Tag Archives: FDA

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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FDA Vaccine Rules Challenged as Weak at Advisory Panel Meeting

Anna Edney and Robert Langreth, Bloomberg Business: October 22, 2020


About two dozen outside advisers to the FDA with expertise in infectious diseases met Thursday 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.

Archana Chatterjee, advisory panel member and dean of Chicago Medical School, said the public has a lot of concern about safety. Meanwhile, she added, “What we’re being asked to do is to build this plane as we fly it.”

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.

Panel member Amanda Cohn, who is chief medical officer at the National Center for Immunization and Respiratory Diseases, worried that the efficacy of vaccines that just meet the 50% threshold after two months may see reduced effectiveness a few months later if the shot doesn’t offer a long period of protection.

“Very rarely do we look at [vaccine efficacy] so shortly after completing a series,” according to Cohn, whose organization is part of the Centers for Disease Control and Prevention.

Design Flaws

The advisers weren’t alone in questioning the standards. Diana Zuckerman of the National Center for Health Research told the committee the vaccine trials “have serious design flaws.”

The two-month follow up the FDA has asked for is too short to establish how long a vaccine will work, and 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 Inc. and Moderna Inc., are based on new technologies that have never been used in an approved product.

The debate over the rigor of the FDA guidelines was one of two main issues debated before the committee, which heard comments from regulators, drugmakers and the public. The second questioned whether trial participants on a placebo should be advised when a vaccine is deemed to be safe and effective.

[…]

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Study finds removing breast implants improved symptoms

Kris Pickel, AzFamily.com: October 1, 2020


PHOENIX (3TV/CBS 5) — A new study may be a game changer in the debate: Is breast implant illness real? Plastic surgeon Dr. Lu-Jean Fang designed the study involving 750 women with a diverse mix of breast implants, including silicone and saline, with shells that were either smooth or textured.

Every patient underwent a total capsulectomy. It’s a surgical procedure which removes the breast implant and all surrounding scar tissue, known as the capsules.

Prior to surgery to remove the implants, patients rated the severity of 11 symptoms commonly associated with breast implant illness, on a scale from 0 to 5.

Symptoms rated in study:

  • numbness and tingling in the extremities
  • joint and/or muscle pain
  • hair loss
  • memory loss/cognitive problems
  • dry eyes and/or blurred vision
  • chronic fatigue
  • breast pain
  • rashes and/or hives
  • food sensitivity/intolerance
  • flu-like symptoms and/or low-grade fever
  • difficulty breathing

Ten days after their implants were removed, the women rated their symptoms again and repeated the survey multiple times over the next year. The data was then analyzed by a team at Case Western University led by Dr. Corinne Wee and published in the Annals of Plastic Surgery.

After years of seeing her patients’ health improve following the removal of their breast implants, Dr. Feng says the results still came as a surprise. “I didn’t think it would be this good,” says Dr. Feng. When averaged out among the group, almost every symptom improved. Most symptoms drop to ratings considered ‘none’ or ‘mild’.

“For each one of these symptoms, there is a statistical difference so it’s not by chance anymore that they improve,” says Dr. Feng.

Researchers found health improvements happened quickly. If a woman saw improvements within the first ten days after surgery, the benefits were still present a year later. The most significant improvements happened in women who were obese or had some type of hardening of the scar tissue around the implant and who made lifestyle changes such as eating a healthy diet and exercise.

Removal of saline and silicone implants resulted in similar levels of improvements. The study notes “silicone is actually present in the shells of many saline implants.”

During years of investigations, numerous women have shared first-hand accounts with CBS 5 Investigates, saying when doctors failed to diagnose the cause of their symptoms, they were led to believe their symptoms were psychosomatic or the result of aging.

Dr. Feng says her study debunks the theory that breast implant illness is something women are imagining. “It is not in their heads,” says Dr. Feng. “This is my life’s work mainly because it’s such a simple solution. You take out the implant and all the surrounding scar tissue that houses the inflammatory reaction and the implant derived material, and the patient gets better.”

DIFFERENT THAN PREVIOUS STUDIES

For breast implants illness advocates, Dr. Feng’s study provides scientific evidence to back up claims made by tens of thousands of women.

Dr. Diana Zuckerman is President of the National Center for Health Research in Washington DC. An expert on national health policy, Dr. Zuckerman has worked for decades to get stronger warnings on the risks of breast implants. “This study absolutely confirms that there are women getting sick from their breast implants, and when their implants are taken out, they get well,” says Dr. Zuckerman.

In analyzing decades of previous studies, Dr. Zuckerman says major studies sponsored or conducted by breast implant manufacturers have a created a misleading perception surrounding the safety of implants.

