BiometricsPub Date : 2025-10-10DOI: 10.1093/biomtc/ujaf132
Jinyuan Liu
{"title":"Computational aspects of psychometric methods with R by Patricia Martinková and Adéla Hladká, Chapman & Hall/CRC, 2023, ISBN: 9781003054313, https://doi.org/10.1201/9781003054313.","authors":"Jinyuan Liu","doi":"10.1093/biomtc/ujaf132","DOIUrl":"https://doi.org/10.1093/biomtc/ujaf132","url":null,"abstract":"","PeriodicalId":8930,"journal":{"name":"Biometrics","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145273395","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"数学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BiometricsPub Date : 2025-10-08DOI: 10.1093/biomtc/ujaf128
Eleanor M Pullenayegum, Di Shan
{"title":"Inverse-intensity weighted generalized estimating equations for longitudinal data subject to irregular observation: which variables should be included in the visit rate model?","authors":"Eleanor M Pullenayegum, Di Shan","doi":"10.1093/biomtc/ujaf128","DOIUrl":"https://doi.org/10.1093/biomtc/ujaf128","url":null,"abstract":"<p><p>Longitudinal data are often subject to irregular and informative visit times. Weighting generalized estimating equations by the inverse of the visit rate yields asymptotically unbiased estimates of regression coefficients provided that outcomes and visit times are conditionally independent, given the covariates in the visit model. Adding other covariates has no impact on the asymptotic bias of estimated regression coefficients, provided that conditional independence is maintained, but the impact on their variances is unknown. We show that variances are unchanged on adding variables associated with neither outcome nor visit process, and decrease on adding variables associated with outcome but not visit process. Adding variables associated with visits but not outcome may either increase or decrease variances of estimated outcome model regression coefficients, depending on the correlation structure of the covariates and the outcome. Application to a study of major depressive disorder found that the variances of estimated regression coefficients were of a similar magnitude when predictors of outcome but not visits were added to the visit rate model but consistently larger, in some cases by a factor of 2, on adding predictors of visits but not outcome. We recommend that visit process models include variables associated with outcome, but that those unassociated with the outcome be treated with caution.</p>","PeriodicalId":8930,"journal":{"name":"Biometrics","volume":"81 4","pages":""},"PeriodicalIF":1.7,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145249508","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"数学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BiometricsPub Date : 2025-10-08DOI: 10.1093/biomtc/ujaf134
Tianchen Qian
{"title":"Distal causal excursion effects: modeling long-term effects of time-varying treatments in micro-randomized trials.","authors":"Tianchen Qian","doi":"10.1093/biomtc/ujaf134","DOIUrl":"https://doi.org/10.1093/biomtc/ujaf134","url":null,"abstract":"<p><p>Micro-randomized trials (MRTs) play a crucial role in optimizing digital interventions. In an MRT, each participant is sequentially randomized among treatment options hundreds of times. While the interventions tested in MRTs target short-term behavioral responses (proximal outcomes), their ultimate goal is to drive long-term behavior change (distal outcomes). However, existing causal inference methods, such as the causal excursion effect, are limited to proximal outcomes, making it challenging to quantify the long-term impact of interventions. To address this gap, we introduce the distal causal excursion effect (DCEE), a novel estimand that quantifies the long-term effect of time-varying treatments. The DCEE contrasts distal outcomes under two excursion policies while marginalizing over most treatment assignments, enabling a parsimonious and interpretable causal model even with a large number of decision points. We propose two estimators for the DCEE-one with cross-fitting and one without-both robust to misspecification of the outcome model. We establish their asymptotic properties and validate their performance through simulations. We apply our method to the HeartSteps MRT to assess the impact of activity prompts on long-term habit formation. Our findings suggest that prompts delivered earlier in the study have a stronger long-term effect than those delivered later, underscoring the importance of intervention timing in behavior change. This work provides the critically needed toolkit for scientists working on digital interventions to assess long-term causal effects using MRT data.</p>","PeriodicalId":8930,"journal":{"name":"Biometrics","volume":"81 4","pages":""},"PeriodicalIF":1.7,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145298424","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"数学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BiometricsPub Date : 2025-10-08DOI: 10.1093/biomtc/ujaf129
Jieru Shi, Walter Dempsey
