WORKSHOP by Luc Boone (EORTC)

WORKSHOP by Luc Boone (EORTC) on "Estimands, Intercurrent Events and Strategies to Handle Intercurrent Events"

Abstract :

The Guidance on Estimands and Sensitivity analyses (ICH E9(R1)) in clinical trials was released in 2019. The need for the estimands framework arose out of the realization that there was a lack of transparency regarding the alignment between clinical trial objectives and study design, data collection and statistical analysis (Mallinckrodt, 2019,2021). The central aim of the estimand is exactly that, to bridge this gap by choosing and specifying beforehand 'what is to be estimated' and ‘how’ to properly evaluate and estimate it. By understanding 'what' is to be estimated, and deciding on 'how' to estimate it, it is easier to foresee and understand events which could hamper that process. More formally, the Guidance denotes these events as "intercurrent events" and defines them as "events occurring after treatment initiation that affect either the interpretation or the existence of measurements associated with the clinical questions of interest (ICH, p.17)". Intercurrent events must be identified upfront, and in conjunction with the population of interest, the treatment (regimen), the endpoint (response/outcome variable) and the population-level summary statistic. These five ingredients are the building blocks required to define an estimand. By making well-informed choices and specifying the five attributes, the trial study team offers a transparent summary regarding 'what' they are estimating, i.e. the estimand. Only once it becomes clear which estimand is of interest can the type of study design, the required data and the statistical analysis methods be specified. In other words, the primary objective drives the estimand choices which in turn inform the decisions regarding the study design, data collection and analysis choices.

This presentation will introduce the different steps on how to define estimands and what the role of the statistician is within the estimands framework. We will cover in depth the notion of intercurrent events and how these can introduce bias into the study. In addition, the different strategies proposed by the Guidance on handling intercurrent events will be introduced and illustrated through examples.

Workshop by TEAMS here : TEAMS