Abstract：
Opinions and practices vary around the issue of performing multiple statistical tests in randomised controlled trials (RCTs). We carried out a study to collate information about opinions and practices using a methodological rapid review and a survey, specifically of publicly funded pragmatic RCTs that are not seeking marketing authorisation. The aim was to identify the circumstances under which researchers would make a statistical adjustment for multiplicity.
A review was performed extracting information from articles reporting primary analyses of pragmatic RCTs in one of seven high quality medical journals, in January to June (inclusive) 2018. A survey (Survey Monkey) eliciting opinions and practices around multiplicity was distributed to the 47 registered clinical trials units (CTUs) in the UK.
One hundred and thirty-eight RCTs were included in the review, and survey responses were received from 27/47 (57%) CTUs. Both the review and survey indicated that adjusting for multiplicity was considered most important for multiple treatment comparisons; adjustment was performed for 11/23 (48%) published trials, and 24/27 (89%) CTU statisticians reported they would consider adjustment. Opinions and practices varied around adjustment for multiplicity arising from multiple primary outcomes and interim analyses. Adjustment was considered less important for multiplicity due to multiple secondary outcomes (adjustment performed for 17/136 [13%] published trials and 3/27 [11%] CTU statisticians would consider adjustment) and subgroup analyses (8/85 [9%] published trials adjusted and 6/27 CTU [22%] statisticians would consider adjustment).
There is variation in opinions about adjustment for multiplicity among both statisticians reporting RCTs and applied statisticians working in CTUs. Further guidance is needed on the circumstances in which adjustment should be considered in relation to primary trial hypotheses, and if there are any situations in which adjustment would be recommended in the context of secondary analyses.
A review was performed extracting information from articles reporting primary analyses of pragmatic RCTs in one of seven high quality medical journals, in January to June (inclusive) 2018. A survey (Survey Monkey) eliciting opinions and practices around multiplicity was distributed to the 47 registered clinical trials units (CTUs) in the UK.
One hundred and thirty-eight RCTs were included in the review, and survey responses were received from 27/47 (57%) CTUs. Both the review and survey indicated that adjusting for multiplicity was considered most important for multiple treatment comparisons; adjustment was performed for 11/23 (48%) published trials, and 24/27 (89%) CTU statisticians reported they would consider adjustment. Opinions and practices varied around adjustment for multiplicity arising from multiple primary outcomes and interim analyses. Adjustment was considered less important for multiplicity due to multiple secondary outcomes (adjustment performed for 17/136 [13%] published trials and 3/27 [11%] CTU statisticians would consider adjustment) and subgroup analyses (8/85 [9%] published trials adjusted and 6/27 CTU [22%] statisticians would consider adjustment).
There is variation in opinions about adjustment for multiplicity among both statisticians reporting RCTs and applied statisticians working in CTUs. Further guidance is needed on the circumstances in which adjustment should be considered in relation to primary trial hypotheses, and if there are any situations in which adjustment would be recommended in the context of secondary analyses.
摘要：
在随机对照试验（RCT）中进行多种统计检验的问题上，意见和做法各不相同。我们进行了一项研究，使用方法快速审查和调查来整理有关意见和实践的信息，特别是不寻求营销授权的公共资助的务实RCT。目的是确定研究人员对多重性进行统计调整的情况。
从七种高质量医学期刊之一的报告语用随机对照试验的主要分析的文章中提取信息进行了综述，2018年1月至6月（含）。一项关于多重性的意见和实践的调查（调查猴子）被分发到英国的47个注册临床试验单位（CTU）。
审查中包括了一百三十八个RCT，和调查答复来自27/47(57%)CTU。审查和调查都表明，多重性调整被认为对多重治疗比较最重要；对11/23(48%)已发表的试验进行了调整，24/27（89%）CTU统计人员报告称，他们将考虑调整。围绕多个主要结果和中期分析产生的多重性调整，意见和做法各不相同。由于多个次要结局(17/136[13%]已发表试验和3/27[11%]CTU统计学家考虑调整)和亚组分析(8/85[9%]已发表试验进行调整和6/27CTU[22%]统计学家考虑调整),调整对于多重性被认为不那么重要。
在报告RCT的统计学家和在CTU工作的应用统计学家之间，关于多重性调整的观点存在差异。需要进一步指导应考虑对主要试验假设进行调整的情况，以及在二次分析的背景下是否有任何建议进行调整的情况。
从七种高质量医学期刊之一的报告语用随机对照试验的主要分析的文章中提取信息进行了综述，2018年1月至6月（含）。一项关于多重性的意见和实践的调查（调查猴子）被分发到英国的47个注册临床试验单位（CTU）。
审查中包括了一百三十八个RCT，和调查答复来自27/47(57%)CTU。审查和调查都表明，多重性调整被认为对多重治疗比较最重要；对11/23(48%)已发表的试验进行了调整，24/27（89%）CTU统计人员报告称，他们将考虑调整。围绕多个主要结果和中期分析产生的多重性调整，意见和做法各不相同。由于多个次要结局(17/136[13%]已发表试验和3/27[11%]CTU统计学家考虑调整)和亚组分析(8/85[9%]已发表试验进行调整和6/27CTU[22%]统计学家考虑调整),调整对于多重性被认为不那么重要。
在报告RCT的统计学家和在CTU工作的应用统计学家之间，关于多重性调整的观点存在差异。需要进一步指导应考虑对主要试验假设进行调整的情况，以及在二次分析的背景下是否有任何建议进行调整的情况。
