Among the whirlwind of news and medical information about President Trump since he was diagnosed with Covid-19, treated with experimental drugs, hospitalized, and released has been a lot of confusion about the “compassionate use” of unapproved drugs. What is it? Who gets it? Who should get it? How do you get it?

We are part of a team that has been studying compassionate use since 2014, and have been carefully following its application to the president, along with the news and social chatter around it. Here we aim to correct and clarify both the process and some of the misleading statements we have encountered over the past several days.

First the facts

For decades, the Food and Drug Administration’s expanded access program has provided a pathway for some patients to access investigational, or experimental, medical products — drugs, devices, and vaccines — before they’ve been approved by the FDA.

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To qualify for expanded access:

  • The patient must have a serious or life-threatening disease or condition for which there is no other FDA-approved treatment option
  • The potential benefit of using the product must outweigh the potential risks.
  • The patient is unable to enroll in a clinical trial.
  • And providing the product will not threaten its clinical development.

In clinical trials, investigational products are tested to advance science and show safety and effectiveness. In expanded access, investigational products are used in the hopes of helping patients.

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There are three types of expanded access: individual expanded access, for just one patient; multiple-patient expanded access, the number is not capped by regulation; and widespread treatment cohort expanded access, which can include thousands, even tens of thousands of patients.

Here we’re discussing only the first of these, individual patient expanded access, commonly referred to as compassionate use, because companies have no legal obligation to offer access and thus are labeled “compassionate” for doing so. This is how the president received Regeneron’s antibody “cocktail” before he was hospitalized.

The compassionate use process goes like this: The patient’s physician identifies a potentially beneficial drug in development and requests it from the entity developing it. If that company, also known as the sponsor, agrees to provide the drug — and there is nothing in any regulation requiring any sponsor to provide compassionate use — then the request goes to the FDA for review. If the FDA allows the request to proceed, an institutional review board, a body charged with the protection of human research participants, must sign off on the protocol proposed for delivering the intervention and the informed consent form the patient would need to complete before beginning it.

The FDA can authorize emergency requests immediately, and the institutional review board must be notified within five business days.

Now to clarify some things

On Oct. 4, Fortune reported, “The FDA had to grant specific permission for Trump himself to receive the Regeneron treatment.” While technically true, the statement is misleading, as it implies that the FDA is the gatekeeper for access to investigational drugs. A compassionate use request goes to the FDA only after a company has already agreed to provide the product. It is also misleading because it implies that Trump received special treatment, when in fact all compassionate use requests for individual patients must receive specific permission from the FDA.

On Oct. 5, CNBC said that Trump was given the Regeneron product because “the president’s doctors were confident enough of the drug’s benefit to administer it.” That’s sort of true. In compassionate use of a drug, its potential benefit must outweigh its potential risks. In the president’s case, his doctors were (or by law should have been) convinced — albeit on the basis of preliminary evidence — that for this particular patient with these particular comorbidities at this stage of illness with this particular prognosis, the possible benefit of providing the REGN-COV2 antibody cocktail outweighed the risks doing so.

The president shouldn’t have to participate in a clinical trial because he’s too important to risk being randomized to a placebo arm. That’s wrong. If a placebo is known to be inferior to an investigational drug, it is unethical for investigators to continue a trial using the placebo. If a drug is in a trial, its benefit and safety have not been established, and it may very well be better not to receive the drug — even if there has been favorable preliminary data. Keep in mind that patients receiving placebo in a clinical trial still get the standard medical treatment for their disease, just not the experimental intervention. Importantly, the president’s possible flouting of the clinical trial requirement of compassionate use could threaten the legitimacy of the trial process in the public’s eyes, making trial enrollment, and thus the ability to bring therapeutics to market, more difficult going forward.

If the president got experimental drugs, that means he was getting the best possible medical care. Wrong again. The majority of drugs in development — up to 90% of them — fail to come to market either because they don’t work or because they cause unacceptable side effects. The president might have gotten compounds that could help him; he might also have gotten compounds that could hurt him, especially because they were administered in untested combinations.

When there are no solid treatment options for a condition, as with Covid-19, trying something has to be better than nothing. No. This was demonstrated earlier in the pandemic with hydroxychloroquine. Approved for malaria and other indications, and widely touted by the president as a cure for Covid-19, hydroxychloroquine proved to be fatal in certain patients. The president is elderly, obese, with known comorbidities and possibly unknown ones. How he would react to any unproven Covid-19 treatment was not known. We have to assume that his physicians had adequate reasons to believe that the risk/benefit profile was favorable for him.

Regeneron should be applauded for offering Biden REGN-COV2, in a show of bipartisanship. Drug developers are prohibited from promoting unapproved products for use. As Regeneron notes in its own brochure, “Understanding the Healthcare Laws that Govern Our Industry,” promotion of a drug candidate before FDA approval “is strictly prohibited.” A strong case could certainly be made that having the company’s offer of REGN-COV2 to Biden widely reported, admiringly, in the press is a type of promotion. Even if the company made no claims of efficacy in its outreach, alerting the Biden campaign team that the drug could be provided circumvents the clinical trials that should always be the preferred route of access.

