Tag Archives: FDA

‘What Happens When the Doctors Can’t Trust the Government?’

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Danielle Ofri, NY Times 7/28/25: Doctors Have Lost Their Mount Olympus of Medicine

This entire essay is worth reading but may be behind a paywall.

An excerpt:

For most of my colleagues and me, the C.D.C. and the N.I.H. were the medical Mount Olympus, the towering pillars of medical authority. Contrary to right-wing portrayals, these were not dictatorial authorities. These were earned authorities, comprising our best, brightest and most dedicated peers. The formidable talents of these doctors and scientists would have commanded enviable salaries had they taken jobs in industry, but they chose the public sector instead — something that we clinicians were forever grateful for… 

While there are some doctors who viewed our public health institutions with disdain — some of them now are running these very organizations — most practicing physicians relied heavily on them to deliver the best care possible to their patients, despite occasional quibbles. What a relief, I always felt, that there were people organizing the things I can’t do — testing new treatments, conducting population studies, keeping tabs on worldwide diseases, issuing guidelines and more.

But now that support is a shell of what it once was. I can no longer automatically rely on these institutions because their scientific North Star, even if imperfect at times, has been replaced by one that seems nakedly political. Remaining staffs are no doubt working valiantly to do their jobs, but they are hobbled by loss of colleagues, resources and reliable leadership. So when I hear that the C.D.C. has changed a vaccine recommendation, I now question whether that’s a recommendation I can trust. When the F.D.A. commissioner says he wants to change how the agency approves or rejects new treatments, I no longer feel sure that science is driving those decisions. It’s hard to convey how profoundly grieved my colleagues and I feel…

Robert F. Kennedy Jr.’s view seems to be that we doctors are shills for corporate interests and government bureaucrats, and that torching our vaunted institutions is the prescription to fix us. Mr. Kennedy’s ire seems oddly directed. I, too, am disgusted by the role of money in health care, but I see it more as a result of the system we’ve set up, rather than the people who labor within it…

Notably missing from Mr. Kennedy’s Make America Healthy Again agenda is any suggestion that we provide universal health care, as most other developed countries do. There is no push to expand Medicare and Medicaid, which help some of our sickest patients. There is no focus on expanding access to early childhood education and supplemental nutrition programs, which offer steep health benefits…[There] is a barely concealed antipathy toward the people who are the engine of these institutions — doctors, scientists, policy wonks…

Cuts to infectious-disease surveillance means that outbreaks will almost certainly creep up more stealthily on our patients. Cuts to the National Center for Chronic Disease Prevention and Health Promotion means fewer resources for prevention of cancer, heart disease and diabetes — some of the leading causes of death. Cuts to the N.I.H and the F.D.A. could drastically reduce the development and approval of new medical treatments. Add in cuts to injury-prevention research and patient safety programs, and it’s a prescription to make America sick again.

Every time you go to your doctor or get treated by a nurse, there’s a chorus of researchers, public health workers, policy experts, epidemiologists and advisory panels arrayed behind them, aided by laboratories, databases, websites, early-detection systems and clinical guidelines. Our current government seems determined to wrench this away, handicapping your health care team’s ability to care for you.

My take (borrowed in part from author): Our health care system needs to improve costs, accessibility, and outcomes. Yet, the changes to our healthcare and research under this administration are making matters worse. “So many of our resources are now gone, and those that remain no longer feel trustworthy. Americans’ health will decline at the hands of our federal government. And there’s no vaccine for that.”

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Giant Lily Pads in Oxford, UK

Silencing the FDA’s Voice on Drug Information

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T Watson, C Robertson. NEJM 2023; 389; 25: 2312-2314. Silencing the FDA’s Voice — Drug Information on Trial

Recently (9/1/23), “a panel of the Fifth Circuit Court of Appeals allowed a case to proceed against the Food and Drug Administration (FDA) concerning its public statements on the use of ivermectin for treating Covid-19.1“ Even though a district court had dismissed the suit due to “sovereign immunity,” the Fifth Court stated the FDA had exceeded its authority.

Some excerpts from this commentary:

Between August 2021 and April 2022, however, the agency released several public messages about ivermectin and Covid-19 — including an informal consumer update titled “Why You Should Not Use Ivermectin to Treat or Prevent COVID-19”…

Three physicians who prescribed and promoted ivermectin for Covid-19 treatment sued the FDA, alleging that its statements interfered with their ability to practice medicine and harmed their professional reputations, even though they hadn’t been named by the FDA. One doctor claimed the agency’s statements had caused him to be referred to his state medical board; the others claimed to have lost admitting privileges at a hospital and a role at a medical school.

