Biostatistics最新文献

{"title":"The impact of coarsening an exposure on partial identifiability in instrumental variable settings.","authors":"Erin E Gabriel, Michael C Sachs, Arvid Sjölander","doi":"10.1093/biostatistics/kxae042","DOIUrl":"10.1093/biostatistics/kxae042","url":null,"abstract":"<p><p>In instrumental variable (IV) settings, such as imperfect randomized trials and observational studies with Mendelian randomization, one may encounter a continuous exposure, the causal effect of which is not of true interest. Instead, scientific interest may lie in a coarsened version of this exposure. Although there is a lengthy literature on the impact of coarsening of an exposure with several works focusing specifically on IV settings, all methods proposed in this literature require parametric assumptions. Instead, just as in the standard IV setting, one can consider partial identification via bounds making no parametric assumptions. This was first pointed out in Alexander Balke's PhD dissertation. We extend and clarify his work and derive novel bounds in several settings, including for a three-level IV, which will most likely be the case in Mendelian randomization. We demonstrate our findings in two real data examples, a randomized trial for peanut allergy in infants and a Mendelian randomization setting investigating the effect of homocysteine on cardiovascular disease.</p>","PeriodicalId":55357,"journal":{"name":"Biostatistics","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142632696","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"数学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Speeding up interval estimation for R2-based mediation effect of high-dimensional mediators via cross-fitting.","authors":"Zhichao Xu, Chunlin Li, Sunyi Chi, Tianzhong Yang, Peng Wei","doi":"10.1093/biostatistics/kxae037","DOIUrl":"10.1093/biostatistics/kxae037","url":null,"abstract":"<p><p>Mediation analysis is a useful tool in investigating how molecular phenotypes such as gene expression mediate the effect of exposure on health outcomes. However, commonly used mean-based total mediation effect measures may suffer from cancellation of component-wise mediation effects in opposite directions in the presence of high-dimensional omics mediators. To overcome this limitation, we recently proposed a variance-based R-squared total mediation effect measure that relies on the computationally intensive nonparametric bootstrap for confidence interval estimation. In the work described herein, we formulated a more efficient two-stage, cross-fitted estimation procedure for the R2 measure. To avoid potential bias, we performed iterative Sure Independence Screening (iSIS) in two subsamples to exclude the non-mediators, followed by ordinary least squares regressions for the variance estimation. We then constructed confidence intervals based on the newly derived closed-form asymptotic distribution of the R2 measure. Extensive simulation studies demonstrated that this proposed procedure is much more computationally efficient than the resampling-based method, with comparable coverage probability. Furthermore, when applied to the Framingham Heart Study, the proposed method replicated the established finding of gene expression mediating age-related variation in systolic blood pressure and identified the role of gene expression profiles in the relationship between sex and high-density lipoprotein cholesterol level. The proposed estimation procedure is implemented in R package CFR2M.</p>","PeriodicalId":55357,"journal":{"name":"Biostatistics","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11823199/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142481495","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"数学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Instrumental variable approach to estimating individual causal effects in N-of-1 trials: application to ISTOP study.","authors":"Kexin Qu, Christopher H Schmid, Tao Liu","doi":"10.1093/biostatistics/kxaf042","DOIUrl":"10.1093/biostatistics/kxaf042","url":null,"abstract":"<p><p>An N-of-1 trial is a multiple crossover trial conducted in a single individual to provide evidence to directly inform personalized treatment decisions. Advances in wearable devices greatly improved the feasibility of adopting these trials to identify optimal individual treatment plans, particularly when treatments differ among individuals and responses are highly heterogeneous. Our work was motivated by the I-STOP-AFib Study, which examined the impact of different triggers on atrial fibrillation (AF) occurrence. We described a causal framework for \"N-of-1\" trial using potential treatment selection paths and potential outcome paths. Two estimands of individual causal effect were defined: (i) the effect of continuous exposure, and (ii) the effect of an individual's observed behavior. We addressed three challenges: (i) imperfect compliance to the randomized treatment assignment; (ii) binary treatments and binary outcomes, which led to the \"non-collapsibility\" issue of estimating odds ratios; and (iii) serial correlation in the longitudinal observations. We adopted the