OBJECTIVES

Historically focused on epidemiological, resource-use, and cost data, real-world evidence (RWE) in health technology assessment (HTA) submissions for orphan drugs has increased and broadened in scope in recent years. This study sought to understand the role of RWE in orphan drug HTA.

METHODS

The UK National Institute for Health and Care Excellence (NICE) and Canadian Agency for Drugs and Technologies in Health (CADTH) guidance documents on use of RWE were reviewed. Orphan drug HTA case studies in asfotase alfa for pediatric-onset hypophosphatasia, and elosulfase alfa for mucopolysaccharidosis type IVa, were compared to explore how guidance was being implemented.

RESULTS

Draft CADTH guidance notes that RWE has value in supporting regulatory and reimbursement decision-making. It identifies situations within orphan drug development where randomized controlled trial (RCT) evidence is not available and RWE may be a suitable alternative.

NICE guidance notes that RWE can be an acceptable source of evidence to inform estimates of treatment effect for cost-effectiveness analysis, as a complement to RCTs or as the sole source of data.

Both NICE and CADTH accepted natural history studies in submissions for asfotase alfa, as historical control data to support single-arm trials. Similarly, both accepted a natural history observational study in submissions for elosulfase alfa, which provided demographic and disease characteristics for cost-effectiveness modelling. NICE also accepted a patient survey, which contributed utility, quality-of-life, and cost data.

For both products, NICE’s recommendation was conditional on the collection of RWE within a managed access agreement (MAA). CADTH also specified RWE collection for elosulfase alfa, through a manufacturer-sponsored registry.

CONCLUSIONS

RWE is increasingly being used by pharmaceutical companies to provide effectiveness or safety data for orphan drug HTA submissions and inputs for pharmacoeconomic modelling, and is accepted by HTA agencies in submissions and as a basis for MAAs.