Statistical Methods in Medical Research最新文献

Group sequential designs for survival outcomes with adaptive randomization. 适应随机化的生存结果组序设计。

IF 1.6 3区医学

Statistical Methods in Medical Research Pub Date : 2025-07-17 DOI: 10.1177/09622802251340250

Yaxian Chen, Yeonhee Park

{"title":"Group sequential designs for survival outcomes with adaptive randomization.","authors":"Yaxian Chen, Yeonhee Park","doi":"10.1177/09622802251340250","DOIUrl":"https://doi.org/10.1177/09622802251340250","url":null,"abstract":"Driven by evolving Food and Drug Administration recommendations, modern clinical trials demand innovative designs that strike a balance between statistical rigor and ethical considerations. Covariate-adjusted response-adaptive randomization (CARA) designs bridge this gap by utilizing patient attributes and responses to skew treatment allocation in favor of the treatment to be best for an individual patient's profiles. However, existing CARA designs for survival outcomes often rely on specific parametric models, constraining their applicability in clinical practice. To overcome this limitation, we propose a novel CARA method for survival outcomes (called CARAS) based on the Cox model, which improves model flexibility and mitigate risks of model misspecification. Additionally, we introduce a group sequential overlap-weighted log-rank test to preserve the type I error rate in group sequential trials using CARAS. Comprehensive simulation studies and a real-world trial example demonstrate the proposed method's clinical benefit, statistical efficiency, and robustness to model misspecification compared to traditional randomized controlled trial designs and response-adaptive randomization designs.","PeriodicalId":22038,"journal":{"name":"Statistical Methods in Medical Research","volume":" ","pages":"9622802251340250"},"PeriodicalIF":1.6,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144650606","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}

引用次数: 0

Optimal treatment regimes in the presence of a cure fraction. 存在治愈分数的最佳治疗方案。

IF 1.6 3区医学

Statistical Methods in Medical Research Pub Date : 2025-07-17 DOI: 10.1177/09622802251338399

Chenrui Qi, Zicheng Lin, Baqun Zhang, Cunjie Lin, Zishu Zhan

{"title":"Optimal treatment regimes in the presence of a cure fraction.","authors":"Chenrui Qi, Zicheng Lin, Baqun Zhang, Cunjie Lin, Zishu Zhan","doi":"10.1177/09622802251338399","DOIUrl":"https://doi.org/10.1177/09622802251338399","url":null,"abstract":"Despite the widespread use of time-to-event data in precision medicine, existing research has often neglected the presence of the cure fraction, assuming that all individuals will inevitably experience the event of interest. When a cure fraction is present, the cure rate and survival time of uncured patients should be considered in estimating the optimal individualized treatment regimes. In this study, we propose direct methods for estimating the optimal individualized treatment regimes that either maximize the cure rate or mean survival time of uncured patients. Additionally, we propose two optimal individualized treatment regimes that balance the tradeoff between the cure rate and mean survival time of uncured patients based on a constrained estimation framework for a more comprehensive assessment of individualized treatment regimes. This framework allows us to estimate the optimal individualized treatment regime that maximizes the population's cure rate without significantly compromising the mean survival time of those who remain uncured or maximizes the mean survival time of uncured patients while having the cure rate controlled at a desired level. The exterior-point algorithm is adopted to expedite the resolution of the constrained optimization problem and statistical validity is rigorously established. Furthermore, the advantages of the proposed methods are demonstrated via simulations and analysis of esophageal cancer data.","PeriodicalId":22038,"journal":{"name":"Statistical Methods in Medical Research","volume":" ","pages":"9622802251338399"},"PeriodicalIF":1.6,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144650607","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}

引用次数: 0

Design of egocentric network-based studies to estimate causal effects under interference. 设计以自我为中心的网络为基础的研究，以估计干扰下的因果效应。

IF 1.6 3区医学

Statistical Methods in Medical Research Pub Date : 2025-07-17 DOI: 10.1177/09622802251357021

