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终末事件存在时多结局总处理效应的非参数估计AI 解读

As standards of care advance, patients are living longer and once-fatal diseases are becoming manageable. Clinical trials increasingly focus on reducing disease burden, which can be quantified by the timing and occurrence of multiple non-fatal clinical events. Most existing methods for the analysis of multiple event-time data require stringent modeling assumptions that can be difficult to verify empirically, leading to treatment efficacy estimates that forego…

非比例风险下平均风险率的高效去偏学习AI 解读

The hazard ratio from the Cox proportional hazards model is a ubiquitous summary of treatment effect. However, when hazards are non-proportional, the hazard ratio can lose a stable causal interpretation and become study-dependent because it effectively averages time-varying effects with weights determined by follow-up and censoring. We consider the average hazard (AH) as an alternative causal estimand: a population-level person-time event rate that remains well-defined and…

基于临床试验主要结局检验结果的次要结局条件推断AI 解读

In clinical trials, inferences on clinical outcomes are often made conditional on specific selective processes. For instance, only when a treatment demonstrates a significant effect on the primary outcome, further analysis is conducted to investigate its efficacy on selected secondary outcomes. Similarly, inferences may also depend on whether a trial is terminated early at interim stage. While conventional approaches primarily aim to control the family-wise error rate…

以无模型方法评估删失中间结局对总生存期的替代作用AI 解读

Clinical trials or studies oftentimes require long-term and/or costly follow-up of participants to evaluate a novel treatment/drug/vaccine. There has been increasing interest in the past few decades in using short-term surrogate outcomes as a replacement of the primary outcome i.e., in using the surrogate outcome, which can potentially be observed sooner, to make inference about the treatment effect on the long-term primary outcome. Very few of the available statistical…

利用主要进展速率量化和比较研究中的疾病进展AI 解读

In comparative studies of progressive diseases, such as randomized controlled trials (RCTs), the mean Change From Baseline (CFB) of a continuous outcome at a pre-specified follow-up time across subjects in the target population is a standard estimand used to summarize the overall disease progression. Despite its simplicity in interpretation, the mean CFB may not efficiently capture important features of the trajectory of the mean outcome relevant to the evaluation of the…

基于生存加权平均风险率的总体治疗效应分层分析AI 解读

Given the limitations of using the Cox hazard ratio to summarize the magnitude of the treatment effect, alternative measures that do not have these limitations are gaining attention. One of the recently proposed alternative methods uses the average hazard with survival weight (AH). This population quantity can be interpreted as the average intensity of the event occurrence in a given time window that does not involve study-specific censoring. Inference procedures for the…

用长期平均风险评估免疫治疗的延迟获益AI 解读

Delayed treatment effects on time-to-event outcomes have often been observed in randomized controlled studies of cancer immunotherapies. In the case of delayed onset of treatment effect, the conventional test/estimation approach using the log-rank test for between-group comparison and Cox's hazard ratio to estimate the magnitude of treatment effect is not optimal, because the log-rank test is not the most powerful option, and the interpretation of the resulting hazard ratio…

优化替代标记的使用以提高检验功效AI 解读

Motivated by increasing pressure for decision makers to shorten the time required to evaluate the efficacy of a treatment such that treatments deemed safe and effective can be made publicly available, there has been substantial recent interest in using an earlier or easier to measure surrogate marker, $S$, in place of the primary outcome, $Y$. To validate the utility of a surrogate marker in these settings, a commonly advocated measure is the proportion of treatment effect…

利用效用异质的替代标记检验处理效应AI 解读

The primary benefit of identifying a valid surrogate marker is the ability to use it in a future trial to test for a treatment effect with shorter follow-up time or less cost. However, previous work has demonstrated potential heterogeneity in the utility of a surrogate marker. When such heterogeneity exists, existing methods that use the surrogate to test for a treatment effect while ignoring this heterogeneity may lead to inaccurate conclusions about the treatment effect,…