The evolution of the role of real-world evidence in health technology assessment (HTA) decision-making in oncology: Opportunities and challenges

The Evolving Role of Real-WorldEvidence in Oncology HTA Table of contents Introduction1Guidelines for the use of RWE in regulatory decisions1RWE in HTA decision-making3RWE and joint clinicalassessment6RWE and international collaborations6Current challenges around the use of RWE in HTA7Application of RWE inOncology7RWE contribution to HTA outcomes9Receptiveness to RWE across HTA bodies11Case studies: Use of RWE as an External Control Arm — Libtayo and Ayvakit12Case study: Use of RWE in Carvykti, Tecvayli and Talvey HTAsubmissions15Discussion18Conclusion20About the authors21References22 Introduction The use of Real-World Evidence (RWE) as a component of Health TechnologyAssessment (HTA) submissions has seen a marked increase in the last 5years, reflecting the growing recognition of RWE’s potential to enhance the Guidelines for the use of RWEin regulatory decisions While Randomised Controlled Trials (RCTs) remain thegold standard for evidence generation, they can bechallenging to conduct in niche oncology populationsor in rare tumours and hampered by long timelines Although the potential of RWE has long beenacknowledged, recent years have marked a transitiontoward its practical application, with increasingemphasis on more formalised guidance for Real- This report builds on IQVIA’s Institute for Data Science2022 report on Impact of RWE on HTA decision-making.2It examines the practical application of RWEin oncology, a therapy area characterized by high levelsof innovation on the one hand and frequent challengesaround evidence uncertainty and data gaps on the Another emerging trend is the use of RWE collectedunder a regulatory mandate for HTA purposes. Forexample, DARWIN EU (Table 1) is also accessible to HTAbodies to generate RWE to inform decisions on the use, •NordicRWE10: The Nordic countries offer a rich source of health data through national registries, cohort studies, andElectronic Medical Records (EMR) systems. NordicRWE, a dedicated real-world evidence company, harnesses this uniquedata infrastructure to provide valuable insights and analyses that support drug development, regulatory requirements,and post-launch surveillance non-RCT data, including SATs with ECA or other formsof indirect comparison, as well as RWE, provided thatit allows for comparison with available treatments,with the objective of facilitating reimbursement for RWE in HTA decision-making With the increasing utilization of RWE, HTA bodiesare recognizing its importance in the evaluation ofnewtechnologies. RWE is increasingly accepted byHTA bodies to complement or supplement RCT data, RWE is increasingly accepted byHTA bodies to complement orsupplement RCT data, especially TheInstitute for Quality and Efficiency inHealthcare (IQWiG) General Methods 7.0 (2023)23established a cautious foundation for the use of RWEin HTAs, but limited to specific contexts, such as whenRCTs are unfeasible or unethical. Emphasis is placed on TheNational Institute for Health and CareExcellence (NICE) Real-World Evidence Framework(2022)20emphasises three core principles: ensuring The2025 IQWiG General Methods 8.024marked ashift toward greater formalization and clarity for theuse of RWE in HTA. It highlighted a methodologicalemphasis on clarity, transparency and scientificrigour. IQWiG acknowledges the value of routinepractice data collection, i.e. ‘AnwendungsbegleitendeDatenerhebungen (AbD)’, which is the formal post- high-quality and relevant data, maintainingtransparency and integrity throughout the studyprocess, and using robust analytical methods tominimise bias and characterise uncertainty. The NICEframework is a ‘living’ document, which aims to adapt TheFrench National Authority for Health (HAS)Methodological Guide on Real-World Studies(2021)21provides practical guidance to improvequality, transparency, and reliability of RWE studiesby offering benchmarks on study design, datasources, and analytical methods. The guide focuses on TheIQWiG preliminary report outlines a scientificframework for the collection and analysis ofroutine practice data where there is limited clinical evidence available at market entry25and emphasisesthe target trial emulation as the preferred designto minimise bias for studies using non-randomisedevidence for causal inference purposes. It further identification, drawing on literature reviews, clinicianinput, and expert validation, as detailed in the 2023 Guidance for Reporting Real-World Evidence, published by Canada’s Drug Agency (CDA-AMC,previously known as Canadian Agency for Drugs andTechnologies in Health (CADTH)), Health Canada, andNational Institute of Excellence in Health and SocialServices (INESSS), lays the foundation for the use ofRWE in regulatory and HTA decision-making in Canada, IQWiG working paper.26The report also provides aquantitative framework for sample size estimationunder uncertainty, offers recommendations forsetting the correct observation start date to avoid Adjusted Indirect Compar