Clinical Trials最新文献_第9页

Using multistate models with clinical trial data for a deeper understanding of complex disease processes. 将多态模型与临床试验数据相结合，加深对复杂疾病过程的理解。

IF 2.2 3区医学

Clinical Trials Pub Date : 2024-10-01 Epub Date: 2024-08-02 DOI: 10.1177/17407745241267862

Terry M Therneau, Fang-Shu Ou

{"title":"Using multistate models with clinical trial data for a deeper understanding of complex disease processes.","authors":"Terry M Therneau, Fang-Shu Ou","doi":"10.1177/17407745241267862","DOIUrl":"10.1177/17407745241267862","url":null,"abstract":"A clinical trial represents a large commitment from all individuals involved and a huge financial obligation given its high cost; therefore, it is wise to make the most of all collected data by learning as much as possible. A multistate model is a generalized framework to describe longitudinal events; multistate hazards models can treat multiple intermediate/final clinical endpoints as outcomes and estimate the impact of covariates simultaneously. Proportional hazards models are fitted (one per transition), which can be used to calculate the absolute risks, that is, the probability of being in a state at a given time, the expected number of visits to a state, and the expected amount of time spent in a state. Three publicly available clinical trial datasets, colon, myeloid, and rhDNase, in the survival package in R were used to showcase the utility of multistate hazards models. In the colon dataset, a very well-known and well-used dataset, we found that the levamisole+fluorouracil treatment extended time in the recurrence-free state more than it extended overall survival, which resulted in less time in the recurrence state, an example of the classic \"compression of morbidity.\" In the myeloid dataset, we found that complete response (CR) is durable, patients who received treatment B have longer sojourn time in CR than patients who received treatment A, while the mutation status does not impact the transition rate to CR but is highly influential on the sojourn time in CR. We also found that more patients in treatment A received transplants without CR, and more patients in treatment B received transplants after CR. In addition, the mutation status is highly influential on the CR to transplant transition rate. The observations that we made on these three datasets would not be possible without multistate models. We want to encourage readers to spend more time to look deeper into clinical trial data. It has a lot more to offer than a simple yes/no answer if only we, the statisticians, are willing to look for it.","PeriodicalId":10685,"journal":{"name":"Clinical Trials","volume":" ","pages":"531-540"},"PeriodicalIF":2.2,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141878507","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

Statistical approaches for component-wise censored composite endpoints. 成分删减复合终点的统计方法。

IF 2.2 3区医学

Clinical Trials Pub Date : 2024-10-01 Epub Date: 2024-08-08 DOI: 10.1177/17407745241265628

Anne Eaton

引用次数: 0

Is inadequate risk stratification diluting hazard ratio estimates in randomized clinical trials? 风险分层不足是否会稀释随机临床试验中的危险比估计值？

IF 2.2 3区医学

Clinical Trials Pub Date : 2024-10-01 Epub Date: 2024-02-02 DOI: 10.1177/17407745231222448

Devan V Mehrotra, Rachel Marceau West

{"title":"Is inadequate risk stratification diluting hazard ratio estimates in randomized clinical trials?","authors":"Devan V Mehrotra, Rachel Marceau West","doi":"10.1177/17407745231222448","DOIUrl":"10.1177/17407745231222448","url":null,"abstract":"In randomized clinical trials, analyses of time-to-event data without risk stratification, or with stratification based on pre-selected factors revealed at the end of the trial to be at most weakly associated with risk, are quite common. We caution that such analyses are likely delivering hazard ratio estimates that unwittingly dilute the evidence of benefit for the test relative to the control treatment. To make our case, first, we use a hypothetical scenario to contrast risk-unstratified and risk-stratified hazard ratios. Thereafter, we draw attention to the previously published 5-step stratified testing and amalgamation routine (5-STAR) approach in which a pre-specified treatment-blinded algorithm is applied to survival times from the trial to partition patients into well-separated risk strata using baseline covariates determined to be jointly strongly prognostic for event risk. After treatment unblinding, a treatment comparison is done within each risk stratum and stratum-level results are averaged for overall inference. For illustration, we use 5-STAR to reanalyze data for the primary and key secondary time-to-event endpoints from three published cardiovascular outcomes trials. The results show that the 5-STAR estimate is typically smaller (i.e. more in favor of the test treatment) than the originally reported (traditional) estimate. This is not surprising because 5-STAR mitigates the presumed dilution bias in the traditional hazard ratio estimate caused by no or inadequate risk stratification, as evidenced by two detailed examples. Pre-selection of stratification factors at the trial design stage to achieve adequate risk stratification for the analysis will often be challenging. In such settings, an objective risk stratification approach such as 5-STAR, which is partly aligned with guidance from the US Food and Drug Administration on covariate-adjustment in clinical trials, is worthy of consideration.","PeriodicalId":10685,"journal":{"name":"Clinical Trials","volume":" ","pages":"571-575"},"PeriodicalIF":2.2,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139671450","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

