PATIENT CENTERED BENEFIT-RISK ANALYSIS IN DUCHENNE MUSCULAR DYSTROPHY

Purpose: We aimed to inform regulatory review by quantifying patient and caregiver preferences for a therapeutic agent for Duchenne muscular dystrophy (DMD) that demonstrated pulmonary benefits in a phase III clinical trial. As an exploratory aim we compared caregiver and patient preferences.

Method: In response to DMD draft guidance for industry and the growing interest in incorporating patient preferences into regulatory decision-making, we conducted a stated-preference study to support regulatory review. A best-worst scaling case 2 survey was developed using a community-engaged approach and then administered to 133 caregivers and patients with DMD. Across 9 choice tasks, respondents selected the best and worst attributes from among 4 attributes at 3 varying levels. Benefits included maintaining level of cough strength and reducing the frequency of lung infections. Risks included diarrhea and burden-related blood monitoring frequency.  Utilities scores were estimated using mixed logistic regression for the stratified samples (parents and caregivers) and the pooled sample. The two groups in the stratified analysis were compared using t-tests at the 95% confidence interval. Coefficients for the standard deviations of each attribute’s choice represent heterogeneity within an attribute.

Result: Respondents demonstrated greatest preference for therapies that maintain their current level of cough strength for 10 years (score=3.893; SE=0.09) and for 2 years (score=3.027; SE=0.09). Preference scores for risks were low; 50% chance of diarrhea (score=-1.943; SE=0.08) and 4 additional blood draws per year (score=-1.883; SE=0.08).  Differences between caregivers and patients were not statistically significant (p=0.25) across caregiver and patient groups. Furthermore, the standard deviations of the preference scores are not statistically significant for 75% of the attribute/level combinations.

Conclusion: This study demonstrates a strong preference for therapies with a pulmonary benefit as illustrated by a willingness to trade-off risks and burden. Specifically, in exchange for maintaining cough strength for 10 years, respondents are willing to tolerate high probabilities of diarrhea and the burden of additional blood draws. Although not powered to detect statistically significant differences, we found no qualitative differences in preferences between caregivers and patients.