Presentation (CTI)

OBJECTIVES: Project ORBIS, led by the United States (US) Food and Drug Administration (FDA), enables concurrent submission and review of oncology therapies across five markets to accelerate patient access. However, differences in national health technology assessment (HTA) requirements, including variation in acceptance of non-trial-based evidence and definitions of unmet need and innovation, may limit its downstream impact on reimbursement. This study assessed cross-country differences in the acceptance of advanced methodologies and implications for global submission strategies within ORBIS-participating jurisdictions.
METHODS: A targeted qualitative review was conducted using ORBIS materials from the US, Canada, Australia, the United Kingdom (UK), Israel, Brazil, Singapore, and Switzerland. Public HTA guidelines, reimbursement decisions, and selected oncology cases with both ORBIS and HTA submissions were analyzed. Acceptance of advanced methodologies was assessed for indirect treatment comparisons (ITC), external control arms (ECA), synthetic control arms (SCA), inverse probability of treatment weighting (IPTW), and real-world evidence (RWE).
RESULTS: RWE was broadly accepted across countries except by Israel; however, ITCs faced greater scrutiny, particularly in the UK, Canada, and Australia with specific reporting guidelines for ITCs, while other countries did not have reporting guidelines. ECAs were accepted in the US, Canada, and the UK, but required case-by-case review in Australia, Brazil, Israel, Singapore, and Switzerland. SCAs, while commonly accepted in the US, were not yet reflected in guidance in other participating countries, limiting applicability. ORBIS submissions must demonstrate clinically meaningful improvement in safety and/or efficacy; however, definitions of unmet need varied. Canada emphasized benefit-risk and access gaps, while the UK and Australia focused more on disease severity and magnitude of clinical benefit.
CONCLUSIONS: While ORBIS enhances regulatory efficiency, it does not ensure alignment with HTA requirements for reimbursement. Differences in methodological acceptance and unmet need definitions highlight the need for earlier HTA engagement and greater cross-country alignment to optimize global evidence strategies.