OBJECTIVES

To investigate real-world evidence (RWE) use in regulatory/health technology assessment (HTA) submissions for gene therapies (GTs), and whether RWE studies recommended by those bodies are subsequently registered by manufacturers.

METHODS

European Medicines Agency (EMA) and US Food and Drug Administration (FDA) websites were searched using GT terms. National Institute for Health and Care Excellence (NICE) and Institute for Clinical and Economic Review (ICER) websites were searched for related HTAs. Details of RWE use/recommendation were then extracted. Finally, five registries (clinicaltrials.gov, European Union Electronic Register of Post-Authorisation Studies [EU PAS], Health Services Research Projects, Research Registry, Open Science Framework) were searched for observational studies. Results were cross-referenced to identify any recommended studies.

RESULTS

Ten GTs were identified; nine were EMA-approved (2012–2019), three were subsequently withdrawn. Six were FDA-approved (2010–2019); five were approved by both the EMA and FDA. While no GT-related RWE was used, RWE was identified in 6/9 EMA submissions – most commonly for matched historical controls. No RWE was identified in FDA submissions. 8/9 EMA and 5/6 FDA approvals recommended post-marketing RWE studies. In HTA, five NICE and three ICER assessments were identified. 5/5 NICE and 3/4 ICER assessments included RWE, primarily as sources of inputs for cost-effectiveness analyses. RWE collection was recommended for 3/4 therapies assessed by ICER but NICE did not specifically recommend RWE collection. Overall, 8/10 GTs used RWE in a submission, all received RWE collection recommendations. Of these, three had registered a recommended observational study on clinicaltrials.gov, while eight had entered a recommended study on EU PAS.

CONCLUSIONS

RWE use in regulatory and HTA submissions was widespread, but primarily to support comparator effectiveness or economic model inputs, rather than in direct support of GT clinical profiles. Registration of recommended studies specifically for GTs was substantially higher in observational study-specific registries, suggesting barriers remain to registration on conventional registries.