Dr. Zuckerman says these studies have flaws, with the results often misrepresented. In some cases, she says, women were kicked out of studies if they got sick. She also points out it can take sometimes a decade or longer for symptoms to develop, which means studies end before some women start to experience problems.

As an example, Dr. Zuckerman cites the 10 year post-approval study by breast implant manufacturer Mentor on its MemoryGel CPG Breast Implants.

She says seven years into the study, 80% percent of the 41,000 women were no longer participating in the study.

Mentor provided CBS 5 Investigates with final data from its post-approval study showing that of  the 41,452 women enrolled in the study only 6,063 completed the study.

[…]

FDA RECOMMENDS NEW WARNINGS FOR BREAST IMPLANTS

On September 29, 2020 the FDA took their strongest steps to date to increase awareness on the risks of breast implants.

The agency is recommending labeling for breast implants include a box warning, the strongest warning by the FDA that a product carries the risk of serious injury or death.

While the FDA did not mandate manufactures include the warning, they recommended the following information be included: breast implants are not lifetime devices; are associated with the cancer of the immune system BIA-ALCL; patients have died from BIA-ALCL; patients have reported systemic symptoms such as joint pain, muscle aches, confusion, chronic fatigue, auto immune disease; and that some patients recover from the symptoms after implants are removed.

The recommendations are carefully worded to acknowledge recovery from systemic symptoms may happen after implants are removed. However, the FDA stopped short of saying the implants cause the symptoms.

The FDA is also recommending a checklist for women to be given when considering breast implants.  The checklist would outline when implants should not be used; risks of implant surgery, cancer, systemic symptoms, rupture and complications; updated screening and follow up tests, implants are not lifetime devices and alternatives to implants.

The FDA says the labeling recommendations are intended to enhance but not replace discussions between patients and their physicians.

[….]

CDC SHUTS DOWN INSURANCE COVERAGE EFFORTS

Efforts to make breast implant illness an official diagnosis covered by insurance came to a sudden stop earlier this year.

Dr. Zuckerman was among the advocates invited to speak at the CDC’s March meeting on ICD-10 codes. The codes are used to diagnose medial conditions and show insurance companies why treatment is necessary. Without the codes, insurance companies will not cover the cost of treatment.

Dr. Zuckerman planned to attend the meeting and built a presentation. She says without explanation, she was notified the agency would not be exploring the option of ICD-10 codes for breast implant illness. “I was not given a reason why, other than it was considered too controversial,” says Dr. Zuckerman.

After months of requests to the CDC asking for an explanation as to why the topic was dropped from their agenda, the agency sent an email to CBS 5 Investigates stating, “There is no definitive evidence that breast implant cause the systemic symptoms.”

The agency also provided a list of ICD-10 codes providers can use for treatment and billing covering conditions ranging from breast deformity to atrophy.

However, the current ICD codes do not cover the symptoms commonly associated with breast implant illness such as fatigue, rash, joint pain and cognitive issues.

Efforts have not stopped to get ICD-10 codes for breast implant illness. Congressman Lloyd Doggett of Texas and Congresswoman Rosa DeLauro of Connecticut sent a letter to CDC Director Dr. Robert Redfield asking for clarification on why the topic was dropped.

Their letter references a growing body of research that thousands of women have been seriously harmed by breast implants and that “women continue to be denied health insurance coverage for medically necessary implant removal.”

Representatives Dogget and DeLauro point out women who elected to undergo breast implant surgery were “unaware of the potentially serious risks.”

[….]

The agency also provided a list of ICD-10 codes providers can use for treatment and billing covering conditions ranging from breast deformity to atrophy.

However, the current ICD codes do not cover the symptoms commonly associated with breast implant illness such as fatigue, rash, joint pain and cognitive issues.

Efforts have not stopped to get ICD-10 codes for breast implant illness. Congressman Lloyd Doggett of Texas and Congresswoman Rosa DeLauro of Connecticut sent a letter to CDC Director Dr. Robert Redfield asking for clarification on why the topic was dropped.

Their letter references a growing body of research that thousands of women have been seriously harmed by breast implants and that “women continue to be denied health insurance coverage for medically necessary implant removal.”

Representatives Dogget and DeLauro point out women who elected to undergo breast implant surgery were “unaware of the potentially serious risks.”

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FDA Updates Breast Implant Labeling Recommendations to Help Inform Patients About Dangerous Potential Side Effects

Beth Fand Incollingo, Cure: September 29, 2020


Makers of breast implants should supplement their labeling to include a boxed warning about health problems that can arise from the devices, along with a patient decision checklist that highlights those concerns, according to final guidance issued today by the Food and Drug Administration.

The guidance, titled “Breast Implants – Certain Labeling Recommendations to Improve Patient Communication,” recommends, but does not mandate, that manufacturers include information about two major health issues that can arise from implant use: breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) and breast implant illness (BII), an autoimmune condition that can result in brain fog, fatigue, rash, and muscle or joint pain. A draft of the document was issued in 2019.

