23 Data and Safety Monitoring of Clinical Trials During Public Health Emergencies

Abstract

AbstractPublic health emergencies present special challenges in the monitoring of clinical trials. There is tremendous pressure to find effective treatments as quickly as possible without jeopardizing the integrity of results. Frequent early monitoring from an experienced data and safety monitoring board (DSMB) is required to ensure patient safety, especially when novel or repurposed interventions may be tested earlier than they would be in a nonemergency setting. This chapter begins by reviewing general monitoring, including the purpose, composition, and operation of DSMBs, efficacy monitoring boundaries, tools such as conditional power and predicted interval plots for judging whether continuation of a trial is futile, and practical aspects of monitoring clinical trials. We offer important historical examples, like the Cardiac Arrhythmia Suppression Trial (CAST), as well as more recent examples specific to infectious disease, such as the Adaptive COVID-19 Treatment Trial (ACTT-1). We highlight the special challenges posed by monitoring clinical trials in public health emergencies and illustrate these with a case study of the Partnership for Research on Ebola Vaccines in Liberia (PREVAIL-I) vaccine trial in West Africa. We conclude with important lessons learned.