Exploring barriers to clinical trial readiness among the myotonic dystrophy community: a mixed-methods study

Myotonic dystrophy (DM) is a multisystemic disorder characterized by significant heterogeneity in symptom manifestation, progression, and severity. This variability complicates clinical trial design and implementation, thereby affecting therapeutic development. This study aimed to identify barriers to clinical trial readiness in DM and explore actionable solutions by incorporating perspectives from pharmaceutical partners, clinical trial site staff, people living with DM (PLDM), and caregivers. Focus groups, surveys, and interviews were conducted with pharmaceutical partners (n = 65), PLDM and caregivers (n = 35), principal investigators (n = 12), and clinical research coordinators (n = 12). Qualitative findings were thematically analyzed and triangulated with survey data to enhance validity. Three major barriers consistently emerged: (1) a lack of comprehensive, validated endpoints that capture outcomes meaningful to patients; (2) insufficient data sharing and coordination across industry; and (3) challenges in trial design, recruitment, and participant burden. PLDM emphasized under-studied but debilitating symptoms-such as dysphagia, fatigue, and cognitive impairment-that are rarely prioritized in clinical trials. Pharmaceutical partners cited regulatory uncertainty surrounding composite outcome measures as well as the value of quantitative myotonia indicators as informative holistic disease indicators. Limited access to natural history data, often prohibitively costly for smaller companies, reinforces competitive rather than collaborative dynamics. PLDM and caregivers also highlighted substantial financial, logistical, and accessibility challenges associated with trial participation. Participants favored several strategies to address these barriers: (1) convening a multi-stakeholder scientific session with the U.S. Food and Drug Administration (FDA) and establishing a working group to define and standardize patient-centered, clinically relevant endpoints; (2) developing a comprehensive, coordinated registry that integrates existing data sources, longitudinal health and study data, genetic diagnostic data, supports recruitment and refinement of study inclusion criteria, and enables post-market surveillance; (3) strengthening trial site preparedness and anticipating recruitment needs, including biomarker-driven cohorts; and (4) adopting patient-centered trial designs that minimize burden, with patient advocacy groups (PAGs) serving a central convening and advocacy role by bringing various groups together to discuss these topics. While barriers to DM clinical trial readiness are significant, they are addressable. Coordinated action among industry, regulators, clinicians, and advocacy groups-guided by patient priorities-will be essential. Implementing these strategies could accelerate therapeutic development, improve trial inclusivity, and ultimately enhance quality of life for individuals living with DM.