Kondo Masahiro, Oba Koji
Biostatistics Unit, Clinical and Translational Research Center, Keio University Hospital, Tokyo, Japan.
Graduate School of Health Management, Keio University, Kanagawa, Japan.
Digit Health. 2024 Apr 30;10:20552076241249631. doi: 10.1177/20552076241249631. eCollection 2024 Jan-Dec.
BACKGROUND: Micro-randomized trials (MRTs) enhance the effects of mHealth by determining the optimal components, timings, and frequency of interventions. Appropriate handling of missing values is crucial in clinical research; however, it remains insufficiently explored in the context of MRTs. Our study aimed to investigate appropriate methods for missing data in simple MRTs with uniform intervention randomization and no time-dependent covariates. We focused on outcome missing data depending on the participants' background factors. METHODS: We evaluated the performance of the available data analysis (AD) and the multiple imputation in generalized estimating equations (GEE) and random effects model (RE) through simulations. The scenarios were examined based on the presence of unmeasured background factors and the presence of interaction effects. We conducted the regression and propensity score methods as multiple imputation. These missing data handling methods were also applied to actual MRT data. RESULTS: Without the interaction effect, AD was biased for GEE, but there was almost no bias for RE. With the interaction effect, estimates were biased for both. For multiple imputation, regression methods estimated without bias when the imputation models were correct, but bias occurred when the models were incorrect. However, this bias was reduced by including the random effects in the imputation model. In the propensity score method, bias occurred even when the missing probability model was correct. CONCLUSIONS: Without the interaction effect, AD of RE was preferable. When employing GEE or anticipating interactions, we recommend the multiple imputation, especially with regression methods, including individual-level random effects.
背景:微随机试验(MRTs)通过确定干预的最佳组成部分、时机和频率来增强移动健康的效果。在临床研究中,正确处理缺失值至关重要;然而,在MRTs的背景下,这方面的研究仍不充分。我们的研究旨在探讨在具有统一干预随机化且无时间依存协变量的简单MRTs中处理缺失数据的合适方法。我们关注取决于参与者背景因素的结局缺失数据。 方法:我们通过模拟评估了广义估计方程(GEE)和随机效应模型(RE)中可用数据分析(AD)和多重填补的性能。根据未测量背景因素的存在情况和交互效应的存在情况来考察各种场景。我们将回归和倾向评分方法作为多重填补方法。这些缺失数据处理方法也应用于实际的MRT数据。 结果:在没有交互效应的情况下,AD对GEE有偏差,但对RE几乎没有偏差。存在交互效应时,两种方法的估计都有偏差。对于多重填补,当填补模型正确时,回归方法的估计无偏差,但模型错误时会出现偏差。然而,通过在填补模型中纳入随机效应,这种偏差会减小。在倾向评分方法中,即使缺失概率模型正确也会出现偏差。 结论:在没有交互效应的情况下,RE的AD更可取。当使用GEE或预期存在交互作用时,我们建议采用多重填补,尤其是采用包括个体水平随机效应的回归方法。
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