ROLE OF REAL-WORLD EVIDENCE IN SUPPORTING AND VALIDATING CROSSOVER ADJUSTMENTS OF OVERALL SURVIVAL IN ONCOLOGY TRIALS: A SYSTEMATIC LITERATURE REVIEW OF HEALTH TECHNOLOGY ASSESSMENTS OF TREATMENTS FOR SELECTED TUMORS
Author(s)
Anandaroop Dasgupta, PhD1, Ankita Kaushik, PhD1, Jens Grueger, PhD2, Sumeet Attri, MPharm3, Sukriti Sharma, MSc3, Barinder Singh, RPh4, Billy Amzal, MBA, MPH, MSc, PhD5;
1Gilead Sciences Inc., Foster city, CA, USA, 2The CHOICE Institute, School of Pharmacy, University of Washington, Seattle, WA, USA, 3Pharmacoevidence, Mohali, India, 4Pharmacoevidence, London, United Kingdom, 5Phastar, Paris, France
1Gilead Sciences Inc., Foster city, CA, USA, 2The CHOICE Institute, School of Pharmacy, University of Washington, Seattle, WA, USA, 3Pharmacoevidence, Mohali, India, 4Pharmacoevidence, London, United Kingdom, 5Phastar, Paris, France
OBJECTIVES: Validation of the crossover-adjusted treatment effect of overall survival (OS) is required to ensure the mix of post progression treatments and survival benefits attributed to it is reflective of the real-world (RW) clinical practice. This systematic literature review assessed how real-world evidence (RWE) supports validation of crossover-adjusted OS in health technology assessment (HTA) of clinical trials studying advanced/metastatic cancer of the lung (non-small cell, NSCLC), breast (BC), prostate, renal, colorectal (CRC), and gastrointestinal stromal tumors.
METHODS: Published reports (2013-2024) of Institute for Clinical and Economic Review, and HTA bodies of the UK (NICE), France (HAS), Germany (IQWiG), Australia (PBAC) and Canada (CDA) were systematically reviewed and assessed.
RESULTS: Of 1,653 records screened, 162 product submissions permitting treatment switches were included. Thirteen submissions reported counterfactual validation of the OS treatment effect associated with the comparator arm using RWE to support decision-making for payer archetypes relying on cost effectiveness evaluation. RWE-based OS validation of the suitability of the comparator arm was most reported in HAS (n=7), followed by NICE (n=5) and CDA/CADTH (n=1) submissions. The target indication in most submissions was NSCLC (n=7), followed by CRC (n=4), and BC (n=2). Validation of OS was accomplished through RW sources (e.g., FLATIRON, ESME, INCA, SEER) or secondary research based on RW population (Tougeron et al.). Study design of these RWE studies was developed by operationalization of a comparator arm treated with standard chemotherapy. In addition to treatment effect, RWE was also used for extrapolation of OS benefits using different parametric survival models and to determine generalizability for a longer time horizon.
CONCLUSIONS: This study highlights the growing importance of RWE in validating the OS estimates in crossover trials of oncology treatments. RWE plays a crucial role in shaping more robust health policies through demonstrated use cases while improving generalizability and external validity of cost effectiveness assessments.
METHODS: Published reports (2013-2024) of Institute for Clinical and Economic Review, and HTA bodies of the UK (NICE), France (HAS), Germany (IQWiG), Australia (PBAC) and Canada (CDA) were systematically reviewed and assessed.
RESULTS: Of 1,653 records screened, 162 product submissions permitting treatment switches were included. Thirteen submissions reported counterfactual validation of the OS treatment effect associated with the comparator arm using RWE to support decision-making for payer archetypes relying on cost effectiveness evaluation. RWE-based OS validation of the suitability of the comparator arm was most reported in HAS (n=7), followed by NICE (n=5) and CDA/CADTH (n=1) submissions. The target indication in most submissions was NSCLC (n=7), followed by CRC (n=4), and BC (n=2). Validation of OS was accomplished through RW sources (e.g., FLATIRON, ESME, INCA, SEER) or secondary research based on RW population (Tougeron et al.). Study design of these RWE studies was developed by operationalization of a comparator arm treated with standard chemotherapy. In addition to treatment effect, RWE was also used for extrapolation of OS benefits using different parametric survival models and to determine generalizability for a longer time horizon.
CONCLUSIONS: This study highlights the growing importance of RWE in validating the OS estimates in crossover trials of oncology treatments. RWE plays a crucial role in shaping more robust health policies through demonstrated use cases while improving generalizability and external validity of cost effectiveness assessments.
Conference/Value in Health Info
2026-05, ISPOR 2026, Philadelphia, PA, USA
Value in Health, Volume 29, Issue S6
Code
HTA77
Topic
Health Technology Assessment
Disease
No Additional Disease & Conditions/Specialized Treatment Areas, SDC: Oncology