Statistical Methods in Medical Research最新文献

{"title":"Long-term Dagum-power variance function frailty regression model: Application in health studies.","authors":"Agatha Sacramento Rodrigues, Patrick Borges","doi":"10.1177/09622802241304113","DOIUrl":"10.1177/09622802241304113","url":null,"abstract":"<p><p>Survival models with cure fractions, known as long-term survival models, are widely used in epidemiology to account for both immune and susceptible patients regarding a failure event. In such studies, it is also necessary to estimate unobservable heterogeneity caused by unmeasured prognostic factors. Moreover, the hazard function may exhibit a non-monotonic shape, specifically, an unimodal hazard function. In this article, we propose a long-term survival model based on a defective version of the Dagum distribution, incorporating a power variance function frailty term to account for unobservable heterogeneity. This model accommodates survival data with cure fractions and non-monotonic hazard functions. The distribution is reparameterized in terms of the cure fraction, with covariates linked via a logit link, allowing for direct interpretation of covariate effects on the cure fraction-an uncommon feature in defective approaches. We present maximum likelihood estimation for model parameters, assess performance through Monte Carlo simulations, and illustrate the model's applicability using two health-related datasets: severe COVID-19 in pregnant and postpartum women and patients with malignant skin neoplasms.</p>","PeriodicalId":22038,"journal":{"name":"Statistical Methods in Medical Research","volume":" ","pages":"407-439"},"PeriodicalIF":1.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143400106","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Weighting methods for truncation by death in cluster-randomized trials.","authors":"Dane Isenberg, Michael O Harhay, Nandita Mitra, Fan Li","doi":"10.1177/09622802241309348","DOIUrl":"10.1177/09622802241309348","url":null,"abstract":"<p><p>Patient-centered outcomes, such as quality of life and length of hospital stay, are the focus in a wide array of clinical studies. However, participants in randomized trials for elderly or critically and severely ill patient populations may have truncated or undefined non-mortality outcomes if they do not survive through the measurement time point. To address truncation by death, the survivor average causal effect has been proposed as a causally interpretable subgroup treatment effect defined under the principal stratification framework. However, the majority of methods for estimating the survivor average causal effect have been developed in the context of individually randomized trials. Only limited discussions have been centered around cluster-randomized trials, where methods typically involve strong distributional assumptions for outcome modeling. In this article, we propose two weighting methods to estimate the survivor average causal effect in cluster-randomized trials that obviate the need for potentially complicated outcome distribution modeling. We establish the requisite assumptions that address latent clustering effects to enable point identification of the survivor average causal effect, and we provide computationally efficient asymptotic variance estimators for each weighting estimator. In simulations, we evaluate our weighting estimators, demonstrating their finite-sample operating characteristics and robustness to certain departures from the identification assumptions. We illustrate our methods using data from a cluster-randomized trial to assess the impact of a sedation protocol on mechanical ventilation among children with acute respiratory failure.</p>","PeriodicalId":22038,"journal":{"name":"Statistical Methods in Medical Research","volume":" ","pages":"473-489"},"PeriodicalIF":1.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11951466/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143068032","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Jointly assessing multiple endpoints in pilot and feasibility studies.","authors":"Robert N Montgomery, Amy E Bodde, Eric D Vidoni","doi":"10.1177/09622802241311219","DOIUrl":"10.1177/09622802241311219","url":null,"abstract":"<p><p>Pilot and feasibility studies are routinely used to determine whether a definitive trial should be pursued; however, the methodologies used to assess feasibility endpoints are often basic and are rarely informed by the requirements of the planned future trial. We propose a new method for analyzing feasibility outcomes which can incorporate relationships between endpoints, utilize a preliminary study design for a future trial and allow for multiple types of feasibility endpoints. The approach specifies a Joint Feasibility Space (JFS) which is the combination of feasibility outcomes that would render a future trial feasible. We estimate the probability of being in the JFS using Bayesian methods and use simulation to create a decision rule based on frequentist operating characteristics. We compare our approach to other general-purpose methods in the literature with simulation and show that our approach has approximately the same performance when analyzing a single feasibility endpoint but is more efficient with more than one endpoint. Feasibility endpoints should be the focus of pilot and feasibility studies. The analyses of these endpoints deserve more attention than they are given, and we have provided a new, effective method their assessment.</p>","PeriodicalId":22038,"journal":{"name":"Statistical Methods in Medical Research","volume":" ","pages":"561-573"},"PeriodicalIF":1.