Content validation of the SF-36v2® Health Survey Acute for use in hypoparathyroidism.

PURPOSE: The purpose of this study was to conduct cognitive debriefing (CD) interviews with adults diagnosed with chronic hypoparathyroidism (HP) to assess the content validity of the SF-36v2® Health Survey Acute (SF-36v2) measure in this population. METHODS: CD interviews were conducted with adults with HP in the United States (US). Interviews were conducted by a trained moderator using a semi-structured interview guide, employing a think-aloud method in conjunction with verbal probing. Participants were asked whether each item was understandable, relevant, important, and sensitive to change in relation to HP. Additionally, comprehension of instructions, response options, and the appropriateness of a 1-week recall period was assessed. RESULTS: Sixteen adults with HP participated in individual CD telephone interviews. All items in the SF-36v2 were reported to be understood, relevant, important, and sensitive to change by at least half, and in most cases, by a strong majority of study participants. Most of the study sample confirmed comprehension of the instructions and the entire sample understood all response options. CONCLUSION: The study findings show that the items in the SF-36v2® are applicable to adults with HP. The overall high levels of endorsement of items provide strong evidence of the measure's content validity for this population. The SF-36v2 is therefore recommended for usage in clinical trials examining adults with HP, although it is recommended that this generic measure be supplemented with disease-specific instruments such as the recently developed Hypoparathyroidism Patient Experience Scale-Symptom (HPES-Symptom) and Hypoparathyroidism Patient Experience Scale-Impact (HPES-Impact) measures.

Functioning and well-being in older children and adolescents with achondroplasia: A qualitative study.

The study aimed to explore how having achondroplasia affects older children and adolescents' day-to-day functioning and well-being. Individual/focus group interviews were conducted with older children/adolescents between the ages of 9 to <18 years and diagnosed with achondroplasia to elicit key concepts. An adapted grounded theory approach informed the qualitative analysis of interview data. Thirty-two children and adolescents completed interviews. Study results revealed five impact domains, including physical health, functioning, school impacts, emotional well-being, and social well-being. Frequently reported impacts on physical health included low stamina/tiring easily (81%) and back pain (69%). Key impacts in the functioning domain were difficulty with reaching objects or high places (84%) and walking long distances (75%). Emotional impacts included feeling different (63%), worried/scared (47%), and embarrassed/self-conscious (47%). Impacts on social well-being included difficulty with sports or physical play (81%) and others treating child as younger than their actual age (75%). The most frequent school impact was trouble participating in physical education (81%). A preliminary theoretical model depicting the experiences of older children/adolescents with achondroplasia was constructed based on the analysis. The preliminary theoretical model of older children and adolescents' experiences of living with achondroplasia may be used to inform future research and clinical practice.

Assessing physical symptoms, daily functioning, and well-being in children with achondroplasia.

This study's purpose was to provide qualitative evidence to support the development of two observer-reported outcome measures assessing the physical symptoms/complications of achondroplasia in children and impacts on children's quality of life. Individual/focus group concept elicitation interviews were conducted with parents of children aged 2 to <12 years with achondroplasia and experts. Qualitative analysis of transcripts, based on an adapted grounded theory approach, informed item generation and measure development. Cognitive debriefing (CD) interviews were conducted with parents to confirm relevance and understanding. Thirty-six parents participated in concept elicitation interviews. The analysis identified major physical symptoms/complications and impacts of achondroplasia, which informed the development of the Achondroplasia Child Experience Measures (ACEMs): ACEM-Symptom and ACEM-Impact. ACEM-Symptom was comprised of eight major symptoms/complications including pain (58%), ear infections/fluid in ear (56%), and low stamina/tiring easily (56%). ACEM-Impact consisted of 31 major impacts in the domains of daily functioning, emotional well-being, social well-being, and need for assistance/adaptive devices. Impacts on functioning included difficulty reaching objects/high places (89%) and toileting (67%). Emotional impacts included feeling different (53%) and feeling frustrated/annoyed (47%). Social impacts included difficulty participating in sports/physical play (86%) and being treated as younger than age (83%). Following CD interviews with 16 additional parents, validation-ready ACEM measures were generated. The study improves our understanding of the experiences of children with achondroplasia and provides evidence supporting the content validity of the ACEMs. Validated ACEMs may be used to assess potential benefits of future treatments for comorbidities of achondroplasia.

