A meta-analysis of clinical studies conducted during the West Africa Ebola virus disease outbreak confirms the need for randomized control groups
- 27 November 2019
- journal article
- research article
- Published by American Association for the Advancement of Science (AAAS) in Science Translational Medicine
- Vol. 11 (520)
- https://doi.org/10.1126/scitranslmed.aaw1049
Abstract
Recent Ebola virus disease outbreaks affirm the dire need for treatments with proven efficacy. Randomized controlled clinical trials remain the gold standard but, during disease outbreaks, may be difficult to conduct due to ethical concerns and challenging field conditions. In the absence of a randomized control group, statistical modeling to create a control group could be a possibility. Such a model-based reference control would only be credible if it had the same mortality risk as that of the experimental group in the absence of treatment. One way to test this counterfactual assumption is to evaluate whether reasonable similarity exists across nonrandomized control groups from different clinical studies, which might suggest that a future control group would be similarly homogeneous. We evaluated similarity across six clinical studies conducted during the 2013–2016 West Africa outbreak of Ebola virus disease. These studies evaluated favipiravir, the biologic ZMapp, the antimalarial drug amodiaquine, or administration of convalescent plasma or convalescent whole blood. We compared the nonrandomized control groups of these six studies comprising 1147 individuals infected with Ebola virus. We found considerable heterogeneity, which did not disappear after statistical modeling to adjust for prognostic variables. Mortality risk varied widely (31 to 66%) across the nonrandomized control arms of these six studies. Models adjusting for baseline covariates (age, sex, and cycle threshold, a proxy for viral load) failed to sufficiently recalibrate these studies and showed that heterogeneity remained. Our findings highlight concerns about making invalid conclusions when comparing nonrandomized control groups to cohorts receiving experimental treatments.This publication has 32 references indexed in Scilit:
- Evaluating Ebola Therapies — The Case for RCTsThe New England Journal of Medicine, 2014
- Clinical Illness and Outcomes in Patients with Ebola in Sierra LeoneThe New England Journal of Medicine, 2014
- Randomised controlled trials for Ebola: practical and ethical issuesThe Lancet, 2014
- Identification of 53 compounds that block Ebola virus-like particle entry via a repurposing screen of approved drugsEmerging Microbes & Infections, 2014
- A Systematic Screen of FDA-Approved Drugs for Inhibitors of Biological Threat AgentsPLOS ONE, 2013
- Meta-Analysis of Phase II Cooperative Group Trials in Metastatic Stage IV Melanoma to Determine Progression-Free and Overall Survival Benchmarks for Future Phase II TrialsJournal of Clinical Oncology, 2008
- Do arrhythmia patients improve survival by participating in randomized clinical trials?: Observations from the Cardiac Arrhythmia Suppression Trial (CAST)and the Antiarrhythmics Versus Implantable Defibrillators Trial (AVID)Controlled Clinical Trials, 2003
- Effect of clinical guidelines on medical practice: a systematic review of rigorous evaluationsThe Lancet, 1993
- A note on graphical presentation of estimated odds ratios from several clinical trialsStatistics in Medicine, 1988