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11951445/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143400103","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Robust propensity score estimation via loss function calibration.","authors":"Yimeng Shang, Yu-Han Chiu, Lan Kong","doi":"10.1177/09622802241308709","DOIUrl":"10.1177/09622802241308709","url":null,"abstract":"<p><p>Propensity score estimation is often used as a preliminary step to estimate the average treatment effect with observational data. Nevertheless, misspecification of propensity score models undermines the validity of effect estimates in subsequent analyses. Prediction-based machine learning algorithms are increasingly used to estimate propensity scores to allow for more complex relationships between covariates. However, these approaches may not necessarily achieve covariates balancing. We propose a calibration-based method to better incorporate covariate balance properties in a general modeling framework. Specifically, we calibrate the loss function by adding a covariate imbalance penalty to standard parametric (e.g. logistic regressions) or machine learning models (e.g. neural networks). Our approach may mitigate the impact of model misspecification by explicitly taking into account the covariate balance in the propensity score estimation process. The empirical results show that the proposed method is robust to propensity score model misspecification. The integration of loss function calibration improves the balance of covariates and reduces the root-mean-square error of causal effect estimates. When the propensity score model is misspecified, the neural-network-based model yields the best estimator with less bias and smaller variance as compared to other methods considered.</p>","PeriodicalId":22038,"journal":{"name":"Statistical Methods in Medical Research","volume":" ","pages":"457-472"},"PeriodicalIF":1.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11951360/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143411114","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Causal survival embeddings: Non-parametric counterfactual inference under right-censoring.","authors":"Carlos García Meixide, Marcos Matabuena","doi":"10.1177/09622802241311455","DOIUrl":"10.1177/09622802241311455","url":null,"abstract":"<p><p>Counterfactual inference at the distributional level presents new challenges with censored targets, especially in modern healthcare problems. To mitigate selection bias in this context, we exploit the intrinsic structure of reproducing kernel Hilbert spaces (RKHS) harnessing the notion of kernel mean embedding. This enables the development of a non-parametric estimator of counterfactual survival functions. We provide rigorous theoretical guarantees regarding consistency and convergence rates of our new estimator under general hypotheses related to smoothness of the underlying RKHS. We illustrate the practical viability of our methodology through extensive simulations and a relevant case study: The SPRINT trial. Our estimatort presents a distinct perspective compared to existing methods within the literature, which often rely on semi-parametric approaches and confront limitations in causal interpretations of model parameters.</p>","PeriodicalId":22038,"journal":{"name":"Statistical Methods in Medical Research","volume":" ","pages":"574-593"},"PeriodicalIF":1.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11951469/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143391932","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Modelling extensions for multi-location studies in environmental epidemiology.","authors":"Pierre Masselot, Antonio Gasparrini","doi":"10.1177/09622802241313284","DOIUrl":"10.1177/09622802241313284","url":null,"abstract":"<p><p>Multi-location studies are increasingly used in environmental epidemiology. Their application is supported by designs and statistical techniques developed in the last decades, which however have known limitations. In this contribution, we propose an improved modelling framework that addresses these issues. Specifically, this flexible framework allows the direct modelling of demographic differences across locations, defining geographical variations linked to multiple vulnerability factors, capturing spatial heterogeneity and predicting risks to new locations, and improving the assessment of uncertainty. We illustrate these new developments in an analysis of temperature-mortality associations in Italian cities, providing fully reproducible R code and data.</p>","PeriodicalId":22038,"journal":{"name":"Statistical Methods in Medical Research","volume":" ","pages":"615-629"},"PeriodicalIF":1.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11951449/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143189642","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Using Bayesian evidence synthesis to quantify uncertainty in population trends in smoking behaviour.","authors":"Stephen Wade, Peter Sarich, Pavla Vaneckova, Silvia Behar-Harpaz, Preston J Ngo, Paul B Grogan, Sonya Cressman, Coral E Gartner, John M Murray, Tony Blakely, Emily Banks, Martin C Tammemagi, Karen Canfell, Marianne F Weber, Michael Caruana","doi":"10.1177/09622802241310326","DOIUrl":"10.1177/09622802241310326","url":null,"abstract":"<p><p>Simulation models of smoking behaviour provide vital forecasts of exposure to inform policy targets, estimates of the burden of disease, and impacts of tobacco control interventions. A key element of useful model-based forecasts is a clear picture of uncertainty due to the data used to inform the model, however, assessment of this parameter uncertainty is incomplete in almost all tobacco control models. As a remedy, we demonstrate a Bayesian approach to model calibration that quantifies parameter uncertainty. With a model calibrated to Australian data, we observed that the smoking cessation rate in Australia has increased with calendar year since the late 20th century, and in 2016 people who smoked would quit at a rate of 4.7 quit-events per 100 person-years (90% equal-tailed interval (ETI): 4.5-4.9). We found that those who quit smoking before age 30 years switched to reporting that they never smoked at a rate of approximately 2% annually (90% ETI: 1.9-2.2%). The Bayesian approach demonstrated here can be used as a blueprint to model other population behaviours that are challenging to measure directly, and to provide a clearer picture of uncertainty to decision-makers.</p>","PeriodicalId":22038,"journal":{"name":"Statistical Methods in Medical Research","volume":" ","pages":"545-560"},"PeriodicalIF":1.