Chapter 9 Estimands
The importance of Estimands is introduced in the ICH E9 addendum.
9.1 Estimands, estimator and estimates
Estimands: the clearly stated, non-ambiguous variable to be estimated
Estimator: the statistics tool used to arrive at the estimands
Estimates: the statistics results for the estimation of the intended estimand
9.2 Strategies for Estimands
Treatment policy strategy
Composite strategy
Principal stratum strategy
Hypothetical strategy
9.3 Estimand thinking for biomarkers
Causal thinking is key in coming up the right strategies for the estimands. It is relatively simple in terms of computational/statistics methods involved for treatment policy and composite strategies. A few examples:
Treatment discontinuation due to biomarker monitoring
Composite endpoints involving biomarkers surrogates
For principal stratum and hypothetical strategies, relatively complicated causal inference methods need to be applied. We will go into details and give some application examples in biomarkers:
anti-drug antibody appearance in the treatment arm
Use of rescue medication in the trial