Systematic Literature Review of Access Pathways to Drugs for Patients with Rare Diseases

Objective: This article reviews the assessment pathways that have been implemented worldwide to facilitate access to drugs for patients with rare diseases.

Methods: The Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines were used to conduct a systematic literature review. The Ovid (Embase/MEDLINE), Cochrane, Web of Science, Econlit, National Institute of Health Research, Centre for Reviews and Dissemination, and International Network of Agencies for Health Technology Assessment databases were searched. Two independent reviewers screened all titles and abstracts; one reviewer did the full-text review and data extraction. Data were extracted on study general characteristics, general aspects of rare diseases, source of funding, allocation of public resources (e.g., use of health technology assessment), and pricing strategies. Assessment pathways were classified as: (1) separate processes; (2) exception to standard process; (3) standard process with no change; and (4) alternative process. Each assessment pathway was characterized based on its unique characteristics specific to rare diseases focusing on whether they targeted specific aspects of the process, utilized particular methodologies during the evaluation of the evidence, or considered specific attributes in the recommendation.

Results: A total of 5604 unique citations were screened and 158 were included for data extraction. Sixty-one assessment pathways were identified in 43 countries, categorized as separate processes (37%), exceptions to standard processes (32%), standard processes with no changes (26%), and alternative processes (5%). Some countries (10/43; 23%) have more than one assessment pathway available. Assessment pathways varied in their inclusion of a health technology assessment, source of funding, consideration of uncertainty, and pricing strategies.

Conclusions: The diversity of assessment pathways reflects the complexity of addressing access to treatments for rare diseases. Furthermore, most assessment pathways are from high-income countries; therefore, there is less clarity on what is happening in low- and middle-income countries.