Overcoming treatment implementation barriers for individuals with rare diseases using single-case experimental designs.

Abstract

Treatments often do not reach individuals affected with a rare disease due to several barriers. Legislation generally requires that therapies for rare diseases are tested and licensed according to the same rules as established for common diseases. However, conventional methods for evaluating treatment effectiveness are hampered by the small patient populations. Single-case experimental designs (SCEDs), including n-of-1 trials, may offer a solution. Advantages of SCEDs include the ability to study individualized treatment options, use of within-participant randomization to generate a high level of evidence, and guaranteeing that each individual receives treatment. Their individualized approach also has a positive impact on ensuring relevance of treatment approaches and outcomes for affected individuals. However, designing and performing SCEDs in rare diseases comes with specific challenges related to heterogeneity, selection of outcome measures, accessibility of therapy, development of study medication, treatment and trial adherence, regulation, reimbursement, and financial limitations. Here the lessons learned from SCEDs in rare diseases are discussed, based on real-world experiences from the involved clinicians and researchers, and informal participants' comments collected during and after participation in a SCED. Following these experiences and a thorough evaluation by an expert group, a manual for conducting SCEDs has been developed. This manual is presented as a steppingstone towards robust evidence generation and better access to treatments for individuals with rare diseases.