Background: Prader-Willi syndrome (PWS) is a rare disease associated with cognitive impairment, hypotonia, hyperphagia (an insatiable hunger), and obesity. Therapies that target hyperphagia are in development, but understanding the value of these therapies to inform patient-focused drug development (PFDD) requires valid data on disease burden. We estimated disease burden by measuring and comparing quality-adjusted life-years (QALYs) for 3 PWS health states relevant to current PFDD initiatives.
Methods: Time trade-off (TTO) and a visual analog scale (VAS) were used to elicit PWS caregivers' values for 3 fixed health states for a standardized patient described with (1) untreated PWS, (2) PWS with controlled obesity, and (3) PWS with controlled obesity and hyperphagia. We excluded participants who left at least 1 TTO or VAS question blank or incomplete (noncompleters) and respondents who reported the same answer for all TTO scenarios (nontraders). The remaining group of respondents (traders) were used for all primary analyses. We assessed validity and bias of QALY estimates by comparing differences in health state valuations, treatment priorities, and characteristics among respondents who did and did not complete the TTO.
Results: A total of 458 respondents completed the survey, including 226 traders, 93 nontraders, and 139 noncompleters. Traders valued untreated PWS at 0.69 QALYs, PWS with controlled obesity at 0.79 QALYs, and controlled hyperphagia/obesity at 0.91 QALY (P < 0.01 for differences among health state values). Reported VAS ratings were similar for traders versus nontraders for untreated PWS (38.64 vs 38.95, P = 0.89) and PWS with controlled obesity (57.36 vs 55.14, P = 0.35) but varied for PWS with controlled obesity and hyperphagia (70.70 vs 64.46, P = 0.02). Exclusion of noncompleters did not introduce obvious bias because traders and noncompleters were similar in treatment priorities and characteristics. The exclusion of nontraders did not meaningfully alter mean or distribution of valuations.
Conclusions: This study found that avoiding hyperphagia decreases the burden of PWS and that these results are robust, even once imposing strict inclusion criteria. Use of fixed health states to estimate QALYs addresses many of the complexities of measuring disease burden in rare and pediatric conditions, indicating the potential value of this approach to inform premarket decision makers in identifying outcome importance.