Living with hypoparathyroidism: development of the Hypoparathyroidism Patient Experience Scale-Impact (HPES-Impact).

PURPOSE: Hypoparathyroidism (HP) is a rare endocrine disorder characterized by absent or inappropriately low levels of circulating parathyroid hormone (PTH). Research indicates that HP patients on conventional therapy may have a reduced quality of life. The study's purpose was to develop a new disease-specific measure of the impacts of hypoparathyroidism on functioning and well-being and provide evidence for its content validity based on rigorous qualitative research methodologies for patient-reported outcomes development. METHODS: Semi-structured, individual concept elicitation (CE) interviews were conducted with 5 clinical experts and 42 adults in the USA with HP to identify impacts of relevance and importance to the target population. Transcripts were coded and analyzed using an adapted grounded theory approach common to qualitative research. Following item generation, the draft measure was cognitive debriefed in an independent sample of 16 adults with HP. RESULTS: Analyses identified four impact domains: physical functioning, including ability to exercise (n = 32, 76%) and mobility (n = 21, 50%); daily life, including ability to do things around the home (n = 33, 79%), and interference with work productivity (n = 18, 43%); psychological well-being, including feeling anxious/anxiety (n = 34, 81%) and frustrated (n = 27, 64%); and social, including ability to participate in social activities (n = 33, 79%) and relationships (n = 32, 76%). Twenty-seven impacts were identified and included in the preliminary measure. After the cognitive debriefing, a validation-ready, 26-item Hypoparathyroidism Patient Experience Scale-Impact (HPES-Impact) was generated. CONCLUSION: Findings provide substantial evidence of content validity for the validation-ready HPES-Impact in adults with HP.

Assessing the impacts of having a child with achondroplasia on parent well-being.

PURPOSE: This study's purpose was to develop a better understanding of the experiences of parents of children with achondroplasia and to provide qualitative evidence to support the development of a patient-reported outcome (PRO) measure of parent impacts. METHODS: Concept elicitation (CE) individual/focus group interviews were conducted with parents of children aged 2 to < 12 years with achondroplasia in the United States and Spain. The qualitative analysis informed the PRO measure development. Cognitive debriefing (CD) interviews were conducted to ensure parent understanding and item relevance. RESULTS: Thirty-six parents participated in individual/focus group CE interviews. The analysis identified parent impacts in four domains, including caretaking responsibilities, emotional well-being, family, and work, and results informed the development of the Achondroplasia Parent Experience Measure (APEM). Caretaking responsibilities included managing child's medical care (92%), helping child with self-care (67%), advocating for child (64%), assisting child (56%), and observing/monitoring child (e.g., to ensure safety; 47%). Impacts on parents' emotional well-being included worry about the future (75%), worry about child's physical health (67%), safety concerns (50%), feeling stressed/overwhelmed (44%), and worry about child's social relationships (42%). Impacts on family and work included family strain (56%), limiting/adapting family activities (42%), and missed work time (50%). CD interviews with an additional 16 parents of children with achondroplasia confirmed understanding and item relevance. CONCLUSION: The results improve our understanding of the experiences of parents of children with achondroplasia and provide qualitative evidence to support the content validity of the APEM. A psychometric study is needed to validate the measure.

Understanding the burden of illness of excessive daytime sleepiness associated with obstructive sleep apnea: a qualitative study.

