An innovative registry-based trials platform to improve clinical care, outcomes, and health policy for children with treatable rare diseases

New treatments for children with rare genetic diseases are appearing at a rapid pace. Many of these treatments have been found to improve outcomes in highly selected groups of patients under very specific conditions. In order to know how best to recommend, use, and pay for these treatments, patients and their families, health care providers, and policy-makers need more evidence about how the treatments work in all patients and settings. We also need to understand what additional supportive interventions are needed to get the best value from new rare disease drugs in order to improve functioning, quality of life, and other patient-centred outcomes. We are a group of patients, family members, health care providers, policy-makers, methodologists, and ethicists. We will work together to develop innovative registry-based randomized trials in order to rapidly develop comparative evidence about the effectiveness of treatments for rare genetic diseases in children. These high-quality trials will make use of comprehensive patient registries to enroll patients and measure outcomes. We will design and implement 3 inaugural trials to address priority questions for 3 rare diseases: spinal muscular atrophy, phenylketonuria, and mucopolysaccharidosis. Our methods are scalable so that we can also rapidly leverage the work to develop additional trials during and after the grant period for these and other rare diseases. We have a strong knowledge user engagement strategy that ensures we partner with patients and family members to co-design our research. We have also established partnerships with patient organizations, policy organizations, newborn screening programs, and other centres and networks. Our patient-partnered, equitable, and scalable approach to generating evidence will inform decisions about rare disease care and health policy, toward improved patient and system outcomes.