Pharmaceutical Statistics最新文献_第2页

Futility Interim Analysis Based on Probability of Success Using a Surrogate Endpoint. 基于使用替代终点的成功概率的无用性中期分析。

IF 1.3 4区医学

Pharmaceutical Statistics Pub Date : 2024-11-01 Epub Date: 2024-07-02 DOI: 10.1002/pst.2410

Ronan Fougeray, Loïck Vidot, Marco Ratta, Zhaoyang Teng, Donia Skanji, Gaëlle Saint-Hilary

{"title":"Futility Interim Analysis Based on Probability of Success Using a Surrogate Endpoint.","authors":"Ronan Fougeray, Loïck Vidot, Marco Ratta, Zhaoyang Teng, Donia Skanji, Gaëlle Saint-Hilary","doi":"10.1002/pst.2410","DOIUrl":"10.1002/pst.2410","url":null,"abstract":"In clinical trials with time-to-event data, the evaluation of treatment efficacy can be a long and complex process, especially when considering long-term primary endpoints. Using surrogate endpoints to correlate the primary endpoint has become a common practice to accelerate decision-making. Moreover, the ethical need to minimize sample size and the practical need to optimize available resources have encouraged the scientific community to develop methodologies that leverage historical data. Relying on the general theory of group sequential design and using a Bayesian framework, the methodology described in this paper exploits a documented historical relationship between a clinical \"final\" endpoint and a surrogate endpoint to build an informative prior for the primary endpoint, using surrogate data from an early interim analysis of the clinical trial. The predictive probability of success of the trial is then used to define a futility-stopping rule. The methodology demonstrates substantial enhancements in trial operating characteristics when there is a good agreement between current and historical data. Furthermore, incorporating a robust approach that combines the surrogate prior with a vague component mitigates the impact of the minor prior-data conflicts while maintaining acceptable performance even in the presence of significant prior-data conflicts. The proposed methodology was applied to design a Phase III clinical trial in metastatic colorectal cancer, with overall survival as the primary endpoint and progression-free survival as the surrogate endpoint.","PeriodicalId":19934,"journal":{"name":"Pharmaceutical Statistics","volume":" ","pages":"971-983"},"PeriodicalIF":1.3,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141492960","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Survival Analysis Without Sharing of Individual Patient Data by Using a Gaussian Copula. 使用高斯 Copula 进行生存分析而无需共享单个患者数据

IF 1.3 4区医学

Pharmaceutical Statistics Pub Date : 2024-11-01 Epub Date: 2024-07-07 DOI: 10.1002/pst.2415

Federico Bonofiglio

{"title":"Survival Analysis Without Sharing of Individual Patient Data by Using a Gaussian Copula.","authors":"Federico Bonofiglio","doi":"10.1002/pst.2415","DOIUrl":"10.1002/pst.2415","url":null,"abstract":"Cox regression and Kaplan-Meier estimations are often needed in clinical research and this requires access to individual patient data (IPD). However, IPD cannot always be shared because of privacy or proprietary restrictions, which complicates the making of such estimations. We propose a method that generates pseudodata replacing the IPD by only sharing non-disclosive aggregates such as IPD marginal moments and a correlation matrix. Such aggregates are collected by a central computer and input as parameters to a Gaussian copula (GC) that generates the pseudodata. Survival inferences are computed on the pseudodata as if it were the IPD. Using practical examples we demonstrate the utility of the method, via the amount of IPD inferential content recoverable by the GC. We compare GC to a summary-based meta-analysis and an IPD bootstrap distributed across several centers. Other pseudodata approaches are also considered. In the empirical results, GC approximates the utility of the IPD bootstrap although it might yield more conservative inferences and it might have limitations in subgroup analyses. Overall, GC avoids many legal problems related to IPD privacy or property while enabling approximation of common IPD survival analyses otherwise difficult to conduct. Sharing more IPD aggregates than is currently practiced could facilitate \"second purpose\"-research and relax concerns regarding IPD access.","PeriodicalId":19934,"journal":{"name":"Pharmaceutical Statistics","volume":" ","pages":"1031-1044"},"PeriodicalIF":1.3,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141555242","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Bayesian Methods for Quality Tolerance Limit (QTL) Monitoring. 质量容限 (QTL) 监测的贝叶斯方法。