BACKGROUND: Obstructive sleep apnea (OSA) is associated with excessive daytime sleepiness (EDS), which may go undiagnosed and can significantly impair a patient's health-related quality of life (HRQOL). This qualitative research examined timing and reasons patients sought medical care for their EDS and OSA symptoms, and the impact of EDS on HRQOL. METHODS: Focus groups were conducted in 3 US cities with 42 participants currently experiencing EDS with OSA. Transcripts were coded and analyzed using an adapted grounded theory approach common to qualitative research. RESULTS: Over three-fifths of study participants (n = 26, 62%) were currently using a positive airway pressure (PAP) or dental device; one-third (n = 14, 33%) had previously used a positive airway pressure (PAP) or dental device, and the remainder had either used another treatment (n = 1, 2%) or were treatment naïve (n = 1, 2%). Twenty-two participants (52%) reported experiencing OSA symptoms for ≥1 year, with an average duration of 11.4 (median 8.0, range 1-37) years before seeking medical attention. Several (n = 7, 32%) considered their symptoms to be "normal," rather than signaling a serious medical condition. Thirty participants (71%) discussed their reasons for ultimately seeking medical attention, which included: input from spouse/partner, another family member, or friend (n = 20, 67%); their own concern about particular symptoms (n = 7, 23%); and/or falling asleep while driving (n = 5, 17%). For all 42 participants, HRQOL domains impacted by EDS included: physical health and functioning (n = 40, 95%); work productivity (n = 38, 90%); daily life functioning (n = 39, 93%); cognition (n = 38, 90%); social life/relationships (n = 37, 88%); and emotions (n = 30, 71%). CONCLUSIONS: Findings suggest that patients may be unaware that their symptoms could indicate OSA requiring evaluation and treatment. Even following diagnosis, EDS associated with OSA can continue to substantially affect HRQOL and daily functioning. Further research is needed to address diagnostic delays and unmet treatment needs for patients with EDS associated with OSA.

Understanding burden of illness for child growth hormone deficiency.

PURPOSE: Research 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. METHODS: Four 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. RESULTS: There 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. CONCLUSIONS: The 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.

Psychometric Evaluation of the Hypogonadism Impact of Symptoms Questionnaire.

INTRODUCTION: The Hypogonadism Impact of Symptoms Questionnaire (HIS-Q) is a patient-reported outcome measurement designed to comprehensively evaluate the symptoms of hypogonadism and to detect changes in these symptoms in response to treatment. AIM: To conduct item analysis and reduction, evaluate the psychometric properties of the HIS-Q, and provide guidance on interpreting the instrument score. METHODS: A 12-week observational, longitudinal study of hypogonadal men was conducted. Participants completed the HIS-Q every 2 weeks. Blood samples were collected to evaluate testosterone levels. Participants also completed the Aging Male's Symptoms Scale, the International Index of Erectile Function, the Short Form-12 Health Survey, and the Patient-Reported Outcomes Measurement Information System Sexual Activity, Satisfaction with Sex Life, Sleep Disturbance, and Applied Cognition Scales (at baseline and weeks 6 and 12). Clinicians completed the Clinical Global Impression of Severity and Change measurements and a clinical form. MAIN OUTCOME MEASURES: Individual item performance was evaluated using descriptive statistics and Rasch analyses. Reliability (internal consistency and test-retest), validity (concurrent and know groups), and responsiveness were assessed. RESULTS: In total, 177 men participated in the study (mean age = 54.1 years, range = 23-83). The original 53-item draft HIS-Q was reduced to 28 items; the final instrument included five domains (sexual, energy, sleep, cognition, and mood) with two sexual subdomains (libido and sexual function). For all domains, test-retest reliability was acceptable (intraclass correlation coefficients > 0.70), construct validity was good (|r > 0.30| for all comparisons). Known-groups validity was demonstrated for all HIS-Q domain scores, subdomain scores, and the total score as measured by the Clinical Global Impression of Severity, and total testosterone level at baseline (P < .05 for all comparisons). All domains and subdomains were responsive to change based on patient-rated anchor questions (P < .05 for all comparisons). CONCLUSION: The final 28-item HIS-Q is reliable, valid, and responsive. The HIS-Q is suitable for inclusion in future clinical trials to help characterize the effects of testosterone replacement therapy.

