Centre for Prognosis Research, School of Medicine, Keele University, Keele, Staffordshire, UK.
Centre for Statistics in Medicine, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK.
Stat Med. 2022 Oct 30;41(24):4822-4837. doi: 10.1002/sim.9538. Epub 2022 Aug 5.
Before embarking on an individual participant data meta-analysis (IPDMA) project, researchers and funders need assurance it is worth their time and cost. This should include consideration of how many studies are promising their IPD and, given the characteristics of these studies, the power of an IPDMA including them. Here, we show how to estimate the power of a planned IPDMA of randomized trials to examine treatment-covariate interactions at the participant level (ie, treatment effect modifiers). We focus on a binary outcome with binary or continuous covariates, and propose a three-step approach, which assumes the true interaction size is common to all trials. In step one, the user must specify a minimally important interaction size and, for each trial separately (eg, as obtained from trial publications), the following aggregate data: the number of participants and events in control and treatment groups, the mean and SD for each continuous covariate, and the proportion of participants in each category for each binary covariate. This allows the variance of the interaction estimate to be calculated for each trial, using an analytic solution for Fisher's information matrix from a logistic regression model. Step 2 calculates the variance of the summary interaction estimate from the planned IPDMA (equal to the inverse of the sum of the inverse trial variances from step 1), and step 3 calculates the corresponding power based on a two-sided Wald test. Stata and R code are provided, and two examples given for illustration. Extension to allow for between-study heterogeneity is also considered.
在进行个体参与者数据荟萃分析(IPDMA)项目之前,研究人员和资助者需要确保这值得他们花费时间和成本。这应包括考虑有多少项研究有希望提供其个体参与者数据,并且考虑到这些研究的特征,包括这些研究在内的 IPDMA 的功效如何。在这里,我们展示如何估计计划中的随机试验 IPDMA 检验参与者水平(即治疗协变量交互作用)的功效。我们专注于二分类结局和二分类或连续协变量,并提出了三步方法,该方法假设所有试验的真实交互作用大小是相同的。在第一步中,用户必须指定最小重要交互作用大小,并且对于每个单独的试验(例如,从试验出版物中获得),必须指定以下汇总数据:对照组和治疗组的参与者和事件数量、每个连续协变量的均值和标准差,以及每个二分类协变量的每个类别中的参与者比例。这允许使用来自逻辑回归模型的 Fisher 信息矩阵的解析解为每个试验计算交互作用估计的方差。第二步计算来自计划 IPDMA 的汇总交互作用估计的方差(等于步骤 1 中逆试验方差的总和的倒数),第三步基于双侧 Wald 检验计算相应的功效。提供了 Stata 和 R 代码,并提供了两个示例来说明。还考虑了允许研究间异质性的扩展。