The president should have gotten his drug via the “right-to-try” law he signed in 2018 and of which he has repeatedly boasted. He probably couldn’t. As the New York Times put it, “The Right to Try law is rarely used, however, with most doctors and hospitals preferring to use the existing process of seeking company and then agency approval,” over a stripped-down process that cuts out expert oversight. That’s also true for pharmaceutical companies, as evidenced both by the fact that maybe a dozen patients have obtained access to unapproved drugs via right to try since the law was signed and because Regeneron’s compassionate use policy posted on its website makes no mention of right to try.

Much has been made about the president’s ability to get compassionate use of a drug while more than 210,000 Americans have died from Covid-19, many because of the inability to access treatment or even diagnostic tests.

As mentioned earlier, companies are the gatekeepers to access; it is up to them whether to institute policies and practices that might ensure more just access to potentially beneficial investigational drugs. This is something that they might want to give serious consideration to now, with experts predicting a flood of compassionate use requests in the aftermath of Trump’s treatment and suggestions that possible financial and personal ties influenced Regeneron’s decision to make the drug available to the president.

It would be a moral tragedy if many desperate, frightened patients were to be met with the reality that only presidents can access potential therapies for life-threatening diseases.

Lisa Kearns is a senior researcher in the Division of Medical Ethics at NYU Langone Health School of Medicine. Alison Bateman-House is an assistant professor in the division. Arthur L. Caplan is the division’s founding director. All three are members of the division’s Working Group on Compassionate Use and Preapproval Access; Caplan and Bateman-House chair the group.

  • Very worthwhile information, but still : only a high-flying hot-shot gets the privilege of instant FDA approval for compassionate use. For a man who received that much quick and easy compassion, he showed zero compassion towards his hurting subjects: he stomped all over hard-hit Covid families with his disgusting show-down of mask defiance. NO class, respect, gratitude or compassion in this dude whatsoever. Time to take the proverbial hike.

  • Information on the FDA’s “final wording” on compassionate use can be found in the Federal Register here: https://www.federalregister.gov/documents/2009/08/13/E9-19005/expanded-access-to-investigational-drugs-for-treatment-use

    Part of it, which is applicable to the discussions is as follows:

    The comment noted that there is a lack of information in the proposed rule concerning differences in patient outcomes between patients treated with investigational drugs in academic medical centers and those treated elsewhere and suggested that, absent such data, it is not necessarily desirable for the use of investigational drugs for treatment use to become significantly more prevalent outside academic medical centers.

    (Response) FDA acknowledges that patients who have the diseases or conditions for which treatment use of investigational drugs is generally sought may be found in greater numbers in academic medical centers specializing in the treatment of serious and immediately life-threatening conditions. FDA does not agree, however, that the intent to facilitate access in all settings requires data on comparative quality of care across different settings, any more than it would require such a comparison among academic centers in geographic regions. FDA believes it is important to foster use of investigational drugs for treatment use in all settings in which eligible patients receive care, provided there are appropriate controls and oversight, as set forth in this final rule.

    The final ruling documents is lengthy and extremely detailed and there is probably more information pertaining to the discussion than what I could find.

    The use of the monoclonal antibody combination in the treatment of Donald Trump’s Covid does, to some extent, fly in the face of the “Final Ruling” presented in the 2009 Federal Register. You can argue for or against a special exception to these rules in this case. It is worth a discussion.

  • Typographical error. (Your science is to good to let a typo downgrade it: “Who should get?” Should be: “Who should get it?” (I would love to work with your company. I am John Salerno, Cybergoal.com) I do most of the ACS educational interactive.

    Among the whirlwind of news and medical information about President Trump since he was diagnosed with Covid-19, treated with experimental drugs, hospitalized, and released has been a lot of confusion about the “compassionate use” of unapproved drugs. What is it? Who gets it? Who should get? How do you get it?

  • Years ago (maybe 14 years ago) there was a policy published in the federal register that it some well know, highly esteemed expert at a university was able to use an investigational agent on their wealthy executive patient the basis of compassionate use then a lowly physician in a rural town could use the same investigational agent on their rural farm hand for the same indication. I wonder if anyone remembers that. (It was tucked in the fine print that we have come to know as the federal register. It was a policy statement that the FDA put in to the federal register to clarify the rules of using investigational drugs on compassionate use. The prime reason was to avoid the possibility that a person could get a special treatment just because they were seeing a famous doctor at a famous institution.). In effect, this means that anyone can use Regeneron’s combo for their sick Covid19 patient and could treat the grape harvester’s father in the middle of the San Joaquin Valley as easy as the president. Something tells me that this paragraph in the federal resister has long been forgotten. Take my word…. it was there.

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