Category Archives: We Are Quoted

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.

4 in 10 Adults Over 50 Consult Online Reviews When Picking a Doctor

Steven Reinberg, HealthDay: April 14, 2021


Finding a new doctor can be a daunting task. For help, many older adults turn to online reviews, a new study finds.

In fact, many people rate online reviews as highly as they would a recommendation from friends and family when picking a doctor, the new research found.

“Doctors and policymakers should know that many older adults are viewing and valuing online ratings and reviews when choosing physicians,” said researcher Dr. Jeffrey Kullgren. He’s an associate professor of internal medicine at the University of Michigan in Ann Arbor.

[….]

Diana Zuckerman is president of the National Center for Health Research, a nonprofit think tank that conducts research on a range of health issues. She said that choosing a doctor is a complex undertaking.

“The trouble with these ratings is they’re not based on how good the physician is,” said Zuckerman, who wasn’t involved in the new study. “They’re usually based on convenience issues, like how long do you have to wait in the waiting room, how nice is the doctor, and does the doctor listen to you. These are all nice things, but they’re not really the important things.”

[….]

In all, the survey found that 40% of adults aged 50 to 80 have used online doctor rating sites and trust them almost as much as recommendations from family or friends for choosing a doctor. Also, online ratings were seen as more important than where a doctor went to medical school or trained.

[….]

Women, people with more education and those with chronic conditions were the most likely to turn to online rating sites, the investigators found.

[….]

Zuckerman said that most people don’t have the expertise to rate a doctor in ways that are meaningful in terms of how good a physician is or how good the medical care that they’re going to get is.

Often, online ratings should be taken with a grain of salt, she said, because you don’t know exactly what the ratings are based on.

The recommendation of friends or family members can be helpful, but in the end, it’s going to be how your experience with a doctor measures up to your needs and expectations that are important. And you shouldn’t be afraid to change doctors if you’re dissatisfied with your care, she advised.

Zuckerman agreed with the researchers that it’s up to policymakers and clinicians to set standards and criteria for online reviews. Patients, too, need to understand the pros and cons of online ratings.

You can read the entire article here.

What Genentech is doing to fix biotech’s diversity problem

Fortune Editors, Fortune: April 7, 2021


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

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

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

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

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

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

[….]

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

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

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

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


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

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

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

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

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

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

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

Conflicts of Interest Cloud Risk Disclosure

[…]

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

[….]

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

[….]

The ASPS Brochure: Current Status

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

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

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

Read the full article here

Congressman calls for FDA to continue vaccine trials

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.

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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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