Development and validation of the Diabetic Peripheral Neuropathic Pain Impact (DPNPI) measure, a patient-reported outcome measure.

PURPOSE: Diabetic peripheral neuropathy (DPN) occurs in 26-47 % of diabetes patients and may have negative impacts on physical functioning, sleep, well-being, and quality of life. The Diabetic Peripheral Neuropathic Pain Impact measure (DPNPI) was developed to measure disease impacts and treatment effects. Presented are the DPNPI conceptual development and validation findings. METHODS: The DPNPI was developed following the FDA Guidance for Industry on patient-reported outcome (PRO) measures. Concept elicitation (CE) included literature review, clinical expert interviews, and patient interviews/focus groups. Qualitative data were analyzed following grounded theory principles, and draft items were cognitively debriefed. The measure underwent psychometric validation, and an a priori statistical analysis plan assessed the measurement model, reliability, and validity. Simultaneous analyses of item functioning were conducted using Rasch measurement theory (RMT). All tests were performed for the total score and each domain. RESULTS: Twenty-five patients and three clinical experts participated in CE which resulted in a 27-item validation ready measure. In the validation study (N = 124), nine draft items were dropped due to high missing data and/or high correlations between items. Factor analysis revealed three domains: physical functioning/mobility, sleep, and daily activities. RMT confirmed adequate item fit and placement within domains. Internal consistency ranged from 0.91 to 0.96 and test-retest from 0.84 to 0.91. All prespecified hypotheses for convergent and discriminant validity were met. CONCLUSIONS: CE and psychometric results provide evidence that the final, 18-item DPNPI is a reliable and valid PRO measure of disease impacts and treatment for DPNP. Further validation work should include responsiveness assessment.

Assessing the impact of non-severe hypoglycemic events and treatment in adults: development of the Treatment-Related Impact Measure-Non-severe Hypoglycemic Events (TRIM-HYPO).

PURPOSE: Non-severe hypoglycemic events (NSHEs) are commonly experienced by diabetes patients, particularly among insulin users, and can have serious impacts on daily functioning, emotional well-being, sleep, work productivity, and treatment adherence. Currently, no PRO measures are available to assess the impacts of non-severe hypoglycemia. To address this gap, the Treatment-Related Impact Measure-Non-severe Hypoglycemic Events (TRIM-HYPO) was developed. This paper describes the TRIM-HYPO development and validation. METHODS: The creation of the TRIM-HYPO followed FDA's guideline for PRO development. Concept elicitation data were gathered from literature review, clinical expert interviews, and focus groups of patients with Type 1 or 2 diabetes in four countries. Based on the qualitative analysis, draft items were generated and cognitively debriefed. Psychometric validation included factor analysis, item response theory analysis, and assessment of psychometric characteristics for the TRIM-HYPO. RESULTS: Eight clinical experts and 167 patients participated in concept elicitation. The validation study included 407 patients. Thirteen of the 46 items from the preliminary measure were dropped due to ceiling/floor effects and high correlations between conceptually similar items. Factor analysis confirmed five domains in the TRIM-HYPO: daily function, emotional well-being, diabetes management, sleep disruption, and work productivity. All scores were internally consistent (0.86-0.95) and reproducible with a test-retest range of 0.75-0.98. All but one a priori hypothesized associations for validity were confirmed. CONCLUSIONS: Study findings demonstrate that the final, 33-item TRIM-HYPO is reliable and valid and may be useful for assessing impacts related to NSHEs in research and clinical practice.

Understanding the economic burden of nonsevere nocturnal hypoglycemic events: impact on work productivity, disease management, and resource utilization.

