van Lent Marlies, Rongen Gerard A, Out Henk J
Clinical Research Centre Nijmegen, Department of Pharmacology - Toxicology, Radboud University Medical Center, Nijmegen, The Netherlands.
BMC Med Ethics. 2014 Dec 10;15:83. doi: 10.1186/1472-6939-15-83.
Submission of study protocols to research ethics committees (RECs) constitutes one of the earliest stages at which planned trials are documented in detail. Previous studies have investigated the amendments requested from researchers by RECs, but the type of issues raised during REC review have not been compared by sponsor type. The objective of this study was to identify recurring shortcomings in protocols of drug trials based on REC comments and to assess whether these were more common among industry-sponsored or non-industry trials.
Retrospective analysis of 226 protocols of drug trials approved in 2010-2011 by three RECs affiliated to academic medical centres in The Netherlands. For each protocol, information on sponsorship, number of participating centres, participating countries, study phase, registration status of the study drug, and type and number of subjects was retrieved. REC comments were extracted from decision letters sent to investigators after review and were classified using a predefined checklist that was based on legislation and guidelines on clinical drug research and previous literature.
Most protocols received comments regarding participant information and consent forms (n = 182, 80.5%), methodology and statistical analyses (n = 160, 70.8%), and supporting documentation, including trial agreements and certificates of insurance (n = 154, 68.1%). Of the submitted protocols, 122 (54.0%) were non-industry and 104 (46.0%) were industry-sponsored trials. Non-industry trials more often received comments on subject selection (n = 44, 36.1%) than industry-sponsored trials (n = 18, 17.3%; RR, 1.58; 95% CI, 1.01 to 2.47), and on methodology and statistical analyses (n = 95, 77.9% versus n = 65, 62.5%, respectively; RR, 1.18; 95% CI, 1.01 to 1.37). Non-industry trials less often received comments on supporting documentation (n = 72, 59.0%) than industry-sponsored trials (n = 82, 78.8%; RR, 0.83; 95% CI, 0.72 to 0.95).
RECs identified important ethical and methodological shortcomings in protocols of both industry-sponsored and non-industry drug trials. Investigators, especially of non-industry trials, should better prepare their research protocols in order to facilitate the ethical review process.
向研究伦理委员会（RECs）提交研究方案是详细记录计划进行的试验的最早阶段之一。以往的研究调查了伦理委员会要求研究人员做出的修改，但尚未按申办方类型对伦理委员会审查期间提出的问题类型进行比较。本研究的目的是根据伦理委员会的意见确定药物试验方案中反复出现的缺陷，并评估这些缺陷在行业申办试验和非行业申办试验中是否更常见。
对荷兰学术医疗中心附属的三个伦理委员会在2010 - 2011年批准的226份药物试验方案进行回顾性分析。对于每份方案，检索有关申办方、参与中心数量、参与国家、研究阶段、研究药物的注册状态以及受试者类型和数量的信息。伦理委员会的意见从审查后发给研究者的决定函中提取，并使用基于临床药物研究法规和指南以及以往文献的预定义清单进行分类。
大多数方案收到了关于参与者信息和知情同意书的意见（n = 182，80.5%）、方法学和统计分析的意见（n = 160，70.8%）以及支持性文件的意见，包括试验协议和保险证书（n = 154，68.1%）。在提交的方案中，122份（54.0%）为非行业申办试验，104份（46.0%）为行业申办试验。非行业申办试验比行业申办试验更常收到关于受试者选择的意见（n = 44，36.1% 对比 n = 18，17.3%；RR，1.58；95% CI，1.01至2.47），以及关于方法学和统计分析的意见（分别为n = 95，77.9% 对比 n = 65，62.5%；RR，1.18；95% CI，1.01至1.37）。非行业申办试验收到关于支持性文件的意见的频率低于行业申办试验（n = 72，59.0% 对比 n = 82，78.8%；RR，0.83；95% CI，0.72至0.95）。
伦理委员会在行业申办和非行业申办的药物试验方案中都发现了重要的伦理和方法学缺陷。研究者，尤其是非行业申办试验的研究者，应更好地准备他们的研究方案，以促进伦理审查过程。
