ICH E9(R1) - Estimands and Sensitivity Analysis in Clinical Trials

What it says

This addendum to ICH E9 introduces the estimand framework to align the clinical question of a trial with its design, conduct, analysis and interpretation. An estimand defines the treatment effect to be estimated, including the population, the variable, how events after treatment starts (intercurrent events, such as stopping treatment or taking rescue medication) are handled, and the summary measure. It also stresses sensitivity analysis.

Paraphrased for plain-language clarity. Always verify against the current published regulation text.

What it means in practice

• The question a trial asks should be stated precisely before the analysis methods are chosen.
• Intercurrent events must be anticipated and a strategy chosen for each, instead of being handled ad hoc.
• Sensitivity analyses show whether conclusions hold under different assumptions.

What inspectors look for

• Whether the protocol and statistical plan define the estimand clearly.
• Whether handling of intercurrent events was planned and applied as written.
• Whether sensitivity analyses were pre-specified.

Related regulations