Related papers: Treatment Effect Quantification for Time-to-event …
Time-to-event estimands are central to many oncology clinical trials. The estimand framework (addendum to the ICH E9 guideline) calls for precisely defining the treatment effect of interest to align with the clinical question of interest…
The estimand framework included in the addendum to the ICH E9 guideline facilitates discussions to ensure alignment between the key question of interest, the analysis, and interpretation. Therapeutic knowledge and drug mechanism play a…
The estimand framework provides guidance on handling intercurrent events, such as treatment discontinuation, in the analysis of clinical trial responses. Under ICH E9(R1), the treatment policy (TP) strategy incorporates post-discontinuation…
The ICH E9(R1) guideline presents a framework of estimand for clinical trials, proposes five strategies for handling intercurrent events (ICEs), and provides a comprehensive discussion and many real-life clinical examples for quantitative…
The COVID-19 pandemic continues to affect the conduct of clinical trials globally. Complications may arise from pandemic-related operational challenges such as site closures, travel limitations and interruptions to the supply chain for the…
The ICH E9 (R1) Estimands Guidance1 terminology does not completely address the conceptual needs of time-to-event estimands in the complex oncology context. We previously described how censoring and censoring mechanisms for time-to-event…
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…
Randomized controlled trials (RCT) are the gold standard for evaluation of the efficacy and safety of investigational interventions. If every patient in an RCT were to adhere to the randomized treatment, one could simply analyze the…
To precisely define the treatment effect of interest in a clinical trial, the ICH E9 estimand addendum describes that relevant so-called intercurrent events should be identified and strategies specified to deal with them. Handling…
In randomized controlled trials (RCTs) that focus on time-to-event outcomes, intercurrent events can arise in two ways: as semi-competing events, which modify the hazard of the primary outcome events, or as competing events, which make the…
The recently published ICH E9 addendum on estimands in clinical trials provides a framework for precisely defining the treatment effect that is to be estimated, but says little about estimation methods. Here we report analyses of a clinical…
The current COVID-19 pandemic poses numerous challenges for ongoing clinical trials and provides a stress-testing environment for the existing principles and practice of estimands in clinical trials. The pandemic may increase the rate of…
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…
The International Council for Harmonization (ICH) E9 (R1) addendum provides the estimand framework to formulate treatment effects in a clinical trial. One of the attributes of an estimand the framework describes is intercurrent events.…
Treatment policy estimands are frequently favored by regulators, as they assess the effect of treatment assignment regardless of post-randomization events. Despite best efforts, missing data due to study discontinuation cannot be fully…
Time-to-event endpoints are central to evaluate treatment efficacy across many disease areas. Many trial protocols include interim analyses within group-sequential designs that control type I error via spending functions or boundary…
The creation of the ICH E9 (R1) estimands framework has led to more precise specification of the treatment effects of interest in the design and statistical analysis of clinical trials. However, it is unclear how the new framework relates…
The analysis of adverse events (AEs) is a key component in the assessment of a drug's safety profile. Inappropriate analysis methods may result in misleading conclusions about a therapy's safety and consequently its benefit-risk ratio. The…
Causal inference methods are gaining increasing prominence in pharmaceutical drug development in light of the recently published addendum on estimands and sensitivity analysis in clinical trials to the E9 guideline of the International…
Since the release of the ICH E9(R1) addendum on estimands, its application in non-inferiority trials has received far less attention than in superiority settings. A key conclusion from Lynggaard et al. was that the "choice of…