OBJECTIVES: To compare uncertainties about the optimal use of three therapies for spinal muscular atrophy (SMA) across Canada and other countries and to determine if ongoing research or future real-world evidence (RWE) studies can address these uncertainties.

METHODS: We reviewed the websites of international health technology assessment (HTA) agencies - CADTH, NICE, SMC, HAS, G-BA, IQWiG, and PBAC - for reimbursement decisions on SMA therapies nusinersen, onasemnogene abeparvovec, and risdiplam. We also evaluated input from additional Canadian stakeholders: patients, payers, and providers. We then identified and categorized uncertainties cited in assessments and compared them across HTA bodies/stakeholders. Additionally, we evaluated ongoing studies in SMA and relevant market access agreements to identify information that could potentially address the stated uncertainties.

RESULTS: Across 59 total documents, 17 uncertainties were identified that encompassed two themes: gaps regarding a therapy’s clinical/economic evidence and SMA health system gaps. Canadian stakeholders expressed concern about the lack of data for key subgroups and the therapies’ long-term safety/efficacy. Among HTA bodies, the most frequently noted uncertainties were unrepresentative clinical trial populations, missing/incomplete data for over 40 key subgroups, lack of comparative effectiveness data, lack of long-term efficacy/safety data, and uncertainties about costing inputs/health economics analyses. SMA health systems gaps regarding access to therapies and patient financial burden were commonly reported across Canadian stakeholders and HTA bodies. Of 97 studies identified that could potentially address uncertainties, 64 were ultimately deemed relevant.

CONCLUSIONS: There was substantial overlap in SMA uncertainties cited across types of stakeholders. RWE was also identified as an appropriate tool to address certain remaining uncertainties, such as missing/incomplete data for key subgroups and variability in the clinical environment. These findings ultimately highlight the need for additional research in SMA and the opportunities for and value of collaboration.