IF 1.3 4区医学

Pharmaceutical Statistics Pub Date : 2024-11-01 Epub Date: 2024-08-09 DOI: 10.1002/pst.2427

J C Poythress, Jin Hyung Lee, Kentaro Takeda, Jun Liu

{"title":"Bayesian Methods for Quality Tolerance Limit (QTL) Monitoring.","authors":"J C Poythress, Jin Hyung Lee, Kentaro Takeda, Jun Liu","doi":"10.1002/pst.2427","DOIUrl":"10.1002/pst.2427","url":null,"abstract":"In alignment with the ICH guideline for Good Clinical Practice [ICH E6(R2)], quality tolerance limit (QTL) monitoring has become a standard component of risk-based monitoring of clinical trials by sponsor companies. Parameters that are candidates for QTL monitoring are critical to participant safety and quality of trial results. Breaching the QTL of a given parameter could indicate systematic issues with the trial that could impact participant safety or compromise the reliability of trial results. Methods for QTL monitoring should detect potential QTL breaches as early as possible while limiting the rate of false alarms. Early detection allows for the implementation of remedial actions that can prevent a QTL breach at the end of the trial. We demonstrate that statistically based methods that account for the expected value and variability of the data generating process outperform simple methods based on fixed thresholds with respect to important operating characteristics. We also propose a Bayesian method for QTL monitoring and an extension that allows for the incorporation of partial information, demonstrating its potential to outperform frequentist methods originating from the statistical process control literature.","PeriodicalId":19934,"journal":{"name":"Pharmaceutical Statistics","volume":" ","pages":"1166-1180"},"PeriodicalIF":1.3,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141907380","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Reparametrized Firth's Logistic Regressions for Dose-Finding Study With the Biased-Coin Design. 采用偏币设计的剂量寻找研究中的重拟合 Firth Logistic 回归。

IF 1.3 4区医学

Pharmaceutical Statistics Pub Date : 2024-11-01 Epub Date: 2024-07-16 DOI: 10.1002/pst.2423

Hyungwoo Kim, Seungpil Jung, Yudi Pawitan, Woojoo Lee

引用次数: 0

Optimal Cut-Point Selection Methods Under Binary Classification When Subclasses Are Involved. 二元分类下涉及子类时的最佳切点选择方法

IF 1.3 4区医学

Pharmaceutical Statistics Pub Date : 2024-11-01 Epub Date: 2024-07-07 DOI: 10.1002/pst.2413

Jia Wang, Lili Tian

引用次数: 0

Visualizing hypothesis tests in survival analysis under anticipated delayed effects. 预期延迟效应下生存分析中的可视化假设检验

IF 1.3 4区医学

Pharmaceutical Statistics Pub Date : 2024-11-01 Epub Date: 2024-05-06 DOI: 10.1002/pst.2393

