PRO‑CTCAE in Oncology Drug Evaluation: Cross-Agency Review of Regulatory and Health Technology Assessment Decision-Making in the United States and Europe.

Abstract

Drug toxicity and tolerability are important considerations of benefit-risk assessment in oncology regulatory and health technology assessment (HTA) decision-making. The Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) was developed to systematically capture patients' experiences of treatment-related symptomatic toxicities. Despite increasing use of PRO-CTCAE in oncology trials, its role in regulatory and HTA decisions has been limited, as has specific guidance or standards about how these data should be collected and used. We conducted a targeted review of oncology drug submissions and assessment reports from the US Food and Drug Administration (FDA), European Medicines Agency (EMA), and HTA bodies to evaluate how PRO-CTCAE data were used in regulatory and HTA decision-making. PRO-CTCAE data were included in 2 FDA oncology drug labels. Across agencies, we found infrequent incorporation of PRO-CTCAE data into regulatory or HTA decisions, despite agencies acknowledging its potential value for supplementing safety data from patients' perspectives. We also identified recurring sponsor limitations (non‑transparent item selection, inadequate endpoint positioning, single‑arm/open‑label trial designs, and missing or inconsistently reported data) that restricted PRO‑CTCAE's use by regulators and HTA bodies. While regulators and HTA bodies recognize the value of PRO-CTCAE and have considered such data in submissions, there remains a limited role for PRO-CTCAE in such decisions resulting from methodological and implementation challenges. Harmonized, cross-agency guidance on PRO-CTCAE item selection, endpoint definition, analysis, and presentation may help support its consistent and meaningful use in future oncology submissions and regulatory and HTA decision-making.