arXiv subjects

Toshio Shimokawa

Publications and source records attributed to Toshio Shimokawa.

10 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.

stat.ME↗

arXiv2026

Geographically Regularized AUC-Maximizing Personalized Federated Learning

Accurate diagnostic and risk-prediction models are important for supporting clinical decision-making during infectious disease outbreaks. However, privacy and governance requirements may restrict patient-level data sharing across healthcare institutions, and data distributions often vary. Moreover, AUC is widely used to evaluate discriminative performance, motivating its direct optimization in model development. We propose geographically regularized AUC-maximizing personalized federated learning (GrAUC-PFL), which directly optimizes a smooth pairwise AUC surrogate to learn personalized models while keeping patient-level data local and accounting for institutional heterogeneity. Graph-based regularization encourages geographically neighboring institutions to have similar coefficient vectors while retaining a personalized models. Simulations and a real-data application suggest improved discriminative performance, particularly when geographically neighboring institutions have similar data-generating characteristics.

cs.LG↗

arXiv2026

Federated Rule Ensemble Method in Medical Data

Machine learning has become integral to medical research and is increasingly applied in clinical settings to support diagnosis and decision-making; however, its effectiveness depends on access to large, diverse datasets, which are limited within single institutions. Although integrating data across institutions can address this limitation, privacy regulations and data ownership constraints hinder these efforts. Federated learning enables collaborative model training without sharing raw data; however, most methods rely on complex architectures that lack interpretability, limiting clinical applicability. Therefore, we proposed a federated RuleFit framework to construct a unified and interpretable global model for distributed environments. It integrates three components: preprocessing based on differentially private histograms to estimate shared cutoff values, enabling consistent rule definitions and reducing heterogeneity across clients; local rule generation using gradient boosting decision trees with shared cutoffs; and coefficient estimation via $\ell_1$-regularized optimization using a Federated Dual Averaging algorithm for sparse and consistent variable selection. In simulation studies, the proposed method achieved a performance comparable to that of centralized RuleFit while outperforming existing federated approaches. Real-world analysis demonstrated its ability to provide interpretable insights with competitive predictive accuracy. Therefore, the proposed framework offers a practical and effective solution for interpretable and reliable modeling in federated learning environments.

cs.LG↗

arXiv2026

Differentially Private One-Shot Federated Inference for Linear Mixed Models via Lossless Likelihood Reconstruction

One-shot federated learning enables multi-site inference with minimal communication. However, sharing summary statistics can still leak sensitive individual-level information when sites have only a small number of patients. In particular, shared cross-product summaries can reveal patient-level covariate patterns under discrete covariates. Motivated by this concern, this study proposes a differentially private one-shot federated inference framework for linear mixed models with a random-intercept working covariance. The method reconstructs the pooled likelihood from site-level summary statistics and applies a Gaussian mechanism to perturb these summaries, ensuring a site-level differential privacy. Cluster-robust variance estimators are developed that are computed directly from the privatized summaries. Robust variance provides valid uncertainty quantification even under covariance mis-specification. Under a multi-site asymptotic regime, the consistency and asymptotic normality of the proposed estimator are established and the leading-order statistical cost of privacy is characterized. Simulation studies show that moderate privacy noise substantially reduces reconstruction risk while maintaining competitive estimation accuracy as the number of sites increases. However, very strong privacy settings can lead to unstable standard errors when the number of sites is limited. An application using multi-site COVID-19 testing data demonstrates that meaningful privacy protection can be achieved with a modest loss of efficiency.

stat.ME↗

arXiv2025

Causal rule ensemble approach for multi-arm data

Heterogeneous treatment effect (HTE) estimation is critical in medical research. It provides insights into how treatment effects vary among individuals, which can provide statistical evidence for precision medicine. While most existing methods focus on binary treatment situations, real-world applications often involve multiple interventions. However, current HTE estimation methods are primarily designed for binary comparisons and often rely on black-box models, which limit their applicability and interpretability in multi-arm settings. To address these challenges, we propose an interpretable machine learning framework for HTE estimation in multi-arm trials. Our method employs a rule-based ensemble approach consisting of rule generation, rule ensemble, and HTE estimation, ensuring both predictive accuracy and interpretability. Through extensive simulation studies and real data applications, the performance of our method was evaluated against state-of-the-art multi-arm HTE estimation approaches. The results indicate that our approach achieved lower bias and higher estimation accuracy compared with those of existing methods. Furthermore, the interpretability of our framework allows clearer insights into how covariates influence treatment effects, facilitating clinical decision making. By bridging the gap between accuracy and interpretability, our study contributes a valuable tool for multi-arm HTE estimation, supporting precision medicine.

stat.ML↗

arXiv2024

Extention of Bagging MARS with Group LASSO for Heterogeneous Treatment Effect Estimation