Bayesian IV approach where the study randomization was the instrumental variable (IV) as it impacted the patient's choice of exposure but not directly the outcome. Estimations were obtained through a system of two parametric Bayesian models to estimate the individual causal effect. Our model got around the non-collapsibility and non-consistency by modeling the confounding mechanism through latent structural models and by inferring with Bayesian posterior of functionals. Autocorrelation present in the repeated measurements was also accounted for. The simulation study showed our method largely reduced bias and greatly improved the coverage of the estimated causal effect, compared to existing methods (ITT, PP, and AT). We applied the method to I-STOP-AFib Study to estimate the individual effect of alcohol on AF occurrence.</p>","PeriodicalId":55357,"journal":{"name":"Biostatistics","volume":"26 1","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12934031/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145745451","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"数学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bayesian mapping of mortality clusters.","authors":"Andrea Sottosanti, Enrico Bovo, Pietro Belloni, Giovanna Boccuzzo","doi":"10.1093/biostatistics/kxaf028","DOIUrl":"10.1093/biostatistics/kxaf028","url":null,"abstract":"<p><p>Disease mapping analyses the distribution of several disease outcomes within a territory. Primary goals include identifying areas with unexpected changes in mortality rates, studying the relation among multiple diseases, and dividing the analysed territory into clusters based on the observed levels of disease incidence or mortality. In this work, we focus on detecting spatial mortality clusters, that occur when neighbouring areas within a territory exhibit similar mortality levels due to one or more diseases. When multiple causes of death are examined together, it is relevant to identify not only the spatial boundaries of the clusters but also the diseases that lead to their formation. However, existing methods in literature struggle to address this dual problem effectively and simultaneously. To overcome these limitations, we introduce perla, a multivariate Bayesian model that clusters areas in a territory according to the observed mortality rates of multiple causes of death, also exploiting the information of external covariates. Our model incorporates the spatial structure of data directly into the clustering probabilities by leveraging the stick-breaking formulation of the multinomial distribution. Additionally, it exploits suitable global-local shrinkage priors to ensure that the detection of clusters depends on diseases showing concrete increases or decreases in mortality levels, while excluding uninformative diseases. We propose a Markov chain Monte Carlo algorithm for posterior inference that consists of closed-form Gibbs sampling moves for nearly every model parameter, without requiring complex tuning operations. This work is primarily motivated by a case study on the territory of a local unit within the Italian public healthcare system, known as ULSS6 Euganea. To demonstrate the flexibility and effectiveness of our methodology, we also validate perla with a series of simulation experiments and an extensive case study on mortality levels in U.S. counties.</p>","PeriodicalId":55357,"journal":{"name":"Biostatistics","volume":"26 1","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12596199/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145477223","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"数学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A scalable two-stage Bayesian approach accounting for exposure measurement error in environmental epidemiology.","authors":"Changwoo J Lee, Elaine Symanski, Amal Rammah, Dong Hun Kang, Philip K Hopke, Eun Sug Park","doi":"10.1093/biostatistics/kxae038","DOIUrl":"10.1093/biostatistics/kxae038","url":null,"abstract":"<p><p>Accounting for exposure measurement errors has been recognized as a crucial problem in environmental epidemiology for over two decades. Bayesian hierarchical models offer a coherent probabilistic framework for evaluating associations between environmental exposures and health effects, which take into account exposure measurement errors introduced by uncertainty in the estimated exposure as well as spatial misalignment between the exposure and health outcome data. While two-stage Bayesian analyses are often regarded as a good alternative to fully Bayesian analyses when joint estimation is not feasible, there has been minimal research on how to properly propagate uncertainty from the first-stage exposure model to the second-stage health model, especially in the case of a large number of participant locations along with spatially correlated exposures. We propose a scalable two-stage Bayesian approach, called a sparse multivariate normal (sparse MVN) prior approach, based on the Vecchia approximation for assessing associations between exposure and health outcomes in environmental epidemiology. We compare its performance with existing approaches through simulation. Our sparse MVN prior approach shows comparable performance with the fully Bayesian approach, which is a gold standard but is impossible to implement in some cases. We investigate the association between source-specific exposures and pollutant (nitrogen dioxide [NO2])-specific exposures and birth weight of full-term infants born in 2012 in Harris County, Texas, using several approaches, including the newly developed method.