Basel Institute for Clinical Epidemiology and Biostatistics, University Hospital Basel, Basel, Switzerland.
BMC Med Res Methodol. 2012 Aug 28;12:131. doi: 10.1186/1471-2288-12-131.
Randomized controlled trials (RCTs) may be discontinued because of apparent harm, benefit, or futility. Other RCTs are discontinued early because of insufficient recruitment. Trial discontinuation has ethical implications, because participants consent on the premise of contributing to new medical knowledge, Research Ethics Committees (RECs) spend considerable effort reviewing study protocols, and limited resources for conducting research are wasted. Currently, little is known regarding the frequency and characteristics of discontinued RCTs.
METHODS/DESIGN: Our aims are, first, to determine the prevalence of RCT discontinuation for specific reasons; second, to determine whether the risk of RCT discontinuation for specific reasons differs between investigator- and industry-initiated RCTs; third, to identify risk factors for RCT discontinuation due to insufficient recruitment; fourth, to determine at what stage RCTs are discontinued; and fifth, to examine the publication history of discontinued RCTs.We are currently assembling a multicenter cohort of RCTs based on protocols approved between 2000 and 2002/3 by 6 RECs in Switzerland, Germany, and Canada. We are extracting data on RCT characteristics and planned recruitment for all included protocols. Completion and publication status is determined using information from correspondence between investigators and RECs, publications identified through literature searches, or by contacting the investigators. We will use multivariable regression models to identify risk factors for trial discontinuation due to insufficient recruitment. We aim to include over 1000 RCTs of which an anticipated 150 will have been discontinued due to insufficient recruitment.
Our study will provide insights into the prevalence and characteristics of RCTs that were discontinued. Effective recruitment strategies and the anticipation of problems are key issues in the planning and evaluation of trials by investigators, Clinical Trial Units, RECs and funding agencies. Identification and modification of barriers to successful study completion at an early stage could help to reduce the risk of trial discontinuation, save limited resources, and enable RCTs to better meet their ethical requirements.
随机对照试验（RCT）可能因明显的危害、益处或无效而中止。其他 RCT 因招募不足而提前中止。试验中止具有伦理意义，因为参与者是基于为新医学知识做出贡献的前提下同意参与的，研究伦理委员会（REC）花费大量精力审查研究方案，而用于进行研究的有限资源也被浪费了。目前，对于中止 RCT 的频率和特征知之甚少。
方法/设计：我们的目的是，首先，确定特定原因导致的 RCT 中止的发生率；其次，确定由研究者和行业发起的 RCT 中特定原因导致的 RCT 中止风险是否存在差异；第三，确定因招募不足导致 RCT 中止的风险因素；第四，确定 RCT 中止的阶段；第五，研究中止 RCT 的发表历史。我们目前正在根据瑞士、德国和加拿大的 6 个 REC 在 2000 年至 2002/3 年期间批准的方案，组建一个多中心 RCT 队列。我们正在提取所有纳入方案的 RCT 特征和计划招募的数据。通过研究者与 REC 之间的通信、文献检索中确定的出版物或与研究者联系，确定完成和发表状态。我们将使用多变量回归模型来确定因招募不足而导致试验中止的风险因素。我们的目标是纳入超过 1000 项 RCT，其中预计有 150 项将因招募不足而中止。
我们的研究将深入了解中止 RCT 的发生率和特征。有效的招募策略和对问题的预期是研究者、临床试验单位、REC 和资助机构在计划和评估试验时的关键问题。在早期识别并解决成功完成研究的障碍，可以帮助降低试验中止的风险，节省有限的资源，并使 RCT 更好地满足其伦理要求。
