Related papers: A New Causal Approach to Account for Treatment Swi…
In a randomized controlled trial, treatment switching (also called contamination or crossover) occurs when a patient initially assigned to one treatment arm changes to another arm during the course of follow-up. Overlooking treatment…
The interpretation of randomised clinical trial results is often complicated by intercurrent events. For instance, rescue medication is sometimes given to patients in response to worsening of their disease, either in addition to the…
In oncology clinical trials, characterizing the long-term overall survival (OS) benefit for an experimental drug or treatment regimen (experimental group) is often unobservable if some patients in the control group switch to drugs in the…
Randomized Controlled Trials (RCT) are the current gold standards to empirically measure the effect of a new drug. However, they may be of limited size and resorting to complementary non-randomized data, referred to as observational, is…
In the absence of data from a randomized trial, researchers often aim to use observational data to draw causal inference about the effect of a treatment on a time-to-event outcome. In this context, interest often focuses on the…
In clinical trials, an experimental treatment is sometimes added on to a standard of care or control therapy in multiple treatment phases (e.g., concomitant and maintenance phases) to improve patient outcomes. When the new regimen provides…
In the presence of heterogeneity between the randomized controlled trial (RCT) participants and the target population, evaluating the treatment effect solely based on the RCT often leads to biased quantification of the real-world treatment…
The ICH E9(R1) addendum provides guidelines on accounting for intercurrent events in clinical trials using the estimands framework. However, there has been limited attention to the estimands framework for meta-analysis. Using treatment…
When choosing estimands and estimators in randomized clinical trials, caution is warranted as intercurrent events, such as - due to patients who switch treatment after disease progression, are often extreme. Statistical analyses may then…
The restricted mean survival time (RMST) difference offers an interpretable causal contrast to estimate the treatment effect for time-to-event outcomes, yet a wide range of available estimators leaves limited guidance for practice. We…
This article studies the estimation of the causal effect of a time-varying treatment on time-to-an-event or on some other continuously distributed outcome. The paper applies to the situation where treatment is repeatedly adapted to…
Instrumental variables (IVs) are widely used to estimate causal effects from non-randomized data. A canonical example is a randomized trial with noncompliance, in which the randomized treatment assignment serves as an IV for the…
Clinical trials often allow patients in the control arm to switch to the treatment arm if their physical conditions are worse than certain tolerance levels. For instance, treatment switching arises in the Concorde clinical trial, which aims…
To draw real-world evidence about the comparative effectiveness of multiple time-varying treatments on patient survival, we develop a joint marginal structural survival model and a novel weighting strategy to account for time-varying…
Sequential multiple assignment randomized trials mimic the actual treatment processes experienced by physicians and patients in clinical settings and inform the comparative effectiveness of dynamic treatment regimes. In such trials,…
When a clinical trial is subject to a series of interim analyses as a result of which the study may be terminated or modified, final frequentist analyses need to take account of the design used. Failure to do so may result in overstated…
Platform trials allow treatment arms to enter and exit over time while maintaining a shared control arm, yielding concurrent and non-concurrent controls (NCC). Pooling NCC is often motivated as a strategy to improve statistical efficiency,…
Objective: Randomised controlled trials (RCTs) are widely considered as gold standard for assessing the effectiveness of new health interventions. When treatment non-compliance is present in RCTs, the treatment effect in the subgroup of…
Randomized trials typically estimate average relative treatment effects, but decisions on the benefit of a treatment are possibly better informed by more individualized predictions of the absolute treatment effect. In case of a binary…
Longitudinal observational patient data can be used to investigate the causal effects of time-varying treatments on time-to-event outcomes. Several methods have been developed for controlling for the time-dependent confounding that…