OBJECTIVE: Nonsevere hypoglycemic events are common and may occur in one-third of persons with diabetes as often as several times a week. This study's objective was to examine the economic burden of nonsevere nocturnal hypoglycemic events (NSNHEs). METHODS: A 20-minute Web-based survey, with items derived from the literature, expert input, and patient interviews, assessing the impact of NSNHEs was administered in nine countries to 18 years and older patients with self-reported diabetes having an NSNHE in the past month. RESULTS: A total of 20,212 persons were screened, with 2,108 respondents meeting criteria and included in the analysis sample. The cost of lost work productivity per NSNHE was estimated to be between $10.21 (Germany) and $28.13 (the United Kingdom), representing 3.3 to 7.5 hours of lost work time per event. A reduction in work productivity (presenteeism) was also reported. Compared with respondents' usual blood sugar monitoring practice, on average, 3.6 ± 6.6 extra tests were conducted in the week following the event at a cost of approximately $87.1 per year. Additional costs were also incurred for doctor visits as well as medical care required because of falls or injuries incurred during the NSNHE for an annual cost of $2,111.3 per person per year. When taking into consideration the multiple impacts of NSNHEs for the total sample and the frequency that these events occur, the resulting total annual economic burden was $288,000 or $127 per person per event. CONCLUSIONS: NSNHEs have serious consequences for patients. Greater attention to treatments that reduce NSNHEs can have a major impact on reducing the economic burden of diabetes.

Validation of the controlled ovarian stimulation impact measure (COSI): assessing the patient perspective.

BACKGROUND: Controlled Ovarian Stimulation (COS) is the first step for in vitro fertilization (IVF) treatment, a treatment often described and experienced as stressful to patients and their partners. COS also requires concerted efforts by the patients in administering medication and general compliance to treatment protocols. Little is known about the impacts on patients that may be specific to this important first step in treatment. The absence of a conceptually sound and well-validated measure assessing patient experience and functioning during ovarian stimulation has been an obstacle to understanding the impacts of ovarian stimulation on women pursuing IVF. To address this gap, the Controlled Ovarian Stimulation Impact Measure (COSI) was developed based upon accepted methods for designing patient reported outcome (PRO) measures. The purpose of this study was to psychometrically validate the COSI. METHODS: 267 patients from three countries (Ireland, United Kingdom, United States) were administered the COSI. Psychometric validation was conducted according to an a priori statistical analysis plan. RESULTS: The final 28-item COSI was found to have robust scale structure with four domains: Interference in Daily Life (Work and Home), Injection Burden, Psychological Health and Compliance Worry. Internal consistency of all domains was adequate (between 0.80 to 0.87) as was test-retest reliability (between 0.72-0.87). All a-priori hypotheses for convergent and known-groups validity tests were met. CONCLUSIONS: There is a measurable impact of COS on patient functioning and well-being. The COSI is a well-developed and validated PRO measure of this impact. Future work should include examination of responsiveness and confirmation of concepts in non-western countries.

Non-severe nocturnal hypoglycemic events: experience and impacts on patient functioning and well-being.

PURPOSE: Non-severe nocturnal hypoglycemic events (NSNHEs) are hypoglycemic events that occur during sleep but do not require medical assistance from another individual. This study was conducted to better understand the NSNHEs as patients actually experience them in their daily life, and how they impacted functioning and well-being. METHODS: Nine focus groups were held in four countries with diabetics (Type 1 and Type 2) who had experienced an NSNHE within the previous month: France (2 groups); Germany (2 groups); United Kingdom (2 groups); and United States (3 groups). These groups were audio-taped, translated to English where applicable, and analyzed thematically. RESULTS: Seventy-eight people with diabetes participated in the focus groups: 41 (53 %) were female and 37 (47 %) were male; 24 (31 %) had Type 1 diabetes, and 54 (69 %) had Type 2 diabetes. Participant reports were grouped into several major themes: next day effects, symptoms, sleep impacts, social impacts, corrective action, practical management, feelings about NSNHEs, and work impacts. CONCLUSIONS: People with both Type 1 and Type 2 diabetes experience NSNHEs. The range of impact on these patients is wide, from very mild to severe with a majority of participants experiencing strong impacts that limit their daily functioning. This finding suggests that NSNHEs are more impactful than previously believed.

Development and Validation of the Diabetes Pen Experience Measure: A New Patient-Reported Outcome Measure.

