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Around 1 in 20 people will live with a rare disease at some point in their life. However, there is no cure for the majority of rare diseases, and many cases go undiagnosed.

Rare Disease Day (taking place this year on Thursday, 28th February) improves public knowledge of rare diseases, while encouraging researchers and decision-makers to address the needs of those living with these conditions.

As part of our ongoing commitment to research into rare diseases, Vitaccess has explored the use of real-world evidence (RWE) in health technology assessments (HTAs) of drugs used to treat rare diseases.

Randomized controlled trials (RCTs) can be difficult to conduct in rare diseases due to low patient numbers, high unmet need, and difficulties in identifying controls group. Additionally, data on burden of disease and epidemiology for rare diseases are often scarce in the literature.


HTA agencies such as the UK’s National Institute for Health and Care Excellence (NICE), and the Canadian Agency for Drugs and Technologies in Health (CADTH) state that RWE can be acceptable for decision-making in cases where RCT data are not available. This can allow generation of the necessary knowledge to support market access of drugs to treat rare diseases through HTA, but can also increase perceived uncertainty around relative clinical- and cost-effectiveness. Guidance on the application of RWE and conditions upon which it will be considered to inform HTA decision-making has been developed to mitigate this uncertainty.

HTA submissions for drugs to treat rare diseases that incorporate RWE have increased in recent years. NICE and CADTH rare disease HTAs, such as those for asfotase alfa for pediatric-onset hypophosphatasia, and elosulfase alfa for mucopolysaccharidosis type IVa, serve as constructive case studies to understand approaches to using RWE. In their assessments of asfotase alfa, both NICE and CADTH accepted two natural history studies. The data were used as historical control data to support single arm trials. Similarly, both agencies accepted a natural history observational study in submissions for elosulfase alfa, which provided useful demographic and disease characteristics for cost-effectiveness modelling. NICE also accepted a patient survey, which contributed utility, quality of life, and cost data.

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RWE is also increasingly featured in the post-approval setting. For both products, NICE requested a managed access agreement (MAA) with five-year RWE collection, specific eligibility criteria, and stopping rules. CADTH also specified further RWE collection, and for elosulfase alfa requested that a manufacturer-sponsored international registry be developed as part of reimbursement.

Overall, RWE is increasingly being used by pharma companies to support market access activities for drugs to treat rare diseases and is widely being accepted by HTA agencies as a sophisticated, robust method of informing efficacy/ effectiveness, providing input for economic models and also being used as a basis for MAAs.

Readers can reach out to the consulting team at to discuss this blog or capabilities in RWE for rare diseases in more detail.