(Accessed 18 Aug 2018)
Choices in vaccine trial design in epidemics of emerging infections
Rebecca Kahn, Annette Rid, Peter G. Smith, Nir Eyal, Marc Lipsitch
| published 07 Aug 2018 PLOS Medicine
:: The 2014–2016 Ebola epidemic highlighted variations in the design of randomized trials to evaluate investigational vaccines in an emergency setting. Here, we summarize scientific, ethical, and feasibility considerations relevant to different trial designs.
:: We focus on four fundamental choices in designing a trial of an experimental vaccine in the setting of an emerging infectious disease for which no proven vaccines exist: randomization unit, trial population, comparator intervention, and trial implementation. We also consider three ethical issues relevant to trial design: the social and scientific value of the trial, its risk–benefit profile, and the fairness of participant selection.
:: We believe that individual rather than cluster randomization is better suited for estimating the direct protective effect of a vaccine, a measure of great intrinsic interest. Individual randomization should therefore be the default strategy for evaluating investigational vaccines during epidemics.
:: Trial participants may be selected either from the general population or from a group at high risk of exposure to infection, depending on the characteristics of the infection together with statistical, fairness, and feasibility considerations.
:: Use of a placebo control, rather than an active control or delayed intervention, is likely to maximize the social and scientific value of the trial because it facilitates double-blinding and removes concerns that the comparison intervention may affect the incidence of the disease under study.
:: Starting the trial at approximately the same time for all participants should minimize the time required to obtain a result. Such a strategy will be facilitated when sufficient supplies of the investigational vaccine and control interventions (if any) are available at the start of a trial, when the geographic area for the trial is clearly identified (and anticipated to have continuing disease transmission throughout the trial), and when logistics permit rapid recruitment of the entire trial population. Otherwise, a stepped rollout may be necessary, in which recruitment to the trial is staggered over a period.