Considerations for the design of vaccine efficacy trials during public health emergencies

Public Health Emergencies (PHEs) provide a complex and challenging environment for vaccine evaluation. Under the R&D Blueprint Plan of Action, the World Health Organization (WHO) has convened a group of experts to agree on standard procedures to rapidly evaluate experimental vaccines during PHEs while maintaining the highest scientific and ethical standards. The Blueprint priority diseases, selected for their likelihood to cause PHEs and the lack of adequate medical countermeasures, were used to frame our methodological discussions. Here, we outline major vaccine study designs to be used in PHEs and summarize high-level recommendations for their use in this setting. We recognize that the epidemiology and transmission dynamics of the Blueprint priority diseases may be highly uncertain and that the unique characteristics of the vaccines and outbreak settings may affect our study design. To address these challenges, our group underscores the need for novel, flexible, and responsive trial designs. We conclude that assignment to study groups using randomization is a key principle underlying rigorous study design and should be utilized except in exceptional circumstances. Advance planning for vaccine trial designs is critical for rapid and effective response to a PHE and to advance knowledge to address and mitigate future PHEs. One Sentence Summary As part of the WHO research and development Blueprint for action to prevent epidemics, we describe key considerations for the design and analysis of trials and studies to evaluate experimental vaccines during public health emergencies.