Evolving Concept of Value in Health Economics and Outcomes Research: Emerging Tools for Innovation and Access to Cell and Gene Therapies for Rare Diseases.

Objectives: Recent scientific breakthroughs have propelled the development of disease-modifying and potentially curative cell and gene therapies (CGTs) for rare diseases, including those diseases previously considered untreatable. The unique characteristics of CGTs, however, pose challenges to the traditional methods of therapy value determination, reimbursement, and outcome evaluation used by regulatory and assessment agencies for product approval and market access. Notably, CGTs are one-time or short-course treatments, often first-in-class (precluding direct comparisons with effective alternatives), and have health benefits that are largely realized over time.

Methods: We summarized emerging health economics and outcomes research (HEOR) solutions in 5 areas pertaining to CGTs for rare diseases using examples from literature and recently approved therapies. These solutions include the collection of real-world data to generate real-world evidence, patient centricity and novel value assessment frameworks, evolution of economic evaluation methodologies, novel reimbursement models and management of affordability, and health equity and societal benefits.

Results: Advances in HEOR methods have informed the design and collection of long-term real-world data for CGT efficacy extrapolation, use of novel (including surrogate) endpoints, integration of the patient's voice and preferences, and application of sophisticated statistical methodology and artificial intelligence/machine learning techniques.

Conclusions: Continuing innovation in HEOR is expected to contribute to improved health outcomes, reduced costs, and enhanced access, ultimately enabling more efficient delivery of CGTs to patients living with rare diseases.