Presentation (CTI)

OBJECTIVES: Multiple sulfatase deficiency (MSD) is an ultra-rare, progressive pediatric-onset neurodegenerative disorder characterized by delayed diagnosis, absence of disease-modifying therapy, and substantial unmet needs. In ultra-rare diseases, uncertainty around patient-centered outcomes particularly constrains early clinical development and value assessment, and is further amplified in pediatric research, where trial participation is contingent on caregivers defining acceptability and meaningful benefit. This REMEDi4ALL study aimed to engage caregivers early to determine key elements of unmet medical need, identify meaningful outcomes, and procedural criteria for patient-centered clinical trial design in a drug repurposing program for MSD.
METHODS: Semi-structured individual and group interviews were conducted with caregivers affected by MSD to explore lived experience, treatment expectations, risk-benefit considerations, and clinical trial participation. Thematic analysis was applied to identify caregiver-defined unmet needs, meaningful benefits (to be translated into patient-centered outcomes), and trial acceptability considerations. Findings were integrated and mapped to clinical trial design considerations, supporting outcome selection and protocol refinement.
RESULTS: Caregiver-defined unmet needs clustered across five domains: therapeutic gaps; clinical care gaps; trial delivery and participation gaps; measurement and evidence gaps; and supportive and mental health care gaps. Caregivers identified meaningful benefits, including disease stability, reduction of symptom burden (particularly pain, vomiting, and sleep disruption), and caregiver quality of life, all informing patient-centered outcome selection. Caregivers reported willingness to participate in clinical trials, provided pain was minimized, communication was transparent, and individual care needs were respected. Caregivers indicated that biomarker endpoints were acceptable as a pragmatic endpoint choice, enabled by low-burden, home-based sample collection (e.g., urine samples).
CONCLUSIONS: This study demonstrates how early caregiver engagement can generate decision-relevant evidence that informed biomarker and patient-relevant endpoint selection and supported scientific advice discussions. These findings contribute to ongoing efforts to formalize patient-defined value in MSD and offer broader insights for patient-centered trial design in ultra-rare diseases.