Qualitative research of Dup15q syndrome symptoms and impacts to inform disease concept models

Background Dup15q syndrome is a rare neurodevelopmental disorder associated with severe disabling symptoms giving substantial caregiver burden. No formal, systematic research of the most common symptoms and lived experience of Dup15q syndrome has been published. Disease concept models are recognized as valuable for reflecting the lived experience of individuals with a condition, including relevant symptoms, and associated impacts. A patient-centered concept model can inform clinical outcome assessment (COA) development and selection for use in clinical trials. This study utilized published literature and concept elicitation interviews with caregivers of individuals with Dup15q syndrome. Methods The study included a targeted review of peer-reviewed publications from 2018 to 2023 and in-depth, semi-structured interviews with 15 caregivers from the United States and United Kingdom. Interview data were coded and analyzed based on the principles of thematic and content analysis using NVivo. The concept model was then reviewed and discussed with an expert panel on multiple occasions. Results Caregivers unanimously reported challenges pertaining to communication, cognition, motor function, behavior, autistic characteristics, and sleep. Gastrointestinal symptoms, anxious behaviors, feeding difficulties, seizures, and high pain thresholds were also frequently reported. The concept models include seven symptom domains and five impact domains, alongside a caregiver/family impact model that covers six domains. The disease concept models reflect both core symptoms and the convergence of challenges across domains that shape daily life for individuals and families affected by Dup15q syndrome. Conclusions This qualitative study summarizes published data as well as novel research from caregivers of individuals with Dup15q syndrome and presents evidence-based concept models of symptoms and impacts on individuals and families. The models support clinical study design and COA development and selection by clearly identifying meaningful concepts of interest based on caregiver-reported experience. These models can serve as a foundation for future endpoint design, and regulatory engagement in Dup15q syndrome clinical trials. Trial registration Not applicable. This study did not involve a health care intervention and was not a clinical trial.