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主方案试验：从目标量定义到治疗效应的稳健推断AI 解读

Master protocol trials use a single overarching protocol to evaluate multiple interventions, diseases, or disease subtypes, where individuals are often randomized to different subsets of intervention arms based on individual characteristics, enrollment timing, and intervention availability. While offering increased flexibility, this constrained and non-uniform intervention assignment poses two fundamental inferential challenges: the precise definition of treatment effects…

通过高斯过程稳健、自适应地整合平台试验非同期数据AI 解读

A platform trial is an innovative clinical trial design that enables simultaneous and continuous evaluation of multiple treatments within a single master protocol. Existing robust methods restrict analyses to concurrently randomized participants due to concerns that including nonconcurrent data may introduce bias from temporal trends. However, this exclusion represents a missed opportunity to improve efficiency. We propose a Gaussian process framework for incorporating…

主方案试验中的纵向患者历史与重复入组AI 解读

A master protocol trial uses a single overarching protocol to test multiple therapies, often across several diseases or subtypes. Although such trials offer considerable flexibility and efficiency, their constrained and non-uniform treatment assignment raises two core challenges: precisely defining treatment effects and conducting robust, efficient inference. These challenges intensify when participants can re-enroll to receive additional eligible therapies over time. To…

随机对照试验中存在竞争性伴发事件的处理效应估计AI 解读

The analysis of randomized controlled trials is often complicated by intercurrent events (IEs) -- events that occur after treatment initiation and affect either the interpretation or existence of outcome measurements. Examples include treatment discontinuation or the use of additional medications. In two recent clinical trials for systemic lupus erythematosus with complications of IEs, we classify the IEs into two broad categories: effect-informative (e.g., treatment…

通过协变量调整提高复发事件曲线下面积估计精度AI 解读

The area under the curve (AUC) of the mean cumulative function (MCF) has recently been introduced as a novel estimand for evaluating treatment effects in recurrent event settings, offering an alternative to the commonly used Lin-Wei-Yang-Ying (LWYY) model. The AUC of the MCF provides a clinically interpretable summary measure that captures the overall burden of disease progression, regardless of whether the proportionality assumption holds. To improve the precision of the…

厘清随机临床试验中 Mantel–Haenszel 风险差估计量的作用AI 解读

The Mantel-Haenszel (MH) risk difference estimator, commonly used in randomized clinical trials for binary outcomes, calculates a weighted average of stratum-specific risk difference estimators. Traditionally, this method requires the stringent assumption that risk differences are homogeneous across strata, also known as the common (constant) risk difference assumption. In our article, we relax this assumption and adopt a modern perspective, viewing the MH risk difference…

随机临床试验中协变量调整的一般形式AI 解读

In randomized clinical trials, adjusting for baseline covariates can improve credibility and efficiency for demonstrating and quantifying treatment effects. This article studies the augmented inverse propensity weighted (AIPW) estimator, which is a general form of covariate adjustment that uses linear, generalized linear, and non-parametric or machine learning models for the conditional mean of the response given covariates. Under covariate-adaptive randomization, we…

二元结局随机试验中协变量调整无条件处理效应的稳健方差估计AI 解读

To improve precision of estimation and power of testing hypothesis for an unconditional treatment effect in randomized clinical trials with binary outcomes, researchers and regulatory agencies recommend using g-computation as a reliable method of covariate adjustment. However, the practical application of g-computation is hindered by the lack of an explicit robust variance formula that can be used for different unconditional treatment effects of interest. To fill this gap,…

协变量调整的对数秩检验：效率增益与广泛适用性AI 解读

Nonparametric covariate adjustment is considered for log-rank type tests of treatment effect with right-censored time-to-event data from clinical trials applying covariate-adaptive randomization. Our proposed covariate-adjusted log-rank test has a simple explicit formula and a guaranteed efficiency gain over the unadjusted test. We also show that our proposed test achieves universal applicability in the sense that the same formula of test can be universally applied to simple…

结合内部与外部对照对临床试验处理效应进行双重检验AI 解读

Leveraging external controls -- relevant individual patient data under control from external trials or real-world data -- has the potential to reduce the cost of randomized controlled trials (RCTs) while increasing the proportion of trial patients given access to novel treatments. However, due to lack of randomization, RCT patients and external controls may differ with respect to covariates that may or may not have been measured. Hence, after controlling for measured…