Document Type

Article

Publication Date

12-1-2025

Journal / Book Title

Orphanet Journal of Rare Diseases

Abstract

Background: Rhizomelic chondrodysplasia punctata (RCDP) is a rare genetic disorder characterized by symptoms such as respiratory dysfunction, seizures, orthopedic issues, and neurodevelopmental delay. Potential therapeutics for RCDP warrant the development of clinical outcome assessments to assess the efficacy of treatment and the well-being of patients. Our study aimed to develop a valid quality-of-life (QOL) caregiver-reported survey instrument, RhizoQOL, to be used as a supportive endpoint in RCDP clinical trials. Methods: Development of the RhizoQOL survey tool included three RCDP caregiver focus groups to elicit concepts to serve as potential domains in a QOL survey instrument for RCDP, pilot survey development and initial testing, cognitive interviewing of revised survey drafts to determine content validity, as well as a three-month longitudinal study for reliability and internal consistency of the survey instrument. Results: Twenty-eight caregivers participated in the focus groups, reporting that concepts that could be appropriate domains of QOL in RCDP include psychosocial behavior, feeding symptoms, mobility symptoms, respiratory symptoms, seizures and related activity, and impact of treatment. Following pilot survey testing (n = 22) and stakeholder feedback, a revised pilot survey instrument was administered to five caregivers for cognitive interviewing. This resulted in a revised survey instrument with 31 question items, six domains, and a 1–5 Likert scale item response assessing frequency or severity of event in the question item. Longitudinal testing (n = 18) of the revised survey instrument found the average response score was 1.98 ± 0.97 for all question items, and a Cronbach’s alpha value of 0.856, suggesting strong intra-survey question reliability. Using individual question item results from reliability testing, linear regression modeling, and testing for required magnitude of significant treatment effects, eight question items were removed from the survey instrument, resulting in a total of 23 question items within 6 discrete domains. Conclusions: The final RhizoQOL survey instrument, consisting of 23 questions, assesses the symptoms and experiences of RCDP patients as observed by caregivers and serves as a novel clinical outcome assessment for RCDP therapeutic clinical trials to assess the impacts of RCDP and support the overall effectiveness of treatments.

DOI

10.1186/s13023-025-03660-0

Rights

This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Published Citation

Bose, M., Anglade, T. C., Donlon, C. I., Kerrihard, A. L., Berger, H. F., Berkowitz, A. S., Ritchie, S. A., & Smith, T. M. (2025). Development and evaluation of RhizoQOL, a quality-of-life caregiver-reported survey for rhizomelic chondrodysplasia punctata, a rare peroxisomal disorder. Orphanet Journal of Rare Diseases, 20(1), 147. https://doi.org/10.1186/s13023-025-03660-0

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