Psychometric Performance of the QoLISSY Questionnaire in a Randomized Clinical Trial for Growth Hormone Treatment in Short Stature Youth in the United States and Chile

Background: Short stature in pediatric populations is associated with negative impacts on psychosocial well-being, higher occurrences of bullying, social isolation and stigmatization, and other negative health outcomes. To facilitate the improvement of the quality of life of this patient group, the Quality of Life in Short Statue Youth (QoLISSY) questionnaire was developed, which assesses the health-related quality of life (HrQoL) of short-statured children and adolescents via self- and proxy reports. This thesis aims to evaluate the psychometric performance of the QoLISSY instrument, using data from a previous study in which a randomized open label comparator trial was conducted that compared treatment of idiopathic short stature (ISS) in adolescent males with aromatase inhibitors (AI), growth hormones (GH), and a combination treatment of both (AI/GH). Methods: In total, 76 boys diagnosed with ISS (12 to 18 years) and their parents were recruited. Patients were treatment naïve and randomized into a treatment type (AI, GH, or AI/GH). In addition to clinical variables, HrQoL was assessed using the QoLISSY and KIDSCREEN questionnaires before and after 12, 24, and 36 months of treatment. Descriptive statistics, content validity, construct validity, internal consistency, responsiveness, and parent-child score agreement were analyzed. Results: The QoLISSY instrument shows good internal consistency, convergent validity, inter-scale correlations, and content validity. This is also true for most scales in terms of skewness, floor and ceiling effects, and divergent validity. The results of this thesis suggest that the QoLISSY instrument can detect significant changes of HrQoL between baseline and 24-months. The combination therapy (GH and AI) group reported higher HrQoL in all scales than the other two treatment types for both the child and parent report. Conclusion: Results support that the QoLISSY is a psychometrically-sound instrument that can be used to track HrQoL changes over time, explore the experiences associated with short stature (and its treatment) through both the perspectives of the patients and their parents, and to highlight areas in life of short-statured children and adolescents that can be improved through intervention. Keywords: health-related quality of life, idiopathic short stature, patient-reported outcomes, aromatase inhibitors, growth hormone, randomized open label comparator trial