Prevalence, Characteristics, and Publication of Discontinued Randomized Trials
Prevalence, Characteristics, and Publication of Discontinued Randomized Trials
复制标题
DOI：
10.1001/jama.2014.1361
复制
发表时间：
2014-03-12
影响因子：
120.7
通讯作者：
Briel, Matthias
中科院分区：
文献类型：
--
作者：
Kasenda, Benjamin;von Elm, Erik;Briel, Matthias
随机临床试验（RCT）的中止引起了伦理问题，并经常浪费稀缺的研究资源。为了确定中止的RCT的流行病学、特征和出版历史，并调查与RCT因招募不足和未出版而中止相关的因素。设计和设置回顾性RCT队列，基于瑞士、德国、瑞士和德国6个研究伦理委员会批准的存档方案。2000年至2003年，加拿大。我们记录了试验特征，并计划从纳入的方案中招募。RCT的最后一次随访时间为2013年4月27日。主要结局和指标完成状态、报告的中止原因和RCT的出版状态，通过与研究伦理委员会的通信、文献检索和研究者调查确定。（范围，8.8 - 12.6年），1017项纳入的RCT中有253项中止（24.9%[95% CI，22.3%-27.6%]）。253例停药中仅96例（37.9%[95% CI，32.0%-44.3%]）报告给伦理委员会。最常见的停药原因是招募不良（101/1017; 9.9%[95% CI，8.2%-12.0%]）。在多变量分析中，行业赞助vs研究者赞助（8.4% vs 26.5%;比值比[OR]，0.25 [95% CI，0.15 - 0.43]; P <.001）和更大的计划样本量，增量为100（-0.7%; OR，0.96 [95% CI，0.92 - 1.00]; P = 0.04）与因招募不良导致的停药率较低相关。中止的试验比已完成的试验更有可能保持未发表状态（55.1%vs 33.6%; OR，3.19 [95%CI，2.29 - 4.43]; P <.001）.结论和相关性在这个基于6个研究伦理委员会RCT方案的试验样本中，中止是常见的，招募不良是最常见的原因。需要作出更大努力，确保向研究伦理委员会报告试验中止情况，并公布中止试验的结果。
IMPORTANCE The discontinuation of randomized clinical trials (RCTs) raises ethical concerns and often wastes scarce research resources. The epidemiology of discontinued RCTs, however, remains unclear.OBJECTIVES To determine the prevalence, characteristics, and publication history of discontinued RCTs and to investigate factors associated with RCT discontinuation due to poor recruitment and with nonpublication.DESIGN AND SETTING Retrospective cohort of RCTs based on archived protocols approved by 6 research ethics committees in Switzerland, Germany, and Canada between 2000 and 2003. We recorded trial characteristics and planned recruitment from included protocols. Last follow-up of RCTs was April 27, 2013.MAIN OUTCOMES AND MEASURES Completion status, reported reasons for discontinuation, and publication status of RCTs as determined by correspondence with the research ethics committees, literature searches, and investigator surveys.RESULTS After a median follow-up of 11.6 years (range, 8.8-12.6 years), 253 of 1017 included RCTs were discontinued (24.9% [95% CI, 22.3%-27.6%]). Only 96 of 253 discontinuations (37.9% [95% CI, 32.0%-44.3%]) were reported to ethics committees. The most frequent reason for discontinuation was poor recruitment (101/1017; 9.9%[95% CI, 8.2%-12.0%]). In multivariable analysis, industry sponsorship vs investigator sponsorship (8.4% vs 26.5%; odds ratio [OR], 0.25 [95% CI, 0.15-0.43]; P < .001) and a larger planned sample size in increments of 100 (-0.7%; OR, 0.96 [95% CI, 0.92-1.00]; P = .04) were associated with lower rates of discontinuation due to poor recruitment. Discontinued trials were more likely to remain unpublished than completed trials (55.1% vs 33.6%; OR, 3.19 [95% CI, 2.29-4.43]; P < .001).CONCLUSIONS AND RELEVANCE In this sample of trials based on RCT protocols from 6 research ethics committees, discontinuation was common, with poor recruitment being the most frequently reported reason. Greater efforts are needed to ensure the reporting of trial discontinuation to research ethics committees and the publication of results of discontinued trials.