arXiv subjects

Kazushi Maruo

Publications and source records attributed to Kazushi Maruo.

5 recordsLinked to original sources

arXiv2026

Modification and extension of the Bayesian clinical trial design using external data for single-arm and hybrid-controlled trials

Limited patient availability complicates sample size determination in pediatric clinical trials. Although Bayesian methods incorporating external data offer a solution, rigorously controlling the type I error rate remains difficult. Psioda and Ibrahim (2019) proposed a simulation-based framework as a practical solution. However, although their framework was designed to relax the type I error control, this relaxation fails when the external data exhibit a large treatment effect, making it difficult to design clinical trials that incorporate external data. Furthermore, restricting the support of sampling priors can cause trial outcomes to fall outside of this support, leading to lower power. Additionally, their analytic prior formulation may induce bias, and their method is not applicable to hybrid-controlled trials involving two-group comparisons. Thus, we propose modifications to both the sampling and analytic prior specifications and extend the framework to hybrid-controlled trials. We redefine the null sampling prior as a normal distribution centered at the null boundary, ensuring a Bayesian type I error evaluation. For the analytic prior, we employ a weakly informative prior for the second component of a robust mixture prior to mitigate bias under prior-data conflict. Furthermore, we extend this methodology to hybrid-controlled trials. Simulation studies and a pediatric case study of cutaneous lupus erythematosus demonstrate that our method substantially reduces the required sample size compared with both frequentist and original Bayesian methods, while maintaining the target operating characteristics and controlling estimation bias under prior-data conflict. This framework provides a reliable and efficient approach for designing clinical trials that incorporate external information.

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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.

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arXiv2024

Nonparametric Bayesian approach for dynamic borrowing of historical control data

When incorporating historical control data into the analysis of current randomized controlled trial data, it is critical to account for differences between the datasets. When the cause of the difference is an unmeasured factor and adjustment for observed covariates only is insufficient, it is desirable to use a dynamic borrowing method that reduces the impact of heterogeneous historical controls. We propose a nonparametric Bayesian approach for borrowing historical controls that are homogeneous with the current control. Additionally, to emphasize the resolution of conflicts between the historical controls and current control, we introduce a method based on the dependent Dirichlet process mixture. The proposed methods can be implemented using the same procedure, regardless of whether the outcome data comprise aggregated study-level data or individual participant data. We also develop a novel index of similarity between the historical and current control data, based on the posterior distribution of the parameter of interest. We conduct a simulation study and analyze clinical trial examples to evaluate the performance of the proposed methods compared to existing methods. The proposed method based on the dependent Dirichlet process mixture can more accurately borrow from homogeneous historical controls while reducing the impact of heterogeneous historical controls compared to the typical Dirichlet process mixture. The proposed methods outperform existing methods in scenarios with heterogeneous historical controls, in which the meta-analytic approach is ineffective.

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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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arXiv2020

Re-evaluation of the comparative effectiveness of bootstrap-based optimism correction methods in the development of multivariable clinical prediction models

Multivariable predictive models are important statistical tools for providing synthetic diagnosis and prognostic algorithms based on multiple patients' characteristics. Their apparent discriminant and calibration measures usually have overestimation biases (known as 'optimism') relative to the actual performances for external populations. Existing statistical evidence and guidelines suggest that three bootstrap-based bias correction methods are preferable in practice, namely Harrell's bias correction and the .632 and .632+ estimators. Although Harrell's method has been widely adopted in clinical studies, simulation-based evidence indicates that the .632+ estimator may perform better than the other two methods. However, there is limited evidence and these methods' actual comparative effectiveness is still unclear. In this article, we conducted extensive simulations to compare the effectiveness of these methods, particularly using the following modern regression models: conventional logistic regression, stepwise variable selections, Firth's penalized likelihood method, ridge, lasso, and elastic-net. Under relatively large sample settings, the three bootstrap-based methods were comparable and performed well. However, all three methods had biases under small sample settings, and the directions and sizes of the biases were inconsistent. In general, the .632+ estimator is recommended, but we provide several notes concerning the operating characteristics of each method.

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