Estimands in clinical trials of complex disease processes. 复杂疾病过程临床试验中的估算。

IF 2.2 3区医学

Clinical Trials Pub Date : 2024-10-01 Epub Date: 2024-08-24 DOI: 10.1177/17407745241268054

Richard J Cook, Jerald F Lawless

引用次数: 0

Inferences for the distribution of the duration of response in a comparative clinical study. 比较临床研究中反应持续时间分布的推论。

IF 2.2 3区医学

Clinical Trials Pub Date : 2024-10-01 Epub Date: 2024-08-08 DOI: 10.1177/17407745241264188

Ying Cui, Bo Huang, Lu Mao, Hajime Uno, Lee-Jen Wei, Lu Tian

{"title":"Inferences for the distribution of the duration of response in a comparative clinical study.","authors":"Ying Cui, Bo Huang, Lu Mao, Hajime Uno, Lee-Jen Wei, Lu Tian","doi":"10.1177/17407745241264188","DOIUrl":"10.1177/17407745241264188","url":null,"abstract":"Duration of response is an important endpoint used in drug development. Prolonged duration for response is often viewed as an early indication of treatment efficacy. However, there are numerous difficulties in studying the distribution of duration of response based on observed data subject to right censoring in practice. The most important obstacle is that the distribution of the duration of response is in general not identifiable in the presence of censoring due to the simple fact that there is no information on the joint distribution of time to response and time to progression beyond the largest follow-up time. In this article, we introduce the restricted duration of response as a replacement of the conventional duration of response. The distribution of restricted duration of response is estimable and we have proposed several nonparametric estimators in this article. The corresponding inference procedure and additional downstream analysis have been developed. Extensive numerical simulations have been conducted to examine the finite sample performance of the proposed estimators. It appears that a new regression-based two-step estimator for the survival function of the restricted duration of response tends to have a robust and superior performance, and we recommend its use in practice. A real data example from oncology has been used to illustrate the analysis for restricted duration of response.","PeriodicalId":10685,"journal":{"name":"Clinical Trials","volume":" ","pages":"541-552"},"PeriodicalIF":2.2,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12113349/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141901174","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}

引用次数: 0

Multiply robust estimation of principal causal effects with noncompliance and survival outcomes. 利用不合规和生存结果对主要因果效应进行稳健的多重估计。

IF 2.2 3区医学

Clinical Trials Pub Date : 2024-10-01 Epub Date: 2024-05-30 DOI: 10.1177/17407745241251773

Chao Cheng, Yueqi Guo, Bo Liu, Lisa Wruck, Fan Li, Fan Li

引用次数: 0

Defining estimand for the win ratio: Separate the true effect from censoring. 定义胜率估计值：将真实效应与普查区分开来。

IF 2.2 3区医学

Clinical Trials Pub Date : 2024-10-01 Epub Date: 2024-07-30 DOI: 10.1177/17407745241259356

Lu Mao

引用次数: 0

15th Annual University of Pennsylvania conference on statistical issues in clinical trial/advances in time to event analyses in clinical trials (morning panel discussion). 宾夕法尼亚大学第 15 届年会，主题为临床试验中的统计问题/临床试验中事件时间分析的进展（上午小组讨论）。