Assessing signs and impacts of achondroplasia

Abstract

BACKGROUND: Achondroplasia, although rare, is the most common genetic form of skeletal dysplasia and is associated with a wide range of clinical manifestations and complications throughout the body. This study evaluated the psychometric measurement properties of the Achondroplasia Child Experience Measures (ACEMs), which were previously conceptually developed as condition-specific, observer-reported outcome measures to assess the signs (ACEM-OSM) and impacts (ACEM-Impact) of achondroplasia in children aged 2 to < 12 years.

METHODOLOGY: Data for the psychometric evaluation were from a non-interventional, observational study (N = 200 (impacts) and N = 148 (signs)) and a phase 2, multicenter, double-blind, randomized, placebo-controlled, dose escalation interventional trial (N = 57) of navepegritide (TransCon CNP) administered once weekly. The larger observational study sample size allowed for evaluation of distributional properties, test-retest reliability, and construct validity. Trial data was analyzed to confirm reliability and validity findings and evaluate responsiveness.

RESULTS: Factor analysis and qualitative results identified six domains for the ACEM-Impact and one domain for the ACEM-OSM. The psychometric properties of both measures were found to be acceptable for reliability and validity for the intended use. An 8-item ACEM-OSM and a 25-item ACEM-Impact were finalized.

CONCLUSIONS: The ACEMs are reliable and valid measures of the signs and impacts of achondroplasia on children. Incorporation of these measures in clinical and research settings can aid in assessing new treatments and improve our understanding of the experience of those living with achondroplasia.

TRIAL REGISTRATION: National Institutes of Health Clinicaltrials.gov (ID NCT04085523) and European Union Drug Regulating Authorities Clinical Trials database (EudraCT 2019-002754-22).