Development and Psychometric Evaluation of the Life Interference Questionnaire for Growth Hormone Deficiency (LIQ-GHD) to Assess Growth Hormone Injection Burden in Children and Adults

摘要

Background Current recombinant human growth hormone (r-hGH) replacement therapy involves long-term daily subcutaneous injections to treat growth hormone deficiency (GHD) in children and adults. Daily r-hGH injections can be burdensome, often resulting in poor treatment compliance. Clinical outcome assessments (COAs) can capture the burden of these injections from the patient (and caregiver) perspective and may demonstrate the benefit of a less-frequent r-hGH injection regimen, which may ultimately improve treatment compliance and long-term outcomes. Objective To address this knowledge gap, qualitative research was conducted to inform the development of a new Life Interference Questionnaire for Growth Hormone Deficiency (LIQ-GHD), designed to measure the experiences of patients taking r-hGH GHD injections. A second objective was to evaluate the hypothesized factor structure and preliminary performance of the LIQ-GHD in a cross-sectional observational study. Methods An empirical literature review and expert advice meetings were conducted to inform development of the draft LIQ-GHD (pediatric and adult versions). In-person concept elicitation and cognitive debriefing interviews were conducted with GHD patients (and patient dyads including caregivers) to explore and confirm concept coverage and evaluate respondents' ability to understand the questionnaire. The draft LIQ-GHD was then tested in a cross-sectional field study involving pediatric and adult patients receiving daily r-hGH injections for GHD. The factor structure, reliability, and validity were analyzed for the overall sample and for pediatric, adolescent, and adult subgroups. Results Results from the literature review and input from six experts were used to develop and refine the LIQ-GHD, with content covering pen ease of use; regimen convenience; life interference due to regimen; benefit/satisfaction/willingness to continue treatment; regimen choice/preference; intent to comply with regimen; injection-related signs/symptoms; and reasons for missed injections. Twenty-one patient interviews confirmed comprehensive concept coverage and patient/caregiver comprehension of the LIQ-GHD. A total of 224 patients (n = 70 children/caregiver dyads, n = 79 adolescents/caregiver dyads, n = 75 adults) participated in the field study. While most items showed floor effects, confirmatory factor analysis fit statistics were good for the overall sample (root mean square error of approximation = 0.07, comparative fit index = 0.98) and for the full pediatric sample after dropping co-dependent questions from the model. Cronbach's alpha (alpha) ranged from 0.746 to 0.905 and intra-class correlation coefficients ranged from 0.761 to 0.918 for the overall sample on LIQ-GHD domains. Scores correlated as predicted with an existing criterion measure in the overall sample and LIQ-GHD domain scores distinguished known groups as expected. Conclusions The LIQ-GHD is a new COA for the measurement of r-hGH injection treatment burden. This research provides evidence supporting its content validity, hypothesized factor structure, score reliability, and construct validity in pediatric and adult populations.