Estimand Framework In Aml Based On A Randomized, Placebo-Controlled, Phase 3 Study Investigating The Effect Of Adding Midostaurin To Standard Chemotherapy In Patients With Newly Diagnosed Aml Without A Flt3 Mutation

In the ongoing randomized, placebo-controlled, phase 3 study in patients with newly diagnosed FLT3-mutation-negative acute myeloid leukemia (AML; NCT03512197) investigating the effect of adding midostaurin to standard chemotherapy, event-free survival (EFS) is the primary endpoint. EFS is a standard endpoint in clinical studies in AML. In a recent FDA submission, EFS was confirmed by an advisory committee to be clinically meaningful in AML (https://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/OncologicDrugsAdvisoryCommittee/UCM570800.pdf. Accessed August 1, 2018). With the release of the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) E9 draft addendum, we describe EFS in the estimand framework to address the scientific question of interest and illustrate the power of this concept to transparently define the relevant population, the variable of interest, and the management of relevant incidents that can occur in a clinical trial (“intercurrent events”).