Recent years, large scale clinical data like patient surveys and medical record data are playing an increasing role in medical data science. These large-scale clinical data, collectively referred to as "real-world data (RWD)". It is expected to be widely used in large-scale observational studies of specific diseases, personal medicine or precise medicine, finding the responder of drugs or treatments. Applying RWD for estimating heterogeneous treat ment effect (HTE) has already been a trending topic. HTE has the potential to considerably impact the development of precision medicine by helping doctors make more informed precise treatment decisions and provide more personalized medical care. The statistical models used to estimate HTE is called treatment effect models. Powers et al. proposed a some treatment effect models for observational study, where they pointed out that the bagging causal MARS (BCM) performs outstanding compared to other models. While BCM has excellent performance, it still has room for improvement. In this paper, we proposed a new treatment effect model called shrinkage causal bagging MARS method to improve their shared basis conditional mean regression framework based on the following points: first, we estimated basis functions using transformed outcome, then applied the group LASSO method to optimize the model and estimate parameters. Besides, we are focusing on pursing better interpretability of model to improve the ethical acceptance. We designed simulations to verify the performance of our proposed method and our proposed method superior in mean square error and bias in most simulation settings. Also we applied it to real data set ACTG 175 to verify its usability, where our results are supported by previous studies.

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arXiv2023

Survival causal rule ensemble method considering the main effect for estimating heterogeneous treatment effects

With an increasing focus on precision medicine in medical research, numerous studies have been conducted in recent years to clarify the relationship between treatment effects and patient characteristics. The treatment effects for patients with different characteristics are always heterogeneous, and various heterogeneous treatment effect machine learning estimation methods have been proposed owing to their flexibility and high prediction accuracy. However, most machine learning methods rely on black-box models, preventing direct interpretation of the relationship between patient characteristics and treatment effects. Moreover, most of these studies have focused on continuous or binary outcomes, although survival outcomes are also important in medical research. To address these challenges, we propose a heterogeneous treatment effect estimation method for survival data based on RuleFit, an interpretable machine learning method. Numerical simulation results confirmed that the prediction performance of the proposed method was comparable to that of existing methods. We also applied a dataset from an HIV study, the AIDS Clinical Trials Group Protocol 175 dataset, to illustrate the interpretability of the proposed method using real data. Consequently, the proposed method established an interpretable model with sufficient prediction accuracy.

stat.ME↗

arXiv2023

Causal rule ensemble method for estimating heterogeneous treatment effect with consideration of main effects

This study proposes a novel framework based on the RuleFit method to estimate Heterogeneous Treatment Effect (HTE) in a randomized clinical trial. To achieve this, we adopted S-learner of the metaalgorithm for our proposed framework. The proposed method incorporates a rule term for the main effect and treatment effect, which allows HTE to be interpretable form of rule. By including a main effect term in the proposed model, the selected rule is represented as an HTE that excludes other effects. We confirmed a performance equivalent to that of another ensemble learning methods through numerical simulation and demonstrated the interpretation of the proposed method from a real data application.

stat.ME↗

arXiv2022

Rules Ensemble Method with Group Lasso for Heterogeneous Treatment Effect Estimation

The increasing scientific attention given to precision medicine based on real-world data has led many recent studies to clarify the relationships between treatment effects and patient characteristics. However, this is challenging because of ubiquitous heterogeneity in the treatment effect for individuals and the real-world data on their background being complex and noisy. Because of their flexibility, various heterogeneous treatment effect (HTE) machine learning (ML) estimation methods have been proposed. However, most ML methods incorporate black-box models that hamper direct interpretation of the interrelationships between individuals' characteristics and the treatments' effects. This study proposes an ML method for estimating HTE based on the rule ensemble method termed RuleFit. The main advantage of RuleFit are interpretability and accuracy. However, HTEs are always defined in the potential outcome framework, and RuleFit cannot be applied directly. Thus, we modified RuleFit and proposed a method to estimate HTEs that directly interpret the interrelationships among the individuals' features from the model.

stat.ME↗

arXiv2021

Concordance Rate of a Four-Quadrant Plot for Repeated Measurements

Before new clinical measurement methods are implemented in clinical practice, it must be confirmed whether their results are equivalent to those of existing methods. The agreement of the trend between these methods is evaluated using the four-quadrant plot, which describes the trend of change in each difference of the two measurement methods' values in sequential time points, and the plot's concordance rate, which is calculated using the sum of data points in the four-quadrant plot that agree with this trend divided by the number of all accepted data points. However, the conventional concordance rate does not consider the covariance between the data on individual subjects, which may affect its proper evaluation. Therefore, we proposed a new concordance rate calculated by each individual according to the number of agreement. Moreover, this proposed method can set a parameter that the minimum concordant number between two measurement techniques. The parameter can provide a more detailed interpretation of the degree of agreement. A numerical simulation conducted with several factors indicated that the proposed method resulted in a more accurate evaluation. We also showed a real data and compared the proposed method with the conventional approach. Then, we concluded the discussion with the implementation in clinical studies.

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