4.1 In Practice: Vaccine Efficacy and Safety Testing—An Ethical Case for Individual Randomization

A scientific trial has individually randomized control when the intervention or control status for each participant is independently chosen at random at the start of the trial. That is in contrast to cluster randomization, where this status is determined for groups of participants, and in contrast to trials without randomization and to non-trial methods of assessing experimental interventions. The individually randomized controlled trial is generally the most effective and thus the most ethical trial design for assessing the safety and efficacy of candidate vaccines against infectious disease. With this trial design, all study participants benefit by receiving protections that other people at similar risk of infection often do not receive. These benefits include close monitoring, enhanced clinician–patient ratios, and the opportunity to be randomized to the preferred arm of the study. Furthermore, individually randomized trials for emergency response usually reach any given level of statistical confidence before alternative designs with group randomization. Individual randomization is also compatible with delayed or active control trial designs, parallel or stepped rollout, a variety of primary endpoint trial population choices, and either environmental or challenge exposure to the pathogen.