The Development of a Clinician-Rated Clinical Outcome Assessment for Wolf-Hirschhorn Syndrome

Wolf-Hirschhorn syndrome (WHS) is a rare genetic illness caused by a deletion of the short arm of chromosome 4. It is a complex, heterogenous illness; clinical features include learning disability, epilepsy, feeding difficulties and cardiac defects. As a result of its low prevalence and lack of appropriate assessments, clinicians unfamiliar with the disease may fail to assess the patients appropriately, resulting in unmet clinical needs of this population. This study utilised a mixed-methods approach to develop a Clinician-rated Clinical Outcome Assessment (COA) to address this, to ensure appropriate and safe assessment of patients with WHS. COA development is a complex and iterative process; the methods of the current project included: • Extensive literature reviews • An interview study with family caregivers of adults and children with WHS living in the UK; results directly informed the content of the COA and highlighted a plethora of previously unreported psychosocial implications of being a caregiver for a relative with WHS • Development of a Conceptual Framework, based on published literature and interview findings, that directly informed COA content (items, domain structure) • A consensus study with international clinician experts on WHS to ensure clinical utility, acceptability and content validity of the COA, changes were made in accordance with comments and suggestions • A validation study to assess accuracy, reliability and construct validity of the COA; using vignettes as a creative, novel method to validate COAs for rare diseases Overall, results indicated moderate to good reliability and high levels of construct validity. Due to the study design, future work is required to ensure field testing with a large patient cohort and an assessment of criterion-related validity