title: Clinical validation trial of a diagnostic for Ebola Zaire antigen detection: Design rationale and challenges to implementation.
abstract: The current Ebola outbreak in West Africa has affected more people than all previous outbreaks combined. The current diagnostic method of choice, quantitative polymerase chain reaction, requires specialized conditions as well as specially trained technicians. Insufficient testing capacity has extended the time from sample collection to results. These delays have led to further delays in the transfer and treatment to Ebola Treatment Units. A sensitive and specific point-of-care device that could be used reliably in low-resource settings by healthcare workers with minimal training would increase the efficiency of triage and appropriate transfer of care. This article describes a study designed to validate the sensitivity and specificity of the ReEBOVTM Rapid Diagnostic Test using venous whole blood and capillary blood obtained via fingerprick. We present the scientific and clinical rationale for the decisions made in the design of a diagnostic validation study to be conducted in an outbreak setting. The multi-site strategy greatly complicated implementation. In addition, a decrease in cases in one geographic area along with a concomitant increase in other areas made site selection challenging. Initiation of clinical trials during rapidly evolving outbreaks requires significant cooperation on a national level between research teams implementing studies and clinical care providers. Coordination and streamlining of approval process are essential if trials are to be implemented in a timely fashion.
authors.affiliation: Department of Pediatrics, Tulane University, New Orleans, LA, USA jschieff@tulane.edu.
authors.forename: John
authors.initials: J
authors.lastname: Schieffelin
authors.affiliation: Department of Microbiology and Immunology, Tulane University, New Orleans, LA, USA.
authors.forename: Lina M
authors.initials: LM
authors.lastname: Moses
authors.affiliation: Department of Biostatistics and Bioinformatics, Tulane University, New Orleans, LA, USA.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Shaffer
authors.affiliation: Kenema Government Hospital-VHF Laboratory, Kenema, Sierra Leone.
authors.forename: Augustine
authors.initials: A
authors.lastname: Goba
authors.affiliation: Ministry of Health and Sanitation, Kenema, Sierra Leone.
authors.forename: Donald S
authors.initials: DS
authors.lastname: Grant
mesh_terms: D000354:Africa, Western / Q000453:epidemiology; D000956:Antigens, Viral / Q000032:analysis*; D004196:Disease Outbreaks; D029043:Ebolavirus / Q000276:immunology*; D019142:Hemorrhagic Fever, Ebola / Q000175:diagnosis* / Q000453:epidemiology / Q000821:virology; D006801:Humans; D019095:Point-of-Care Systems; D011933:Reagent Kits, Diagnostic; D012107:Research Design; D012680:Sensitivity and Specificity; D054928:Validation Studies as Topic
chemical_list: D000956:Antigens, Viral; D011933:Reagent Kits, Diagnostic
keywords: Ebola; diagnostic; lateral flow; validation trial