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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…

利用负对照结局事件时间提高传染病预防试验效率AI 解读

Baseline covariate adjustment can enhance the efficiency of randomized trials by improving precision of treatment effect estimates. However, the precision gain depends on how strongly the baseline covariates are prognostic for the primary outcome. In randomized trials of infectious disease prevention interventions (e.g., vaccines or passively administered antibodies), an individual's exposure to the pathogen is a leading prognostic factor but is rarely measurable at…

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…

利用外部对照开展试验近端学习：HIV 预防案例AI 解读

With the advent of effective pre-exposure prophylaxis agents, active-controlled HIV prevention trials have become a common study design. Nevertheless, estimating absolute efficacy relative to a placebo remains important. In this paper, we introduce a novel application of proximal causal inference methods to estimate the counterfactual cumulative HIV incidence under placebo for participants in an active-controlled trial of cabotegravir, using external control data from a…

用于自助法的生成式建模AI 解读

Generative modeling builds on and substantially advances the classical idea of simulating synthetic data from observed samples. This paper shows that this principle is not only natural but also theoretically well-founded for bootstrap inference: it yields statistically valid confidence intervals that apply simultaneously to both regular and irregular estimators, including settings in which Efron's bootstrap fails. In this sense, the generative modeling-based bootstrap can be…

利用疫苗无关感染去偏随时间变化的风险率型疫苗效应AI 解读

Understanding how vaccine effectiveness (VE) changes over time can provide evidence-based guidance for public health decision making. While commonly reported by practitioners, time-varying VE estimates obtained using Cox regression are vul- nerable to hidden biases. To address these limitations, we describe how to leverage vaccine-irrelevant infections to identify hazard-based, time-varying VE in the pres- ence of unmeasured confounding and selection bias. We articulate…

高度相关暴露下多变量孟德尔随机化的分组识别与变量选择AI 解读

Multivariable Mendelian Randomization (MVMR) estimates the direct causal effects of multiple risk factors on an outcome using genetic variants as instruments. The growing availability of summary-level genetic data has created opportunities to apply MVMR in high-dimensional settings with many strongly correlated candidate risk factors. However, existing methods face three major limitations: weak instrument bias, limited interpretability, and the absence of valid…

大量弱矩条件与干扰参数下的 GMM：一般理论及因果推断应用AI 解读

Weak identification arises in many statistical problems when key variables exhibit weak correlations-for example, when instrumental variables correlate weakly with treatment, or when proxy variables correlate weakly with unmeasured confounders. Under weak identification, standard estimation methods such as the generalized method of moments (GMM) can produce substantial bias, both in finite samples and asymptotically. This challenge is compounded in modern applications that…

稳定隐性混杂与二元结果的准工具变量方法AI 解读

Instrumental variable (IV) methods are central to causal inference from observational data, particularly when a randomized experiment is not feasible. However, of the three conventional core IV identification conditions, only one, IV relevance, is empirically verifiable; often one or both of the other conditions, exclusion restriction and IV independence from unmeasured confounders, are unmet in real-world applications. These challenges are compounded when the outcome is…

多变量孟德尔随机化的一种更稳健方法AI 解读

Multivariable Mendelian randomization (MVMR) uses genetic variants as instrumental variables to infer the direct effects of multiple exposures on an outcome. However, unlike univariable Mendelian randomization, MVMR often faces greater challenges with many weak instruments, which can lead to bias not necessarily toward zero and inflation of type I errors. In this work, we introduce a new asymptotic regime that allows exposures to have varying degrees of instrument strength,…

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…

随机系数模型的切片 Wasserstein 距离与扩散方法AI 解读

We propose a new minimum-distance estimator for linear random coefficient models. This estimator integrates the recently advanced sliced Wasserstein distance with the nearest neighbor methods, both of which enhance computational efficiency. We demonstrate that the proposed method is consistent in approximating the true distribution. Moreover, our formulation naturally leads to a diffusion process-based algorithm and is closely connected to treatment effect distribution…

病例—病例研究中可归因效应的敏感性分析AI 解读

The case$^2$ study, also referred to as the case-case study design, is a valuable approach for conducting inference for treatment effects. Unlike traditional case-control studies, the case$^2$ design compares treatment in two types of cases with the same disease. A key quantity of interest is the attributable effect, which is the number of cases of disease among treated units which are caused by the treatment. Two key assumptions that are usually made for making inferences…

随机试验中不完整基线协变量的调整：跨世界插补框架AI 解读

In randomized controlled trials, adjusting for baseline covariates is often applied to improve the precision of treatment effect estimation. However, missingness in covariates is common. Recently, Zhao & Ding (2022) studied two simple strategies, the single imputation method and missingness indicator method (MIM), to deal with missing covariates, and showed that both methods can provide efficiency gain. To better understand and compare these two strategies, we propose and…

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…

交叉试验中的行为延续效应与功效权衡AI 解读

A crossover trial is an efficient trial design when there is no carry-over effect. To reduce the impact of the biological carry-over effect, a washout period is often designed. However, the carry-over effect remains an outstanding concern when a washout period is unethical or cannot sufficiently diminish the impact of the carry-over effect. The latter can occur in comparative effectiveness research where the carry-over effect is often non-biological but behavioral. In this…

GENIUS-MAWII：应对大量弱且无效工具变量的稳健孟德尔随机化AI 解读

Mendelian randomization (MR) has become a popular approach to study causal effects by using genetic variants as instrumental variables. We propose a new MR method, GENIUS-MAWII, which simultaneously addresses the two salient phenomena that adversely affect MR analyses: many weak instruments and widespread horizontal pleiotropy. Similar to MR GENIUS (Tchetgen Tchetgen et al., 2021), we achieve identification of the treatment effect by leveraging heteroscedasticity of the…

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…

随机实验中回归调整的统一分析AI 解读

Regression adjustment is broadly applied in randomized trials under the premise that it usually improves the precision of a treatment effect estimator. However, previous work has shown that this is not always true. To further understand this phenomenon, we develop a unified comparison of the asymptotic variance of a class of linear regression-adjusted estimators. Our analysis is based on the classical theory for linear regression with heteroscedastic errors and thus does not…

工具变量双重差分的结构均值模型AI 解读

In the standard difference-in-differences research design, the parallel trends assumption may be violated when the relationship between the exposure trend and the outcome trend is confounded by unmeasured confounders. Progress can be made if there is an exogenous variable that (i) does not directly influence the change in outcome means (i.e. the outcome trend) except through influencing the change in exposure means (i.e. the exposure trend), and (ii) is not related to the…