PDF(Pubmed)
Abstract：
The stepped-wedge cluster randomized trial (SW-CRT), in which clusters are randomized to a time at which they will transition to the intervention condition - rather than a trial arm - is a relatively new design. SW-CRTs have additional design and analytical considerations compared to conventional parallel arm trials. To inform future methodological development, including guidance for trialists and the selection of parameters for statistical simulation studies, we conducted a review of recently published SW-CRTs. Specific objectives were to describe (1) the types of designs used in practice, (2) adherence to key requirements for statistical analysis, and (3) practices around covariate adjustment. We also examined changes in adherence over time and by journal impact factor.
We used electronic searches to identify primary reports of SW-CRTs published 2016-2022. Two reviewers extracted information from each trial report and its protocol, if available, and resolved disagreements through discussion.
We identified 160 eligible trials, randomizing a median (Q1-Q3) of 11 (8-18) clusters to 5 (4-7) sequences. The majority (122, 76%) were cross-sectional (almost all with continuous recruitment), 23 (14%) were closed cohorts and 15 (9%) open cohorts. Many trials had complex design features such as multiple or multivariate primary outcomes (50, 31%) or time-dependent repeated measures (27, 22%). The most common type of primary outcome was binary (51%); continuous outcomes were less common (26%). The most frequently used method of analysis was a generalized linear mixed model (112, 70%); generalized estimating equations were used less frequently (12, 8%). Among 142 trials with fewer than 40 clusters, only 9 (6%) reported using methods appropriate for a small number of clusters. Statistical analyses clearly adjusted for time effects in 119 (74%), for within-cluster correlations in 132 (83%), and for distinct between-period correlations in 13 (8%). Covariates were included in the primary analysis of the primary outcome in 82 (51%) and were most often individual-level covariates; however, clear and complete pre-specification of covariates was uncommon. Adherence to some key methodological requirements (adjusting for time effects, accounting for within-period correlation) was higher among trials published in higher versus lower impact factor journals. Substantial improvements over time were not observed although a slight improvement was observed in the proportion accounting for a distinct between-period correlation.
Future methods development should prioritize methods for SW-CRTs with binary or time-to-event outcomes, small numbers of clusters, continuous recruitment designs, multivariate outcomes, or time-dependent repeated measures. Trialists, journal editors, and peer reviewers should be aware that SW-CRTs have additional methodological requirements over parallel arm designs including the need to account for period effects as well as complex intracluster correlations.
We used electronic searches to identify primary reports of SW-CRTs published 2016-2022. Two reviewers extracted information from each trial report and its protocol, if available, and resolved disagreements through discussion.
We identified 160 eligible trials, randomizing a median (Q1-Q3) of 11 (8-18) clusters to 5 (4-7) sequences. The majority (122, 76%) were cross-sectional (almost all with continuous recruitment), 23 (14%) were closed cohorts and 15 (9%) open cohorts. Many trials had complex design features such as multiple or multivariate primary outcomes (50, 31%) or time-dependent repeated measures (27, 22%). The most common type of primary outcome was binary (51%); continuous outcomes were less common (26%). The most frequently used method of analysis was a generalized linear mixed model (112, 70%); generalized estimating equations were used less frequently (12, 8%). Among 142 trials with fewer than 40 clusters, only 9 (6%) reported using methods appropriate for a small number of clusters. Statistical analyses clearly adjusted for time effects in 119 (74%), for within-cluster correlations in 132 (83%), and for distinct between-period correlations in 13 (8%). Covariates were included in the primary analysis of the primary outcome in 82 (51%) and were most often individual-level covariates; however, clear and complete pre-specification of covariates was uncommon. Adherence to some key methodological requirements (adjusting for time effects, accounting for within-period correlation) was higher among trials published in higher versus lower impact factor journals. Substantial improvements over time were not observed although a slight improvement was observed in the proportion accounting for a distinct between-period correlation.
Future methods development should prioritize methods for SW-CRTs with binary or time-to-event outcomes, small numbers of clusters, continuous recruitment designs, multivariate outcomes, or time-dependent repeated measures. Trialists, journal editors, and peer reviewers should be aware that SW-CRTs have additional methodological requirements over parallel arm designs including the need to account for period effects as well as complex intracluster correlations.
