Ebola clinical trials: Five lessons learned and a way forward.

BACKGROUND: Little progress was made in advancing Ebola-specific therapies during the epidemic that began in West Africa in late 2013. Throughout the last quarter of 2014, which saw the greatest numbers of cases, only a handful of clinical trials were underway. Subsequently, as incident cases dwindled, the number of clinical trials increased dramatically, but few, were destined to recruit to their accrual targets. The predictable barriers to implementing clinical trials in resource-constrained settings are compounded by unique characteristics of Ebola — including its high fatality rate, its swift transmission through populations, and the grave risks for exposed health care workers. METHODS: As members from a group hastily configured as the Ebola Clinical Research Consortium, we sought to implement two clinical trials beginning in late 2014 in Liberia and Sierra Leone: one to evaluate the efficacy and safety of convalescent plasma for Ebola treatment (ClinicalTrials.gov Identifier: NCT02333578) and another, an adaptive platform protocol to evaluate multiple treatments for Ebola Virus Disease (ClinicalTrials.gov Identifier: NCT02380625). RESULTS: Here, we offer five lessons learned from our experiences that may help inform future efforts to conduct clinical trials targeting Ebola or Ebola-like outbreaks: (1) Research should be an integral part of the public health emergency response in outbreak settings; (2) conducting emergency clinical trials requires experienced research staff at all levels from the start; (3) public health officials should coordinate with scientific leadership to direct resources towards the most meritorious research questions; (4) a platform trial design is well-suited to ethically and efficiently identify effective therapies in the setting of a high-fatality, dynamic outbreak; (5) to advance therapeutics in the midst of an emerging outbreak, academic and research communities need to respond as boldly and as swiftly as the humanitarian community. CONCLUSIONS: Clinical research to evaluate Ebola therapeutics in the West Africa Ebola epidemic was initiated too late to yield optimal results. In seeking to conduct two clinical studies in this region, we learned valuable lessons and suggest a way forward for implementing therapeutic clinical trials in the next epidemic.

Duke Scholars

Author Nathan Maclyn Thielman Medicine, Infectious Diseases

Author Christopher Wildrick Woods Medicine, Infectious Diseases