BACKGROUND: Satisfaction with insulin-delivery devices has been shown to improve treatment adherence, translating into better glycemic control. The Diabetes Pen Experience Measure (DPEM) is a new patient-reported outcome measure to evaluate patients' experience when using an injection device. METHODS: The DPEM was developed using literature review and concept elicitation interviews with clinical experts and patients. This led to a theoretical model and a draft measure of the diabetes pen experience, which was refined following cognitive debriefing. Validation entailed a web-based, noninterventional survey; psychometric analyses conducted according to a statistical analysis plan; and refinement and finalization of the DPEM and theoretical model. RESULTS: In total, 42 patients participated in concept elicitation interviews. Analysis of the qualitative interviews resulted in a preliminary theoretical model. Based on this model, DPEM items were generated; the preliminary version of the DPEM contained 30 items. Following cognitive debriefing, the validation-ready version comprised 28 items. These were later reduced to 7 higher-order items owing to ceiling/floor effects. In total, 300 patients participated in the web-based validation study. The item statistics were all adequate. Item-to-item correlations were good. Item-to-total correlations displayed acceptable associations between each item against the rest of the items, with correlations of 0.68 to 0.79. The internal consistency was adequate, with a Cronbach's alpha of 0.91. The DPEM is scored by summing the 7 item scores and transforming the sum onto a 100-point scale. CONCLUSION: The evidence presented supports the use of the DPEM in clinical trials to evaluate the patients' experience with diabetes injection devices.

Understanding treatment burden in hemophilia: development and validation of the Hemophilia Treatment Experience Measure (Hemo-TEM).

BACKGROUND: To capture the broad range of treatment burden issues experienced by adolescent and adult people with hemophilia (PWH), the Hemophilia Treatment Experience Measure (Hemo-TEM) was developed. We describe the development of this new hemophilia-specific patient-reported outcome (PRO) measure including concept elicitation, cognitive debriefing, and psychometric validation. RESULTS: Concept elicitation interviews were conducted with 5 clinical experts and 30 adult PWH in the United States (US). The qualitative analysis of these interviews and a review of the literature informed the PRO measure development. The project team reviewed concept endorsement rates and generated a 27-item preliminary version of the Hemo-TEM. Cognitive debriefing interviews were conducted to ensure participant understanding and item relevance in samples of (adolescent (n = 20) and adult (n = 14)) PWH in the US. The refined, validation-ready version of the Hemo-TEM included 30 items. Lastly, data from 3 clinical trials comprised the 4 analysis sets used for the psychometric validation with a sample size of N = 88. Item reduction dropped 4 items resulting in a final 26-item measure. Factor analysis generated 5 domains in the Hemo-TEM [injection difficulties (3 items), physical impact (6 items), treatment bother (7 items), interference with daily life (4 items), and emotional impact (6 items)] and a total score. All scores were reliable [internally consistent (0.84-0.88)]. For convergent validity, with the exception of one domain, all hypothesized associations were met. Preliminary sensitivity to change effect sizes were between - 0.30 and - 0.70. Meaningful change thresholds ranged from 6 points (physical impact and emotional impact) to 10 points (treatment bother) with 8 points for the Hemo-TEM total score. CONCLUSIONS: Findings from the concept elicitation, cognitive debriefing, and psychometric validation phases provide evidence that the Hemo-TEM is a well-designed, valid, and reliable measure of the burden of hemophilia treatment, including treatment impact on adolescent and adult PWH.

Weekly Somapacitan in GH Deficiency: 4-Year Efficacy, Safety, and Treatment/Disease Burden Results From REAL 3.

