzuriaga, director of the University of Massachusetts Center for Clinical and Translational Science; and Florence Houn, who worked at the FDA during multiple administrations.

[….]

Some experts emphasized that it’s more important to get the right nominee than to rush one through the Senate.

“It’s taken the administration rather a long time to make a decision,” said Diana Zuckerman, president of the National Center for Health Research. “It makes it even more important that they make the right decision, not just be pushed into making a decision in the next X number of weeks or months.”

Zuckerman called for the Biden administration to prioritize choosing a nominee with a “very strong public health perspective,” noting that Woodcock has become an “untenable” candidate amid the opposition and “controversial” decisions at the agency during her tenure, which dates back to 1986.

[….]

To read the entire article, click here.

Beleaguered FDA in talks for drug-company funding

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Eleanor Laise, Marketwatch: July 13, 2021

Amid a firestorm over its approval of a new Alzheimer’s treatment, the Food and Drug Administration is holding closed-door meetings with companies it regulates — talks that critics say allow drug and device makers to exert outsize influence over the agency’s operations, threatening to erode public trust in the agency at a critical moment.

The talks focus on “user fees” that pharmaceutical and medical-device companies pay to the FDA annually and when applying for approval of new products. The FDA in recent years has become increasingly reliant on such payments, which funded nearly half of the agency’s total spending in fiscal year 2020. In exchange for the fees, the FDA agrees to certain deadlines for reviewing new-product applications, the type and frequency of meetings with companies submitting applications, and other commitments. The medical-product user-fee agreements are generally renegotiated every five years — a process that’s happening now, in advance of the current agreements’ expiration next year — and submitted to Congress for authorization.

Although the FDA is required by law to consult with patient and consumer advocacy groups on the discussions and make minutes of its industry meetings public, the meat of the talks often remains hidden, observers say. Since September of last year, the FDA has held more than 150 meetings with industry to discuss fee agreements for brand-name prescription drugs, generics, medical devices and biosimilars (products similar to branded biologic drugs), which together are expected to generate nearly $2 billion for the agency this fiscal year. Yet consumer advocates and other outside groups attempting to track the discussions say they remain in the dark about most of the details. FDA summaries of some recent meetings have been posted months after the fact or sum up a discussion in a single sentence. Medical-product safety experts say they’ve repeatedly asked for more access and details on the negotiations, to no avail.

“We simply can’t get a view into this process, and the lack of transparency is deliberate,” says Madris Kinard, a former public health analyst at the FDA and CEO of Device Events, which tracks medical-device adverse-event reports.

Details about the negotiations that have trickled out raise alarms among some medical-product safety experts, academic researchers and consumer advocates that the industry’s leverage in these talks ultimately puts patients at risk. User fees are speeding more products to market without a corresponding increase in resources to track the safety of those products, critics say. Yet in the current round of negotiations, FDA efforts to allocate more user fees toward monitoring the safety of medical products already on the market have met industry resistance.

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The main idea behind the user-fee programs was to speed up FDA review of medical-product marketing applications — and they’ve delivered on that front. The median time to approval for standard new-drug applications was 10 months in fiscal 2018. In the years before user fees were first enacted, the median FDA application review time was nearly three years, according to a study by Kesselheim and colleagues at Harvard and Brigham and Women’s Hospital.

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But user-fee deadlines can have serious side effects, some experts say. As the opioid crisis was exploding, “there was a question of ‘Why does the FDA keep approving the opioids?’ ” says a former FDA official. “One reason was that they had applications and had user-fee obligations to review the applications.” So long as an application met the standard requirements, “it would be approved,” he says. “That’s an example of the mindset” created by the deadlines.

Several studies have linked faster drug-approval timelines to safety issues. A 2014 study in Health Affairs found that drugs approved after user fees were enacted were more likely to get new black-box warnings or be withdrawn from the market than drugs approved in the pre-user-fee era. Other studies have found that, compared with drugs approved at other times, drugs given the green light shortly before their user-fee deadlines were more likely to have subsequent safety issues.

