OBJECTIVES: Evidence submitted for health technology assessments (HTAs) of gene therapies (GTs) are limited and associated with uncertainty. Real-world evidence (RWE) may address these uncertainties, with many health authorities adopting new guidelines and increasingly requesting RWE. Our aim was to evaluate the role of RWE in the HTA decision-making of GTs.

METHODS: Official regulatory websites in the US, Canada, UK, EU4 (Germany, France, Italy, and Spain), and Japan were reviewed to identify GTs with current marketing authorization (MA). Official HTA websites of the respective countries were reviewed to extract HTAs of these GTs. From these HTAs and reports, RWE-relevant data were then further extracted for analysis. While Japan had no formal HTA body prior to 2019, it was included as an important Asian perspective, with its official regulatory sites being the main source of information.

RESULTS: A total of 18 GTs were found to have MA within the geographical scope. Of these 18 GTs, 17 had HTAs and 1 was approved but not yet assessed. A total of 61 HTA reports and an additional 6 Japanese reports were extracted. The 61 HTAs includes initial assessments, re-assessments, and assessments of all indications where there was more than one indication for a single therapy (i.e. Yescarta®). Overall, RWE was mentioned in 69% assessments for 12 GTs. All 6 Japanese reports requested RWE. France, Germany, and Italy have the majority of HTAs utilizing RWE by leveraging registries for reimbursement decisions and re-assessments. Most HTA bodies mentioned uncertainty of evidence submissions translating to real-world practice.

CONCLUSIONS: As GTs are increasingly seeking market access with limited evidence, HTAs’ request of RWE is expected to increase. However, the role of RWE in HTA decision-making for GTs is not well-defined and varied. Understanding RWE requirements will be critical for successful future EU HTA. Further analysis is ongoing.