December 2, 2020

Drug companies shouldn’t play favorites in granting access to experimental covid-19 treatments

In the past month, US President Donald Trump and former New Jersey governor Chris Christie...

In the past month, US President Donald Trump and former New Jersey governor Chris Christie were diagnosed with covid-19 and spent time in the hospital, just like tens of thousands of other Americans nearly every day since the pandemic began.

But Trump and Christie were special cases. They received experimental covid-19 treatments that are not readily available to the general public. They have both since recovered and publicly acknowledged that US companies granted them access to drugs still off-limits to the vast majority of Americans with the disease.

Their treatment has generated a lot of conversation about the perception that the rich and famous have priority access to health care. What has received much less attention is whether these two men circumvented the rules to get access to experimental drugs outside clinical trials, and if so, how their actions could affect drug development.

Seriously ill patients with no other options are permitted by law to receive drugs in development before the drugs have been approved by the US Food and Drug Administration. Regulations governing this access are necessarily strict, to protect not just the parties involved but the clinical development process itself.

Allowing people to skirt these regulations could delay or derail that process. Even the perception that rules are being bent this way could raise public doubts about participating in clinical trials. This is problematic in any case, but especially so when the drugs in question are being developed to help stem a pandemic.

What is expanded access?

For decades, drug companies have granted some patients access to investigational products outside clinical trials via a pathway known as expanded access. Historically referred to as “compassionate use,” expanded access permits a patient with a serious or life-threatening condition to try such products as a last-ditch move.

Patients must meet several criteria to qualify for expanded access. There must be no FDA-approved therapies available to the patient; the request for access must be made by a physician, who has determined that the possible benefits outweigh potential risks; the patient must be unable to enroll in a clinical trial; and the company must believe that granting access will not interfere with clinical trials of the product.

Those last two requirements are especially important because the FDA evaluates safety and efficacy data collected during clinical trials to determine whether to approve new treatments, thus making them available to many more patients. It’s already difficult to get enough people to participate in clinical trials. If patients can access experimental drugs without enrolling in one, it will become even harder to collect that critical data. Flouting the letter or spirit of the expanded-access law could seriously harm not only the drug development system, but the public’s trust in it and the public’s health at large.

Trump tested positive for covid-19 on or around September 30. After being discharged from the hospital, he boasted repeatedly that he’d gotten “Regeneron”—that is, he received Regeneron Pharmaceuticals’ investigational antibody cocktail called REGN-COV2 via expanded access. He even said that it cured him.

Christie more recently received an Eli Lilly covid-19 drug via expanded access. It too was a monoclonal antibody cocktail.

We haven’t seen either man’s private medical information, and Trump’s physician has been accused of obfuscating the details of his patient’s covid-19 experience. However, based on what we do know, we doubt that one or both fully met the criteria for expanded access.

We acknowledge that covid-19 was a serious diagnosis for Trump and Christie; as older, obese men, they are among the population for whom the infection has been most lethal. And we presume that the men’s physicians believed the potential benefits of the investigational drugs outweighed the risks for their patients.

We’ll also grant there were no suitable alternative treatments. Dexamethasone, a commonly available steroid, has been shown to lessen some symptoms of the virus, but it’s not a cure-all for covid-19. And despite Trump’s claim earlier this year that hydroxychloroquine, an older drug used to treat malaria, lupus, and rheumatoid arthritis, was a miracle cure, clinical trials have not borne this out.

Of course, there are some clear differences between these two covid-19 patients. Trump is a sitting president while Christie, the former governor of New Jersey, does not currently hold political office, though remains active in politics (Christie helped Trump prepare for the recent presidential debates). However, both VIPs appear to have sidestepped the FDA’s clinical trial requirements. This point bears closer scrutiny than it has received.

Special treatment

Many patients cannot participate in clinical trials for many different reasons. They may not meet a trial’s inclusion criteria—they may be too old or too young, or have comorbidities such as high blood pressure that make them ineligible. Or they may be unable to travel to the trial site.

Trump was treated at Walter Reed National Military Medical Center, which is not listed as a trial site for REGN-COV2. That would have rendered him ineligible for a clinical trial and therefore a suitable candidate for expanded access, as he also met the criterion of having no approved treatment option. Without transparency into his medical condition, we can’t know if he met the Regeneron trial’s criteria regarding illness and hospitalization status.

Christie’s case is much more concerning. He was in a hospital that was participating in the Regeneron trial. According to a report by the trade publication BioCentury that cited an anonymous source, Regeneron, in accordance with FDA regulations, declined Christie’s request for expanded access to REGN-COV2, the product used by Trump, and instead offered Christie a spot in the randomized controlled trial. BioCentury reports that Christie did not want to participate for fear that he might receive a placebo treatment.

Christie certainly was under no obligation to join the trial. But if he was eligible for a trial of an investigational drug, he should not have been able to obtain that drug via expanded access. Regeneron, to its credit, appears to have appropriately refused this.

When Ajay Nirula, VP of Immunology for Eli Lilly, was asked earlier this week at the EmTech MIT conference about how Christie gained access to his own company’s medicine, he said Lilly’s expanded-access program was “generally the path that was pursued here,” but he did not provide further details.

Christie’s fears of receiving a placebo reflect a common but mistaken belief: that trial participants who receive placebos are worse off than patients who get the investigational product. If a trial has a placebo arm, it’s because the safety and efficacy of the drug being tested are unknown. The vast majority of investigational medical products are rejected for FDA approval because they either don’t work or are unsafe. Patients in placebo arms receive the standard medical care for their disease. In a trial testing a drug against a placebo, then, it may be safer for a participant not to receive the drug, which could in fact cause harm.

Christie’s actions as they have been reported imply that anyone who can avoid clinical trials—particularly trials involving a placebo—should do so, and should try to get the investigational drug through expanded access. Such actions stoke public distrust of drug development at a time when clinical trials are crucial to mounting an effective pandemic response. They could also lead to a spike in the number of requests for expanded access, thus increasing the burden on physicians, drug companies, the FDA, and hospitals—all of which may be equipped to handle such requests occasionally but not in volume.

This is about more than just powerful politicians receiving unapproved drugs that are not available to others. It’s also about whether rich, famous people may have worked around a system that exists both to help patients in devastating circumstances and to preserve the system’s ability to help future patients.

Our colleagues have warned about the dangers of “pandemic research exceptionalism” in the context of clinical trials for covid-19 agents. They argue that during desperate times, scientists and regulators shouldn’t relax regulations governing trials but should follow them all the more closely, because trustworthy data is especially important when no treatments are available and there’s intense pressure to develop one. For the same reason, there should be no expanded-access exceptionalism. Regulations should be applied consistently and fairly, no matter who the patient is.

Lisa Kearns is a senior researcher in the Division of Medical Ethics at the NY Grossman School of Medicine and a member of the division’s Working Group on Compassionate Use and Preapproval Access (CUPA). Alison Bateman-House is an assistant professor at the division and a cochair of CUPA.

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