Drugs for Rare Diseases: A Review of National and International Health Technology Assessment Agencies and Public Payers’ Decision-Making Processes

Key Messages

• Drugs for rare diseases can address significant unmet therapeutic needs for patients living with seriously debilitating and life-threatening conditions; however, the high costs of these drugs can pose challenges for public drug programs and health care systems.
• There are challenges with the application of standard health technology assessment methods for the assessment of drugs for rare diseases, including uncertainty with the clinical and economic evidence due to small sample sizes, poorly characterized natural history of disease, uncertain epidemiology, absence of comparative studies, heterogenous phenotypes, and lack of diagnostic accuracy. In addition, there are challenges applying commonly accepted economic benchmarks due to the very high cost of these drugs.
• To address these challenges, agencies and public payers have established separate or modified processes and programs to review and make reimbursement recommendations for drugs for rare diseases. There is a lack of consistency across agencies with respect to how drugs for rare diseases are defined and what aspects of the process are modified to address the challenges with these drugs; however, common features include greater acceptance of uncertainty with the clinical and economic evidence and a higher willingness-to-pay threshold.
• The majority of health technology assessment agencies have highlighted that drugs for ultra-rare diseases are particularly challenging and warrant special consideration. This includes the creation of completely separate review processes for drugs indicated for use in the treatment of ultra-rare conditions in the UK (both England and Scotland).
• The majority of processes for funding drugs for rare diseases by public drug programs included in this report manage the drugs through standard formulary processes involving the use of special authorization to ensure that patients meet the eligibility criteria for the drugs. Those that have specialized formularies have largely focused on providing access to ultra-rare conditions.