Junhan Fang, Donna Spiegelman, Ashley L Buchanan, Laura Forastiere

{"title":"Design of egocentric network-based studies to estimate causal effects under interference.","authors":"Junhan Fang, Donna Spiegelman, Ashley L Buchanan, Laura Forastiere","doi":"10.1177/09622802251357021","DOIUrl":"https://doi.org/10.1177/09622802251357021","url":null,"abstract":"Many public health interventions are conducted in settings where individuals are connected and the intervention assigned to some individuals may spill over to other individuals. In these settings, we can assess: (a) the individual effect on the treated, (b) the spillover effect on untreated individuals through an indirect exposure to the intervention, and (c) the overall effect on the whole population. Here, we consider an egocentric network-based randomized design in which a set of index participants is recruited and randomly assigned to treatment, while data are also collected on their untreated network members. Such a design is common in peer education interventions conceived to leverage behavioral influence among peers. Using the potential outcomes framework, we first clarify the assumptions required to rely on an identification strategy that is commonly used in the well-studied two-stage randomized design. Under these assumptions, causal effects can be jointly estimated using a regression model with a block-diagonal structure. We then develop sample size formulas for detecting individual, spillover, and overall effects for single and joint hypothesis tests, and investigate the role of different parameters. Finally, we illustrate the use of our sample size formulas for an egocentric network-based randomized experiment to evaluate a peer education intervention for HIV prevention.","PeriodicalId":22038,"journal":{"name":"Statistical Methods in Medical Research","volume":" ","pages":"9622802251357021"},"PeriodicalIF":1.6,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144650605","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}

引用次数: 0

Semiparametric regression analysis of interval-censored failure time data with a cure subgroup and nonignorable missing covariates. 具有可治愈子群和不可忽略的缺失协变量的间隔截尾失效时间数据的半参数回归分析。

IF 1.6 3区医学

Statistical Methods in Medical Research Pub Date : 2025-07-14 DOI: 10.1177/09622802251356592

Yichen Lou, Mingyue Du, Peijie Wang, Xinyuan Song

引用次数: 0

Model-based approach for two-stage group sequential or adaptive designs in bioequivalence studies using parallel and crossover designs. 采用平行和交叉设计的生物等效性研究中两阶段组序贯或自适应设计的基于模型的方法。

IF 1.6 3区医学

Statistical Methods in Medical Research Pub Date : 2025-07-13 DOI: 10.1177/09622802251354925

Florence Loingeville, Manel Rakez, Thu Thuy Nguyen, Mark Donnelly, Lanyan Fang, Kevin Feng, Liang Zhao, Stella Grosser, Guoying Sun, Wanjie Sun, France Mentré, Julie Bertrand

{"title":"Model-based approach for two-stage group sequential or adaptive designs in bioequivalence studies using parallel and crossover designs.","authors":"Florence Loingeville, Manel Rakez, Thu Thuy Nguyen, Mark Donnelly, Lanyan Fang, Kevin Feng, Liang Zhao, Stella Grosser, Guoying Sun, Wanjie Sun, France Mentré, Julie Bertrand","doi":"10.1177/09622802251354925","DOIUrl":"https://doi.org/10.1177/09622802251354925","url":null,"abstract":"In pharmacokinetic (PK) bioequivalence (BE) analysis, the recommended approach is the two one-sided tests (TOSTs) on non-compartmental analysis (NCA) estimates of area under the plasma drug concentration versus time curve and <math><msub><mi>C</mi><mrow><mi>m</mi><mi>a</mi><mi>x</mi></mrow></msub></math> (NCA-TOST). Sample size estimation for a BE study requires assumptions on between/within subject variability (B/WSV). When little prior information is available, interim analysis using two-stage group sequential (GS) or adaptive designs (ADs) may be beneficial. GS fixes the second stage size, while AD requires sample re-estimation based on first-stage results. Recent research has proposed model-based (MB) TOST, using nonlinear mixed effects models, as an alternative to NCA-TOST. This work extends GS and AD approaches to MB-TOST. We evaluated these approaches on simulated parallel and two-way crossover designs for a one-compartment PK model, considering three variability levels for initial sample size calculation. We compared final sample size, type I error, and power estimates from one-stage, GS, and AD designs using NCA-TOST and MB-TOST. Results showed both NCA-TOST and MB-TOST reasonably controlled type I error while maintaining adequate power in two-stage GS and AD approaches, based on our limited computation power. Two-stage designs reduced sample size compared to traditional designs, especially for highly variable drugs, with many trials stopping at Stage 1 in AD designs. Our findings suggest MB-TOST may serve as a viable alternative to NCA-TOST for BE assessment in two-stage designs, especially when B/WSV impacts BE results.","PeriodicalId":22038,"journal":{"name":"Statistical Methods in Medical Research","volume":" ","pages":"9622802251354925"},"PeriodicalIF":1.6,"publicationDate":"2025-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144627016","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}

引用次数: 0

Estimation of receiver operating characteristic curve when case and control require different transformations for normality. 病例与对照需要不同正态变换时的受试者工作特性曲线估计。

IF 1.6 3区医学

Statistical Methods in Medical Research Pub Date : 2025-07-09 DOI: 10.1177/09622802251354921

