No matter how robust in design, clinical trials can never fully address the uncertainty surrounding the comparative effectiveness and safety of a novel product in the real world. This is particularly pertinent in rare diseases for several reasons: small sample sizes and heterogeneous populations create challenges in demonstrating clinically significant benefits, randomized head-to-head comparisons are often unfeasible or unethical, and relationships between measurable trial endpoints and patient-relevant outcomes are under-studied and poorly understood. When preparing for health technology assessments and reimbursement discussions for a rare disease product, we believe that it is both feasible and advisable to anticipate and subsequently minimize the key uncertainties before starting the later phases of clinical programmes. While this is not a new proposition, our experience suggests that this rarely happens in practice, and there is therefore a need to reinforce the value of this simple recommendation.
In this White Paper, we outline eight key challenges that manufacturers face when demonstrating the value of rare disease products to decision-makers, and set out our framework for proactively overcoming these challenges. Using this framework, we believe that manufacturers can achieve earlier access to market, at a price that reflects product value.