[…]

Roxane Vermeland, a breast cancer survivor who was treated for BIA-ALCL after receiving implants as part of breast reconstruction after mastectomy, was pleased to hear about the FDA’s decision.

“This is great news,” she said in a statement to CURE®. “We have been advocating hard for this, as women need to know the risks of implants up front so they can make an informed decision. The black-box warning alone is a major accomplishment for us which will truly make women think about the decision to put implants into their bodies. I am in tears as I write this.”

Guidance details

According to the guidance, the boxed warning should state that breast implants are not considered lifetime devices; the chance of developing complications increases over time; some complications will require more surgery; implants, particularly textured ones, have been associated with the development of BIA-ALCL; and implants have been associated with systemic symptoms. The checklist should note situations in which the device should not be used; considerations for a successful breast implant candidate; risks associated with surgery and BIA-ALCL; the importance of appropriate physician education, training and experience; the risk of BII; and should suggest discussion of options other than breast implants, the guidance states.

The guidance also suggests updates to the silicone gel-filled breast implant rupture screening recommendations, stating when MRIs should be conducted; inclusion of an easy-to-find description of the materials used to make the implants; and provision of patient device cards that will inform patients about what kind of implants they have, state a serial or lot number for the specific devices and include a toll-free phone number for the manufacturer.

The labeling recommendations are intended to enhance, but not replace, discussions between doctors and patients about the benefits and risks of breast implants, the FDA wrote in a press release.

Finally, the FDA has updated its guidance titled “Saline, Silicone Gel, and Alternative Breast Implants” to make it consistent with the new labeling recommendations. The FDA stated that it will continue to work with professional medical societies, patient advocacy groups and women’s health organizations to help ensure that risk information about breast implants is disseminated to patients.

“As new information has become available about the risks and complications of breast implants, it is critical that women have access to information they need to make informed decisions,” Dr. Binita Ashar, director of the Office of Surgical and Infection Control Devices in the Center for Devices and Radiological Health, said in the release. “After working with stakeholders, including patients, today we are recommending format and content changes to breast implant labeling so the information is presented in an easy-to-understand way. It is important that patients discuss the risks and benefits of breast implants with their health care provider, and we hope that these labeling recommendations will help in facilitating these discussions.”

[…]

Diana Zuckerman, president of the National Center for Health Research and its Cancer Prevention and Treatment Fund, also had a concern, pointing out that guidance from the FDA usually consists of recommendations that are not enforceable.

“That’s a big question for us,” she said in an interview with CURE®. “Because we know from experience that, if it’s a suggestion, there are just a lot of doctors who aren’t going to follow through. We think this needs to be required, and we will be working with the plastic surgeons’ medical societies to try to ensure that they urge their members in the strongest possible terms to use this checklist, either the FDA’s version of it or our version, which we think is better.”

An ongoing issue

The FDA also acted on testimony given at the March panel when it requested in July that Allergan, which was since purchased by AbbVie, issue a worldwide recall of any of its Natrelle Biocell textured implants and tissue expanders that remained on shelves. That’s because textured implants, particularly the Natrelle Biocell product line filled with either saline or silicone, have been linked with BIA-ALCL. As of Jan. 5, the cancer had been diagnosed in 733 patients and killed 36, the FDA reported Aug. 20.

“Although the overall incidence of BIA-ALCL appears to be relatively low, once the evidence indicated that a specific manufacturer’s product appeared to be directly linked to significant patient harm, including death, the FDA took action to alert the firm to new evidence indicating a recall is warranted to protect women’s health,” Dr. Amy Abernethy, the FDA’s principal deputy commissioner, said in July.

[…]

First identified about 20 years ago, BIA-ALCL is a rare type of non-Hodgkin lymphoma that arises specifically in women with implants. The FDA first warned women about BIA-ALCL in 2011.

Breast implant illness, meanwhile, seems to occur more often in women who have a personal or family history of autoimmune conditions, experts said, suggesting that more research is needed and that these women should be warned before getting implants. One expert at the 2019 hearing said that this group should opt against implants.

Jennifer Cook of Georgia, who received a diagnosis of BIA-ALCL in 2017, told the 2019 FDA panel that she received her implants as part of a clinical trial and signed a consent form stating that there was no established scientific evidence linking them with cancer. Over many years, she said, no one informed her that a risk had been established, and she found out only by watching a play on the topic at the middle school where she taught.

“I was shocked and thought I would need to reprimand the students for making false statements, and then I learned the horrifying truth,” Cook said. “Shortly thereafter, I recognized that I had symptoms. I was blindsided. I was deceived, and I don’t want anyone else to go through that.”