Xiaoyu Cai, Wei Zhang, Huiyun Li, Zhaohai Li, Aiyi Liu

{"title":"Estimation of receiver operating characteristic curve when case and control require different transformations for normality.","authors":"Xiaoyu Cai, Wei Zhang, Huiyun Li, Zhaohai Li, Aiyi Liu","doi":"10.1177/09622802251354921","DOIUrl":"https://doi.org/10.1177/09622802251354921","url":null,"abstract":"The receiver operating characteristic curve is a popular tool for evaluating the discriminative ability of a diagnostic biomarker. Parametric and nonparametric methods exist in the literature for estimation of a receiver operating characteristic curve and its associated summary measures using data usually collected from a case-control study. Since the receiver operating characteristic curve remains unchanged under a monotone transformation, the biomarker data from both cases (diseased subjects) and controls (non-diseased subjects) are often transformed based on a common Box-Cox transformation (or other appropriate transformation) prior to the application of a parametric estimation method. However, careful examination of the data often reveals that the biomarker values in the diseased and non-diseased population can only be normally approximated via different transformations. In this situation, existing estimation methods cannot be directly applied to the heterogeneously-transformed data. In this article, we deal with the situation that biomarker data from both diseased and non-diseased population are normally distributed after being transformed with different Box-Cox transformations. Under this assumption, we show that existing methods based on a common Box-Cox transformation are invalid in that they possess substantial biases. We move on to propose a method to estimate the underlying receiver operating characteristic curve and its area under the curve, and investigate its performance as compared to the nonparametric estimator that ignores any distributional assumptions as well as the estimators based on a common Box-Cox transformation assumptions. The method is exemplified with HIV infection data from the National Health and Nutrition Examination Survey (NHANES).","PeriodicalId":22038,"journal":{"name":"Statistical Methods in Medical Research","volume":" ","pages":"9622802251354921"},"PeriodicalIF":1.6,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144592388","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}

引用次数: 0

Inference procedures in sequential trial emulation with survival outcomes: Comparing confidence intervals based on the sandwich variance estimator, bootstrap and jackknife. 具有生存结果的序贯试验模拟中的推理程序：比较基于三明治方差估计器、bootstrap和jackknife的置信区间。

IF 1.6 3区医学

Statistical Methods in Medical Research Pub Date : 2025-07-09 DOI: 10.1177/09622802251356594

Juliette M Limozin, Shaun R Seaman, Li Su

{"title":"Inference procedures in sequential trial emulation with survival outcomes: Comparing confidence intervals based on the sandwich variance estimator, bootstrap and jackknife.","authors":"Juliette M Limozin, Shaun R Seaman, Li Su","doi":"10.1177/09622802251356594","DOIUrl":"https://doi.org/10.1177/09622802251356594","url":null,"abstract":"Sequential trial emulation (STE) is an approach to estimating causal treatment effects by emulating a sequence of target trials from observational data. In STE, inverse probability weighting is commonly utilised to address time-varying confounding and/or dependent censoring. Then structural models for potential outcomes are applied to the weighted data to estimate treatment effects. For inference, the simple sandwich variance estimator is popular but conservative, while nonparametric bootstrap is computationally expensive, and a more efficient alternative, linearised estimating function (LEF) bootstrap, has not been adapted to STE. We evaluated the performance of various methods for constructing confidence intervals (CIs) of marginal risk differences in STE with survival outcomes by comparing the coverage of CIs based on nonparametric/LEF bootstrap, jackknife, and the sandwich variance estimator through simulations. LEF bootstrap CIs demonstrated better coverage than nonparametric bootstrap CIs and sandwich-variance-estimator-based CIs with small/moderate sample sizes, low event rates and low treatment prevalence, which were the motivating scenarios for STE. They were less affected by treatment group imbalance and faster to compute than nonparametric bootstrap CIs. With large sample sizes and medium/high event rates, the sandwich-variance-estimator-based CIs had the best coverage and were the fastest to compute. These findings offer guidance in constructing CIs in causal survival analysis using STE.","PeriodicalId":22038,"journal":{"name":"Statistical Methods in Medical Research","volume":" ","pages":"9622802251356594"},"PeriodicalIF":1.6,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144592390","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}

引用次数: 0

Health utility adjusted survival: A composite endpoint for clinical trial designs. 健康效用调整生存率：临床试验设计的复合终点。

IF 1.6 3区医学

Statistical Methods in Medical Research Pub Date : 2025-07-09 DOI: 10.1177/09622802251338409

