arXiv subjects

Tomoyuki Sugimoto

Publications and source records attributed to Tomoyuki Sugimoto.

3 recordsLinked to original sources

arXiv2026

A flexible framework for treatment effect inference in longitudinal clinical studies with skewed outcomes

Longitudinal continuous outcomes in clinical trials are commonly analyzed using mixed models for repeated measures (MMRM) under normality assumptions. However, many clinical outcomes are skewed, making mean-based treatment effects difficult to interpret and potentially reducing statistical efficiency. The Box--Cox MMRM (BCMMRM) approach accommodates skewness by enabling inference on model-based median differences via inverse transformation. However, BCMMRM typically assumes a common transformation parameter across treatment groups and time points. When distributional shapes differ between groups or evolve over time, this assumption may lead to biased treatment effect. Furthermore, when treatment affects not only central tendency but also distributional shape or tail behavior, treatment effects may not be adequately characterized by a single location summary such as the median. We propose the Box--Cox multivariate regression (BCMVR) framework for longitudinal data with skewed outcomes. BCMVR relaxes this restriction by allowing transformation parameters to vary across groups and time points. The framework enables inference based on interpretable summaries, including median differences and a probability-based treatment effect quantifying the probability that a randomly selected patient in one group has a better outcome than one in another group. This measure integrates information over the entire outcome distribution and provides a complementary summary when distributional shapes differ. Simulation studies demonstrate that BCMMRM can produce biased estimates when distributions differ in shape, whereas BCMVR provides nearly unbiased estimation. The probability-based measure achieves a favorable balance between robustness and statistical efficiency. The proposed framework provides a flexible and interpretable approach to treatment effect inference under distributional heterogeneity.

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arXiv2025

Random-effects meta-analysis via generalized linear mixed models: A Bartlett-corrected approach for few studies

Random-effects models are central to meta-analysis, yet the between-study variance is often underestimated when the number of studies is small. In such settings, confidence intervals become unduly narrow and fail to attain the nominal coverage probability. Although several small-sample corrections, including the Bartlett correction, have been developed under the normal-normal model, corresponding methodology for generalized linear mixed models (GLMMs) remains limited. This study proposes a unified framework for random-effects meta-analysis within the GLMM that relies exclusively on aggregate data and accommodates outcomes that follow any distribution in the exponential family, including the binomial, Poisson, and gamma distributions. To improve interval estimation with few studies, we develop a profile likelihood method with a simplified Bartlett correction (PLSBC), which refines the chi-squared approximation of the profile likelihood ratio statistic without requiring higher-order derivatives. We show theoretically that the proposed estimators preserve the consistency and asymptotic normality of the maximum likelihood estimators. Simulation studies demonstrate that the PLSBC yields nearly unbiased estimates and maintains nominal coverage across a variety of outcome types. Applications to three published meta-analyses with binomial, Poisson, and gamma outcomes indicate that the proposed approach provides robust and interpretable inference with few studies. The PLSBC therefore offers a practical and broadly applicable framework for random-effects meta-analysis when the number of studies is limited.

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arXiv2024

Moment-based Random-effects Meta-analysis Equipped with Huber's M-Estimation

Meta-analyses are commonly used to provide solid evidence across numerous studies. Traditional moment methods, such as the DerSimonian-Laird method, remain popular in spite of the availability of more accurate alternatives. While moment estimators are simple and intuitive, they are known to underestimate the variance of the overall treatment effect, particularly when the number of studies is small. This underestimation can lead to excessively narrow confidence intervals that do not meet the nominal confidence level, potentially resulting in misleading conclusions. In this study, we improve traditional moment-based meta-analysis methods by incorporating Huber's M-estimation to more accurately capture the distributional characteristics of between-study variance. Our approach enables conservative parameter estimation, even when almost all existing methods lead to underestimation of between-study variance under a small number of studies. Additionally, by deriving the simultaneous distribution of overall treatment effect and between-study variance, we propose facilitating a visual exploration of the relationship between these two quantities. Our method provides more reliable estimators for the overall treatment effect and between-study variance, particularly in situations with few studies. Using simulations and real data analysis, we demonstrate that our approach always yields more conservative results compared to traditional moment methods, and ensures more accurate confidence intervals in meta-analyses.

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