ObjectiveGrowth hormone deficiency (GHD) treatment for children requires growth hormone injections, typically administered daily until the child reaches adult height. Child GHD treatment burden is not well understood and no disease-specific measures exist to assess this burden. The purpose of the study was to explore GHD treatment burden for children and their parents by conducting concept elicitation interviews supporting a theoretical model of the impact of GHD treatment.MethodsFour focus groups (in Germany) and 52 telephone interviews (in the UK and USA) were conducted with children/adolescents with GHD aged 8 to <13 years and parents of children with GHD aged ≥4 to <13 years. The purpose of the interviews was to understand the experience of GHD treatment from the child’s perspective, and for parents, the impact of their child’s treatment on themselves. Interview transcripts were analyzed thematically based on modified grounded theory principles.ResultsInterviews with 70 respondents who produced descriptions (n = 73) of patients experiences with GHD treatment (three parents spoke for two children each) were conducted. Analysis identified three major areas of GHD treatment burden for children: physical; emotional well-being; and interference. Parent burdens identified were: emotional well-being and interference. Modifiers such as treatment efficacy and duration, which may impact the degree of treatment burden severity, were identified.ConclusionsOverall treatment burden of child GHD is considerable for children and their parents. The concept elicitation and theoretical model can be used to develop a disease-specific outcome measure, which adequately reflects the burden of GHD treatment for children and their parents.

PurposeResearch demonstrates that children and adolescents with growth hormone deficiency (GHD) are impacted in multiple ways beyond their short stature; however, there are no disease-specific measures to assess these impacts. The purpose of this study was to examine the burden of GHD on children and adolescents, and to conduct concept elicitation to develop a model of the impact of GHD to support a disease-specific outcome measure.MethodsFour focus groups and 52 telephone interviews were conducted with children with GHD and parents/guardians of children with GHD to understand the experience and impacts from the child’s perspective, reported by children or parent-observers about the impact on the child. The interviews and focus groups were conducted in Germany, the United Kingdom, and the United States. Interview transcripts were analyzed thematically based on modified grounded theory principles.ResultsThere were 73 descriptions of patient’s experiences elicited from 70 respondents, as three respondents spoke for two children each. A majority of GHD descriptive narratives refer to boy children (n = 51, 69.9%) and a majority of children had taken GHD treatment (n = 64, 89%). Analysis identified four major areas of GHD impact: Signs and Symptoms (beyond short stature), Physical Aspects of Daily Life, Social Well-Being, and Emotional Well-Being.ConclusionsThe burden of GHD in children and adolescents is considerable and not limited to short stature. The severity of GHD impact on children and adolescents appears to be variable and individualized, but these data indicate that early identification and growth hormone treatment may lead to fewer impacts.

At University College Hospital and the Whittington Hospital in London we have 31 children with thalassemia major, most of them under 16 years of age. They are mostly the offspring of parents who have emigrated from Cyprus in the last 20 years. The 24 who require transfusion are maintained on a moderateley high scheme; i.e., the hemoglobin is raised from 9 up to 14 g % by six or eight weekly transfusions. Since there can no longer be any doubt that thalassemic patients with transfusional siderosis develop symptoms attributable to iron overload, usually starting around puberty, we have felt that the only hope of a reasonable long-term prognosis lies in the use of iron-chelating agents. Thalassemic patients on maintenance transfusion do not usually excrete significant quantities of iron in the urine in response to desferrioxamine until they are about three years old, because they must have an abnormal iron load to respond to the drug at all. This in itself is the central problem of chelation therapy. Once they have passed their third birthday, all our patients receive desferrioxamine, 500 mg intramuscularly six days a week, and 2 g/pint in the blood at transfusion. We have had twelve patients on long-term chelation, ten for three years and two for five years; the remaining patients are either too young or have only recently come into our care. The injections have been well tolerated, and there have been no complications of any kind from the use of desferrioxamine. We have measured the amount of iron excreted in the urine, and clinical observations have included liver biopsy and endocrinological studies in some patients. Measurements of liver-iron concentration have been done by Dr. Michael Barry.It is still too early to assess the clinical value of the chelation scheme we are using, but nevertheless some useful observations can be made at this stage. These clinical observations will be presented under the three headings of our expectations, our findings, and improvements in our chelation scheme in the light of these findings.Our expectations are outlined in FIGURE 1, which shows the factors affecting iron balance in a thalassemic patient on chelation therapy. First on the input side is excessive gastrointestinal iron absorption, which can reach 10 mg/day in an anemic patient. We know little about this except that it is reduced by transfusion,l and that it can be a substantial item in our patients. The major factor on the input side is iron received as blood, which averages 5-15 mg/day in our patients, according to age and transfusion status. On the output side, there are spontaneous losses of iron in the urine and stool. Our patients over four years old, when not chelated, lose on average 1.5 mg/24 hr (range 0.1-2.2

PurposeThe 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 Wellbeing 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 an...