Yangqing Deng, John de Almeida, Wei Xu

{"title":"Health utility adjusted survival: A composite endpoint for clinical trial designs.","authors":"Yangqing Deng, John de Almeida, Wei Xu","doi":"10.1177/09622802251338409","DOIUrl":"https://doi.org/10.1177/09622802251338409","url":null,"abstract":"Many randomized trials have used overall survival as the primary endpoint for establishing non-inferiority of one treatment compared to another. However, if a treatment is non-inferior to another treatment in terms of overall survival, clinicians may be interested in further exploring which treatment results in better health utility scores for patients. Examining health utility in a secondary analysis is feasible, however, since health utility is not the primary endpoint, it is usually not considered in the sample size calculation, hence the power to detect a difference of health utility is not guaranteed. Furthermore, often the premise of non-inferiority trials is to test the assumption that an intervention provides superior quality of life or toxicity profile without compromising survival when compared to the existing standard. Based on this consideration, it may be beneficial to consider both survival and utility when designing a trial. There have been methods that can combine survival and quality of life into a single measure, but they either have strong restrictions or lack theoretical frameworks. In this manuscript, we propose a method called health utility adjusted survival, which can combine survival outcome and longitudinal utility measures for treatment comparison. We propose an innovative statistical framework as well as procedures to conduct power analysis and sample size calculation. By comprehensive simulation studies involving summary statistics from the PET-NECK trial, we demonstrate that our new approach can achieve superior power performance using relatively small sample sizes, and our composite endpoint can be considered as an alternative to overall survival in future clinical trial design and analysis where both survival and health utility are of interest.","PeriodicalId":22038,"journal":{"name":"Statistical Methods in Medical Research","volume":" ","pages":"9622802251338409"},"PeriodicalIF":1.6,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144592389","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}

引用次数: 0

Population-adjusted unanchored indirect comparisons of cancer therapies with borrowing of pan-tumor information. 人口调整的非锚定癌症治疗与泛肿瘤信息的间接比较。

IF 1.6 3区医学

Statistical Methods in Medical Research Pub Date : 2025-07-04 DOI: 10.1177/09622802251354922

Dylan Maciel, Shannon Cope, Walter Bouwmeester, Chunlin Qian, Beata Korytowsky, Jeroen P Jansen

{"title":"Population-adjusted unanchored indirect comparisons of cancer therapies with borrowing of pan-tumor information.","authors":"Dylan Maciel, Shannon Cope, Walter Bouwmeester, Chunlin Qian, Beata Korytowsky, Jeroen P Jansen","doi":"10.1177/09622802251354922","DOIUrl":"https://doi.org/10.1177/09622802251354922","url":null,"abstract":"In clinical research of cancer therapy for rare mutations, trial designs must be adapted to accommodate the typically small sample sizes, and single-arm and basket trials have gained prominence. In this paper, we apply principles of Bayesian hierarchical methods and multilevel network meta-regression to propose a model for a pairwise population-adjusted unanchored indirect comparison of cancer therapies in different tumor types with borrowing of pan-tumor information. An individual-level regression model is defined for the single-arm trial of the intervention for which we have individual patient data. The aggregate data of the other trial for the competing intervention are fitted by integrating the covariate effects at the individual level over its covariate distribution to form the aggregate likelihood. To improve the estimation of the tumor type-specific relative treatment effects, we assume exchangeability reflecting the belief of a pan-tumor effect. The method is illustrated with a case study of adagrasib versus sotorasib in previously treated KRASG12C-mutated advanced/metastatic tumors: non-small cell lung cancer (NSCLC), colorectal cancer (CRC), and pancreatic ductal adenocarcinoma (PDAC). Adagrasib was associated with a greater tumor response than sotorasib according to the analyses: The odds ratios were 1.87 (1.21-2.84) for NSCLC; 2.08 (1.22-3.93) for CRC; and 2.02 (1.14-4.05) for PDAC. The analysis illustrated that a reasonably conservative assumption about the degree of similarity can result in more meaningful and interpretable findings. The proposed model allows for population adjustment and information sharing across tumor types when performing an unanchored indirect comparison of interventions for which it is believed a pan-tumor effect holds.","PeriodicalId":22038,"journal":{"name":"Statistical Methods in Medical Research","volume":" ","pages":"9622802251354922"},"PeriodicalIF":1.6,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144561190","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}

引用次数: 0

Closed-form confidence intervals for saved time using summary statistics in Alzheimer's disease studies. 阿尔茨海默病研究中使用汇总统计节省时间的封闭式置信区间。

IF 1.6 3区医学

Statistical Methods in Medical Research Pub Date : 2025-07-04 DOI: 10.1177/09622802251348796

Guogen Shan, Yahui Zhang, Guoqiao Wang, Samuel S Wu, Aidong A Ding

引用次数: 0