Biostatistics Department, University of Liverpool, Liverpool, England.
Clinical Trials Research Centre, University of Liverpool, Liverpool, England.
JAMA. 2017 Dec 19;318(23):2337-2343. doi: 10.1001/jama.2017.18556.
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.
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.
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.
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.
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.
虽然存在临床试验统计原则的指南，但缺乏支持透明度和可重复性的统计分析计划 (SAP) 所需内容的指南。
在统计学家、前指南作者、期刊编辑、监管机构和资助者的参与下，制定一份 SAP 中应包含的最小项目集的建议。
联系了随机试验的资助者和监管者（n=39），并搜索文献以确定现有的指南；对英国临床研究协作组织注册试验单位网络（n=46，1 个单位有 2 个回复者）进行了当前实践调查，并进行了德尔菲调查（n=73 名受邀参与者），以就 SAP 达成共识。德尔菲调查被发送给完成当前实践调查的试验单位的统计学家（n=46）、CONSORT（报告临床试验的统一标准）和 SPIRIT（干预试验标准协议项目：建议）指南作者（n=16）、制药行业统计学家（n=3）、期刊编辑（n=9）和监管者（n=2）（3 名参与者被包括在 2 个组中），最终由来自每个组的专家参加了共识会议（N=12）。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的成员（N=51）进行了严格审查，随后在 5 项试验的 SAP 中进行了指南文件的试点。
没有发现现有的指南。注册试验单位调查（46 个回复）突出了当前实践的多样性，并证实了制定指南的支持。德尔菲调查（73 名参与者中的 54 名，完成了两轮调查）就 110 个项目中的 42%（n=46）达成了共识。专家组（N=12）一致认为，指南应包括 63 个项目，另外还有 17 个项目被认为很重要，但可能在其他地方引用。经过严格审查和试点，一些重叠的项目被合并，留下 55 个项目。
为临床试验的 SAP 中应包含和解决的最小项目集提供了建议。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。