According to the Fifth Circuit, the FDA “has authority to inform, announce, and apprise — but not to endorse, denounce, or advise”….

The Fifth Circuit panel’s opinion is puzzling in light of the FDA’s long-standing and generally unquestioned role as a public health educator. The agency routinely releases consumer-directed information; for example, its website instructs consumers about the appropriate use of antibiotics and includes related clinical information. The opinion suggests the FDA may need to reevaluate each of these communications — an impractical proposition.

The opinion is also in tension with a long-standing constitutional principle known as the government speech doctrine, according to which the government can itself be a speaker, like any person or corporation, and isn’t required to be neutral when it expresses an opinion..

The Fifth Circuit’s holding reflects suspicion of agency influence, even in matters in which the agency is an expert speaking directly about products it regulates. The court’s interpretation of the FDA’s proper role may permit only narrow forms of expression...

Subsequent courts could use the Fifth Circuit’s logic to disempower other agencies with health-related missions, such as the Centers for Disease Control and Prevention and the Environmental Protection Agency… Meanwhile, “junk science” pervades social media and harms public health.2

My take: It is hard to believe that the justification for this challenge comes from three physicians prescribing ivermectin. It turns out the FDA’s advice was spot on and that these physicians were offering an ineffective therapy. This is a worrisome trend in which the judicial branch seeks

  1. To limit government agencies without explicit line-by-line authorization by a dysfunctional congress
  2. And to substitute its judgement over matters in which it has little expertise over governmental agencies tasked with protecting our country (eg. FDA, CDC, EPA, and others)

Here is a link to one of the FDA’s communications on Ivermectin –good advice (12/10/21): Why You Should Not Use Ivermectin to Treat or Prevent COVID-19

Related blog posts:

Misinformation in Medicine

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RJ Baron, YD Ejnes. NEJM 2022; 387:1-3. Physicians Spreading Misinformation on Social Media — Do Right and Wrong Answers Still Exist in Medicine?

The authors, representing the American Board of Internal Medicine (ABIM), assert that “there aren’t always right answers, but some answers are clearly wrong.” In their commentary, they note that there is “growing allegiance to crowd-endorsed ‘facts.'” Yet, they expect physicians to adhere to higher standards; however, they note the inherent conflict between speech that can be prohibited by licensing boards and speech protected by the First Amendment.

My take: While the authors state that physicians risk disciplinary action for spreading misinformation, I remain skeptical that licensing boards have the appetite to do this, particularly when it comes to disciplining high-profile offenders like Mehmet Oz or Joseph Ladapo (Florida Surgeon General) (Business Insider: Dr. Oz is running for US Senate in Pennsylvania. Here are 8 times he’s made false or baseless medical claims; Insider: Florida’s surgeon general breaks with CDC advice, says the state will be the first to ‘officially recommend against the COVID-19 vaccine for healthy children‘).

PA Cohen et al. NEJM 2022; 387: 3-5. Institutionalizing Misinformation — The Dietary Supplement Listing Act of 2022

Dietary supplements are another part of medicine with rampant misinformation. In fact, there is nearly ubiquitous misinformation through advertisements across all media segments. Americans spent ~$55 billion on dietary supplements in 2020. This commentary discusses a Senate bill, the Dietary Supplement Listing Act of 2022, which ostensibly would improve this situation.

However, this is NOT the case. This bill requires manufacturers to provide the FDA with a product’s name, ingredients and health claims. It mandates the FDA create a searchable database. What the legislation doesn’t do:

  • Provide the the FDA with a mechanism to confirm a product’s ingredients
  • Enable regulation of misleading health claims
  • Stop the promotion and sale of supplements with dangerous ingredients
  • Allow the FDA to remove products from its registry determined to have unlawful ingredients and remove products deemed hazardous

My take: This legislation needs to be strengthened to limit deception. In its current form, this registry would appear to confer FDA oversight to dietary supplements (which is minimal) and paradoxically legitimize dietary supplements .

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Hilton Head at Sunrise

Genus Medical Technologies v FDA -Lack of Judicial Deference to FDA Expertise

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A recent commentary (PJ Zettler et al. NEJM 2021; 385: 2409-2411. A Divisive Ruling on Devices — Genus Medical Technologies v. FDA) highlights another challenge facing the FDA’s role in regulating devices, especially as the definition of devices and medications becomes more murky.

