22 Vaccine Trial Designs

Abstract

AbstractVaccine efficacy trials conducted during epidemics of emerging infectious diseases have three main objectives: (1) to test the null hypothesis in a rigorous fashion, (2) to estimate the efficacy of the vaccine candidate, and (3) to maximize the trial’s public health impact. All of these objectives create urgency for planning and implementing vaccine trials. Ideally, a preferred design choice, based on the anticipated aims of a trial, should be chosen as early as possible. Here we discuss five key choices that must be made in trial design: (1) randomization unit, (2) comparator intervention, (3) trial population, (4) trial implementation, and (5) primary endpoint. We examine each of these choices in the context of each of the three objectives. We also describe the opportunities and challenges of employing adaptive designs for vaccine trials. Where possible, simple, familiar designs should be chosen to make the trial easier to conduct, results easier to interpret, and authorization or approval easier to obtain. However, in some circumstances, innovative designs may be called for, and having preapproved protocols with adaptive elements incorporated can help expedite such trials during an outbreak. The contrast between vaccine trial conditions and choices during the West African Ebola outbreak and the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic is a reminder of the unique challenges arising in each infectious disease emergency and the importance of these conditions in guiding trial design.