Statistical Methods in Medical Research最新文献

{"title":"Sample size calculation for mixture cure model with restricted mean survival time as a primary endpoint.","authors":"Zhaojin Li, Xiang Geng, Yawen Hou, Zheng Chen","doi":"10.1177/09622802241265501","DOIUrl":"10.1177/09622802241265501","url":null,"abstract":"<p><p>It is not uncommon for a substantial proportion of patients to be cured (or survive long-term) in clinical trials with time-to-event endpoints, such as the endometrial cancer trial. When designing a clinical trial, a mixture cure model should be used to fully consider the cure fraction. Previously, mixture cure model sample size calculations were based on the proportional hazards assumption of latency distribution between groups, and the log-rank test was used for deriving sample size formulas. In real studies, the latency distributions of the two groups often do not satisfy the proportional hazards assumptions. This article has derived a sample size calculation formula for a mixture cure model with restricted mean survival time as the primary endpoint, and did simulation and example studies. The restricted mean survival time test is not subject to proportional hazards assumptions, and the difference in treatment effect obtained can be quantified as the number of years (or months) increased or decreased in survival time, making it very convenient for clinical patient-physician communication. The simulation results showed that the sample sizes estimated by the restricted mean survival time test for the mixture cure model were accurate regardless of whether the proportional hazards assumptions were satisfied and were smaller than the sample sizes estimated by the log-rank test in most cases for the scenarios in which the proportional hazards assumptions were violated.</p>","PeriodicalId":22038,"journal":{"name":"Statistical Methods in Medical Research","volume":" ","pages":"1546-1558"},"PeriodicalIF":1.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141898272","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\">Accounting for regression to the mean under the bivariate <ns0:math><ns0:mi>t</ns0:mi></ns0:math>-distribution.","authors":"Muhammad Umair, Manzoor Khan, Jake Olivier","doi":"10.1177/09622802241267808","DOIUrl":"10.1177/09622802241267808","url":null,"abstract":"<p><p>Regression to the mean occurs when an unusual observation is followed by a more typical outcome closer to the population mean. In pre- and post-intervention studies, treatment is administered to subjects with initial measurements located in the tail of a distribution, and a paired sample <math><mi>t</mi></math>-test can be utilized to assess the effectiveness of the intervention. The observed change in the pre-post means is the sum of regression to the mean and treatment effects, and ignoring regression to the mean could lead to erroneous conclusions about the effectiveness of the treatment effect. In this study, formulae for regression to the mean are derived, and maximum likelihood estimation is employed to numerically estimate the regression to the mean effect when the test statistic follows the bivariate <math><mi>t</mi></math>-distribution based on a baseline criterion or a cut-off point. The pre-post degrees of freedom could be equal but also unequal such as when there is missing data. Additionally, we illustrate how regression to the mean is influenced by cut-off points, mixing angles which are related to correlation, and degrees of freedom. A simulation study is conducted to assess the statistical properties of unbiasedness, consistency, and asymptotic normality of the regression to the mean estimator. Moreover, the proposed methods are compared with an existing one assuming bivariate normality. The <math><mi>p</mi></math>-values are compared when regression to the mean is either ignored or accounted for to gauge the statistical significance of the paired <math><mi>t</mi></math>-test. The proposed method is applied to real data concerning schizophrenia patients, and the observed conditional mean difference called the total effect is decomposed into the regression to the mean and treatment effects.</p>","PeriodicalId":22038,"journal":{"name":"Statistical Methods in Medical Research","volume":" ","pages":"1624-1636"},"PeriodicalIF":1.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141907755","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":"Inference for restricted mean survival time as a function of restriction time under length-biased sampling.","authors":"Fangfang Bai, Xiaoran Yang, Xuerong Chen, Xiaofei Wang","doi":"10.1177/09622802241267812","DOIUrl":"10.1177/09622802241267812","url":null,"abstract":"<p><p>The restricted mean survival time (RMST) is often of direct interest in clinical studies involving censored survival outcomes. It describes the area under the survival curve from time zero to a specified time point. When data are subject to length-biased sampling, as is frequently encountered in observational cohort studies, existing methods cannot estimate the RMST for various restriction times through a single model. In this article, we model the RMST as a continuous function of the restriction time under the setting of length-biased sampling. Two approaches based on estimating equations are proposed to estimate the time-varying effects of covariates. Finally, we establish the asymptotic properties for the proposed estimators. Simulation studies are performed to demonstrate the finite sample performance. Two real-data examples are analyzed by our procedures.</p>","PeriodicalId":22038,"journal":{"name":"Statistical Methods in Medical Research","volume":" ","pages":"1610-1623"},"PeriodicalIF":1.