Key points/excerpts:

  • In April 2021, however, the U.S. Court of Appeals for the District of Columbia decided, in Genus Medical Technologies v. FDA, that products meeting the FDCA’s definition of a device “must be regulated as devices”…The Genus case concerned a challenge to the discretion of the FDA to classify Genus Medical Technologies’ Vanilla SilQ line of diagnostic barium sulfate contrast agents as drugs rather than as devices…FDCA’s drug and device definitions overlap.
  • Ultimately, the D.C. Circuit Court held that products meeting both definitions must be regulated as devices because the FDCA’s “text unambiguously forecloses the FDA’s interpretation.” The court did not give the FDA so-called Chevron deference, a doctrine under which courts defer to an agency’s reasonable interpretation of a statute that it implements, if the statute is ambiguous.
  • Because technological innovation often outpaces legal change, we believe it could serve both public health and industry for the FDA to retain some discretion regarding the most appropriate regulatory pathways for anticipated and as-yet-unforeseen device classes… overly restricting the FDA’s flexibility to use its expertise could endanger important public health priorities, especially when there are compelling reasons why Congress permitted flexibility.
  • The Genus decision comes at the end of a decade of growing challenges to the FDA’s authority to regulate. From court decisions in the early 2010s that were sympathetic to arguments that FDA policies regarding off-label drug promotion violate the Constitution’s First Amendment, [and] to the political (and legislative) success of right-to-try laws

My take: This commentary shows the difficulties the FDA faces as the judiciary curtails its discretion. While the legislative branch could codify FDA authority, this is unlikely. As such, this will limit FDA oversight in some new medical products. When problems arise, it is likely that the FDA (not the courts) will be blamed despite the fact that their ability to regulate has been undermined.

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Huntingdon Lake. Sandy Springs, GA

Eric Topol to Stephen Hahn/FDA: “Tell the Truth or Resign”

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An open letter from Eric Topol to Dr.Stephen Hahn details a number of glaring mistakes at the FDA which threaten its credibility and its mission.

Here’s the link: Dear Commissioner Hahn: Tell the Truth or Resign

The letter points to three high profile, politically-fraught decisions at the FDA:

  1. Authorization of hydroxychloroquine
    • “Immediately after President Trump widely and aggressively promoted hydroxychloroquine as a “miracle drug,” on March 30, 2020, you granted an Emergency Use Authorization (EUA) for this drug without any sufficient or meaningful supportive evidence”
  2. Authorization of convalescent plasma
    • “This is a major advance…[A]nd a 35% improvement in survival is a pretty substantial clinical benefit. What that means is — and if the data continue to pan out — [of] 100 people who are sick with COVID-19, 35 would have been saved because of the admission of plasma.” Every part of that statement is incorrect and a blatant misrepresentation of the data. “
  3. Authorizaton of remdesevir
    • The third breach of evidence-based data was your EUA issued August 28, 2020 broadening the remdesivir approval to include any patient hospitalized with moderate COVID-19. There are insufficient data to support this approval, as it is based on small, open-label studies with subjective endpoints.

Dr. Topol worries that Dr. Hahn will further erode confidence in the FDA by approval of a SARS-CoV-2 vaccine prematurely.  “Any shortcuts will not only jeopardize the vaccine programs but betray the public trust, which is already fragile about vaccines, and has been made more so by your lack of autonomy from the Trump administration and its overt politicization of the FDA.”

Food-borne Outbreaks and Lack of FDA Transparency

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A recent opinion piece from FoodSafetyNews highlights the lack of transparency from the FDA regarding food-borne outbreaks (several more listed below).

Bill Marler: Publisher’s Platform: A bit more about the FDA and lack of Transparency

Here’s an excerpt:

The Halloween disclosure of a multistate E. coli outbreak linked to romaine lettuce raises another concern about the FDA and transparency — the failure to disclose where consumers purchased the tainted product..

Under the Freedom of Information Act and Title 21 of the Code of Regulations, government agencies — and specifically, the FDA — are told to exempt trade secrets and commercial information from any of their releases…

Formulations, ingredients and how products are made are trade secrets.  Who supplied the tainted raw material, who made the tainted product and where the tainted product was sold are not a trade secrets – especially during an outbreak.  Simplicity, transparency and consistency allows for a visible supply chain and one that consumers can have confidence in. 

