A Systematic Review of Ebola Treatment Trials to Assess the Extent to Which They Adhere to Ethical Guidelines

Abstract

BackgroundObjective: To determine to what extent each trial met criteria specified in three research frameworks for ethical trial conduct.Design: Systematic review and narrative analysisMethods and findingsData sources: MEDBASE and EMBASE databases were searched using a specific search strategy. The Cochrane database for systematic reviews, the PROSPERO database and trial registries were examined. A grey literature search and citation search were also carried out.Eligibility criteria for selecting studies: Studies were included where the intervention was being used to treat Ebola in human subjects regardless of study design, comparator or outcome measured. Studies were eligible if they had taken place after the 21st March 2014. Unpublished as well as published studies were included.Included studies: Sixteen studies were included in the data synthesis. Data was extracted on study characteristics as well as any information relating to ten ethical areas of interest specified in the three research frameworks for ethical trial conduct and an additional criterion of whether the study received ethics approval from a research ethics committee.Synthesis of results: Eight studies were judged to fully comply with all eleven criteria. The other eight studies all had at least one criteria where there was not enough information available to draw any conclusions. In two studies there were ethical concerns regarding the information provided in relation to at least one ethical criteria.Description of the effect: One study did not receive ethical approval as the authors argued that treating approximately one hundred patients consecutively for compassionate reasons did not constitute a clinical trial. Furthermore, after the patients were treated, physicians in Sierra Leone did not release reports of treatment results and so study conclusions had to be made based on unpublished observations. In another study the risk-benefit ratio of the trial drug does not appear to be favourable and the pre-trial evidence base for its effectiveness against Ebola is speculative.ConclusionsSome limited and appropriate deviation from standard research expectations in disaster situations is increasingly accepted. However, this is not an excuse for poor ethics oversight and international regulations are in place which should not be ignored. New guidelines are needed that better define the boundaries between using medicines for compassionate use and conducting a clinical trial. Greater support should be offered for local research ethics committees in affected areas so that they can provide robust ethical review. Further systematic reviews should be carried out in epidemics of any novel infectious diseases to assess if comparable findings arise.

Addressing challenges for clinical research responses to emerging epidemics and pandemics: a scoping review

“…Ethical issues also arose around equity in access to health care for participants and nonparticipants [44,50,59]. There were calls for international standards for the conduct of emergency research [21,51,60,62], [51], acceptable study designs [14] and simplified consent methods [2,3,6,25,37,46,51,70,74]. Some studies explored waivered consent [2,25,69,70,74] and/or proxy consent [69].…”

What treating Ebola means for pandemic influenza

“…A systematic review has reported on whether the Ebola clinical treatment trials in West Africa adhered to ethical guidelines [29]. The authors of the report excluded the experience in Sierra Leone because it appeared that "giving 100 consecutive patients atorvastatin and irbesartan constituted 'compassionate use' and did not require ethical approval" [29].…”

“…A systematic review has reported on whether the Ebola clinical treatment trials in West Africa adhered to ethical guidelines [29]. The authors of the report excluded the experience in Sierra Leone because it appeared that "giving 100 consecutive patients atorvastatin and irbesartan constituted 'compassionate use' and did not require ethical approval" [29]. The authors of this review mistakenly assumed that all four authors of one of the two statin/ARB treatment reports (DSF, SMO, JRJ, and OMR; [8]) had known of plans to give the two drugs to Ebola patients, when in fact three of the authors (DSF, SMO, and JRJ) first learned that they had been given in late November 2014, several weeks after news first emerged that treatment appeared to have been successful.…”

Windows of opportunity for Ebola virus infection treatment and vaccination

“…with promising results for certain antivirals [4][5][6] , passive immunotherapy and vaccinations 7,8 . On one hand, EBOV 14 infected nonhuman primates (NHPs) treated early with monoclonal antibodies (mAbs) were able to recover after 15 challenged with a lethal dose of EBOV 9 .…”

“…Eq. (5). For simplicity, the mAbs are assumed to have a stable and long elimination half-life of 28 days across the 132 subjects 30 .…”