Estimands in Hematologic Oncology Trials

TL;DR

This paper discusses how the estimand framework can be applied to hematologic oncology trials to improve trial design, analysis, and interpretation amidst complex treatment scenarios and intercurrent events.

Contribution

It provides practical guidance and a template for applying the estimand framework in hematologic cancer trials, linking ICH E9 addendum concepts to real-world applications.

Findings

Application of estimand framework clarifies trial objectives.

Addresses challenges of intercurrent events in hematology trials.

Provides standardized language for estimand description.

Abstract

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.