Key measurement concepts and appropriate clinical outcome assessments in pediatric achondroplasia clinical trials

This is the authors' abstract. We don't add key points for this paper.

Background: This study aimed to identify t-for-purpose clinical outcome assessments (COAs) to evaluate physical function and social and emotional well-being in clinical trials enrolling a pediatric population with achondroplasia.Qualitative interviews lasting 90 minutes were conducted in the US with children/adolescents with achondroplasia and/or their caregivers.Interviews utilized concept elicitation methodology to explore experiences and priorities for treatment outcomes.Cognitive debrie ng methodology explored relevance and understanding of selected COAs.Results: Interviews (N=36) were conducted with caregivers of children age 0-2 years (n=8) and 3-7 years (n=7) and child/caregiver dyads with children age 8-11 years (n=15) and 12-17 years (n=6).Children/caregivers identi ed pain, short stature, impacts on physical functioning (e.g.reach), and impacts on well-being (e.g.negative attention/comments) as key bothersome aspects of achondroplasia.Caregivers considered an increase in height (n=9/14, 64%) and an improvement in limb proportion (n=11/14, 71%) as successful treatment outcomes.The Childhood Health Assessment Questionnaire (CHAQ) and Quality of Life in Short Stature Youth (QoLISSY-Brief) were cognitively debriefed.CHAQ items evaluating activities, reaching, and hygiene were most relevant.QoLISSY-Brief items evaluating reaching, height bother, being treated differently, and height preventing doing things others could were most relevant.The CHAQ and QoLISSY-Brief instructions, item wording, response scales/options and recall period were well understood by caregivers and adolescents age 12-17.Some children aged 8-11 had di culty reading, understanding, or required caregiver input.Feedback informed minor amendments to the CHAQ and the addition of a seven-day recall period to the QoLISSY-Brief.These amendments were subsequently reviewed and con rmed in N=12 interviews with caregivers of children age 0-11 (n=9) and adolescents age 12-17 (n=3).Conclusions: Achondroplasia impacts physical functioning and well-being.An increase in height and improvement in limb proportion are considered to be important treatment outcomes, but children/adolescents and their caregivers expect that a successful treatment should also improve important functional outcomes such as reach.The CHAQ (adapted for achondroplasia) and QoLISSY-Brief are relevant and appropriate measures of physical function and emotional/social well-being for pediatric achondroplasia trials; patient-report is recommended for age 12-17 years and caregiver-report is recommended for age 0-11 years.