Using a meta-narrative literature review and focus groups with key stakeholders to identify perceived challenges and solutions for generating robust evidence on the effectiveness of treatments for rare diseases.

Over time, discussions about clinical research for interventions for rare diseases have moved beyond methodological approaches to overcome challenges related to explanatory evidence generation, with increased recognition of the importance of pragmatic and patient-oriented evidence. Future directions for our work include developing a framework to expand current evidence synthesis practices to take into consideration many of the concepts discussed in this paper.