The Use of Ebola Convalescent Plasma to Treat Ebola Virus Disease in Resource-Constrained Settings: A Perspective From the Field

van Griensven, Johan; De Weiggheleire, Anja; Delamou, Alexandre; Smith, Peter G.; Edwards, Tansy; Vandekerckhove, Philippe; Bah, Elhadj Ibrahima; Colebunders, Robert; Herve, Isola; Lazaygues, Catherine; Haba, Nyankoye; Lynen, Lutgarde

Designing trials, and recruiting patients, to evaluate CWB and CP has been challenging. Only Ebola-Tx has achieved a relatively high sample size (>80 CP-treated patients). The design that would provide the best evaluation would be a randomized trial in which one or other intervention would be compared with control patients not receiving the intervention. However, such randomized designs have proved unacceptable in the volatile settings of the current Ebola outbreak, and researchers have at the early stages resorted to nonrandomized study designs [29] . All CP trials were designed to include concurrent control patients. For example, in the Ebola-Tx trial, controls were to be patients presenting when no ABO-compatible plasma was available. However, when the trial started, the supply of CP increased significantly and the number of patients decreased, resulting in sufficient supply of CP to treat nearly all patients. Consequently, it will compare the mortality of treated patients with that of historical controls, with the inherent possibility of biased comparisons. Key concerns in all trials regarded potential confounding factors including variations in patient characteristics, Ebola virulence on presentation, and differences in standards of supportive care over time. For example, the systematic placement of intravenous access lines in patients for CP treatment could encourage more aggressive intravenous hydration during the trial period. How easy it will be to interpret the results of the trials will depend, to a large extent, on the size of the mortality reduction, if any, associated with the intervention.