{"title":"A meta-learning method for estimation of causal excursion effects to assess time-varying moderation.","authors":"Jieru Shi, Walter Dempsey","doi":"10.1093/biomtc/ujaf129","DOIUrl":"https://doi.org/10.1093/biomtc/ujaf129","url":null,"abstract":"<p><p>Advances in wearable technologies and health interventions delivered by smartphones have greatly increased the accessibility of mobile health (mHealth) interventions. Micro-randomized trials (MRTs) are designed to assess the effectiveness of the mHealth intervention and introduce a novel class of causal estimands called \"causal excursion effects.\" These estimands enable the evaluation of how intervention effects change over time and are influenced by individual characteristics or context. Existing methods for analyzing causal excursion effects assume known randomization probabilities, complete observations, and a linear nuisance function with prespecified features of the high-dimensional observed history. However, in complex mobile systems, these assumptions often fall short: randomization probabilities can be uncertain, observations may be incomplete, and the granularity of mHealth data makes linear modeling difficult. To address this issue, we propose a flexible and doubly robust inferential procedure, called \"DR-WCLS,\" for estimating causal excursion effects from a meta-learner perspective. We present the bidirectional asymptotic properties of the proposed estimators and compare them with existing methods both theoretically and through extensive simulations. The results show a consistent and more efficient estimate, even with missing observations or uncertain treatment randomization probabilities. Finally, the practical utility of the proposed methods is demonstrated by analyzing data from a multi-institution cohort of first-year medical residents in the United States.</p>","PeriodicalId":8930,"journal":{"name":"Biometrics","volume":"81 4","pages":""},"PeriodicalIF":1.7,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145249539","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"数学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BiometricsPub Date : 2025-10-08DOI: 10.1093/biomtc/ujaf131
Guangcai Mao, Shu Yang, Xiaofei Wang
{"title":"Statistical inference for heterogeneous treatment effect with right-censored data from synthesizing randomized clinical trials and real-world data.","authors":"Guangcai Mao, Shu Yang, Xiaofei Wang","doi":"10.1093/biomtc/ujaf131","DOIUrl":"10.1093/biomtc/ujaf131","url":null,"abstract":"<p><p>The heterogeneous treatment effect plays a crucial role in precision medicine. There is evidence that real-world data, even subject to biases, can be employed as supplementary evidence for randomized clinical trials to improve the statistical efficiency of the heterogeneous treatment effect estimation. In this paper, for survival data with right censoring, we consider estimating the heterogeneous treatment effect, defined as the difference of the treatment-specific conditional restricted mean survival times given covariates, by synthesizing evidence from randomized clinical trials and the real-world data with possible biases. We define an omnibus bias function to characterize the effect of biases caused by unmeasured confounders, censoring, and outcome heterogeneity, and further, identify it by combining the trial and real-world data. We propose a penalized sieve method to estimate the heterogeneous treatment effect and the bias function. We further study the theoretical properties of the proposed integrative estimators based on the theory of reproducing kernel Hilbert space and empirical process. The proposed methodology outperforms the approach solely based on the trial data through simulation studies and an integrative analysis of the data from a randomized trial and a real-world registry on early-stage non-small-cell lung cancer.</p>","PeriodicalId":8930,"journal":{"name":"Biometrics","volume":"81 4","pages":""},"PeriodicalIF":1.7,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12505326/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145249501","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"数学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BiometricsPub Date : 2025-10-08DOI: 10.1093/biomtc/ujaf138
Xinyu Yan, Ji-Hyun Lee, Xiang-Yang Lou
{"title":"A regularized continuous-time hidden Markov model for identifying latent state transition patterns of poly-tobacco use.","authors":"Xinyu Yan, Ji-Hyun Lee, Xiang-Yang Lou","doi":"10.1093/biomtc/ujaf138","DOIUrl":"https://doi.org/10.1093/biomtc/ujaf138","url":null,"abstract":"<p><p>Hidden Markov models (HMMs) are widely used to characterize latent state transition patterns in substance use. However, traditional HMM frameworks are incompetent when dealing with the complexities introduced by high-dimensional risk factors and varying time intervals, particularly in determining the number of hidden states and selecting variables for state transition parameters. To tackle the analytical challenges in the Population Assessment of Tobacco and Health (PATH) Study, a nationally representative longitudinal cohort study on tobacco use, we propose a continuous-time HMM framework with a regularization algorithm to identify multi-dimensional risk factors underlying complex poly-tobacco use transitions. We develop an elastic-net regularization on the transition covariates to identify informative covariates and improve model estimation accuracy. The inclusion of key covariates enables accurate determination of the number of hidden states. We incorporate survey weights and information on strata and clustering throughout the modeling framework. We demonstrate the validity of our approach in determining state numbers, identifying informative covariates, and estimating model parameters through a series of simulations. Application of the proposed approach to PATH data analysis revealed several demographic, behavioral, and psychosocial factors that contribute to the differential risks of transition between tobacco-use states among youth and young adults. The model's capacity in identifying high-dimensional risk factors for underlying hidden variables substantiates its potential for enhancing public health research and informing interventions.</p>","PeriodicalId":8930,"journal":{"name":"Biometrics","volume":"81 4","pages":""},"PeriodicalIF":1.7,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145298373","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"数学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BiometricsPub Date : 2025-10-08DOI: 10.1093/biomtc/ujaf133