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In the current round of medical-device user-fee negotiations, one of the FDA’s goals is to improve device safety, including through increased funding for surveillance of devices already on the market, the agency says. That proposal met stiff resistance from the industry, according to outside groups that have received FDA briefings on the talks. At an April 7 negotiation meeting, the industry expressed the view that fees “should be solely for the premarket review process,” according to a summary posted by FDA. Medical-device trade group AdvaMed didn’t respond to requests for comment.

At the start of the prescription-drug user-fee negotiations, the FDA also emphasized its hope of improving the Sentinel Initiative, a system for assessing the safety of approved medical products. But a related proposal advanced by the FDA during the negotiations was shot down by the industry, a December meeting summary notes.  

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Revolving doors

“There’s not a lot of friction between the industry and the agency” in prescription-drug user-fee negotiations, says a former FDA official. “The industry knows it’s getting good value.”

A sign of the amicable relations: One FDA official leading the current round of prescription-drug user-fee negotiations left the agency in April of this year, according to her LinkedIn profile, to become vice president of science and regulatory affairs at BIO — one of the industry groups she’d just been negotiating with. The former FDA official, Khushboo Sharma, participated in a user-fee negotiation meeting with BIO and other industry representatives as recently as Feb. 12, according to meeting summaries posted by the agency. “That is obviously an outrageous situation and clearly undermines the integrity” of the process, says Diana Zuckerman, president of the National Center for Health Research, a nonprofit think tank.

Asked for comment, the FDA sent a link to its post-employment restrictions, which say in part that current employees who have begun seeking employment outside the federal government must immediately recuse from certain matters that affect “the discrete industry, economic sector, or other defined class of organizations in which the prospective employer operates.” BIO didn’t respond to a request for comment. Sharma says that she worked with FDA ethics officials “to ensure I was recusing myself from all appropriate activities. I started seeking post-employment opportunities after negotiations had concluded.”

When the agency’s position does conflict with an industry’s, the FDA “is not going to come out on top,” says Lisa McGiffert, a patient-safety advocate at the nonprofit Patient Safety Action Network. Given the industry’s track record of snagging many items on its wish list, some observers are concerned that the current round of negotiations could chip away at FDA standards for approving new drugs. One issue: the use of “real-world data,” which can come from insurance claims, medical records, disease registries and other sources beyond the bounds of clinical trials. In an August 2020 letter to the FDA about user-fee reauthorization, PhRMA said that real-world data and evidence “may, in some circumstances, be adequate on their own to satisfy the substantial evidence criteria for demonstrating effectiveness” of drugs.

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My breast implants are making me sick — and I’m not alone

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Pamela Appea, Salon: June 20, 2021

In November 2016, a few weeks after I had breast implant surgery, I came down with an unexpected case of thrush (an unappealing fungal infection characterized by a thick white coating on my tongue). As a Black married mother of two, even though I was still sick, I tried — but failed — to power through and take care of my kids. With intense flu-like aches, pain, and fever, it hurt to eat, drink, swallow, or even open my mouth. I couldn’t properly brush my teeth for several days.

Unfortunately, my primary care physician was on vacation. Panicked, I called the Manhattan oncologist whom I had seen a few weeks earlier. He’d been very kind to me following my DCIS breast cancer diagnosis, unilateral mastectomy and post-surgical treatment. The officer’s medical team could barely understand me when I tried to make the appointment on the phone.

“I don’t think you have thrush — didn’t I just see you a few weeks ago?” he said, trying to put me at ease as I stared at his cheerful neon tie. (I think he prided himself on his fun ties.)

It was torture opening my mouth so the doctor could diagnose me.

“Okay, that’s the worst case of thrush I’ve seen in some time,” the seasoned specialist said. He said he was putting me on antibiotics stat. I asked — or rather, wrote on a notepad, since I couldn’t speak clearly — if there could be any connection between the my immune system and the very new breast implant that was now in my body. The oncologist emphatically dismissed the notion as impossible.

