Mitochondrial disease patient motivations and barriers to participate in clinical trials

Background: Clinical treatment trials are increasingly being designed in primary mitochondrial disease (PMD), a phenotypically and genetically heterogeneous collection of inherited multi- system energy deficiency disorders that lack effective therapy. We sought to identify motivating factors and barriers to clinical trial participation in PMD. Methods: A survey study was conducted in two independent mitochondrial disease subject cohorts. A discovery cohort invited subjects with well-defined biochemical or molecularly- confirmed PMD followed at a single medical center (CHOP, n = 30/67 (45%) respondents). A replication cohort included self-identified PMD subjects in the Rare Disease Clinical Research Network (RDCRN) national contact registry (n = 290/1119 (26%) respondents). Five-point Likert scale responses were analyzed using descriptive and quantitative statistics. Experienced and prioritized symptoms for trial participation, and patient attitudes toward detailed aspects of clinical trial drug features and study design. Results: PMD subjects experienced an average of 16 symptoms. Muscle weakness, chronic fatigue, and exercise intolerance were the lead symptoms encouraging trial participation. Conclusions: These data are the first to convey clear PMD subject preferences and priorities to enable improved clinical treatment trial design that cuts across the complex diversity of disease. Partnering with rare disease patient communities is essential to effectively design robust clinical trials that engage patients and enable meaningful evaluation of emerging treatment interventions.