OBJECTIVES : Prader-willi syndrome (PWS) is a rare genetic disorder associated with varying degrees of hyperphagia, obesity, intellectual disability, and anxiety across the affected individuals’ lifetime. We quantified caregiver priorities for possible treatment endpoints to identify unmet needs across the natural history of the disease.

METHODS : We partnered with the PWS Clinical Trials Consortium and a diverse stakeholder advisory board to develop a best-worst scaling instrument to assess seven relevant endpoints. A balanced incomplete block design was used to develop seven choice tasks where caregivers were asked to determine the most and least important of a subset of four treatment benefits listed in each task. Caregivers were recruited nationally though patient registry, email lists, blogs and Facebook. Best-worst score was calculated to determine caregiver priorities; with a range between -1 and 1, 1 being most important. A novel kernel-smoothing approach was used to analyze across age.

RESULTS : Of the 457 participants, caregivers were predominately parents (97%), female (83%) and Caucasian (87%) who cared for a patient with PWS ranging from 4-54 years (mean=15.6). The respondents value treatments addressing hyperphagia (score=0.417, SE: 0.01) and anxiety (score = 0.217, SE: 0.01) as most important. Key variations in priorities were observed across age, including reducing anxiety, decreasing temper outbursts, and improving intellectual functions.

CONCLUSIONS : We demonstrated variation in prioritized endpoints throughout the natural disease history of a broad-spectrum disease. The study provides a model to engage diverse stakeholders to assess unmet needs and determine treatment priorities. The study is limited in that we used caregivers’ as surrogates and the patients’ perspectives have not been fully explored.