SUN-248 Growth Hormone Deficiency (GHD): Assessing Burden of Treatment in Children and Adolescents

Abstract

Background: Growth hormone deficiency treatment involves daily injections, which can be difficult to administer, incorporate into daily routines, and lead to poor treatment compliance. The Treatment Burden–Child Growth Hormone Deficiency (TB-CGHD) measure was developed according to FDA and EMA regulatory guidance to assess key aspects of GHD treatment burden experience in children. There are two versions of the measure: self-report (PRO) for children 9 to <13 years and observer-report (ObsRO) for parents/guardians of children 4 to <9 years. Items are based on qualitative interviews with 39 children and 34 parents of children with GHD. This study presents TB-CGHD validation study results. Methods: A non-interventional, multi-clinic-based study (US and UK) of pre-pubertal children diagnosed with GHD (treatment naïve [TN] or ongoing treatment) and parents/guardians of similar children was conducted. All subjects completed a baseline assessment battery in clinic, with in-person follow-up for the TN group. Psychometric analyses were conducted according to an a-priori statistical analysis plan to determine the measurement model, internal consistency, construct validity, test-retest reproducibility, sensitivity to change and minimally important difference (MID). Results: The analytic data set was comprised of 243 subjects (145 children and 98 parents/guardians). Children were on average 9.2 years, 72% male, with average child’s age at diagnosis 6.9 years. Post item reduction resulted in a 14-item measure. Factor analyses identified 3 domains (Physical (PHYS), Emotional Well-being (EWB), Interference (INT)). Internal consistency reliability was acceptable (Cronbach’s alpha >0.70) as was test-retest for the Total, PHYS and EWB domains (ICC >0.70) and slightly lower than expected for INT (0.64). At least one of the convergent validity hypotheses for total and domains were significant. For known-groups validity, TB-CGHD discriminated between length of time to administer injections (p<0.01) and a trend showing scores differed by length of time on treatment. Improvements in scores at 12-week follow-up were shown for EWB and Overall domains (range: 3.6-14.3 points). Associated effect sizes (mean change divided by the baseline standard deviation) ranged from -0.27 to -0.57, indicating that the TB-CGHD is sensitive to change at low to moderate levels depending on domain. Triangulating (averaging various MID calculation methods) found the MID for the Total scores of PHYS and INT to be 6 points, and 9 for EWB. Conclusions: The final TB-CGHD was found to be reliable and valid and is considered ready for inclusion in clinical trials and clinical practice. Accurate and reliable assessment of treatment burden can help researchers and clinicians better assess and address impacts of treatment, factors that may affect compliance, and may improve the quality of doctor-patient communications.