title: Trial design for evaluating novel treatments during an outbreak of an infectious disease.
abstract: Tragically, the outbreak of Ebola that started in West Africa in 2014 has been far more extensive and damaging than any previous outbreaks. The duration of the outbreak has, for the first time, allowed the clinical evaluation of Ebola treatments. This article discusses the designs used for two such clinical trials which have recruited patients in Liberia and Sierra Leone. General principles are outlined for trial designs intended to be deployed quickly, adapt flexibly and provide results soon enough to influence the course of the current epidemic rather than just providing evidence for use should Ebola break out again. Lessons are drawn for the conduct of clinical research in future outbreaks of infectious diseases, where the sequence of events may or may not be similar to the West African Ebola epidemic.
authors.affiliation: Department of Mathematics and Statistics, Fylde College, Lancaster University, Lancaster, UK j.whitehead@lancaster.ac.uk.
authors.forename: John
authors.initials: J
authors.lastname: Whitehead
authors.affiliation: Centre for Tropical Medicine and Global Health, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK UNICEF-UNDP-World Bank-WHO Special Programme for Research and Training in Tropical Diseases, Geneva, Switzerland.
authors.forename: Piero
authors.initials: P
authors.lastname: Olliaro
authors.affiliation: Centre for Tropical Medicine and Global Health, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK.
authors.forename: Trudie
authors.initials: T
authors.lastname: Lang
authors.affiliation: Centre for Tropical Medicine and Global Health, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK.
authors.forename: Peter
authors.initials: P
authors.lastname: Horby
mesh_terms: D000998:Antiviral Agents / Q000627:therapeutic use*; D002985:Clinical Protocols; D017322:Clinical Trials, Phase II as Topic / Q000379:methods; D017326:Clinical Trials, Phase III as Topic / Q000379:methods; D003596:Cytosine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004196:Disease Outbreaks; D019142:Hemorrhagic Fever, Ebola / Q000188:drug therapy* / Q000401:mortality; D006801:Humans; D007988:Liberia / Q000453:epidemiology; D063065:Organophosphonates / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic / Q000379:methods*; D012107:Research Design; D012807:Sierra Leone / Q000453:epidemiology; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D063065:Organophosphonates; C525733:brincidofovir; D003596:Cytosine
keywords: Ebola; infectious disease; multi-stage approach; sequential design; single-arm design; stopping rule