Duration of and time to response in oncology clinical trials from the perspective of the estimand framework

TL;DR

This paper clarifies the definitions and implementation of duration of response and time to response in oncology trials using the estimand framework, addressing current ambiguities and providing practical guidance.

Contribution

It introduces estimand-based definitions for DOR and TTR, addressing intercurrent events, and offers practical recommendations for their implementation in clinical protocols.

Findings

Case study in mantle cell lymphoma demonstrates estimand application

Provides clear definitions aligned with the estimand framework

Offers practical guidance for clinical trial protocol design

Abstract

Duration of response (DOR) and time to response (TTR) are typically evaluated as secondary endpoints in early-stage clinical studies in oncology when efficacy is assessed by the best overall response (BOR) and presented as the overall response rate (ORR). Despite common use of DOR and TTR in particular in single-arm studies, the definition of these endpoints and the questions they are intended to answer remain unclear. Motivated by the estimand framework, we present relevant scientific questions of interest for DOR and TTR and propose corresponding estimand definitions. We elaborate on how to deal with relevant intercurrent events which should follow the same considerations as implemented for the primary response estimand. A case study in mantle cell lymphoma illustrates the implementation of relevant estimands of DOR and TTR. We close the paper with practical recommendations to implement DOR and TTR in clinical study protocols.