A scoping review identified additional considerations for defining estimands in cluster randomised trials
Listed in
This article is not in any list yet, why not save it to one of your lists.Abstract
Background and objective
An estimand is a clear description of the treatment effect a study aims to quantify. The ICH E9(R1) addendum lists five attributes that should be described when defining an estimand. However, the addendum was primarily developed for individually randomised trials. Cluster randomised trials (CRTs), in which groups of individuals are randomised, have additional considerations for defining estimands, such as how individuals and clusters are weighted. We aimed to identify a list of additional items that may need to be considered when defining estimands in CRTs.
Study design
We conducted a systematic search of multiple databases as well as the authors’ personal libraries to identify articles that described an aspect of an estimand definition for CRTs which was not explicitly covered by one of the five attributes listed in the ICH E9 (R1) addendum. From this, we generated a list of items that may require consideration when defining estimands for CRTs beyond the five attributes listed in the ICH E9(R1) addendum.
Results
From 46 eligible articles, we identified 8 items that may need to be considered when defining estimands in CRTs: (i) population of clusters; (ii) population of individuals under selection bias; (iii) exposure time of individuals/clusters on treatment; (iv) how individuals and clusters are weighted (e.g. individual-average vs. cluster-average); (v) whether summary measures are marginal or cluster-specific; (vi) strategies used to handle cluster-level intercurrent events; (vii) how interference/spillover is handled; and (viii) how individuals who leave or change clusters are handled.
Conclusion
This review has identified additional items that may need to be considered when defining estimands for CRTs. Study investigators undertaking CRTs should consider these items when defining estimands for their trials, to ensure estimands are unambiguous and relevant for end-users such as clinicians, patients, and policy makers.
What is new?
Key findings
-
The review identified eight additional items that are not explicitly described by the existing attributes listed in the ICH E9(R1) addendum, but that may need to be considered when defining estimands for cluster randomised trials
What this adds to what is known
-
Defining estimands using the attributes set out in the ICH E9(R1) addendum can promote clarity, however these attributes alone are not sufficient to describe a clearly defined research question in cluster randomised trials
-
In addition to the five attributes set out in ICH E9(R1), investigators conducting cluster randomised trials need to consider which additional items are relevant to describe when defining their estimand
What is the implication and what should we change now
-
Items identified in this review can be used by investigators conducting cluster randomised trials to help define their estimand to ensure it is clear
-
Specific guidance on defining estimands for cluster randomised trials is required to ensure that research questions are fully described in these trials
