Tag Archives: FDA

Beleaguered FDA in talks for drug-company funding

Eleanor Laise, Marketplace: July 13, 2021


Fees paid by drug and device makers influence agency operations at the expense of patient safety, critics say.

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.

[….]

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.

[….]

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.

[….]

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.  

[….]

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.

[….]

To read the entire article, click here.

Former ‘Bachelorette’ Clare Crawley Is Removing Her Breast Implants Over Health Concerns—Here’s What to Know

Korin Miller, Health: July 06, 2021


Clare Crawley is opening up about her decision to have her breast implants removed over concerns they’re impacting her health.

The Bachelorette star shared the news in a video posted to Instagram that she titled, “Coming to Terms.”

“I’m sharing this in hopes that it might help others going through something similar feel not so alone,” Crawley, 40, wrote in the caption. “I feel that this was important to share so I can be a resource for anyone going through this as well. I know how being your own health advocate is hard sometimes, and can feel like an uphill battle. This is the reality of life for so many people though! I’m just so incredibly thankful to all the people who are in my life that support me not only in my peaks but in the valleys as well.”

In the video, Crawley revealed that she’s been struggling with persistent medical issues over several years. “I’ve been going through things medically with my body that I have not had answers to, to be honest,” she said. “My skin has been having really bad hives and rash. My whole body is just inflamed and itchy.”

Crawley said that she’s also had “blood test after blood test” and seen several doctors. But test results didn’t give her answers about what is going on in her body.

After having two mammograms and an ultrasound—which revealed what she said were sacs of fluid behind her implants—she consulted with her doctor and decided to have her implants removed. “As much as I love my implants, my body is fighting them and recognizes it as something obviously foreign in my body,” she said, adding that blood tests showed an elevated white blood cell count over the past few years. “My body can’t heal. My body is in fight mode, constantly. It’s exhausting, it’s frustrating. It’s all making sense.”

While Crawley said that her decision isn’t the right one for everyone, it’s what’s best for her. “My health is the most important thing. They are coming out,” she said.

Crawley received messages of support in the comments, including from Kayla Lochte, wife of Olympic swimmer Ryan Lochte, who shared in March that she had her implants removed over health concerns—specifically she specifically cited as breast implant illness (BII). “Best of luck Clare! Get those toxic bags out,” she said.

While Crawley herself didn’t specifically say that she has BII, she implies it. Here’s what you need to know about the condition—and what to do if you think your breast implants may be impacting your health.

What is breast implant illness, exactly?

It’s important to get this out of the way upfront: Breast implant illness (again, BII) isn’t a medical diagnosis, and there are no hard numbers on how often BII happens.

[….]

That said, the US Food and Drug Administration (FDA) concluded last year that breast implants should have a “black box” warning to help women make “informed decisions” about potential risks associated with breast implants, including BII, which the FDA labels as “systemic symptoms.” It’s also important to note that BII is different from breast implant-associated anaplastic large cell lymphoma (BIA-ALCL), a type of non-Hodgkin’s lymphoma that can develop following breast implants, per the FDA.

BII is tricky to diagnose. “The symptoms women report are pretty nonspecific, and could be related to another illness,” Janie Grumley, MD, a breast surgical oncologist and director of the Margie Petersen Breast Center at Providence Saint John’s Center and associate professor of surgery at Saint John’s Cancer Institute in Santa Monica, Calif., tells Health. “It ends up being that, once we’ve worked out everything else and can’t figure out what’s going on, that’s when we think the issue may be breast implants.”

Research has suggested this is a real health concern. One July 2020 retrospective study published in the Annals of Plastic Surgery looked at 750 patients who had their breast implants removed by a surgeon over a two-year period. Researchers found that patients had “significant and sustained improvement” in 11 different symptoms after surgery. Patients found their symptoms improved within 30 days after having their implants removed.

Another study published in the same journal in January 2019, found that people with silicone breast implants had higher rates of the autoimmune conditions Sjogren syndrome, scleroderma, and rheumatoid arthritis than those who don’t have implants. They also had a higher risk of stillbirth and melanoma.

Why might breast implants make some people sick?

“All breast implants have a silicone shell that also contains various chemicals and small amounts of heavy metals,” Constance M. Chen, MD, a board-certified plastic surgeon and breast reconstruction specialist, tells Health. “Some breast implants also have a silicone filling that can leach off an intact implant or spill out of a ruptured implant. The silicone, chemicals, and/or heavy metals in the body can make some women sick.”

[….]

Scar tissue usually develops around the implant inside the body in an attempt to protect it from the “invader,” Diana Zuckerman, PhD, president of the National Center for Health Research who has researched breast implant safety, tells Health. “For some women, the scar tissue provides the protection they need, and they feel fine,” she says. “For other women, their bodies react more strongly, with an autoimmune reaction or other kind of reaction.”

What should you do if you suspect your implants might be causing your health issues?

You should talk to your doctor, Dr. Grumley says. Just know this, per Dr. Zuckerman: There’s no test that can tell if the implants are making you sick while they’re still in your body. But, she says, “if women find that they are developing symptoms that don’t go away, they should consider getting their implants and the scar capsule removed.”

It’s important to see a doctor who has experience in breast implant removal, Dr. Zuckerman says. Not only do they know what they’re doing, they’ll also know to remove the scar tissue that’s formed, which can contain silicone gel. If they don’t, “the chances of your health improving is not as good,” she explains.

[….]

To read the entire article, click here.

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

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.

[….]

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.

[….]

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.

To read the entire article, click here.

Congressman calls for FDA to continue vaccine trials

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


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

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

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

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

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

[…]

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

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

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

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

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

[…]

Read the full article here

Covid-19: Should vaccine trials be unblinded?

Jeanne Lenzer, BMJ: December 29, 2020.


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

 

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

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

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

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

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

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

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

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

Loss of data

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

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

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

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

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

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

Footnotes

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

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

https://bmj.com/coronavirus/usage

References

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

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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. 

Read the full article here

FDA Panel To Lay Regulatory Groundwork For COVID-19 Vaccine


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


NOEL KING, HOST:

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

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

SYDNEY LUPKIN, BYLINE: Good morning.

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

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

KING: How?

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

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

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

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

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

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

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

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

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

[…]

Read or listen to the full article here

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.  

Read the full article here.

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.

[…]

Read the full article here.

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.”

Read the full article here