In preparation for Duchenne Muscular Dystrophy (DMD) clinical trials, valid, reliable, and responsive outcome measures are needed to measure the symptoms most relevant to patients.
Our goal was to develop and validate DMD-specific instruments: The Duchenne Muscular Dystrophy-Health Index (DMD-HI) and the Duchenne Muscular Dystrophy Caregiver Reported-Health Index (DMDCR-HI), to measure small, clinically relevant changes in therapeutic gain over time and to support drug labeling claims. We then translated and culturally validated these instruments for use in a United Kingdom (UK) population.
We previously performed qualitative interviews and conducted two cross-sectional studies to ascertain the most prevalent and impactful symptoms in DMD. We selected questions for the DMD-HI and DMDCR-HI based on their high relevance and potential responsiveness to therapeutic intervention. We performed factor analysis, beta testing, test-retest reliability assessments, and known groups testing to generate instrument subscales and optimize instrument clarity, usability, meaningfulness, responsiveness, and reliability. Lastly, we conducted interviews with patients with DMD and caregivers in the UK to translate and validate the DMD-HI and DMDCR-HI for the UK population of patients with DMD.
Thirty-seven patients with DMD and caregivers participated in qualitative interviews, and 200 participants completed the cross-sectional surveys. We found, through validation testing, that the DMD-HI and DMDCR-HI are highly relevant, reliable, and capable of distinguishing between patients with different levels of disease burden. The final DMD-HI and DMDCR-HI each contain 16 subscales that measure how a patient feels and functions. Twenty-eight patients with DMD and caregivers in the UK participated in the cultural validation of the DMD-HI and DMDCR-HI.
The development, validation, optimization, and UK translation of the DMD-HI and DMDCR-HI provide researchers and clinicians with highly sensitive and reliable mechanisms to measure relevant changes in patient health and disease burden over time and in response to therapeutic intervention.