Background: The United States Food and Drug Administration (FDA) has identified patient-reported outcome (PRO) measures as valid tools to assess patient health during clinical trials and to support drug-labeling claims. In preparation for future clinical trials in myotonic dystrophy type 2 (DM2), we developed and validated the Myotonic Dystrophy Type 2 Health Index (MD2HI), a novel and multifactorial PRO designed in accordance with FDA guidelines.
Objectives: To develop and validate a disease-specific patient-reported outcome measure to improve clinical trial infrastructure and monitor clinically relevant changes in DM2 health.
Methods: Semi-structured qualitative interviews and a cross-sectional study were conducted with individuals with DM2 to determine the importance and frequency of symptoms identified in this population. The symptoms with the highest frequency and relative impact to the cross-sectional cohort were selected as questions in the first version of the MD2HI. Subsequently, we conducted beta interviews to discuss the relevance and clarity of the instrument. Test-retest evaluations, factor analysis and known groups analysis were completed to further validate the final version of the MD2HI.
Results: Fifteen individuals with DM2 participated in the qualitative interviews resulting in 943 direct quotes representing 310 potential symptoms of importance. Seventy-four DM2 patients participated in the cross-sectional study providing more than 12,000 symptom rating responses. We then conducted beta testing with 20 individuals with DM2 who found the MD2HI to be highly relevant, clear and easy to use. Test-retest evaluation and known groups analysis indicated that the MD2HI is reliable and capable of differentiating between patients with differing levels of disease burden.
Conclusions: The MD2HI provides researchers and clinicians with a reliable and valid regulatory-grade instrument capable of detecting clinically relevant changes in response to therapeutic intervention.