Richardson Thomas, Johnston Andrew McDonald, Draper Heather
College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom.
Academic Department of Military Anaesthesia and Critical Care, Royal Centre for Defence Medicine, Queen Elizabeth Hospital, Birmingham, United Kingdom.
PLoS One. 2017 Jan 17;12(1):e0168975. doi: 10.1371/journal.pone.0168975. eCollection 2017.
Objective: To determine to what extent each trial met criteria specified in three research frameworks for ethical trial conduct. Design: Systematic review and narrative analysis.
Data 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 Unpublished as well as published studies were included.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in Sierra Leone did not release reports of treatment results and so study conclusions had to be made based on unpublished observations.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.
Some 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.
目的：确定每项试验在何种程度上符合三项临床试验伦理规范研究框架中规定的标准。设计：系统评价和叙述性分析。
数据来源：使用特定检索策略检索MEDBASE和EMBASE数据库。查阅Cochrane系统评价数据库、PROSPERO数据库及试验注册库。还进行了灰色文献检索和引文检索。选择研究的纳入标准：纳入使用干预措施治疗人类埃博拉患者的研究，无论研究设计、对照或测量的结局如何。如果研究在2014年3月21日之后进行，则符合纳入标准。纳入未发表及已发表的研究。纳入研究：16项研究纳入数据综合分析。提取了关于研究特征以及三项临床试验伦理规范研究框架中规定的十个感兴趣伦理领域的任何相关信息，以及该研究是否获得研究伦理委员会伦理批准的额外标准。结果综合：八项研究被判定完全符合所有十一项标准。其他八项研究均至少有一项标准缺乏足够信息以得出任何结论。两项研究在至少一项伦理标准方面提供的信息存在伦理问题。效果描述：一项研究未获得伦理批准，因为作者认为出于同情原因连续治疗约100名患者不构成临床试验。此外，患者接受治疗后，塞拉利昂的医生未公布治疗结果报告，因此研究结论不得不基于未发表的观察结果得出。在另一项研究中，试验药物的风险效益比似乎不理想，其抗埃博拉有效性的试验前证据基础具有推测性。
在灾难情况下，适度偏离标准研究预期越来越被接受。然而，这不是伦理监督不力的借口，现有国际法规不应被忽视。需要新的指南来更好地界定同情用药和开展临床试验之间的界限。应向受影响地区的当地研究伦理委员会提供更多支持，以便它们能够进行有力的伦理审查。对于任何新型传染病的流行，都应进行进一步的系统评价，以评估是否会出现类似的结果。
