Translating rare-disease therapies into improved care for patients and families: what are the right outcomes, designs, and engagement approaches in health-systems research?

There is a need for research to understand and improve health systems for rare diseases in order to ensure that new, efficacious therapies developed through basic and early translational science lead to real benefits for patients. Such research must (i) focus on appropriate patient-oriented outcomes, (ii) include robust study designs that can accommodate real-world decision priorities, and (iii) involve effective stakeholder-engagement strategies. For transformative therapies, study outcomes will need to shift toward longer-term goals in recognition of success in preventing catastrophic outcomes. For incremental therapies, outcomes should be selected in recognition of the impact of care on quality of life for patients and families. To generate new evidence, we suggest that hybrid study designs integrating elements of practice-based observational research and pragmatic trials hold the most promise for addressing priorities such as minimizing bias, accounting for cointerventions, identifying long-term impacts, and considering clinical heterogeneity. To effectively engage with stakeholders, a knowledge exchange infrastructure is needed to foster collaboration among patients with rare diseases and their families, health-care providers, researchers, and policy decision makers. A key priority for these groups must be collaboration toward a shared understanding of the outcomes that are of most relevance to the facilitation of patient-centered care.