Purpose: The aim was to evaluate the measurement properties of the Growth Hormone Deficiency-Child Treatment Burden Measure-Child (GHD-CTB-Child), a patient-reported outcome (PRO) for children aged 9 to < 13 years; the Growth Hormone Deficiency-Child Treatment Burden Measure-Observer (GHD-CTB-Observer), an observer-reported outcome (ObsRO) version completed by parents/guardians of children with growth hormone deficiency (GHD) aged 4 to < 9 years; and the Growth Hormone Deficiency-Parent Treatment Burden Measure (GHD-PTB), a PRO that assesses the treatment burden of parents/guardians living with children with GHD aged 4 to < 13 years.
Methods: A non-interventional, multi-center, clinic-based study across 30 private practice and large institutional sites in the United States and the United Kingdom was conducted. The sample consisted of 145 pre-pubertal children aged 9 to < 13 years at enrollment with a physician confirmed GHD diagnosis as well as 98 parents/guardians of pre-pubertal younger children aged 4 to < 9 years at enrollment with a physician confirmed GHD diagnosis. The child sample consisted of 59 treatment-naïve children (no prior exposure to growth hormone [GH] therapy; were starting GH treatment at study start per standard of care) and 184 children already maintained on treatment for at least 6 months. At baseline, all study participants completed a paper validation battery including all measures needed to conduct the validation analyses. Follow-up assessments with children in the maintenance group and their caregiver/parent were conducted approximately 2 weeks post-baseline to evaluate test-retest reproducibility. To evaluate sensitivity to change and meaningful change thresholds, treatment-naïve participants in both child and parent/guardian populations were assessed within 1 week of report of minimal improvement between week 3 and week 11 and at week 12. Psychometric analyses were implemented following an a priori statistical analysis plan.
Results: Factor analyses confirmed the a priori conceptual domains and Overall score for each measure (GHD-CTB-Child and GHD-CTB-Observer domains: Physical, Emotional Well-being, and Interference; GHD-PTB domains: Emotional Well-being and Interference). Internal consistency was acceptable for all measures (Cronbach's alpha > 0.70). Test-retest reliability was acceptable for the Physical, Emotional, and Overall domains of the GHD-CTB versions, and the Emotional and Overall domains of the GHD-PTB (intraclass correlation coefficient above 0.70). All but one of the convergent validity hypotheses for the GHD-CTB versions and all hypotheses for the GHD-PTB were proven (r > 0.40). Known-groups validity hypotheses were significant for length of time to administer the injections in the GHD-CTB versions (p < 0.001 for Physical, Emotional, and Overall, and p < 0.01 for Interference) and whether parents/guardians versus child gave the injections more often for the Emotional domain of the GHD-PTB (p < 0.05). Associated effect sizes ranged from -0.27 to -0.57 for GHD-CTB versions and from -0.74 to -0.69 for the GHD-PTB, indicating that the measures are sensitive to change. Anchor-based patient and parent/guardian ratings of severity suggest preliminary meaningful change thresholds (GHD-CTB: 6 points for Physical score, 9 for Emotional, and 6 for Interference; GHD-PTB: 10 points for Emotional and 6 for Interference scores).
Conclusions: The psychometric properties of the GHD-CTB-Child, GHD-CTB-Observer, and GHD-PTB support the validity of their use as PRO and ObsRO measures to capture the experiences associated with treatment burden for children with GHD and their parents/guardians in both clinical and research settings. The Clinicaltrials.gov registration number NCT02580032 was first posted October 20, 2015.
© 2022. The Author(s).