Notice: This commentary was written by Eric Topol, MD, editor-in-chief of Medscape, as an open letter to FDA Commissioner Stephen Hahn, MD. It first appeared on Medscape, WebMD’s website for well being care professionals.
Aug. 31, 2020 — I am writing as a result of I am gravely involved about your management of the Meals and Drug Administration (FDA). The circumstances of your statements in latest days has led to a disaster in confidence. Not solely has your credibility been diminished however so has that of the FDA, its 15,000-plus workers members, and, most significantly, your potential to supervise the well being pursuits of the American individuals.
Let me remind you of the FDA’s mission assertion:
“FDA is liable for advancing the general public well being by serving to to hurry improvements that make medical merchandise more practical, safer, and extra reasonably priced and by serving to the general public get the correct, science-based data they should use medical merchandise and meals to keep up and enhance their well being.”
The emphasis right here is on correct, science-based data. Because you have been sworn in on December 17, 2019, you may have serially demonstrated your willingness to deviate from this bedrock premise. Instantly after President Trump broadly and aggressively promoted hydroxychloroquine as a “miracle drug,” on March 30, 2020, you granted an Emergency Use Authorization (EUA) for this drug with none enough or significant supportive proof. Proof of that was borne out on June 15, 2020 while you revoked that EUA, acknowledging lack of efficacy and “ongoing critical cardiac adversarial occasions and different potential critical negative effects.”
The second main breach of correct, science-based data got here on August 23, 2020 while you participated in a press convention with President Trump and Well being and Human Providers Secretary Alex Azar billed as a “very historic breakthrough.” You mentioned, “I simply wish to emphasize this level, as a result of I do not need you to gloss over this quantity. We dream in drug growth of one thing like a 35% mortality discount. This can be a main advance within the remedy of sufferers. This can be a main advance…[A]nd a 35% enchancment in survival is a fairly substantial medical profit. What meaning is — and if the information proceed to pan out — [of] 100 people who find themselves sick with COVID-19, 35 would have been saved due to the admission of plasma.”
Each a part of that assertion is inaccurate and a blatant misrepresentation of the information. Your assertion was based mostly on a preprint, which by definition has not been peer-reviewed, printed by Mayo Clinic’s Michael Joyner and coauthors. It’s a retrospective, observational examine of over 35,000 sufferers who acquired convalescent plasma, with none controls or untreated sufferers for comparability. The declare of discount of mortality is completely unsubstantiated. That was based mostly on improved survival in a subgroup of a subgroup of a subgroup from about 1000 sufferers, who have been partitioned by timing of plasma administration (early vs late), whether or not they had endotracheal intubation, their age, and degree of antibody within the plasma they acquired. The antibody degree was decided publish facto. You realize full properly as an oncologist and researcher that that is an illegitimate evaluation that, at greatest, is hypothesis-generating, requiring a potential, placebo-controlled trial to substantiate.
Nonetheless, you posted this data-dredging subgroup evaluation on the FDA web site with the headline assertion “One other Achievement in Administration’s Battle In opposition to Pandemic.” Your EUA announcement got here the day after President Trump tweeted “The deep state, or whoever, over on the FDA is making it very tough…@SteveFDA”, addressing you straight together with your Twitter deal with.
It took 24 hours earlier than you began to make a correction on Twitter. You wrote “What I ought to have mentioned higher is that the information present a relative danger discount, not an absolute discount.”
That could be a grossly inadequate correction and doesn’t characterize the reality. This is what you did not say:
1. There aren’t any information or proof from potential, randomized trials for convalescent plasma to assist any survival profit.
2. The information I’m citing are from a subgroup evaluation from a preprint, which is meant to formulate a speculation with none definitive findings or conclusions.
3. The 35% survival profit, and 35 individuals’s lives saved per 100 sick with COVID-19, was utterly off-base. If the preprint information held up in a correct randomized managed trial, it might be avoiding deaths of three or 4 individuals per 100 who would have died. We all know that fewer than 1 out of 100 individuals who have a COVID-19 an infection die, so it’s not possible to save lots of 35 individuals’s lives of 100 individuals sick with COVID-19. I made a horrible, monstrous error and I deeply apologize for that.
4. It’s frankly unlikely for there to be a significant survival advantage of convalescent plasma, because it accommodates a broad admixture of affected person antibodies, most of which aren’t neutralizing — that’s having no impact in opposition to the virus. We want randomized trials to find out if there’s any profit and, if that’s the case, what’s the magnitude of profit. Such trials are ongoing and want strong assist and participation.
5. There are nonetheless potential issues of safety of convalescent plasma which might be unresolved, reminiscent of transmission of a virus or immune response.
The third breach of evidence-based information was your EUA issued August 28, 2020 broadening the remdesivir approval to incorporate any affected person hospitalized with reasonable COVID-19. There are inadequate information to assist this approval, as it’s based mostly on small, open-label research with subjective endpoints. Remdesivir is an costly drug, costing roughly $3000 per remedy, briefly provide, and even its approval for extreme COVID-19 was based mostly on time to restoration in a comparatively small trial of simply over 1000 sufferers. That’s in contrast to the proof of dexamethasone profit for survival in a randomized trial of over 6400 sufferers.
These repeated breaches exhibit your willingness to disregard the dearth of scientific proof, and to be complicit with the Trump Administration’s politicization of America’s healthcare establishments.
In a latest interview with the Monetary Occasions, you mentioned you have been ready to authorize a vaccine earlier than Part 3 trials have been full. Could I remind you that Part 3 trials are in progress for just a few vaccine applications and have solely now fulfilled half of their enrollment? It can take many months to determine each security and efficacy. Whereas most vaccines are protected, trials are wanted to exhibit that contributors in these trials don’t develop extreme immune-mediated reactions to publicity of the virus through antibody-dependent enhancement or immune complicated illness. Efficacy information are wanted to show there’s a substantial suppression of infections within the vaccine group, in contrast with placebo. Each security and efficacy endpoints require sufficient statistical energy. All of this takes time.
Any shortcuts is not going to solely jeopardize the vaccine applications however betray the general public belief, which is already fragile about vaccines, and has been made extra so by your lack of autonomy from the Trump administration and its overt politicization of the FDA.
You’ve got one final likelihood, Dr Hahn, for saving any credibility and preserving belief within the FDA at this vital juncture amidst the pandemic. It is advisable arrange a press convention and inform the reality. Inform Individuals precisely the way you have been pressured to make a breakthrough announcement. Inform all of us the way you utterly misrepresented the details about convalescent plasma, and never disguise this with the obscurity of technical phrases reminiscent of relative and absolute variations. Inform us that you’re succesful and worthy of this pivotal management place and that you’ll not, underneath any situation, authorize a SARS-CoV-2 vaccine approval earlier than the complete Part 3 completion and read-out of a program.
In any other case, it is advisable to resign. We can not entrust the well being of 330 million Individuals to an individual who’s subservient to President Trump’s whims, unprecedented promotion of unproven therapies, outrageous lies, and political motivations. You’ve got two decisions to do the appropriate factor. We can not and won’t relaxation till you make that selection.
Eric J. Topol, MD, the editor-in-chief of Medscape, is without doubt one of the high 10 most cited researchers in medication and regularly writes about expertise in healthcare, together with in his newest e book, Deep Medicine: How Artificial Intelligence Can Make Healthcare Human Again.
Supply: Medscape Medical Information