Guidelines for the Content of Statistical Analysis Plans in Clinical Trials
Guidelines for the Content of Statistical Analysis Plans in Clinical Trials
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DOI：
10.1001/jama.2017.18556
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发表时间：
2017-12-19
影响因子：
120.7
通讯作者：
Loder, Elizabeth
中科院分区：
文献类型：
--
作者：
Gamble, Carrol;Krishan, Ashma;Loder, Elizabeth
虽然存在临床试验统计原则的指导，但缺乏涵盖统计分析计划（sap）所需内容的指导，以支持透明度和可重复性。目的：根据统计学家、以前的指南作者、期刊编辑、监管机构和资助者的意见，为临床试验的sap中应解决的最小项目集提出建议。联系随机试验的资助者和监管机构（n = 39），检索文献以确定现有的指导；在英国临床研究合作注册的试验单位（n = 46, 1个单位有2个应答者）和德尔菲调查（n = 73邀请参与者）进行了当前实践调查，以建立对sap的共识。德尔菲调查被发送给试验单位的统计学家，他们完成了当前实践调查（n = 46）， CONSORT（合并报告试验标准）和SPIRIT（标准方案项目）：《介入性试验建议》指南作者（n = 16）、制药行业统计学家（n = 3）、期刊编辑（n = 9）和监管机构（n = 2）（每组3名参与者），最终由专家（n = 12）和每组代表参加了一次共识会议。该指南随后由接受调查的试验单位的统计学家和共识会议专家小组成员（N = 51）进行了严格审查，随后在5个试验的SAPs中试用了指导文件。没有发现现有的指南。注册试验单位调查（46份答复）强调了当前实践的多样性，并确认了对制定指南的支持。德尔菲调查（73,74%的参与者中有54人完成了两轮调查）对110个项目中的42%（n = 46）达成了共识。专家小组（N = 12）同意应将63个项目列入指南，另外17个项目确定为重要但可在其他地方参考。经过严格的审查和试点，将一些重叠的项目合并，留下55个项目。结论和相关性提供了一组最低限度的项目建议，这些项目应该被处理并包括在临床试验的sap中。试验注册、方案和统计分析计划对于确保临床试验的适当报告至关重要。
IMPORTANCE While guidance on statistical principles for clinical trials exists, there is an absence of guidance covering the required content of statistical analysis plans (SAPs) to support transparency and reproducibility.OBJECTIVE To develop recommendations for a minimum set of items that should be addressed in SAPs for clinical trials, developed with input from statisticians, previous guideline authors, journal editors, regulators, and funders.DESIGN Funders and regulators (n = 39) of randomized trials were contacted and the literature was searched to identify existing guidance; a survey of current practice was conducted across the network of UK Clinical Research Collaboration-registered trial units (n = 46, 1 unit had 2 responders) and a Delphi survey (n = 73 invited participants) was conducted to establish consensus on SAPs. The Delphi survey was sent to statisticians in trial units who completed the survey of current practice (n = 46), CONSORT (Consolidated Standards of Reporting Trials) and SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) guideline authors (n = 16), pharmaceutical industry statisticians (n = 3), journal editors (n = 9), and regulators (n = 2) (3 participants were included in 2 groups each), culminating in a consensus meeting attended by experts (N = 12) with representatives from each group. The guidance subsequently underwent critical review by statisticians from the surveyed trial units and members of the expert panel of the consensus meeting (N = 51), followed by piloting of the guidance document in the SAPs of 5 trials.FINDINGS No existing guidance was identified. The registered trials unit survey (46 responses) highlighted diversity in current practice and confirmed support for developing guidance. The Delphi survey (54 of 73, 74% participants completing both rounds) reached consensus on 42%(n = 46) of 110 items. The expert panel (N = 12) agreed that 63 items should be included in the guidance, with an additional 17 items identified as important but may be referenced elsewhere. Following critical review and piloting, some overlapping items were combined, leaving 55 items.CONCLUSIONS AND RELEVANCE Recommendations are provided for a minimum set of items that should be addressed and included in SAPs for clinical trials. Trial registration, protocols, and statistical analysis plans are critically important in ensuring appropriate reporting of clinical trials.