PULMONARY BENEFITS OF TREATING DUCHENNE MUSCULAR DYSTROPHY: A REGULATORY BENEFIT-RISK ANALYSIS

Abstract

Objectives: There is growing interest in incorporating patient preferences into regulatory decision-making, especially in rare diseases and when there is high uncertainty. We sought to quantify 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. Methods: In response to DMD draft guidance for industry, we conducted a stated-preference study to measure patient preferences information for a therapeutic agent for DMD to support regulatory review. A best-worst scaling case 2 survey was 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. Utilities scores were estimated using mixed logistic regression. Results: 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 significant (p= 0.25). Conclusions: 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.