Caregiver priorities for endpoints to evaluate treatments for Prader-Willi syndrome: a best–worst scaling

Abstract

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’ lifetimes. This study quantified caregiver priorities for potential treatment endpoints to identify unmet needs in PWS.

Methods: The authors partnered with the International Consortium to Advance Clinical Trials for PWS (PWS-CTC) and a diverse stakeholder advisory board to develop a best–worst scaling instrument. Seven relevant endpoints were assessed using a balanced incomplete block design. Caregivers were asked to determine the most and least important of a sub-set of four endpoints in each task. Caregivers were recruited nationally though patient registries, email lists, and social media. Best–worst score was calculated to determine caregiver priorities; ranging from 0 (least important) to 10 (most important). A novel kernel-smoothing approach was used to analyze caregiver endpoint priority variations with relation to age of the PWS individual.

Results: In total, 457 caregivers participated in the study. Respondents were mostly parents (97%), females (83%), and Caucasian (87%) who cared for a PWS individual ranging from 4–54 years. Caregivers value treatments addressing hyperphagia (score = 7.08, SE = 0.17) and anxiety (score = 6.35, SE = 0.16) as most important. Key variations in priorities were observed across age, including treatments targeting anxiety, temper outbursts, and intellectual functions.

Conclusions: This study demonstrates that caregivers prioritize hyperphagia and, using a novel method, demonstrates that this is independent of the age of the person with PWS. This is even the case for parents of young children who have yet to experience hyperphagia, indicating that these results are not subject to a hypothetical bias.

Keywords:

• Patients’ perspectives
• patients’ preferences
• rare disease
• Prader-Willi Syndrome
• hyperphagia
• endpoint prioritization
• best–worst scaling

JEL codes:

• *C99
• C89

Transparency

Declaration of funding

Research reported in this publication was supported by a grant from the International Consortium to Advance Clinical Trials for PWS (PWS-CTC). The purpose of this funding is to understand patient perspectives.

Declaration of financial/other interests

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from that disclosed. JME peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Acknowledgments

The authors appreciate the leadership and dedication of the community advisory board, including Theresa Strong, Nathalie Kayadjanian, Ann Scheimann, Shawn McCandless, Lauren Roth, Emma Roth, Sara Cotter, Maria Picone, Rob Lutz, Vonnie Sheadel, John Heybach, Conner Heybach, and Mark Greenberg, that contributed in the study design and the survey development. We are grateful for the caregivers who responded to the survey, and Winter Maxwell Thayer, who assisted in the recruitment, qualitative interviews, and survey data imputation. Special thanks to the Prader-Willi Syndrome Association and Foundation for Prader-Willi Research for assisting with recruitment.

Previous presentations

This study was presented at the 22^nd and 23^rd Annual Meeting of the International Society for Pharmacoeconomics and Outcomes Research as poster presentations.