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Michael Nagle/Bloomberg
President
Donald Trump
is illustrating the ethical perils of the “compassionate use” of unapproved medical products in real time. The president’s use of an experimental drug outside of a clinical trial, and the company’s offer of the product to the president’s political rival, raise questions about special treatment for certain VIPs. Furthermore, the presidential hawking of yet another unproven Covid-19 “cure” may undermine evidence-based decision-making while raising fears about the U.S. Food & Drug Administration’s independence from the White House.
Following Trump’s Covid-19 diagnosis, a New York State-based biotech company,
Regeneron Pharmaceuticals,
granted his doctor’s request for nontrial, preapproval “compassionate use” access to REGN-COV2, its investigational cocktail of two monoclonal antibodies. The company also divulged that it had reached out to former vice president
Joe Biden
’s team. Yesterday, Trump declared this unapproved treatment “a cure,” saying “it made me better.” Today, Regeneron said it applied for an emergency use authorization for REGN-COV2, a temporary approval by the FDA that would allow wide nontrial access to the drug, potentially endangering the completion of ongoing trials for the product. The FDA has not acted on that request, so any patients inspired by the president’s messages to seek nontrial access to the drug will need their physicians to request it through expanded access, as did the president’s doctors.
Regeneron does not appear to have sought to unlawfully promote its experimental Covid-19 therapeutic by giving it to the president. But the president, who has the authority to overrule the FDA, has raved about REGN-COV2, much like he did with hydroxychloroquine just months ago. In that case, White House pressure resulted in the FDA temporarily approving hydroxycholoroquine for use in treating Covid-19 in hospitalized patients, only to end that emergency authorization when clinical trials demonstrated that the drug did not offer sufficient benefit against Covid-19 to justify its risk. Hydroxychloroquine had been previously granted full approval by the FDA as a treatment for lupus and other conditions, and it was available—and legal—for clinicians to prescribe to patients for any reason. REGN-COV2, by contrast, remains an unapproved, experimental product. Until and unless REGN-COV2 receives full or temporary approval from the FDA, it is likely that Regeneron will face a crush of requests for expanded access, not all of which it will be able to fulfill, even if it wants to do so.
These events raise myriad red flags. First, by law, the only patients eligible for experimental drugs through the expanded access pathway are those who cannot join an ongoing trial. In the case of Trump, it is unclear what effort was made to determine if he was eligible for Regeneron’s trial. This should be publicly and immediately clarified, so that we know whether the president met the legal criteria for expanded access. The same would apply to Biden, if he were to receive the investigational drug. (Biden has tested negative for Covid-19.) Ensuring both men participate in clinical trials, were they eligible, would be important for two reasons. First, regulations should be applied uniformly to all. Second, allowing important people access to an investigational product outside of a clinical trial when they are eligible for the study makes trials appear as something to be avoided, if possible. Trump’s actions have reinforced that message, missing a major opportunity to affirm the societal importance of trials.
This case demonstrates the U.S. cultural tendency—shared in spades by Trump—to overstate the therapeutic potential of investigational products. The vast majority of drugs-in-development fail and never receive approval from the FDA for sale or use. Data from early trials frequently look good, but very often, that early hope fails to translate into reliable, robust evidence of clinical effectiveness. It is for that reason that investigational drugs go through a development process in which they are tested in increasingly larger number of patients, and, in some cases, compared to a placebo. The sequence of events with Regeneron’s product has reinforced the fallacy that treatment with an experimental drug is inherently better care.
Inarguably, the presidential candidates are being treated differently from others who have a diagnosed Covid-19 infection or potential exposure to the Sars-CoV-2 virus. Before granting even a single request for nontrial access, a company must decide how it will allocate its limited supply in a situation of numerous requests. This is a difficult decision, but there are publicly available models of how companies have allocated scarce investigational products. None of these models state, as a principle, “prioritize important people.” Rather, they endorse such strategies as picking at random from all requests or selecting patients who seem the most likely to benefit from the product.
Are presidential candidates more deserving than others to access a drug in limited supply that might provide medical benefit? Some would argue yes. But it is worth emphasizing again that all drugs pose potentially dangerous side effects and, even with initial favorable data, there is no determinative evidence that an unapproved drug is medically advantageous. Is it important to shield presidential candidates from the unknowns of unproven treatments, especially when used in untested combinations with other interventions? Maybe. These are questions that should be discussed and answered by companies before decisions about who gets access are made.
Regeneron’s decision to reach out to the Biden team, even if it was merely sharing information, raises the ethical questions of why and how should companies make public their access policies. The company had already posted its policy on its website. Why, then, reach out directly to Biden? Companies post public policies to even the playing field, to make all patients equally aware of the availability of expanded access. Direct contact does the exact opposite.
Covid-19 has starkly demonstrated the disparities in the U.S. with regard to who gets sick, who gets prompt testing, who gets ventilators, and even who gets safe housing during an infectious pandemic. The Regeneron case has now revealed further disparities in how patients learn about and access investigational medical products. It should prompt companies to think seriously about how, if they chose to permit nontrial access, they will allocate scarce investigational drugs, and how they will publicize and defend their actions. Do their policies align with common conceptions of justice, which treat those in need alike? Or do they afford heads of state, potentates, and presidential candidates easier access than you or me?
Alison Bateman-House is assistant professor in the Division of Medical Ethics at the New York University Grossman School of Medicine in New York Cityand co-chair of the NYU Working Group on Compassionate Use and Preapproval Access.
M. Sage Gustafson is a research associate in the Division of Medical Ethics at the NYU Grossman School of Medicine and the project manager of the NYU Working Group on Compassionate Use and Preapproval Access.
Arthur Caplan is the Drs. William F. and Virginia Connolly Mitty Professor and founding head of the Division of Medical Ethics at NYU Grossman School of Medicine.