CONTEXT: Growth hormone deficiency (GHD) in children is currently treated with daily injections of GH, which can be burdensome for patients and their parents/guardians. Somapacitan is a GH derivative in development for once-weekly treatment of GHD. OBJECTIVE: This work aimed to assess the efficacy and safety of somapacitan, and associated disease/treatment burden, after 4 years of treatment and 1 year after switching to somapacitan from daily GH. METHODS: This long-term safety extension of a multicenter, controlled phase 2 trial (NCT02616562) took place at 29 sites in 11 countries. Patients were prepubertal, GH-naive children with GHD. Fifty patients completed 4 years of treatment. Patients in the pooled group received somapacitan (0.04, 0.08, 0.16 mg/kg/week) for 1 year, followed by the highest dose (0.16 mg/kg/week) for 3 years. Patients in the switched group received daily GH 0.034 mg/kg/day for 3 years, then somapacitan 0.16 mg/kg/week for 1 year. Main outcome measures were height velocity (HV), change from baseline in HV SD score (SDS), change from baseline in height SDS, disease burden, and treatment burden for patients and parents/guardians. RESULTS: Changes from baseline in HV and HV SDS were similar and as expected in both groups. Observer-reported outcomes showed that patients and parents/guardians seem to have experienced a reduced treatment burden when switching from daily GH to somapacitan. Most parents/guardians (81.8%) strongly/very strongly preferred somapacitan over daily GH. CONCLUSIONS: Somapacitan showed similar efficacy and safety in patients who continued somapacitan treatment and those who switched from daily GH to somapacitan. Once-weekly injections may lead to a reduced treatment burden relative to once-daily injections. A plain-language summary of this work is available.

Psychometric Validation of the Growth Hormone Deficiency-Child Treatment Burden Measure (GHD-CTB) and the Growth Hormone Deficiency-Parent Treatment Burden Measure (GHD-PTB).

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.

Comparison of the burden of illness for adults with ADHD across seven countries: a qualitative study.

BACKGROUND: The purpose of this study was to expand the understanding of the burden of illness experienced by adults with Attention Deficit-Hyperactivity Disorder (ADHD) living in different countries and treated through different health care systems. METHODS: Fourteen focus groups and five telephone interviews were conducted in seven countries in North America and Europe, comprised of adults who had received a diagnosis of ADHD. The countries included Canada, France, Germany, Italy, The Netherlands, United Kingdom, and United States (two focus groups in each country). There were 108 participants. The focus groups were designed to elicit narratives of the experience of ADHD in key domains of symptoms, daily life, and social relationships. Consonant with grounded theory, the transcripts were analyzed using descriptive coding and then themed into larger domains. RESULTS: Participants' statements regarding the presentation of symptoms, childhood experience, impact of ADHD across the life course, addictive and risk-taking behavior, work and productivity, finances, relationships and psychological health impacts were similarly themed across all seven countries. These similarities were expressed through the domains of symptom presentation, childhood experience, medication treatment issues, impacts in adult life and across the life cycle, addictive and risk-taking behavior, work and productivity, finances, psychological and social impacts. CONCLUSIONS: These data suggest that symptoms associated with adult ADHD affect individuals similarly in different countries and that the relevance of the diagnostic category for adults is not necessarily limited to certain countries and sociocultural milieus.

ADHD burden of illness in older adults: a life course perspective.

PURPOSE: To explore the burden of illness and impact on patients' quality of life (QoL) experiences in older ADHD adults. METHODS: Telephone interviews were conducted with older adult participants diagnosed with ADHD later in life. Transcripts were analyzed following a grounded theory approach. RESULTS: Mean age of participants (N = 24) was 66 years, and mean age at diagnosis was 57 years; 68% were men and 63% reported other comorbid mental health conditions. ADHD symptoms reported were inattention (71%), impulsivity (58%), hyperactivity (54%), and disorganization (54%). The majority of participants (63%) experienced an accumulated lifetime burden of illness and reported being financially less-well-off, had lower educational achievement, job performance, and greater social isolation due to their ADHD. Older adults reported significantly greater impairments in productivity (P ≤ 0.02) and a better life outlook (P ≤ 0.05) than younger ADHD adults. CONCLUSIONS: Older adults' QoL suffers from the accumulative negative impact of ADHD symptoms/impairments on their professional, economic, social, and emotional well-being.