Word: 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 web site 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 means to supervise the well being pursuits of the American folks.
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 simpler, safer, and extra reasonably priced and by serving to the general public get the correct, science-based info they should use medical merchandise and meals to keep up and enhance their well being.”
The emphasis right here is on correct, science-based info. 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 extensively and aggressively promoted hydroxychloroquine as a “miracle drug,” on March 30, 2020, you granted an Emergency Use Authorization (EUA) for this drug with none adequate 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 opposed occasions and different potential critical unwanted side effects.”
The second main breach of correct, science-based info 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. It is a main advance within the remedy of sufferers. It is a main advance…[A]nd a 35% enchancment in survival is a reasonably substantial scientific profit. What which means is — and if the info 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 wrong and a blatant misrepresentation of the info. Your assertion was primarily based on a preprint, which by definition has not been peer-reviewed, revealed by Mayo Clinic’s Michael Joyner and coauthors. It’s a retrospective, observational research of over 35,000 sufferers who obtained convalescent plasma, with none controls or untreated sufferers for comparability. The declare of discount of mortality is completely unsubstantiated. That was primarily based 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 obtained. The antibody degree was decided submit facto. You already know 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 verify.
Nonetheless, you posted this data-dredging subgroup evaluation on the FDA web site with the headline assertion “One other Achievement in Administration’s Struggle Towards 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 instantly along 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 info present a relative threat discount, not an absolute discount.”
That may be a grossly inadequate correction and doesn’t characterize the reality. This is what you did not say:
1. There are not 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 folks’s lives saved per 100 sick with COVID-19, was fully off-base. If the preprint information held up in a correct randomized managed trial, it could be avoiding deaths of three or 4 folks 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 inconceivable to avoid wasting 35 folks’s lives of 100 folks 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’d like 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, akin to 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 average COVID-19. There are inadequate information to assist this approval, as it’s primarily based 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 primarily based 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 display 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 Instances, you mentioned you have been ready to authorize a vaccine earlier than Section 3 trials have been full. Might I remind you that Section 3 trials are in progress for a number of vaccine packages and have solely now fulfilled half of their enrollment? It should take many months to ascertain each security and efficacy. Whereas most vaccines are protected, trials are wanted to display that members in these trials don’t develop extreme immune-mediated reactions to publicity of the virus by way of antibody-dependent enhancement or immune advanced 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 enough statistical energy. All of this takes time.
Any shortcuts won’t solely jeopardize the vaccine packages 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 may have one final probability, Dr Hahn, for saving any credibility and preserving belief within the FDA at this essential juncture amidst the pandemic. You could 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 fully misrepresented the details about convalescent plasma, and never disguise this with the obscurity of technical phrases akin to relative and absolute variations. Inform us that you’re succesful and worthy of this pivotal management place and that you’ll not, beneath any situation, authorize a SARS-CoV-2 vaccine approval earlier than the complete Section 3 completion and read-out of a program.
In any other case, you have to resign. We can’t 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 may have two selections to do the suitable factor. We can’t 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 prime 10 most cited researchers in drugs and steadily 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