Beyond the skeletal muscle

Abstract

Patient preferences are increasingly important for regulatory decision-making. Less attention has been given to their use in early stage drug development. This study's objective was to quantify patient and caregiver priorities for therapeutic targets relevant to Duchenne (DMD) and Becker (BMD) that extend beyond motor ability and skeletal muscle strength. This study utilizes a best-worst scaling case 1 experiment to assess caregiver and patients' treatment priorities. We used a community-engaged approach to identify a meaningful set of 11 symptoms. Priority scores were calculated using conditional logistic regression for the aggregate sample and stratified by caregivers and patients. Of the 155 respondents, 62% were caregivers and 38% were patients; the majority had DMD (85%). Respondents prioritized “weaker heart pumping'' (score = 4.67; 95% CI = [4.22, 5.12]) and pulmonary symptoms: lung infections (score = 3.82; 95% CI = [3.39, 4.24]) and weaker ability to cough (score = 3.45; 95% CI = [3.05, 3.85]). The next most prioritized intervention targets were bone fractures (score = 2.42, 95% CI = [2.04,2.78]), non-healthy weight (score = 1.78; 95% CI = [1.44, 2.22]), depression, (score = 1.74; 95% CI = [1.49, 1.99]), and constipation (score = 1.20; 95% CI [0.88 ,1.52]). These were followed by: headaches, frequent waking at night, feeling tired, and poor attention span. Following Bonferroni correction, there were no significant differences between caregivers and patients (p = 0.14). Our results indicate prioritization of symptoms related to quality-of-life that have direct links to mortality. The overlapping confidence intervals suggest strong prioritization of, but no significant differentiation between, pulmonary and cardiac targets. The differences in relative importance for many middle-importance attributes were not statistically significant. These data provide input into desired treatment targets for DBMD that may complement treatments targeted at skeletal muscle strength.