José L Jiménez, Isobel Barrott, Francesca Gasperoni, Dominic Magirr

{"title":"Visualizing hypothesis tests in survival analysis under anticipated delayed effects.","authors":"José L Jiménez, Isobel Barrott, Francesca Gasperoni, Dominic Magirr","doi":"10.1002/pst.2393","DOIUrl":"10.1002/pst.2393","url":null,"abstract":"What can be considered an appropriate statistical method for the primary analysis of a randomized clinical trial (RCT) with a time-to-event endpoint when we anticipate non-proportional hazards owing to a delayed effect? This question has been the subject of much recent debate. The standard approach is a log-rank test and/or a Cox proportional hazards model. Alternative methods have been explored in the statistical literature, such as weighted log-rank tests and tests based on the Restricted Mean Survival Time (RMST). While weighted log-rank tests can achieve high power compared to the standard log-rank test, some choices of weights may lead to type-I error inflation under particular conditions. In addition, they are not linked to a mathematically unambiguous summary measure. Test statistics based on the RMST, on the other hand, allow one to investigate the average difference between two survival curves up to a pre-specified time point <math><mrow><mi>τ</mi></mrow> </math> -a mathematically unambiguous summary measure. However, by emphasizing differences prior to <math><mrow><mi>τ</mi></mrow> </math> , such test statistics may not fully capture the benefit of a new treatment in terms of long-term survival. In this article, we introduce a graphical approach for direct comparison of weighted log-rank tests and tests based on the RMST. This new perspective allows a more informed choice of the analysis method, going beyond power and type I error comparison.","PeriodicalId":19934,"journal":{"name":"Pharmaceutical Statistics","volume":" ","pages":"870-883"},"PeriodicalIF":1.3,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140859909","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Using an early outcome as the sole source of information of interim decisions regarding treatment effect on a long-term endpoint: The non-Gaussian case. 将早期结果作为临时决定对长期终点治疗效果的唯一信息来源：非高斯情况

IF 1.3 4区医学

Pharmaceutical Statistics Pub Date : 2024-11-01 Epub Date: 2024-06-05 DOI: 10.1002/pst.2398

Leandro Garcia Barrado, Tomasz Burzykowski

引用次数: 0

A model-assisted design for partially or completely ordered groups. 部分或完全有序群体的模型辅助设计。

IF 1.3 4区医学

Pharmaceutical Statistics Pub Date : 2024-11-01 Epub Date: 2024-05-20 DOI: 10.1002/pst.2396

Connor Celum, Mark Conaway

引用次数: 0

Variable Duration Trial as an Alternative Design for Continuous Endpoints. 可变持续时间试验作为连续终点的替代设计

IF 1.3 4区医学

Pharmaceutical Statistics Pub Date : 2024-11-01 Epub Date: 2024-07-11 DOI: 10.1002/pst.2418

Jitendra Ganju, Julie Guoguang Ma

{"title":"Variable Duration Trial as an Alternative Design for Continuous Endpoints.","authors":"Jitendra Ganju, Julie Guoguang Ma","doi":"10.1002/pst.2418","DOIUrl":"10.1002/pst.2418","url":null,"abstract":"Clinical trials with continuous primary endpoints typically measure outcomes at baseline, at a fixed timepoint (denoted T min), and at intermediate timepoints. The analysis is commonly performed using the mixed model repeated measures method. It is sometimes expected that the effect size will be larger with follow-up longer than T min. But extending the follow-up for all patients delays trial completion. We propose an alternative trial design and analysis method that potentially increases statistical power without extending the trial duration or increasing the sample size. We propose following the last enrolled patient until T min, with earlier enrollees having variable follow-up durations up to a maximum of T max. The sample size at T max will be smaller than at T min, and due to staggered enrollment, data missing at T max will be missing completely at random. For analysis, we propose an alpha-adjusted procedure based on the smaller of the p values at T min and T max, termed <math> <semantics><mrow><mtext>minP</mtext></mrow> </semantics> </math> . This approach can provide the highest power when the powers at T min and T max are similar. If the power at T min and T max differ significantly, the power of <math> <semantics><mrow><mtext>minP</mtext></mrow> </semantics> </math> is modestly reduced compared with the larger of the two powers. Rare disease trials, due to the limited size of the patient population, may benefit the most with this design.","PeriodicalId":19934,"journal":{"name":"Pharmaceutical Statistics","volume":" ","pages":"1059-1064"},"PeriodicalIF":1.3,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141591009","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Sample Size Estimation Using a Partially Clustered Frailty Model for Biomarker-Strategy Designs With Multiple Treatments. 使用部分聚类虚弱模型估算具有多种治疗方法的生物标记物策略设计的样本量。

IF 1.3 4区医学

Pharmaceutical Statistics Pub Date : 2024-11-01 Epub Date: 2024-07-16 DOI: 10.1002/pst.2407

Derek Dinart, Virginie Rondeau, Carine Bellera

引用次数: 0