Promoting meaningful clinical trial outcome measures for Duchenne muscular dystrophy

Abstract

There is increasing support to incorporate endpoints meaningful to patients and families into trials. This raises particular challenges and opportunities for Duchenne/Becker muscular dystrophy (DBMD). We conducted a series of community engagement activities relevant to trial outcomes. (1) An advisory meeting engaged teens and adults with DBMD about activities of daily living they would most like improved, followed by a ranking survey for ages 14 to adult. (2) We facilitated expert deliberation, an online focus group, and interviews on meaningful outcomes that extend beyond function. This effort used the PODCI measure as a baseline and identified missing domains associated with QoL. For the first activity, 60 with DBMD and 187 caregivers completed the online survey. Ambulatory individuals received a separate question set from non-ambulatory. Ambulatory patients' top ranked activities were (1) stand from chair; (2) pick up object from floor; and (3) walk up 3 stairs. Parents of ambulatory patients chose (1) stand from chair; (2) stand easily for 10 minutes; (3) pick up object from floor. Non-ambulatory patients' top activities were (1) reposition at night; (2) bring hands to mouth; (3) shift position while seated. Parents of non-ambulatory patients prioritized (1) bring hands to mouth; (2) reposition at night; and (3) control a joystick. For the second activity, the expert committee, online focus group (n = 12), and interviews (n = 4) identified domains of vitality/fatigue; mental health; peer relationships; self-efficacy and autonomy; and a sense of hope and purpose. Pediatric self-report measures are needed. While our results provide insight into meaningful trial impact and outcome choice, there is variation across age and stage. The QoL-related outcomes may not be responsive to change and may measure ancillary outcomes (i.e., optimism; burden) rather than the therapeutic under trial. Continued community engagement about outcomes may enhance the clinical trial experience.