Baoying Yang, Jing Qin, Jing Ning, Yukun Liu
{"title":"Double robust conditional independence test for novel biomarkers given established risk factors with survival data.","authors":"Baoying Yang, Jing Qin, Jing Ning, Yukun Liu","doi":"10.1093/biomtc/ujaf133","DOIUrl":"https://doi.org/10.1093/biomtc/ujaf133","url":null,"abstract":"<p><p>Conditional independence is a foundational concept for understanding probabilistic relationships among variables, with broad applications in fields such as causal inference and machine learning. This study focuses on testing conditional independence, $Tperp X|Z$, where T represents survival data possibly subject to right censoring, Z represents established risk factors for T, and X represents potential novel biomarkers. The goal is to identify novel biomarkers that offer additional merits for further risk assessment and prediction. This can be achieved by using either the partial or parametric likelihood ratio statistic to evaluate whether the coefficient vector of X in the conditional model of T given $(X^{ mathrm{scriptscriptstyle top } }, Z^{ mathrm{scriptscriptstyle top } })^{ mathrm{scriptscriptstyle top } }$ is equal to zero. Traditional tests such as directly comparing likelihood ratios to chi-squared distributions may produce erroneous type-I error rates under model misspecification. As an alternative, we propose a resampling-based method to approximate the distribution of the likelihood ratios. A key advantage of the proposed test is its double robustness: it achieves approximately correct type-I error rates when either the conditional outcome model or the working model of ${rm pr} (X|Z)$ is correctly specified. Additionally, machine learning techniques can be incorporated to improve test performance. Simulation studies and the application to the Alzheimer's Disease Neuroimaging Initiative (ADNI) data demonstrate the finite-sample performance of the proposed tests.</p>","PeriodicalId":8930,"journal":{"name":"Biometrics","volume":"81 4","pages":""},"PeriodicalIF":1.7,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145336170","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"数学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BiometricsPub Date : 2025-10-08DOI: 10.1093/biomtc/ujaf124
Shuqi Wang, Ying Yuan, Suyu Liu
{"title":"Randomized optimal selection design for dose optimization.","authors":"Shuqi Wang, Ying Yuan, Suyu Liu","doi":"10.1093/biomtc/ujaf124","DOIUrl":"10.1093/biomtc/ujaf124","url":null,"abstract":"<p><p>The US Food and Drug Administration (FDA) launched Project Optimus to shift the objective of dose selection from the maximum tolerated dose to the optimal biological dose (OBD), optimizing the benefit-risk tradeoff. One approach recommended by the FDA's guidance is to conduct randomized trials comparing multiple doses. In this paper, using the selection design framework, we propose a Randomized Optimal SElection (ROSE) design, which minimizes sample size while ensuring the probability of correct selection of the OBD at pre-specified accuracy levels. The ROSE design is simple to implement, involving a straightforward comparison of the difference in response rates between two dose arms against a predetermined decision boundary. We further consider a two-stage ROSE design that allows for early selection of the OBD at the interim when there is sufficient evidence, further reducing the sample size. Simulation studies demonstrate that the ROSE design exhibits desirable operating characteristics in correctly identifying the OBD. A sample size of 15-40 patients per dosage arm typically results in a percentage of correct selection of the optimal dose ranging from 60% to 70%.</p>","PeriodicalId":8930,"journal":{"name":"Biometrics","volume":"81 4","pages":""},"PeriodicalIF":1.7,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12505323/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145249541","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"数学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BiometricsPub Date : 2025-10-08DOI: 10.1093/biomtc/ujaf130
Jiarui Zhang, Hongsheng Liu, Xin Chen, Jinfeng Xu
{"title":"SPLasso for high-dimensional additive hazards regression with covariate measurement error.","authors":"Jiarui Zhang, Hongsheng Liu, Xin Chen, Jinfeng Xu","doi":"10.1093/biomtc/ujaf130","DOIUrl":"https://doi.org/10.1093/biomtc/ujaf130","url":null,"abstract":"<p><p>High-dimensional error-prone survival data are prevalent in biomedical studies, where numerous clinical or genetic variables are collected for risk assessment. The presence of measurement errors in covariates complicates parameter estimation and variable selection, leading to non-convex optimization challenges. We propose an error-in-variables additive hazards regression model for high-dimensional noisy survival data. By employing the nearest positive semi-definite matrix projection, we develop a fast Lasso approach (semi-definite projection Lasso, SPLasso) and its soft thresholding variant (SPLasso-T), both with theoretical guarantees. Under mild assumptions, we establish model selection consistency, oracle inequalities, and limiting distributions for these methods. Simulation studies and two real data applications demonstrate the methods' superior efficiency in handling high-dimensional data, particularly showcasing remarkable performance in scenarios with missing values, highlighting their robustness and practical utility in complex biomedical settings.</p>","PeriodicalId":8930,"journal":{"name":"Biometrics","volume":"81 4","pages":""},"PeriodicalIF":1.7,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145273319","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"数学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}