DEVELOPING A STATED-PREFERENCES INSTRUMENT FOR DUCHENNE/BECKER MUSCULAR DYSTROPHY– A COMMUNITY-ENGAGED RESEARCH APPLICATION

Purpose:

We describe the application of a community-engaged research (CEnR) approach to stated-preferences instrument design in a rare disease setting: patients and caregivers of people with Duchenne/Becker Muscular Dystrophy (DBMD), a life-shortening neuromuscular disease with limited treatment options.  We developed an instrument to quantify preferences to inform regulatory review for a therapeutic agent that demonstrated pulmonary benefits in a phase III clinical trial. Although previous research demonstrates the community’s willingness to accept risk for muscle stabilization, we sought to understand how the community values a pulmonary outcome. The study was co-led by advocacy and academic institutions, with support from the trial sponsor.

Method:

A three-tiered approach to CEnR was used to develop a stated-preference instrument. A leadership committee (n=5) guided the entire project, including advising inclusion and exclusion criteria, informing initial survey development and subsequent refinement, and addressing concerns during development. The second tier included a stakeholder committee (n=9) that contributed to creating and refining a pool of potential treatment attributes and levels, and survey language. For the final tier, a review committee (n=6) underwent cognitive interviews to finalize the instrument. The leadership and stakeholder committees comprised adults with DBMD, parents, advocacy organization leadership, clinicians and the industry sponsor representative. The review committee consisted of people eligible for the study: parents of children with DBMD and adults with DBMD. Ad-hoc advice was sought from additional stakeholders to inform final survey language.

Result:

CEnR entailed over 13 hours of formal engagement including 15 interviews and recorded conference calls plus in-person conversations and email communications. We conducted six cognitive interviews contributing to over 50 iterations of the survey. CEnR was vital to inform the presentation of meaningful pulmonary benefits, especially given that many people do not experience obvious respiratory symptoms until later stages in the natural history of the disease.

Conclusion:

This community-engaged approach represents a robust example of patient-centered drug development in response to regulatory guidance. We establish that CEnR provides important information in stated-preference survey development and offer a model for its use in patient-centered drug development. We demonstrate that a community-engaged approach can incorporate community members as varied as adult patients, caregivers, clinicians, clinical trial sponsors, and professional advocates who can contribute important information to the survey design.