</p>","PeriodicalId":55357,"journal":{"name":"Biostatistics","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11823266/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142378644","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"数学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adaptive Gaussian Markov random fields for child mortality estimation.","authors":"Serge Aleshin-Guendel, Jon Wakefield","doi":"10.1093/biostatistics/kxae030","DOIUrl":"10.1093/biostatistics/kxae030","url":null,"abstract":"<p><p>The under-5 mortality rate (U5MR), a critical health indicator, is typically estimated from household surveys in lower and middle income countries. Spatio-temporal disaggregation of household survey data can lead to highly variable estimates of U5MR, necessitating the usage of smoothing models which borrow information across space and time. The assumptions of common smoothing models may be unrealistic when certain time periods or regions are expected to have shocks in mortality relative to their neighbors, which can lead to oversmoothing of U5MR estimates. In this paper, we develop a spatial and temporal smoothing approach based on Gaussian Markov random field models which incorporate knowledge of these expected shocks in mortality. We demonstrate the potential for these models to improve upon alternatives not incorporating knowledge of expected shocks in a simulation study. We apply these models to estimate U5MR in Rwanda at the national level from 1985 to 2019, a time period which includes the Rwandan civil war and genocide.</p>","PeriodicalId":55357,"journal":{"name":"Biostatistics","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141894969","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"数学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Incorporating historic information to further improve power when conducting Bayesian information borrowing in basket trials.","authors":"Libby Daniells, Pavel Mozgunov, Helen Barnett, Alun Bedding, Thomas Jaki","doi":"10.1093/biostatistics/kxaf016","DOIUrl":"10.1093/biostatistics/kxaf016","url":null,"abstract":"<p><p>In basket trials a single therapeutic treatment is tested on several patient populations simultaneously, each of which forming a basket, where patients across all baskets on the trial share a common genetic aberration. These trials allow testing of treatments on small groups of patients, however, limited basket sample sizes can result in inadequate precision and power of estimates. It is well known that Bayesian information borrowing models such as the exchangeability-nonexchangeability (EXNEX) model can be implemented to tackle such a problem, drawing on information from one basket when making inference in another. An alternative approach to improve power of estimates, is to incorporate any historical or external information available. This paper considers models that amalgamate both forms of information borrowing, allowing borrowing between baskets in the ongoing trial whilst also drawing on response data from historical sources, with the aim to further improve treatment effect estimates. We propose several Bayesian information borrowing approaches that incorporate historical information into the model. These methods are data-driven, updating the degree of borrowing based on the level of homogeneity between information sources. A thorough simulation study is presented to draw comparisons between the proposed approaches, whilst also comparing to the standard EXNEX model in which no historical information is utilized. The models are also applied to a real-life trial example to demonstrate their performance in practice. We show that the incorporation of historic data under the novel approaches can lead to a substantial improvement in precision and power of treatment effect estimates when such data is homogeneous to the responses in the ongoing trial. Under some approaches, this came alongside an inflation in type I error rate in cases of heterogeneity. However, the use of a power prior in the EXNEX model is shown to increase power and precision, whilst maintaining similar error rates to the standard EXNEX model.