Orphan drug development to treat rare diseases has been proposed as an indication of pharmaceutical innovation in Europe. Moreover, successfully developing an orphan drug entails unique challenges, in particular with clinical trial design, therefore to overcome these challenges requires innovation of development and an adaptation from those that regulate it.
The rarity of the disease itself forces drug developers to evolve from traditional clinical development design, and generate compelling and significant data from small patient populations that portray value in both a regulatory and reimbursement context.
While all of drug development and the challenges are unique, especially in the field of rare diseases, we surveyed and accumulated a list of the major challenges faced by orphan drug developers during the design of their rare disease clinical trial:
- Establishing and validating clear endpoints for regulatory approval
- Transportation cost of patient enrolment (and their families)
- Lack of understanding of how and why patients might participate in the design phase
- Ability (and ethics) to run a controlled trial or have a robust control population against which to demonstrate benefit
- Overcoming patient availability, population size and its impact on development time
- The right outcome parameter
- How to engage with and harness scientific advice from regulatory authorities
- Aligning across a large number of sites.
- If another drug is available, is it still possible to conduct placebo controlled trials?
- Lack of knowledge of patient characteristics
- Accelerating escalating dose studies to establish therapeutic levels an any toxicity
- Cooperation of clinical investigators to lower costs of the study for small biotech
Here are some associated blogs that take these challenges further, provide possible solutions and display successful case studies to orphan drug clinical trial design.