The estimands framework: a primer on the ICH E9(R1) addendum

Abstract

Estimands can be used in studies of healthcare interventions to clarify the interpretation of treatment effects. The addendum to the ICH E9 harmonised guideline on statistical principles for clinical trials (ICH E9(R1)) describes a framework for using estimands as part of a study. This paper provides an overview of the estimands framework, as outlined in the addendum, with the aim of explaining why estimands are beneficial; clarifying the terminology being used; and providing practical guidance on using estimands to decide the appropriate study design, data collection, and estimation methods. This article illustrates how to use the estimands framework by applying it to an ongoing trial in emergency bowel surgery. Estimands can be a useful way of clarifying the exact research question being evaluated in a study, both to avoid misinterpretation and to ensure that study methods are aligned to the overall study objectives.

Why is target trial emulation not being used in health technology assessment real-world data submissions?

“…R Reynolds also highlighted the fact that TTE is not the only framework to provide best practice around RWD study design and execution. Notably, the estimand [ 9 ] and the SPIFD2 frameworks [ 10 ] could also be used to minimize bias. SPIFD2 calls for the selection of fit for purpose RWD, articulation of the hypothetical target trial and transparent documentation of the rationale for decisions made which can then be used to populate the STaRT-RWE or HARPER templates [ 11 , 12 ].…”