</p>","PeriodicalId":55357,"journal":{"name":"Biostatistics","volume":"26 1","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12204204/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144327836","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"数学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The winner's curse under dependence: repairing empirical Bayes using convoluted densities.","authors":"Stijn Hawinkel, Olivier Thas, Steven Maere","doi":"10.1093/biostatistics/kxaf025","DOIUrl":"10.1093/biostatistics/kxaf025","url":null,"abstract":"<p><p>The winner's curse is a form of selection bias that arises when estimates are obtained for a large number of features, but only a subset of most extreme estimates is reported. It occurs in large scale significance testing as well as in rank-based selection, and imperils reproducibility of findings and follow-up study design. Several methods correcting for this selection bias have been proposed, but questions remain on their susceptibility to dependence between features since theoretical analyses and comparative studies are few. We prove that estimation through Tweedie's formula is biased in presence of strong dependence, and propose a convolution of its density estimator to restore its competitive performance, which also aids other empirical Bayes methods. Furthermore, we perform a comprehensive simulation study comparing different classes of winner's curse correction methods for point estimates as well as confidence intervals under dependence. We find a bootstrap method and empirical Bayes methods with density convolution to perform best at correcting the selection bias, although this correction generally does not improve the feature ranking. Finally, we apply the methods to a comparison of single-feature versus multi-feature prediction models in predicting Brassica napus phenotypes from gene expression data, demonstrating that the superiority of the best single-feature model may be illusory.</p>","PeriodicalId":55357,"journal":{"name":"Biostatistics","volume":"26 1","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144979577","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"数学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Stochastic EM algorithm for partially observed stochastic epidemics with individual heterogeneity.","authors":"Fan Bu, Allison E Aiello, Alexander Volfovsky, Jason Xu","doi":"10.1093/biostatistics/kxae018","DOIUrl":"10.1093/biostatistics/kxae018","url":null,"abstract":"<p><p>We develop a stochastic epidemic model progressing over dynamic networks, where infection rates are heterogeneous and may vary with individual-level covariates. The joint dynamics are modeled as a continuous-time Markov chain such that disease transmission is constrained by the contact network structure, and network evolution is in turn influenced by individual disease statuses. To accommodate partial epidemic observations commonly seen in real-world data, we propose a stochastic EM algorithm for inference, introducing key innovations that include efficient conditional samplers for imputing missing infection and recovery times which respect the dynamic contact network. Experiments on both synthetic and real datasets demonstrate that our inference method can accurately and efficiently recover model parameters and provide valuable insight at the presence of unobserved disease episodes in epidemic data.</p>","PeriodicalId":55357,"journal":{"name":"Biostatistics","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141903694","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"数学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Predicting distributions of physical activity profiles in the National Health and Nutrition Examination Survey database using a partially linear Fréchet single index model.","authors":"Marcos Matabuena, Aritra Ghosal, Wendy Meiring, Alexander Petersen","doi":"10.1093/biostatistics/kxaf013","DOIUrl":"10.1093/biostatistics/kxaf013","url":null,"abstract":"<p><p>Object-oriented data analysis is a fascinating and evolving field in modern statistical science, with the potential to make significant contributions to biomedical applications. This statistical framework facilitates the development of new methods to analyze complex data objects that capture more information than traditional clinical biomarkers. This paper applies the object-oriented framework to analyze physical activity levels, measured by accelerometers, as response objects in a regression model. Unlike traditional summary metrics, we utilize a recently proposed representation of physical activity data as a distributional object, providing a more nuanced and complete profile of individual energy expenditure across all ranges of monitoring intensity. A novel hybrid Fréchet regression model is proposed and applied to US population accelerometer data from National Health and Nutrition Examination Survey (NHANES) 2011 to 2014. The semi-parametric nature of the model allows for the inclusion of nonlinear effects for critical variables, such as age, which are biologically known to have subtle impacts on physical activity. Simultaneously, the inclusion of linear effects preserves interpretability for other variables, particularly categorical covariates such as ethnicity and sex. The results obtained are valuable from a public health perspective and could lead to new strategies for optimizing physical activity interventions in specific American subpopulations.</p>","PeriodicalId":55357,"journal":{"name":"Biostatistics","volume":"26 1","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144129647","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"数学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}