Development and Validation of a Disease-Specific, Patient-Reported Outcome Measure: The Myotonic Dystrophy Type 2...

To optimize therapeutic trials involving individuals with myotonic dystrophy type 2 (DM2), it is useful to have a fully validated, regulatory-grade, disease-specific patient-reported outcome (PRO) measure that is capable of detecting clinically relevant changes in response to therapeutic interventions and designed in accordance with U.S. Food and Drug Administration guidelines. The purpose of this research was to develop and validate a DM2-specific instrument that is relevant to the patient population and capable of quantifying multifactorial disease.

We conducted semi-structured qualitative interviews and a cross-sectional study to identify the most important and prevalent symptoms for individuals with DM2. Symptom items were selected for inclusion in the Myotonic Dystrophy Type 2 Health Index (MD2HI) based on their high prevalence, relative impact, and potential ability to respond to therapeutic intervention. Further validation and optimization of the MD2HI were performed through beta interviews, test-retest reliability assessments, factor analysis, and subgroup analysis.

Seventy-four individuals with DM2 participated in a cross-sectional study to identify the most common and important symptoms to include in the MD2HI. Beta testing with 20 participants with DM2 demonstrated that the MD2HI is highly relevant, easy to use, and comprehensive. During a short longitudinal study of 24 DM2 participants, the MD2HI depicted high reliability (ICC = 0.97) and high internal consistency (Cronbach's α = 0.98), resulting in a 17-subscale instrument.

Initial assessment of the MD2HI provides evidence that it is a valid and reliable PRO capable of quantifying a patient's perception of their disease burden to better detect clinically relevant changes in response to therapeutic intervention.