During the 2014–2015 Ebola outbreak in Guinea, Liberia and Sierra Leone, many opposed the use of individually randomised controlled trials to test candidate Ebola vaccines. For a raging fatal disease, they explained, it is unethical to relegate some study participants to control arms. In Zika and future emerging infections, similar opposition may hinder urgent vaccine research, so it is best to address these questions now. This article lays out the ethical case for individually randomised control in testing vaccines against many emerging infections, including lethal infections in low-income countries, even when at no point in the trial do the controls receive the countermeasures being tested. When individual randomisation is feasible—and it often will be—it tends to save more lives than alternative designs would. And for emerging infections, individual randomisation also tends as such to improve care, access to the experimental vaccine and prospects for all participants relative to their opportunities absent the trial, and no less than alternative designs would. That obtains even under placebo control and without equipoise—requiring which would undermine individual randomisation and the alternative designs that opponents proffered. Our arguments expound four often-neglected factors: benefits to non-participants, benefits to participants once a trial is over including post-trial access to the study intervention, participants' prospects before randomisation to arms and the near-inevitable disparity between arms in any randomised controlled trial.
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Contributors NE wrote the first draft. NE and ML both contributed to subsequent drafts.
Funding ML was supported by Award Number U54GM088558 from the National Institute of General Medical Sciences. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of General Medical Sciences or the National Institutes of Health.
Competing interests ML served on the Scientific Advisory Group for the Ebola ça Suffit vaccine efficacy trial (unpaid position) and has received consulting fees or honoraria from Merck, Pfizer, Antigen Discovery and Affinivax. His research has received funding (through his employer) from Pfizer and PATH Vaccine Solutions.
Provenance and peer review Not commissioned; externally peer reviewed.
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