On Monday, Pfizer and BioNTech announced that their experimental Covid-19 vaccine candidate prevented more than 90% of infections in healthy volunteers. Based on these encouraging data — potentially among the most effective for any infectious disease — the companies plan to apply for emergency use authorization, which would let the Food and Drug Administration formally authorize an unapproved medical product during a state of emergency. While well-intentioned, this approach is ultimately misguided. The world faces a crisis not an emergency.
An emergency use authorization would potentially open the floodgates to deploy an unapproved and unlicensed vaccine to millions (or tens of millions) of individuals before gathering the proof of safety and efficacy that licensing a new vaccine typically demands.
This was never the intent of emergency use authorization, which was actually designed for counterterrorism measures to address chemical, biological, radiological, and nuclear hazards — not necessarily a pandemic. (The first use of EUA authority was in 2005 through the Project Bioshield Act to authorize military vaccinations against anthrax).
We fear that an emergency use authorization for Covid-19 vaccines at this stage of development would not require careful reporting of adverse events and could potentially undermine ongoing and future clinical trials that are still necessary to determine safety and efficacy.
There is a better way to provide Americans with access to a new vaccine.
If the FDA and its independent review committees decide the early evidence supplied by Pfizer and BioNTech — or other companies down the road — is sufficiently promising, the agency should grant early access to their Covid-19 vaccines through a process known as expanded access. Expanded access is the use of an investigational new drug product outside of clinical trials to treat patients with serious or immediately life-threatening diseases of conditions when there is no comparable or satisfactory alternate treatment options.
Expanded access is fundamentally different from emergency use authorization, and the distinction between the two is vitally important. Expanded access will preserve the integrity of ongoing large-scale clinical trials under the banner of experimentation while ensuring that high-risk individuals have a pathway to access experimental vaccines that could mean the difference between life and death. An emergency use authorization would not.
Through the expanded access pathway, the FDA would not determine if an investigational Covid-19 vaccine actually works. Instead, via expanded access, it would facilitate access for those at greatest risk without opening the floodgates to access in the way that an EUA might do (although the targeted population for a Covid-19 vaccine could be as limited as the FDA thinks the data support, but that would be difficult to enforce). It would be up to a doctor and his or her eligible patient to determine on a case-by-case basis the risks and benefits of trying a still-experimental vaccine.
The FDA’s history of expanding access to investigational products dates back to the 1970s, but the process first received national attention when patient dying with HIV/AIDS fought for access to antiviral drugs that were available only through clinical trials. The public battle led to much-needed reforms and popularized the idea of compassionate use: allowing broader access to experimental drugs while still classifying them as unproven and experimental.
As expanded access has matured — it is now used for all sorts of diseases beyond HIV — the process has been streamlined. Today, it takes less than an hour to complete an expanded access application and the FDA approves 99% of requests. Expanded access is not a formal approval process, just as the EUA is not a formal approval process.
Certain requirements apply for expanded access:
- The patient must have a serious or immediately life-threatening disease or condition and have no comparable or satisfactory alternative therapy.
- The potential benefit must justify the potential risks.
- Providing the treatment must not interfere with or compromise the ongoing vaccine approval process.
Invoking expanded access for a Covid-19 vaccine would be unusual, but not unprecedented. Meningococcal vaccines and non-U.S.-licensed yellow fever vaccines have been made available through this process, and with good results. Expanded access remains controversial, however. It leads some patients and their doctors to pursue products that are neither safe nor effective. Given these competing interests, we believe expanded access is not only appropriate in the midst of a worsening pandemic, but also necessary.
Roughly 40% of reported Covid-19 deaths in the United States have occurred in long-term care facilities such as skilled nursing facilities, assisted living centers, veterans’ homes, and the like, and the virus continues to surge across the United States. While it is important to allow ongoing vaccine trials to finish, we simply cannot wait to inoculate the most vulnerable citizens. Vaccination of high-risk individuals and clinical trials should proceed in concert, with doctors and eligible high-risk patients deciding when benefits of inoculation outweigh risks.
Why does this matter? A recent poll indicates that just over half of all Americans (58%) would get inoculated as soon as a vaccine was available, down from 69% who said the same thing in August. The FDA has used emergency use authorizations to facilitate the use of ineffective treatments such as hydroxychloroquine and fraudulent diagnostics such as point-of-care serology tests that have shaken public trust. The agency should not further jeopardize its credibility by authorizing a Covid-19 vaccine for emergency use before Phase 3 clinical trials have been completed. Without public support of a vaccine, it will be difficult to protect everyone from the virus, and the pandemic will persist. A vaccine that few will take is of little value.
The FDA cannot require Pfizer or any other manufacturer to provide a vaccine through expanded access. Given the robust support of the unfortunately titled Operation Warp Speed, however, expanded access will not impair ongoing clinical trials or sap a limited supply chain. But expanded access can work only if drug companies agree to provide Covid-19 vaccines through the expanded access pathway and the FDA agrees to their doing that.
Americans will soon have access to Covid-19 vaccines, but the manner in which these potentially lifesaving inoculations are authorized and distributed must be carefully thought through in order to ensure public trust in the rollout. Key stakeholders must make the commitment to expanded access.
Matthew W. McCarthy is an associate professor of medicine at Weill Cornell Medicine in New York City. David Oshinsky is director of the Division of Medical Humanities at NYU Langone Health and professor of history at NYU. Arthur Caplan is the founding director of the Division of Medical Ethics at NYU Langone Health School of Medicine. They write on behalf of the Vaccine Working Group on Ethics and Policy.