Quality and Interpretability of PFS and OS in Oncology Clinical - ICH E9(R1) Perspective

Music City Center 

In oncology drug development, the quality and interpretability of time-to-event endpoints, progression-free survival (PFS) and overall survival (OS), have long been recognized as significant challenges. These challenges arise from multiple factors, including issues related to data collection, analysis methodology for handling intercurrent events (ICEs) and missing data, trial integrity concerns related to study conduct, and complexities in interpreting multiple endpoints. For example, data challenges include imbalanced schedules of radiographic assessments, informative censoring due to Blinded Independent Central Review (BICR), incomplete or absent survival sweeps, a lack of clarity in defining lost-to-follow-up and withdrawal of consent, and inadequate collection of intercurrent event data. Adopting a prospective estimand framework helps mitigating risks associated with data collection, analysis methodology and interpretability. In this work, the DahShu Innovative Design Scientific Working Group (IDSWG) Oncology team systematically investigates the complexities of PFS and OS and presents practical recommendations according to E9(R1).

Progression Free Survival

Overall Survival

Estimand

Oncology clinical trials

E9(R1) 

Biopharmaceutical Section