Recent outbreaks (thanks to colleague for these references):

Multistate Salmonella Outbreak Linked To Ground Beef Causes One Death, Eight Hospitalizations

  • Reuters (11/1, Maddipatla) reported, “A multistate outbreak of salmonella linked to ground beef has caused one death in California and eight hospitalizations, U.S. health officials said on Friday. A total of 10 people in six U.S. states were infected with a strain of the bacteria called Salmonella Dublin, according to the Centers for Disease Control and Prevention.”
  • TIME (11/2, Carlisle) reported, “Officials have not yet identified a single common source of the ground beef that is believed to be spreading the Salmonella Dublin based on epidemiological and laboratory evidence. According to the CDC, the sick individuals reported eating different brands of ground beef at different locations.”
  • CNN (11/1, Christensen) also reported the story.

Previously Undisclosed E. Coli Outbreak Linked To Romaine Lettuce Sickened Nearly Two Dozen People, FDA Says

  • The Washington Post (11/1, Brice-Saddler) reported, “A previously undisclosed E. coli outbreak linked to romaine lettuce sickened nearly two dozen people between July and early September, the Food and Drug Administration said Thursday – a delayed announcement one food safety lawyer called a ‘lie to the public in all respects.’” The piece added, “Illnesses associated with the outbreak infected 23 people across 12 states from July 12 to Sept. 8, according to the FDA. No patients died of their illnesses, and officials say there is no ongoing public health risk.”

Dozens more fresh vegetable products because of Listeria monocytogenes risk (11/4) (FoodSafetyNews.com)

  • A (Canadian) nationwide recall of freshcut vegetables continues to expand with dozens of products and multiple brands now on the list. Products potentially contaminated with Listeria monocytogenes are cole slaw, riced cauliflower, green beans, noodles, kale salads and more.  Some of the products do not expire for 10 days or more, so consumers and businesses are urged to check their supplies for the recalled products listed here by the Canadian government

My take: Food-borne illnesses cause 48 million cases in U.S. each year (CDC estimates) and 3000 deaths (MMWR 64:2, 2015). More transparency is needed.

Related blog post: Food Safety Lecture-It’s Still A Jungle Out There

 

Big Pharma Neglecting ‘Required’ Pediatric Studies

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A recent retrospective study (TJ Hwang et al. JAMA Pediatr 2019; 173: 68-74) examined the completion rate of FDA-required pediatric studies. Thanks to Ben Gold for this reference.

Background: In 2003, the Pediatric Research Equity Act (PREA) was signed into law and authorized the FDA to require clinical stuides to assess the safety and efficacy of new drugs and drugs with new indications in pediatric subpopulations.  However, the FDA cannot withdraw approval for a drug if a manufacturer fails to comply with PREA.  In addition, the authors note that “to our knowledge, to date, no financial penalties or enforcement proceedings have been brought against manufacturers fo noncompliance…and only 31 noncompliance letters have been issued.”

Key findings:

  • Between 2007-2014, there were 438 new drugs and/or new indications.  114 were subject to PREA. 84 were new drugs and 30 were new indications.
  • 222 studies required pediatric postmarketing clinical studies (in these 114 drugs). Only 75 (33.8%) were completed; rates were lower for efficacy studies (38 of 132 –28.8%) compared to pharmacokinetic studies (19 of 34 –55.9%).
  • As a result of the PREA-mandated studies, there was an increase in some pediatric information of drug labels in 41.2% after a median follow-up of 6.8 years, compared with 15.8% at time of approval of these 114 drugs.

The authors note that PREA is responsible for “nearly 80% of pediatric drug studies completed for FDA.” Congress also passed the Best Pharmaceuticals for Children Act which provides a financial incentive to companies if they perform certain pediatric studies.

My take: Pharmaceutical companies, for a multitude of reasons, are not completing requied pediatric studies.

Can the FDA stop snake oil salesmen?

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A recent commentary (C Robertson, AS Kesselheim. NEJM 2016; 375: 2313-5) examines how the issue of “free speech” may undermine the FDA’s ability to regulate ineffective or dangerous medications. This has been discussed in a previous blog:

Can the FDA prohibit free speech?

In a previous case, Caronia had promoted sodium oxybate for a wide range of nonapproved uses; some of these uses “were likely to cause patients substantial harm.”

Yet, the 2nd Circuit court reversed a lower court in ruling that Caronia’s sale pitches were protected free speech.  This decision “subverted decades of presumptions about how the government could oversee the behavior of the pharmaceutical and medical device industries.”