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11951451/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143400108","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Semiparametric estimator for the covariate-specific receiver operating characteristic curve.","authors":"Pablo Martínez-Camblor, Juan Carlos Pardo-Fernández","doi":"10.1177/09622802241311458","DOIUrl":"10.1177/09622802241311458","url":null,"abstract":"<p><p>The study of the predictive ability of a marker is mainly based on the accuracy measures provided by the so-called confusion matrix. Besides, the area under the receiver operating characteristic curve has become a popular index for summarizing the overall accuracy of a marker. However, the nature of the relationship between the marker and the outcome, and the role that potential confounders play in this relationship could be fundamental in order to extrapolate the observed results. Directed acyclic graphs commonly used in epidemiology and in causality, could provide good feedback for learning the possibilities and limits of this extrapolation applied to the binary classification problem. Both the covariate-specific and the covariate-adjusted receiver operating characteristic curves are valuable tools, which can help to a better understanding of the real classification abilities of a marker. Since they are strongly related with the conditional distributions of the marker on the positive (subjects with the studied characteristic) and negative (subjects without the studied characteristic) populations, the use of proportional hazard regression models arises in a very natural way. We explore the use of flexible proportional hazard Cox regression models for estimating the covariate-specific and the covariate-adjusted receiver operating characteristic curves. We study their large- and finite-sample properties and apply the proposed estimators to a real-world problem. The developed code (in R language) is provided on Supplemental Material.</p>","PeriodicalId":22038,"journal":{"name":"Statistical Methods in Medical Research","volume":" ","pages":"594-614"},"PeriodicalIF":1.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143024802","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<ArticleTitle xmlns:ns0=\"http://www.w3.org/1998/Math/MathML\">High-dimensional, outcome-dependent missing data problems: Models for the human <ns0:math><ns0:mi>K</ns0:mi><ns0:mi>I</ns0:mi><ns0:mi>R</ns0:mi></ns0:math> loci.","authors":"Lars Leonardus Joannes van der Burg, Hein Putter, Henning Baldauf, Jürgen Sauter, Johannes Schetelig, Liesbeth C de Wreede, Stefan Böhringer","doi":"10.1177/09622802241304112","DOIUrl":"10.1177/09622802241304112","url":null,"abstract":"<p><p>Missing data problems are common in biological, high-dimensional data, where data can be partially or completely missing. Algorithms have been developed to reconstruct the missing values by means of imputation or expectation-maximization algorithms. For missing data problems, it has been suggested that the regression model of interest should be incorporated into the imputation procedure to reduce bias of the regression coefficients. We here consider a challenging missing data problem, where diplotypes of the <i>KIR</i> loci are to be reconstructed. These loci are difficult to genotype, resulting in ambiguous genotype calls. We extend a previously proposed expectation-maximization algorithm by incorporating a potentially high-dimensional regression model to model the outcome. Three strategies are evaluated: (1) only allelic predictors, (2) allelic predictors and forward-backward selection on haplotype predictors, and (3) penalized regression on a saturated model. In a simulation study, we compared these strategies with a baseline expectation-maximization algorithm without outcome model. For extreme choices of effect sizes and missingness levels, the outcome-based expectation-maximization algorithms outperformed the no-outcome expectation-maximization algorithm. However, in all other cases, the no-outcome expectation-maximization algorithm performed either superior or comparable to the three strategies, suggesting the outcome model can have a harmful effect. In a data analysis concerning death after allogeneic hematopoietic stem cell transplantation as a function of donor <i>KIR</i> genes, expectation-maximization algorithms with and without outcome showed very similar results. In conclusion, outcome based missing data models in the high-dimensional setting have to be used with care and are likely to lead to biased results.</p>","PeriodicalId":22038,"journal":{"name":"Statistical Methods in Medical Research","volume":" ","pages":"440-456"},"PeriodicalIF":1.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11951372/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143068018","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multicategory matched learning for estimating optimal individualized treatment rules in observational studies with application to a hepatocellular carcinoma study.","authors":"Xuqiao Li, Qiuyan Zhou, Ying Wu, Ying Yan","doi":"10.1177/09622802241310328","DOIUrl":"10.1177/09622802241310328","url":null,"abstract":"<p><p>One primary goal of precision medicine is to estimate the individualized treatment rules that optimize patients' health outcomes based on individual characteristics. Health studies with multiple treatments are commonly seen in practice. However, most existing individualized treatment rule estimation methods were developed for the studies with binary treatments. Many require that the outcomes are fully observed. In this article, we propose a matching-based machine learning method to estimate the optimal individualized treatment rules in observational studies with multiple treatments when the outcomes are fully observed or right-censored. We establish theoretical property for the proposed method. It is compared with the existing competitive methods in simulation studies and a hepatocellular carcinoma study.</p>","PeriodicalId":22038,"journal":{"name":"Statistical Methods in Medical Research","volume":" ","pages":"508-522"},"PeriodicalIF":1.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143024790","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}