  The estimand framework included in the addendum to the ICH E9 guideline
facilitates discussions to ensure alignment between the key question of
interest, the analysis, and interpretation. Therapeutic knowledge and drug
mechanism play a crucial role in determining the strategy and defining the
estimand for clinical trial designs. Clinical trials in patients with
hematological malignancies often present unique challenges for trial design due
to complexity of treatment options and existence of potential curative but
highly risky procedures, e.g. stem cell transplant or treatment sequence across
different phases (induction, consolidation, maintenance). Here, we illustrate
how to apply the estimand framework in hematological clinical trials and how
the estimand framework can address potential difficulties in trial result
interpretation.
  This paper is a result of a cross-industry collaboration to connect the
International Conference on Harmonisation (ICH) E9 addendum concepts to
applications. Three randomized phase 3 trials will be used to consider common
challenges including intercurrent events in hematologic oncology trials to
illustrate different scientific questions and the consequences of the estimand
choice for trial design, data collection, analysis, and interpretation.
Template language for describing estimand in both study protocols and
statistical analysis plans is suggested for statisticians' reference.