Once he got the results of my lab work back, my physician said there was no evidence of anything wrong; I should bounce back in a few days. “These things sometimes happen,” he told me, smiling as he ushered me out.

While the antibiotics eventually cleared up the thrush, unfortunately I have never fully bounced back. In subsequent years since my breast implants were put in, it became even more clear that something was going on with my immune system. But none of my doctors really listened.

Although it was not formerly recognized by the medical community until recently, Breast Implant Illness (BII) has, in the past few years, finally received attention from both media and researchers. Nicole Daruda founded a Facebook’s support group, called Breast Implant Illness Healing by Nicole, in 2013; now, it boasts over 145,000 members. Daruda tentatively estimates that 50,000 women in the US have BII, although precise research-backed numbers are not readily available

“We are overwhelmed by women trying to join the Facebook group to be educated about Breast Implant Illness,” Daruda said. She estimates that 3,000 to 5,000 women message the group’s moderators every month. To try to meet the demand, Daruda later founded a nonprofit, Healing Breast Implant Illness Society of North America.

Research is just barely starting to emerge on BII. One study, published in Annals of Plastic Surgery in 2020, followed 750 women suffering from Breast Implant Illness over a multi-year time period. Once these women surgically removed their breast implants, the vast majority reported the majority of their symptoms had significantly improved or disappeared entirely.

Awareness appears to be growing, too. A wave of celebrities are talking more openly about breast implants and their health and wellness — including Victoria Beckham, Ayesha Curry, Ashley Tisdale, Chrissy Teigen and others.

A documentary that touches on the subject of BII, “Explant,” is screening right now at the Tribeca Film Festival. The film follows Michelle Visage, one of the celebrity judges on “RuPaul’s Drag Race.” Visage, a media personality, singer, DJ and actor who was well known for her signature Double-D breasts, found that doctors didn’t take her seriously when she told the specialists her immune system was out of whack. Visage experienced chronic health issues, including Hashimoto’s disease, that she now attributes to her breast implants.

Awareness of BII is crucial given the popularity of breast implants. Since 1998, the number of breast augmentation procedures in the US has increased threefold; now, they are one of the most sought-out cosmetic procedures.

“The desire for breast augmentation seems so powerful regardless of what else is going on in the world,” said Dr. Diana Zuckerman, founder of the National Center for Health Research. “What most concerns me is how reluctant most plastic surgeons have been to make sure their patients know the risks before making a decision.”

Because breast implant technology has existed for decades, many women erroneously believe they are safe.

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In the years after my implant, some of my symptoms mirrored women on support groups I found online, which is how I figured out I had Breast Implant Illness. While symptoms sometimes waxed and waned, I got used to experiencing a host of autoimmune and other symptoms like insomnia, brain fog, extreme breathlessness, cuts that took weeks to heal, rashes, frequent colds and much more.

But BII is no longer regarded as a myth. Many or even most doctors, including plastic surgeon Dr. Anthony Youn, believe Breast Implant Illness is real. Dr. Youn acknowledges it is a controversial topic among many of his fellow American plastic surgeons.

“If you’re happy with your breast implants and you don’t believe they are adversely affecting your health, then there is no need for treatment. If you are sick and believe your implants may be the cause, speak with your primary care physician and a board-certified plastic surgeon about whether explantation may be a possible solution for you,” Dr Youn said. “There are many causes of the symptoms of Breast Implant Illness (BII) that don’t involve breast implants, so it’s often best to rule those out first,” he continued.

In his 17 years of practice in the metro Detroit region, Dr. Youn, a member of the American Society of Plastic Surgeons and The Aesthetic Society, has performed surgery on thousands of women who elected to get breast implants. Anecdotally, he estimates the number patients who later returned to his practice stating they had Breast Implant Illness symptoms is an extremely small percentage.

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Though not all women with breast implants go on to develop Breast Implant Illness, all women deserve education, informed consent, insurance coverage and most important information about potential risks. If, in 2015, there had been an FDA Breast Implant Black Box Warning (which was officially unveiled in late 2020), I honestly never would have gotten breast implants in the first place.

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