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141898271","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":"Cause-specific hazard Cox models with partly interval censoring - Penalized likelihood estimation using Gaussian quadrature.","authors":"Joseph Descallar, Jun Ma, Houying Zhu, Stephane Heritier, Rory Wolfe","doi":"10.1177/09622802241262526","DOIUrl":"10.1177/09622802241262526","url":null,"abstract":"<p><p>The cause-specific hazard Cox model is widely used in analyzing competing risks survival data, and the partial likelihood method is a standard approach when survival times contain only right censoring. In practice, however, interval-censored survival times often arise, and this means the partial likelihood method is not directly applicable. Two common remedies in practice are (i) to replace each censoring interval with a single value, such as the middle point; or (ii) to redefine the event of interest, such as the time to diagnosis instead of the time to recurrence of a disease. However, the mid-point approach can cause biased parameter estimates. In this article, we develop a penalized likelihood approach to fit semi-parametric cause-specific hazard Cox models, and this method is general enough to allow left, right, and interval censoring times. Penalty functions are used to regularize the baseline hazard estimates and also to make these estimates less affected by the number and location of knots used for the estimates. We will provide asymptotic properties for the estimated parameters. A simulation study is designed to compare our method with the mid-point partial likelihood approach. We apply our method to the Aspirin in Reducing Events in the Elderly (ASPREE) study, illustrating an application of our proposed method.</p>","PeriodicalId":22038,"journal":{"name":"Statistical Methods in Medical Research","volume":" ","pages":"1531-1545"},"PeriodicalIF":1.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11523552/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141760989","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":"Maintaining the validity of inference from linear mixed models in stepped-wedge cluster randomized trials under misspecified random-effects structures.","authors":"Yongdong Ouyang, Monica Taljaard, Andrew B Forbes, Fan Li","doi":"10.1177/09622802241248382","DOIUrl":"10.1177/09622802241248382","url":null,"abstract":"<p><p>Linear mixed models are commonly used in analyzing stepped-wedge cluster randomized trials. A key consideration for analyzing a stepped-wedge cluster randomized trial is accounting for the potentially complex correlation structure, which can be achieved by specifying random-effects. The simplest random effects structure is random intercept but more complex structures such as random cluster-by-period, discrete-time decay, and more recently, the random intervention structure, have been proposed. Specifying appropriate random effects in practice can be challenging: assuming more complex correlation structures may be reasonable but they are vulnerable to computational challenges. To circumvent these challenges, robust variance estimators may be applied to linear mixed models to provide consistent estimators of standard errors of fixed effect parameters in the presence of random-effects misspecification. However, there has been no empirical investigation of robust variance estimators for stepped-wedge cluster randomized trials. In this article, we review six robust variance estimators (both standard and small-sample bias-corrected robust variance estimators) that are available for linear mixed models in R, and then describe a comprehensive simulation study to examine the performance of these robust variance estimators for stepped-wedge cluster randomized trials with a continuous outcome under different data generators. For each data generator, we investigate whether the use of a robust variance estimator with either the random intercept model or the random cluster-by-period model is sufficient to provide valid statistical inference for fixed effect parameters, when these working models are subject to random-effect misspecification. Our results indicate that the random intercept and random cluster-by-period models with robust variance estimators performed adequately. The CR3 robust variance estimator (approximate jackknife) estimator, coupled with the number of clusters minus two degrees of freedom correction, consistently gave the best coverage results, but could be slightly conservative when the number of clusters was below 16. We summarize the implications of our results for the linear mixed model analysis of stepped-wedge cluster randomized trials and offer some practical recommendations on the choice of the analytic model.</p>","PeriodicalId":22038,"journal":{"name":"Statistical Methods in Medical Research","volume":" ","pages":"1497-1516"},"PeriodicalIF":1.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11499024/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141162723","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":"Estimating individualized treatment rules by optimizing the adjusted probability of a longer survival.","authors":"Qijia He, Shixiao Zhang, Michael L LeBlanc, Ying-Qi Zhao","doi":"10.1177/09622802241262525","DOIUrl":"10.1177/09622802241262525","url":null,"abstract":"<p><p>Individualized treatment rules inform tailored treatment decisions based on the patient's information, where the goal is to optimize clinical benefit for the population. When the clinical outcome of interest is survival time, most of current approaches typically aim to maximize the expected time of survival. We propose a new criterion for constructing Individualized treatment rules that optimize the clinical benefit with survival outcomes, termed as the adjusted probability of a longer survival. This objective captures the likelihood of living longer with being on treatment, compared to the alternative, which provides an alternative and often straightforward interpretation to communicate with clinicians and patients. We view it as an alternative to the survival analysis standard of the hazard ratio and the increasingly used restricted mean survival time. We develop a new method to construct the optimal Individualized treatment rule by maximizing a nonparametric estimator of the adjusted probability of a longer survival for a decision rule. Simulation studies demonstrate the reliability of the proposed method across a range of different scenarios. We further perform data analysis using data collected from a randomized Phase III clinical trial (SWOG S0819).</p>","PeriodicalId":22038,"journal":{"name":"Statistical Methods in Medical Research","volume":" ","pages":"1517-1530"},"PeriodicalIF":1.