Related papers: Dealing with multiple intercurrent events using hy…
The ICH E9 addendum introduces the term intercurrent event to refer to events that happen after randomisation and that can either preclude observation of the outcome of interest or affect its interpretation. It proposes five strategies for…
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…
Intercurrent (post-treatment) events occur frequently in randomized trials, and investigators often express interest in treatment effects that suitably take account of these events. A naive conditioning on intercurrent events does not have…
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 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.…
Estimands can help to clarify the research questions being addressed in randomised trials. Because the choice of estimand can affect how relevant trial results are to patients and other stakeholders, such as clinicians or policymakers, it…
The estimand framework proposes different strategies to address intercurrent events. The treatment policy strategy seems to be the most favoured as it is closely aligned with the pre-addendum intention-to-treat principle. All data for all…
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…
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 estimand framework proposed by ICH in 2017 has brought fundamental changes in the pharmaceutical industry. It clearly describes how a treatment effect in a clinical question should be precisely defined and estimated, through attributes…
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…
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…
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…
For handling intercurrent events in clinical trials, one of the strategies outlined in the ICH E9(R1) addendum targets the hypothetical scenario of non-occurrence of the intercurrent event. While this strategy is often implemented by…
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…
Many research questions concern treatment effects on outcomes that can recur several times in the same individual. For example, medical researchers are interested in treatment effects on hospitalizations in heart failure patients and sports…
Under a composite estimand strategy, the occurrence of the intercurrent event is incorporated into the endpoint definition, for instance by assigning a poor outcome value to patients who experience the event. Composite strategies are…
The estimand framework is increasingly established to pose research questions in confirmatory clinical trials. In evidence synthesis, the uptake of estimands has been modest, and the PICO (Population, Intervention, Comparator, Outcome)…
The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) E9 (R1) Addendum provides a framework for defining estimands in clinical trials. Treatment policy strategy is the mostly used…
A randomized trial allows estimation of the causal effect of an intervention compared to a control in the overall population and in subpopulations defined by baseline characteristics. Often, however, clinical questions also arise regarding…