By Holly Fernandez Lynch, Alison Bateman-House, and Arthur Caplan
The U.S. Food and Drug Administration (FDA) is expected to grant emergency use authorization (EUA) for one or more COVID-19 vaccines before the end of the year — perhaps even before the end of the day, given today’s advisory committee meeting.
The agency’s decision on these EUAs will balance the need for additional data on safety and efficacy against the potential to protect at-risk groups as quickly as possible. EUAs tip the balance in favor of speed, which can be reasonable for these populations given the circumstances, especially in light of the strong trial data reported for three COVID-19 vaccines since mid-November. But the tradeoff is very real: vaccine EUAs will substantially lower the likelihood of ongoing trials completing and new trials successfully recruiting volunteers. There are a few ways to minimize these consequences.
Emergency use authorization, which has been used repeatedly for drugs and devices in the context of COVID-19, sets a lower bar for evidence than required for full FDA approval — although FDA has heightened its expectations for vaccine EUAs, as compared to EUAs for treatments, since vaccines are administered to healthy people. This lower bar means that research must continue even after an EUA is granted to answer important questions related to a vaccine’s efficacy in different populations, impact on disease transmission, duration of protection, and long-term safety. It’s also important to make sure that other vaccines continue to be studied, as multiple vaccines will be needed to provide global protection.
A key difficulty is that once an EUA-bearing vaccine becomes available, many of those eligible to receive it are likely to do so outside of trials. Those already in trials who received placebo may withdraw to seek vaccination elsewhere if it’s not provided as part of the study, and those newly approached about participation are likely to find placebo controls far less palatable. This will make it very hard to continue rigorous trials of vaccines under EUA, as well as all other COVID-19 vaccines.
An EUA acknowledges uncertainty about a product’s safety and efficacy but temporarily grants access anyway. Yet the impact of EUAs on trials risks potentially entrenching that uncertainty in the long-term. Initial supply constraints may buy some time during which trial participation will remain an attractive option for vaccine access, but three policies can help maximize the collection of meaningful evidence before vaccination becomes more widely available.
First, FDA should limit recipients of EUA-bearing vaccines only to a defined group of high-risk people — and include clear, meaningful, and attainable reporting requirements. The EUA tradeoff between speed and certainty makes the most sense for those who are at highest risk, such as healthcare workers and others. Limiting the population eligible to get the vaccine also will help minimize the impact on trials, allowing continued data collection in lower risk groups. Meanwhile, strong reporting requirements can help make sure that we are able to learn as much as possible from real-world use in groups eligible for vaccination under an EUA.
Second, hospitals, pharmacies, and clinicians responsible for vaccine administration must commit to rigorous adherence to EUA provisions. This means that vaccines must be provided only to those individuals falling within the scope of the EUA. To help buttress this expectation, it’s important for FDA to make clear that the standard practice of “off-label use” (by which traditionally-approved products may be legally prescribed for unapproved uses) is not permitted for vaccines distributed under EUA. EUA products are legally authorized for use only under specific terms and otherwise remain unapproved. Importantly, failure to adhere to EUA terms may result in loss of the liability protection normally available when using pandemic countermeasures. Beyond limiting use only to authorized groups, those responsible for administering vaccines also must establish and follow clear procedures for meeting EUA data collection requirements.
Third, we need a plan for handling these data. In the tumult of producing, distributing, and continuing to test vaccines, pharmaceutical companies may be unable to prioritize the collection and conversion of raw, non-trial data into useable evidence for regulatory purposes. Leaving them to shoulder this burden without help is not in the interest of the public good. Instead, we must quickly establish a data coordinating center based in a university, philanthropy, or governmental agency — the FDA makes the most sense, but it may likewise be overwhelmed. This coordinating center should be responsible for communicating with front-line entities about who is eligible to receive EUA-bearing vaccines, what information must be collected, and how. It would also develop standardized procedures so that all data, no matter its origin, may be pooled. This will be especially important if multiple EUAs for COVID-19 vaccines are granted, to promote uniform data collection for each.
Taking these three steps — narrow EUAs for vaccines, rigorous adherence to those EUAs, and coordinated data collection — will help justify the prioritization of speed over certainty. We can simultaneously get COVID vaccines to those most at risk while minimizing harm to our ability to fully evaluate their safety and efficacy, which is essential to justifying their widespread national and global use.
The authors are ethicists working on clinical research, pre-approval access, and FDA policy. Holly Fernandez Lynch is an assistant professor of medical ethics at the University of Pennsylvania’s Perelman School of Medicine. Alison Bateman-House is an assistant professor in the NYU Grossman School of Medicine Division of Medical Ethics, and Arthur Caplan is the Mitty Professor of Bioethics at NYU Grossman School of Medicine.