Health technology assessments of new specialized therapies: A typology of key challenges and potential policy solutions

Objectives: Current transformations in the pharmaceutical sector raise pressing questions about what is considered acceptable evidence for the effects of new therapies. This article aims to identifying key challenges in clinical effectiveness evaluation of new therapies and discuss possible policy responses to these challenges. Methods: The study builds on a systematic review of the 41 appraisals issued in 2019 by the Danish Medicines Council (DMC), which is responsible for the appraisal of new specialized therapies in Denmark. Results: While much political attention currently centers on the use of 'real-world evidence', we find that clinical effectiveness evaluation based solely on non-RCT evidence still constitutes an exception in the Danish setting (9% of the evaluations). Yet, challenges of indirectness were prevalent even when evaluations were based on RCT data (54% of the evaluations). Challenges of effect extrapolation arose in about a third of the evaluations. Discussion: As the identified challenges are likely to increase with the current trend from 'blockbuster' to 'niche' products in the pharmaceutical sector, we point to a need for regulators and health technology assessment agencies to collaborate about the development of guidance on the use of other study designs than traditional RCTs, methods that can reduce the risk of bias when conducting indirect comparisons, and principles for managed entry agreements.