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Women with Breast Implants Should Not Need to Wait for Safety Information They Urgently Need

Rose Weitz and Diana Zuckerman, Our Bodies Ourselves: July 1, 2020


Although breast implants have been sold since the 1960s, the U.S. Food and Drug Administration (FDA) first approved the use of silicone gel breast implants in 2006. By then, many women with implants had already reported a range of problems, which result in many women seeking additional surgery within just a few years of implantation.

And the problems have become more serious. Last year, for example, Allergan did a worldwide recall of their textured Biocell breast implants and expanders because of evidence that these implants caused an increased risk of a type of lymphoma called ALCL.

The FDA has the authority both to require solid evidence of safety before putting any implant on the market and to require companies to collect health data from implant patients for years afterward. Without these data, it is impossible for women or their doctors to know what are the possible consequences of different implants, what symptoms to look for, and which implants should be surgically removed – assuming an individual knows the make and model of their implant and can afford up to several thousand dollars to remove it.

Collecting data is a small thing to ask of manufacturers who have been profiting from breast implants for many years. Yet even this has proven too much for these companies, or for the FDA to enforce. For example, in May 2019 the FDA sent letters to two manufacturers, Mentor Worldwide and Sientra, warning that the manufacturers had failed to collect the required data for implants that were already on the market and would need to improve their data gathering or face potential criminal or civil penalties. The FDA also sent warning letters in May 2020 to Allergan and Ideal. The FDA criticized Allergan for their failure to recruit and follow-up with as many patients as had been promised. The agency warned Ideal that the companies’ efforts to rectify previous problems were inadequate, including failing to accurately report consumer complaints, failing to keep adulterants out of its silicone, and failing to notify the FDA about malfunctions of its implants that could result in death or serious injury. Meanwhile, all these implants are still on the market.

Last October, in response to the pleas and demands of thousands of breast implant patients, the FDA proposed that a black box warning be affixed to all implant packages to inform women and their doctors about the most serious risks of breast implants. In addition, the FDA proposed that all patients be required to sign an easy-to-understand checklist of possible risks before implant surgery is scheduled.

These proposals were much weaker than what patients and their advocates had demanded. In response to the FDA’s request for public comments, a Working Group of patients, public health advocates, and plastic surgeons submitted a critique — along with a petition signed by over 70,000 people – urging the FDA to be more explicit about the proposed warnings. Public comments were due in December 2019, but as of June 2020 the agency has still not revised its proposal.

Buyer beware, indeed.

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CRS: Congress Can Rein in FDA’s Flexible Covid-19 Vaccine Trial Policies

Beth Wang, Inside Health Policy: June 03, 2020


The Congressional Research Service says Congress could rein in FDA’s broad discretionary authority over vaccine clinical trial policies by legislating how the agency and Institutional Review Boards approach clinical trial designs and reviews for the current COVID-19 pandemic, as well as for future emergencies. In a Tuesday (June 2) report, CRS suggests Congress could provide more specific direction to FDA and IRBs on how to approach clinical trials in emergency situations, and also could appoint a neutral scientific body to consider ethical and scientific issues as well as general guidelines for trials. Congress also could fund global collaboration among regulators, and provide additional funding and resources to facilitate clinical trials, the report suggests, echoing recent calls from lawmakers who have said the United States should get involved with global efforts to fund and develop COVID-19 vaccines and treatments.

Diana Zuckerman, president of the National Center for Health Research, applauded CRS for explaining the vaccine approval process to Congress and for telling lawmakers what their options are so Congress can, in Zuckerman’s words, “ensure a better outcome than we’ve seen with the disastrous coronavirus testing situation (in terms of accuracy, transparency, and availability).” The document, she told Inside Health Policy, does a good job of explaining that FDA has authority to lower approval standards for any drug or vaccine unless Congress steps in. “[B]ased on FDA’s actions of the last 3 months, it seems likely that they will do so in ways that could create the free-for-all that currently exists for coronavirus testing,” Zuckerman wrote in an email. “So the CRS is telling Congress that legislation is the option they have if they want to ensure a better outcome.”

Existing law, CRS says, requires FDA and IRBs to weigh considerations about safety and effectiveness against the desire to bring products to market quickly when evaluating proposed clinical trial designs for vaccines.

[…]

Congress previously told FDA what to do in the drug trial and approval space through passage of the 21st Century Cures Act, but FDA was given leeway in how to interpret the law, Zuckerman explained. “It pushed FDA in a particular direction but still gave the FDA the authority to rely on the agency’s subjective judgment,” she said. If Congress were to step in and tell FDA what it should do, it would be a radical departure, Zuckerman added. “[But it’s] probably necessary given FDA’s response to the pandemic so far, and the Administration’s track record of ignoring Congress when it suits them,” she said.

Read the entire article here.