Bioethics Forum Essay
Efficacy is Relative in a Public Health Crisis: Evaluating the Next Wave of Covid-19 Vaccines
Among the safe and effective vaccines against Covid-19 already authorized by the Food and Drug Administration or likely to be added to the public health armamentarium in the coming months, there will undoubtedly be a range of performance profiles. Vaccines will differ with respect to their efficacy and other characteristics including duration of protection and storage and handling requirements. In principle, one would prefer that only the most effective vaccine be distributed, one that ideally would also provide long-lasting protection and prevent not only Covid-19 disease but also transmission of SARS-CoV-2, the virus that causes it. However, in the setting of an ongoing global pandemic with emerging virus variants that appear to more transmissible and possibly associated with a higher risk of mortality, there is good reason to consider whether a vaccine that performs less well in clinical testing than those already in use may still be ethically acceptable, perhaps even preferable, in order to preserve as many lives as possible and potentially hasten the end of the pandemic.
In the context of medical product development and regulation, new interventions in development, including vaccines, are typically viewed and evaluated in the context of existing preventive or therapeutic tools against disease. Two Covid-19 vaccines currently authorized for use and in large-scale use in the United States and elsewhere globally have demonstrated in controlled clinical trials efficacy of 95% (Pfizer-BioNTech) and 94.1% (Moderna) in preventing symptomatic Covid-19. These results far exceeded the 50% efficacy threshold established by the FDA in a June 2020 guidance document. Neither vaccine has yet been shown to prevent asymptomatic infection with the SARS-CoV-2 virus or person-to-person transmission, although at least partial protection against transmission is widely believed to exist. In addition to a two-shot regimen required for complete protection, both of these vaccines have demanding cold chain and handling requirements.
A third vaccine candidate moving closer to potential FDA authorization is the Johnson & Johnson vaccine that today reported preliminary Phase III clinical trial results demonstrating an overall efficacy of 66% against moderate and severe illness and 85% efficacy against severe disease. Johnson & Johnson plans to file for an emergency use authorization from the FDA in the coming days. This vaccine requires only a single dose, is far less demanding with respect to transport, storage, and handling, and comes at a lower cost than its counterparts, a consideration that will be keenly important in the future if the government does not commit to purchasing future doses of vaccines. Importantly, this vaccine—like those already authorized—was studied through placebo-controlled trials, limiting our current knowledge of their head-to-head performance relative to one another.
Nations, nongovernmental organizations, and scholars have long debated whether such contingent factors, for example, varying efficacy, provide ethical justification for the testing, approval, or distribution of products with clear clinical differences. At a time when novel viral variants are emerging in the U.S. and worldwide, the urgency for reaching herd immunity—the population-level benefits that result from a large proportion of the population having immunity through vaccination or natural infection—is increasing, particularly in large urban centers and dense cities. Secondly, with pandemic fatigue weighing heavily on society, the pressing need to return children to in-person learning at schools and universities, and the imperative to jump-start the economy, the singular focus of government-elected officials, public health agencies, and other federal and state policymakers—should be on vaccinating as many people as possible as rapidly and equitably as possible. Doing so need not require the exclusive use of vaccines with extremely high levels of efficacy. In fact, modeling studies of vaccine implementation suggest that even vaccines with moderate or modest efficacy, 75% or much lower, can still result in large reductions in Covid infections and deaths if they are swiftly delivered to a large percentage of a population. A one-dose vaccine can be particularly advantageous to that end, additional research has shown.
The trade-offs associated with a lower-efficacy vaccine administered via a single-dose regimen and with relatively easy storage and handling requirements more closely resembling routine vaccinations given in doctors’ offices could be acceptable, given the potential of such a vaccine to rapidly accelerate the capacity of vaccination programs delivering more vaccines to more people more swiftly. Twelve months into a raging, global pandemic, time and vaccine doses are our most scarce resources, and such trade-offs could be well justified in order to strengthen efforts to mitigate the effects of the pandemic.
The urgency of the current crisis; its public health, economic, and social consequences; and the vast logistical challenges associated with the rollout of vaccines thus far mean that the FDA ought to and will most likely evaluate subsequent candidate vaccines not in comparison to the high bar set by the Pfizer-BioNTech and Moderna vaccines, but instead based on the well-defined performance benchmarks that it has wisely established. Such an approach would affirm the range of vaccine perfomance profiles that could make valuable contributions to the overall vaccination effort and the coordinated campaign to end this pandemic, providing badly needed additional sources of vaccine supply at a time when vaccination efforts are expanding and existing vaccines and vaccine supplies are clearly insufficient to meet demand.
However, favorable FDA decisions on future vaccines with less impressive efficacy profiles than those already in use will introduce additional issues for health officials and policymakers, with similarly difficult ethical and policy questions. Chief among them will be determining how to deploy these lower-efficacy vaccines—allocation questions highly relevant to their deployment both in the U.S. and globally. Clinical trial results might offer relevant findings regarding subgroups that may inform these determinations, but in general, vaccines with lower efficacy might best be directed to younger populations without underlying medical conditions, groups for whom the risk of severe outcomes from Covid-19 are lower but among whom vaccination would provide essential population benefits in addition to individual protection.
The large-scale deployment of vaccines that may be viewed as inferior will add to the already immense public education and communication challenges associated with Covid-19 vaccines and vaccination programs. Their use will also raise new questions about fairness and equity in the design of vaccination programs. The experience in the U.S. during the past year has demonstrated the life-or-death importance of decision-making grounded in evidence and communicated clearly and consistently to the public. No aspect of the ongoing vaccination effort can repeat the failings seen at earlier stages of the pandemic, particularly the imminent issues related to how best to use our expanding arsenal of vaccines to best promote individual and population health.
Conveying to the public the rationale for regulatory and policy decisions related to the next wave of Covid-19 vaccines will demand heightened care and sensitivity, most especially to and for those groups to whom vaccines with comparatively lower efficacy are recommended. With attention to those efforts and a corresponding perspective on vaccine efficacy that recognizes the unprecedented crisis in which we find ourselves, health officials and policymakers can best support the expansion of rapid and equitable vaccination programs that offer the greatest hope for ending the Covid-19 pandemic.
Jonathan D. Moreno, PhD, is the David and Lyn Silfen University Professor at the University of Pennsylvania, where he is also professor of medical ethics and health policy, of history and sociology of science, and of philosophy. He is a Hastings Center fellow, @pennprof. Angela K. Shen, ScD, MPH is a visiting research scientist at the Vaccine Education Center at the Children’s Hospital of Philadelphia, a retired captain in the U.S. Public Health Service, and a public health consultant, @AngelaKShen. Jason L. Schwartz, PhD, is an assistant professor of health policy and the history of medicine at the Yale School of Public Health, @jasonlschwartz.
Support for this work was provided by a grant from The Greenwall Foundation.