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11671293/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141760990","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":"A useful parametric specification to model epidemiological data: Revival of the Richards' curve.","authors":"Marco Mingione, Pierfrancesco Alaimo Di Loro, Antonello Maruotti","doi":"10.1177/09622802241262522","DOIUrl":"https://doi.org/10.1177/09622802241262522","url":null,"abstract":"<p><p>A useful parametric specification for the expected value of an epidemiological process is revived, and its statistical and empirical efficacy are explored. The Richards' curve is flexible enough to adapt to several growth phenomena, including recent epidemics and outbreaks. Here, two different estimation methods are described. The first, based on likelihood maximisation, is particularly useful when the outbreak is still ongoing and the main goal is to obtain sufficiently accurate estimates in negligible computational run-time. The second is fully Bayesian and allows for more ambitious modelling attempts such as the inclusion of spatial and temporal dependence, but it requires more data and computational resources. Regardless of the estimation approach, the Richards' specification properly characterises the main features of any growth process (e.g. growth rate, peak phase etc.), leading to a reasonable fit and providing good short- to medium-term predictions. To demonstrate such flexibility, we show different applications using publicly available data on recent epidemics where the data collection processes and transmission patterns are extremely heterogeneous, as well as benchmark datasets widely used in the literature as illustrative.</p>","PeriodicalId":22038,"journal":{"name":"Statistical Methods in Medical Research","volume":"33 8","pages":"1473-1494"},"PeriodicalIF":1.6,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142366594","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":"Measuring the individualization potential of treatment individualization rules: Application to rules built with a new parametric interaction model for parallel-group clinical trials.","authors":"Francisco J Diaz","doi":"10.1177/09622802241259172","DOIUrl":"10.1177/09622802241259172","url":null,"abstract":"<p><p>For personalized medicine, we propose a general method of evaluating the potential performance of an individualized treatment rule in future clinical applications with new patients. We focus on rules that choose the most beneficial treatment for the patient out of two active (nonplacebo) treatments, which the clinician will prescribe regularly to the patient after the decision. We develop a measure of the individualization potential (IP) of a rule. The IP compares the expected effectiveness of the rule in a future clinical individualization setting versus the effectiveness of not trying individualization. We illustrate our evaluation method by explaining how to measure the IP of a useful type of individualized rules calculated through a new parametric interaction model of data from parallel-group clinical trials with continuous responses. Our interaction model implies a structural equation model we use to estimate the rule and its IP. We examine the IP both theoretically and with simulations when the estimated individualized rule is put into practice in new patients. Our individualization approach was superior to outcome-weighted machine learning according to simulations. We also show connections with crossover and N-of-1 trials. As a real data application, we estimate a rule for the individualization of treatments for diabetic macular edema and evaluate its IP.</p>","PeriodicalId":22038,"journal":{"name":"Statistical Methods in Medical Research","volume":" ","pages":"1355-1375"},"PeriodicalIF":1.6,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141894391","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":"Optimal designs using generalized estimating equations in cluster randomized crossover and stepped wedge trials.","authors":"Jingxia Liu, Fan Li","doi":"10.1177/09622802241247717","DOIUrl":"10.1177/09622802241247717","url":null,"abstract":"<p><p>Cluster randomized crossover and stepped wedge cluster randomized trials are two types of longitudinal cluster randomized trials that leverage both the within- and between-cluster comparisons to estimate the treatment effect and are increasingly used in healthcare delivery and implementation science research. While the variance expressions of estimated treatment effect have been previously developed from the method of generalized estimating equations for analyzing cluster randomized crossover trials and stepped wedge cluster randomized trials, little guidance has been provided for optimal designs to ensure maximum efficiency. Here, an optimal design refers to the combination of optimal cluster-period size and optimal number of clusters that provide the smallest variance of the treatment effect estimator or maximum efficiency under a fixed total budget. In this work, we develop optimal designs for multiple-period cluster randomized crossover trials and stepped wedge cluster randomized trials with continuous outcomes, including both closed-cohort and repeated cross-sectional sampling schemes. Local optimal design algorithms are proposed when the correlation parameters in the working correlation structure are known. MaxiMin optimal design algorithms are proposed when the exact values are unavailable, but investigators may specify a range of correlation values. The closed-form formulae of local optimal design and MaxiMin optimal design are derived for multiple-period cluster randomized crossover trials, where the cluster-period size and number of clusters are decimal. The decimal estimates from closed-form formulae can then be used to investigate the performances of integer estimates from local optimal design and MaxiMin optimal design algorithms. One unique contribution from this work, compared to the previous optimal design research, is that we adopt constrained optimization techniques to obtain integer estimates under the MaxiMin optimal design. To assist practical implementation, we also develop four SAS macros to find local optimal designs and MaxiMin optimal designs.</p>","PeriodicalId":22038,"journal":{"name":"Statistical Methods in Medical Research","volume":" ","pages":"1299-1330"},"PeriodicalIF":1.6,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141176266","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":"Erratum to \"A dose-effect network meta-analysis model with application in antidepressants using restricted cubic splines\".","authors":"","doi":"10.1177/09622802241254569","DOIUrl":"10.1177/09622802241254569","url":null,"abstract":"","PeriodicalId":22038,"journal":{"name":"Statistical Methods in Medical Research","volume":" ","pages":"NP1"},"PeriodicalIF":1.6,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11532931/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141752830","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}