In preparation for upcoming clinical trials involving patients with DMD, there is a clear need for reliable, sensitive, and disease-specific patient and caregiver reported outcome measures capable of detecting small, clinically relevant changes in therapeutic gain over time. According to the Food and Drug Administration (FDA), patient-measuring reported outcome measures are an effective mechanism to support drug-labeling claims.
In response to the need for therapeutic advancement for the DMD community, we have developed and validated the DMD-HI (Duchenne Muscular Dystrophy Health Index) and the DMDCR-HI (Duchenne Muscular Dystrophy Caregiver Reported Health Index) for use in DMD therapeutic trials and clinical monitoring.
We conducted semi-structured qualitative interviews with DMD patients and caregivers to identify symptoms of potential importance in DMD. Next, we conducted a cross-sectional study to determine the DMD symptoms of greatest prevalence and importance. We selected questions for the DMD-HI and the DMDCR-HI based on their high relevance and potential responsiveness to therapeutic intervention. Instrument subscales, measuring granular areas of symptomatic health, were generated using factor analysis. We performed beta testing, known groups testing, and test-retest reliability assessments to optimize instrument clarity, usability, meaningfulness, responsiveness, and reliability.
Thirty-seven patients and caregivers participated in the qualitative interviews and 200 participants completed the cross-sectional study. The final DMD-HI and DMDCR-HI each contain 16 subscales that measure how a patient feels and functions. Validation testing found the DMD Health-Indices and their subscales to be highly relevant, reliable, and capable of differentiating between patients with different levels of disease state.
The development, optimization, and validation of the DMD-HI and the DMDCR-HI provide researchers and clinicians with highly sensitive and reliable mechanisms to measure relevant changes in patient feel and function over time or in response to therapeutic intervention.
Funding for this project was provided by the MDA (Muscular Dystrophy Association), PPMD (Parent Project Muscular Dystrophy), and Duchenne UK.