Abstract
The 2014–2016 Ebola epidemic highlighted the lack of consensus on the design of trials for investigational vaccine products in an emergency setting. With the advent of the ring vaccination strategy, it also underscored that the range of design options is evolving according to scientific need and creativity. Ideally, principles and protocols will be drawn up in advance, facilitating expediency and trust, for rapid deployment early in an epidemic. Here, we attempt a summary of the scientific, ethical and feasibility considerations relevant to different trial designs. We focus on four elements of design choices which, in our view, are most fundamental to designing an experimental vaccine trial and for which the most distinctive issues arise in the setting of an emerging infectious disease for which no proven vaccines exist: 1) randomization unit, 2) trial population, 3) comparator intervention and 4) trial implementation. Likewise, we focus on three of several ethical considerations in clinical research, namely the trial’s social and scientific value, its risk-benefit profile and its participant selection. A catalogue of possible designs to guide trial design choices is offered, along with a systematic evaluation of the benefits and drawbacks of each in given contexts.