The authors hope that an upcoming case to the 1st circuit will uphold the FDAs ability to assure that patients are protected and that the use of drugs is driven by science and not marketing.  If manufacturers are allowed to promote a wide range of uses for drugs with narrow indications, there will not be an incentive to determine if these medications are safe and effective.

My take: If the principles of free speech are extended to promoting bogus claims about pharmaceuticals and medical devices, this would be a huge blow to medical science.

Acadia Natl Park

Acadia Natl Park

The Problem with Black Box Warnings

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A short article (T Elraiyah, et al. Ann Intern Med. Published online 29 September 2015 doi:10.7326/M15-1097) explains the problem with current black box warnings and what can be done to improve them. “A black box warning (BBW) is the highest level of warning issued by the U.S. Food and Drug Administration (FDA)…These warnings are required when there is reasonable evidence of association between the drug and a significant safety concern.” Key points:

  • BBWs “have been the subject of controversy, due in part to their opaque connection to the underlying body of evidence.”
  • The authors reviewed 70 BBWs from the top 200 drugs.  “We found only 19 (27%) provided an estimate of the likelihood of harm, and only 8 (11%) reported a CI for that estimate.”
  • “Fewer than half (43%) presented the source of evidence. None described the quality (certainty of the evidence).”
  • “None provided guidance on how to communicate or act on the evidence.”

The authors state that “BBWs infrequently contain 3 elements required for evidence-based practice (estimate of effect, source and trustworthiness of evidence, and guidance on implementation).” There are some medicines that already have a well-presented BBW, including Advair-diskus.

My take: Black box warnings can generate a lot of anxiety and may adversely affect the calculation of benefit versus harm.  Improving them could be helpful for patients and doctors alike.

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Atlanta Botanical Gardens

Atlanta Botanical Gardens

 

Critique of the 21st Century Cures Act

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The most compelling article (Avorn J, Kesselheim AS. NEJM 2015; 372: 2473-5) in a recent edition of the NEJM delved into the 21st Century Cures Act which was recently introduced in the U.S. House of Representatives; it was approved 51 to 0 in committee but continues to be debated.

One of the underlying premises of the bill is accelerate approval for new products. Key features:

  1. Increase in National Institutes of Health (NIH) of about 3% per year for 3 years. And, additional $2 billion per year for 5 years to create an “NIH Innovation Fund”
  2. Instructs FDA to consider nontraditional study designs for clinical trials.  This is aimed at shorter, smaller and less expensive studies.  This could allow FDA to rely on “observational studies” and “clinical experience.”
  3. The bill encourages the FDA to rely more on surrogate end points
  4. The bill would allow informed consent to be bypassed if the “proposed testing poses no more than minimal risk.”

Critiques for each point, point by point:

1. The funding increases largely counterbalance stagnating funds at the NIH secondary to sequestration and budget cuts.

2.  The premise that the FDA is inefficient is not accurate.

  • “A third of new drugs are currently approved on the basis of a single pivotal trial” with a median of 760 patients.
  • Most drugs are approved based on studies with a duration of 6 months or less, even medications taken for a lifetime.
  • Evaluation of nearly all new drug applications is completed within 6 to 10 months.

3.  Surrogate markers often overestimate the potential benefit of medications.  The FDA “already uses surrogate end points in about half of new drug approvals.” Specific examples:

  • Bevacizumab has been shown to delay tumor progression in breast cancer “but was shown not to benefit patients.
  • Rosiglitazone “lowered glycated hemoglobin levels in patients with diabetes even as it increased their risk of myocardial infarction.”
  • One new tuberculosis drug improved bacterial counts in the sputum but “the treatment group had a death rate four times that in the comparison group.”

4.  Informed consent has been “sacrosanct, with exceptions made only when consent is impossible or contrary to a patient’s best interests.”  With this new proposal, “it is not clear who gets to determine whether a given trial of a new drug poses “minimal risk.”

Bottomline (from authors): The 21st Century Cures Act’s call for increased NIH funding may prove to be its most useful component.  But political forces…could lead to the approval of drugs and devices that are less safe or effective than existing criteria would permit.”

Audio interview with Jerry Avorn: nej.md/1TPy6Ta

Some pictures from yesterday’s Peachtree Road Race:

Coveted T-shirt -2015 Edition

Coveted T-shirt -2015 Edition

Screen Shot 2015-07-04 at 6.34.03 PM

Rainy Day for a 10K

Largest 10K in U.S

Largest 10K in the World