We need a framework for the ethics of secondary epidemic vaccine trials

By Joshua Teperowski Monrad

Introduction

In the 21st century, few medical innovations have been as intensely anticipated as an effective vaccine for COVID-19. The pipeline of candidates now includes more than a hundred potential products, as governments, pharmaceutical companies, and researchers engage in an unprecedented effort to combat the worst pandemic of a century. This vast number of candidates is both necessary and reassuring since so many vaccines do not make it all the way through clinical trials. But the parallel development of multiple candidates also creates a predictable ethical dilemma: what happens when one effective vaccine has been licensed against COVID-19, and developers wish to test the efficacy of other candidates in clinical trials? In my paper, I lay out a framework for examining the reasons for and against continuing trials for a secondary vaccine.

 

Historical background

This situation is not merely a hypothetical possibility. Last year, the second-deadliest outbreak of Ebola in history was spreading through the eastern parts of the Democratic Republic of the Congo (DRC). Building on research conducted during the 2014-2015 Ebola outbreak, multiple pharmaceutical companies were working to finally develop the vaccine that had eluded researchers since the virus was first identified in 1976. In the spring of 2019, these efforts reached a historical milestone, when preliminary analyses showed that the rVSV-ZEBOV-GP vaccine owned by Merck had proven highly effective in clinical trials. However, even after these results became available, other vaccine developers, including the pharmaceutical company Johnson & Johnson (J&J), continued efficacy trials of their own candidates. In practice, this meant that Congolese people involved in these trials received the investigational J&J shot, and not the Merck vaccine for which there was more evidence of efficacy. Notwithstanding support from major international institutions, this decision proved controversial and faced skepticism from Dr. Oly Ilunga Kalenga, the former Minister of Health of the DRC, among others.

Despite this historical precedent, bioethicists have given relatively little attention to the ethics of trialing a secondary vaccine for an epidemic disease, when an effective vaccine already exists. Considering that this situation is likely to arise in the context of COVID-19 vaccines, the time is now to ensure that researchers and pharmaceutical developers will conduct future vaccine trials under ethical conditions.

 

The argument for why a secondary vaccine trial may be unethical

Once a vaccine for a deadly disease like COVID-19 has been developed and licensed for use, it becomes a top public health priority to distribute it as widely as possible, especially where active outbreaks are happening. However, the nature of efficacy trials is such that participating in the trial for a novel vaccine would almost certainly preclude receiving the existing shot. Because of this, going ahead with a secondary trial may violate the core principle of medical ethics stating that effective vaccines for deadly diseases cannot be withheld from subjects for the sake of research.

Given the global nature of the COVID-19 pandemic, there is a pronounced risk that any trial withholding an effective vaccine would disproportionately affect communities in lower-income countries. From the infamous syphilis studies in Tuskegee and Guatemala to more recent examples, researchers have historically been more likely to violate ethical requirements against human research subjects from vulnerable populations. In light of past injustices, we must be especially vigilant when considering proposed research in the Global South.

 

Potentially legitimate reasons to pursue a second vaccine

The point I am trying to make here is not that trialing a secondary vaccine for an epidemic disease will never be permissible. Many critical medical innovations have been realized because of attempts to improve existing products. Rather, my argument is that such clinical trials may be unethical unless there are adequate reasons to believe that the vaccine candidate is superior to the existing product. For example, we might have theory or evidence suggesting that the novel vaccine has greater efficacy. In the case of COVID-19 – where there is no guarantee that the first successful vaccine will be 100% effective – it may legitimate to argue that patients receiving an investigational vaccine will have a shot at being better off than those receiving the first licensed product. Vaccines can also be improved along a number of other dimensions, such as the length of immunity, the mildness of side effects, or the ease of administering the vaccine (e.g., oral vs injection). Moreover, some non-immunological factors may have relevance for whether a secondary trial is desirable, such as the availability of the existing vaccine as well as the robustness of its supply chain.

 

Getting the ethics right

We already know that pharmaceutical companies will be highly motivated to continue trials for products that they have invested so heavily in. But we also know that some medical innovations can save millions of lives, and that clinical trials can be an essential part of developing them. To ensure that decisions to pursue clinical trials for secondary epidemic vaccines are made for the right reasons, we need a more systematic approach to evaluating their merit.

We need scientists to compare the immunological and epidemiological merits of different vaccines, but also economists and security experts weighing in on matters of pricing and production. And we need bioethicists to scrutinize cases where well-established ethical principles come under pressure.

Getting the ethics right matters, and not just for research participants. Unethical research will only backfire dramatically by eroding public trust in medical institutions. When our lives and economies depend on compliance with public health advice and high vaccination rates, few things could be costlier than jeopardizing that trust.

 

Paper title: Ethical Considerations for Epidemic Vaccine Trials

Author(s): Joshua Teperowski Monrad

Affiliations:  Joshua Teperowski Monrad is a recent graduate of the Program in Ethics, Politics, and Economics at Yale University and an incoming MSc student at the London School of Hygiene and Tropical Medicine as well as the London School of Economics and Political Science.

Acknowledgments: The author wishes to thank Alejandra Padín-Dujon, Brian Earp, Carolyn Roberts, Debbie Dada, Jason Schwartz, and Stephen Latham for many edifying conversations on this topic.

Competing interests: The author has no competing personal or financial interests with regards to the content of this post.

Social media accounts of post author(s): @jtmonrad

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