23.1 In Practice: Monitoring the PALM Ebola Therapeutics Study in the Democratic Republic of the Congo

Abstract

AbstractThis chapter outlines the demanding, complex task of monitoring an expedited clinical trial in a resource-limited, insecure setting. The PALM Ebola therapeutics trial was implemented in the Democratic Republic of the Congo (DRC) despite minimal basic infrastructure, widespread suspicion and hostility among the population, and outbreaks of violence in the region. In order to keep participant enrollment numbers manageable, the PALM trial was designed to detect a large treatment effect, and its primary endpoint was mortality within 28 days after randomization. The course of an Ebola epidemic can wax and wane unpredictably, causing fluctuations in enrollment and a lag in information presented to the data and safety monitoring board (DSMB). The DSMB had to meet frequently, usually virtually, to monitor the four treatments being investigated and detect safety and efficacy signals. Since both resources and medical personnel were at their limits, collecting and verifying all data was difficult. Therefore, streamlining data collection and focusing on the most critical outcomes for safety and efficacy monitoring were paramount. Results indicated that two of the four agents under study, MAb114 and REGN-EB3, were clearly superior to the ZMapp control arm, so much so that the trial was stopped early.