Background: Metachromatic leukodystrophy (MLD) is a rare disease with three forms based on the age at onset of signs and symptoms. The objective of this study was to develop a caregiver-reported clinical outcome assessment that measures impairments in physical functioning related to activities of daily living in patients with juvenile MLD., Methods: A targeted literature review and exploration of proprietary research, including a conceptual model, were conducted. Concept elicitation interviews were conducted to elicit additional concepts related to impairments in patients' physical functioning with caregivers of five individuals with juvenile MLD. Based on the research review and concept elicitation interviews, the conceptual model was updated and the Impact of Juvenile Metachromatic Leukodystrophy on Physical Activities (IMPA) scale draft items were created. Cognitive debriefing interviews were conducted with six additional caregivers to finalize the conceptual model and to refine the IMPA scale., Results: Initially, 17 potentially important concepts were identified and addressed in the draft IMPA scale. Following the cognitive debriefing interviews, 15 activities/items remained: brush teeth, comb/brush hair, bathe/shower, dress self, eat, drink, use pencil/crayon, sit upright, use toilet, get on/off toilet, walk, use stairs, get in/out of bed, get in/out of chair/wheelchair, and get in/out of vehicle. Items that did not uniquely contribute to the purpose of the instrument were removed., Conclusion: The IMPA scale, developed according to regulatory standards, provides a means of detecting changes in activities of daily living in individuals with juvenile MLD and can hence be used in future studies to measure benefits of therapeutic interventions., Competing Interests: This study was conducted in accordance with the ethical principles outlined in the Declaration of Helsinki 2008 and reviewed and approved by the RTI International Institutional Review Board. Informed consent was obtained before participation.All authors approved this manuscript and provided consent for publication.The authors declare the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article. This study was conducted by RTI Health Solutions under the direction and funding of Shire Development LLC. RTI Health Solutions was contracted by Shire to design and implement this project. T.M.B., S.M., and S.E.F. are employees of RTI Health Solutions. L.S.D. is currently at Pfizer, Inc. but was employed at Shire Development LLC during the conduct of this project and is currently a shareholder of Shire stock. Shire develops and manufactures treatments for rare diseases, including metachromatic leukodystrophy. The authors have no additional financial relationships or otherwise to declare.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.