摘要：
目的：阶梯式楔形整群随机试验（SW-CRT），在这种情况下,集群被随机分配到将过渡到干预条件的时间-而不是试验组-是一种相对较新的设计.与传统的平行臂试验相比,SW-CRT具有额外的设计和分析考虑。为今后的方法学发展提供信息，包括对试验者的指导和统计模拟研究参数的选择，我们对最近发表的SW-CRT进行了回顾.具体目标是描述(1)在实践中使用的设计类型，(2)坚持统计分析的关键要求，和(3)围绕协变量调整的实践。我们还检查了依从性随时间和期刊影响因子的变化。
方法：我们使用电子搜索来识别2016-2022年发布的SW-CRT的主要报告。两名审稿人从每份试验报告及其方案中提取信息，如果可用，并通过讨论解决分歧。
结果：我们确定了160项符合条件的试验，将11（8-18）簇的中位数（Q1-Q3）随机化为5（4-7）序列。大多数(122，76%)是横断面的(几乎都是持续招聘的)，23(14%)是封闭队列，15(9%)是开放队列。许多试验具有复杂的设计特征，例如多个或多变量主要结果（50,31%）或时间依赖性重复测量（27,22%）。最常见的主要结局类型是二元结局（51％）；连续结局较不常见（26％）。最常用的分析方法是广义线性混合模型（112，70％）；广义估计方程的使用频率较低（12，8％）。在142项少于40组的试验中，只有9例(6%)报告使用适用于少数集群的方法。统计分析明确调整了119例(74%)的时间效应，对于132(83%)的集群内相关性，以及13个（8%）中不同的时期间相关性。共变量包括在82（51%）的主要结果的主要分析中，最常见的是个体水平的共变量；然而，明确和完整的协变量的预规范并不常见.遵守一些关键的方法论要求(针对时间效应进行调整，在较高和较低影响因子期刊上发表的试验中，对期间内相关性的考虑）较高。没有观察到随着时间的推移的实质性改善,尽管观察到占不同时期间相关性的比例略有改善。
结论：未来的方法开发应优先考虑具有二元或时间到事件结果的SW-CRT方法，少量的集群，持续的招聘设计，多变量结果，或时间相关的重复措施。审判人员,期刊编辑,和同行评审员应该意识到，SW-CRT对平行臂设计有额外的方法学要求，包括需要考虑周期效应以及复杂的内部相关性。
方法：我们使用电子搜索来识别2016-2022年发布的SW-CRT的主要报告。两名审稿人从每份试验报告及其方案中提取信息，如果可用，并通过讨论解决分歧。
结果：我们确定了160项符合条件的试验，将11（8-18）簇的中位数（Q1-Q3）随机化为5（4-7）序列。大多数(122，76%)是横断面的(几乎都是持续招聘的)，23(14%)是封闭队列，15(9%)是开放队列。许多试验具有复杂的设计特征，例如多个或多变量主要结果（50,31%）或时间依赖性重复测量（27,22%）。最常见的主要结局类型是二元结局（51％）；连续结局较不常见（26％）。最常用的分析方法是广义线性混合模型（112，70％）；广义估计方程的使用频率较低（12，8％）。在142项少于40组的试验中，只有9例(6%)报告使用适用于少数集群的方法。统计分析明确调整了119例(74%)的时间效应，对于132(83%)的集群内相关性，以及13个（8%）中不同的时期间相关性。共变量包括在82（51%）的主要结果的主要分析中，最常见的是个体水平的共变量；然而，明确和完整的协变量的预规范并不常见.遵守一些关键的方法论要求(针对时间效应进行调整，在较高和较低影响因子期刊上发表的试验中，对期间内相关性的考虑）较高。没有观察到随着时间的推移的实质性改善,尽管观察到占不同时期间相关性的比例略有改善。
结论：未来的方法开发应优先考虑具有二元或时间到事件结果的SW-CRT方法，少量的集群，持续的招聘设计，多变量结果，或时间相关的重复措施。审判人员,期刊编辑,和同行评审员应该意识到，SW-CRT对平行臂设计有额外的方法学要求，包括需要考虑周期效应以及复杂的内部相关性。
