OBJECTIVES: The use of real-world evidence (RWE) by health technology assessment (HTA) agencies varies around the world. This may impact decisions for drugs for rare diseases (DRDs) where it may not be possible to meet traditional evidence standards. The objective of this analysis was to determine how Canadian and international HTA agencies are using RWE, to understand how RWE is influencing recommendations, and to better inform stakeholders on best practices for including RWE in submissions.

METHODS: Canadian Agency for Drugs and Technologies in Health (CADTH) DRD recommendations issued between January 2020 and June 2023 were reviewed. Recommendations for the same drugs were then identified from HTA agencies in Quebec, the United Kingdom (England, Scotland), France, the Netherlands, Australia, and New Zealand. The use of RWE in the evaluation, the RWE methods, and the recommendations were extracted and compared to identify the role and impact of including RWE on the recommendations.

RESULTS: CADTH reviewed 40 DRDs and 9 of the submissions included RWE. The number of DRD recommendations that included RWE ranged from 0 (Scotland) to 9 (Canada). Submissions considered RWE from simulation and observational studies (including registry analyses and both retrospective and prospective cohort studies). Among the identified submissions to all HTA agencies combined, RWE was mostly used in the assessment of safety (n=15) and efficacy (n=18). Two drug products (trientine hydrochloride (2 formulations)) were given positive recommendations based on RWE alone by 4 HTA agencies. The same RWE studies were submitted across HTA agencies for the same drugs.

CONCLUSIONS: The use and impact of RWE varied across agencies and transparency in reporting limited the comparisons that could be drawn. It is encouraging that RWE is being included in DRD submissions and in situations where evidence from randomized controlled studies is not feasible, drugs may be recommended based on RWE.