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BACKGROUND: Data on health state utility in Duchenne muscular dystrophy (DMD) are few. This study estimated mean utility values by age, ambulatory status and over time, and investigated which aspects of health-related quality-of-life (HRQoL) are most strongly associated with utility in DMD. METHODS: Data from placebo-treated ambulant boys with DMD with exon 51 skip amenable mutations, (NCT01254019), were included. Ambulatory function assessments were conducted at baseline and every 12 weeks for the trial duration. Family member proxies completed the Health Utility Index (HUI) at baseline, 24 and 48 weeks; and HUI3 and HUI2 utility values were summarized. Changes in HUI attribute level over time, and predictors of changes in utility, were explored. RESULTS: Sixty-one boys (mean [range] age of 8.0 [5-16] years) were included in the analysis. Mean baseline utilities were 0.82 (HUI3) and 0.87 (HUI2); and utilities were 0.35 (HUI3) and 0.55 (HUI2) after loss of ambulation (LOA, where applicable). Over the follow-up period mean utility declined more among the older versus younger boys. Pain accounted for the highest proportion of variability (42%) in change in HUI3 utility from baseline to week 48, while for HUI2, self-care (39%) did. After LOA, change in ambulation levels explained 88% of the decline in mean HUI3 utility and change in mobility levels explained 66% of the decline in mean HUI2 utility. CONCLUSIONS: Utility values among this sample were higher than previously published estimates. In younger boys utility remained relatively stable, but older boys and those losing ambulation experienced important declines over follow-up.
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Distrofia Muscular de Duchenne , Calidad de Vida , Adolescente , Niño , Preescolar , Humanos , Masculino , Dolor , Autocuidado , Encuestas y CuestionariosRESUMEN
BACKGROUND: Preferences for health states for Duchenne muscular dystrophy (DMD) are necessary to assess costs and benefits of novel therapies. Because DMD progression begins in childhood, the impact of DMD on health-related quality-of-life (HRQoL) affects preferences of both DMD patients and their families. The objective of this review was to synthesize published evidence for health state utility from the DMD patient and caregiver perspectives. METHODS: A systematic review was performed using MEDLINE and Embase, according to best practices. Data were extracted from studies reporting DMD patient or caregiver utilities; these included study and patient characteristics, health states considered, and utility estimates. Quality appraisal of studies was performed. RESULTS: From 888 abstracts, eight publications describing five studies were identified. DMD utility estimates were from preference-based measures presented stratified by ambulatory status, ventilation, and age. Patient (or patient-proxy) utility estimates ranged from 0.75 (early ambulatory DMD) to 0.05 (day-and-night ventilation). Caregiver utilities ranged from 0.87 (for caregivers of adults with DMD) to 0.71 (for caregivers of predominantly childhood patients). Both patient and caregiver utilities trended lower with higher disease severity. Variability in utilities was observed based on instrument, respondent type, and country. Utility estimates for health states within non-ambulatory DMD are under reported; nor were utilities for DMD-related health states such as scoliosis or preserved upper limb function identified. CONCLUSION: Published health state utilities document the substantial HRQoL impacts of DMD, particularly with disease progression. Additional research in patient utilities for additional health states, particularly in non-ambulatory DMD patients, is warranted.
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Servicios de Salud/normas , Distrofia Muscular de Duchenne/terapia , Calidad de Vida/psicología , Adolescente , Adulto , Niño , Femenino , Humanos , MasculinoRESUMEN
OBJECTIVES: There is increasing interest in expanding the elements of value to be considered when making health policy decisions. To help inform value frameworks, this study quantified preferences for disease attributes in a general public sample and examined which combination of attributes (disease profiles) are considered most important for research and treatment. METHODS: A discrete choice experiment (DCE) was conducted in a US general population sample, recruited through online consumer panels. Respondents were asked to select one of a set of health conditions they believed to be most important, characterized by attributes defined by a previous qualitative study: onset age; cause of disease; life expectancy; caregiver requirement; symptom burden (characterized by the Health Utilities Index with varying levels of ambulation independence, dexterity limitations, and degree of pain and discomfort); and disease prevalence. A fractional factorial DCE design was implemented using R, and 60 choice sets were generated (separated into blocks of 10 per participant). Data were analyzed using a mixed-logit regression model, and results used to assess the likelihood of preferring disease profiles. Based on individual attribute preferences, overall preferences for disease profiles, including a profile aligned with Duchenne muscular dystrophy (DMD), were compared. RESULTS: Fifty-two percent of respondents (n = 537) were female, and 70.6% were aged 18-54 years. Attributes considered most important were those related to life expectancy (odds ratio [OR], 95% confidence interval [CI] 1.88 [1.56-2.27] for a 50% reduction in remaining life expectancy vs no impact), and symptom burden (OR [95% CI] 1.84 [1.47-2.31] for severe vs mild burden). Greater importance was also found for pediatric onset, caregiver requirement, and diseases affecting more people. As an example of disease profile preferences, a DMD-like pediatric inherited disease with 50% reduction in life expectancy, extensive caregiver requirement, severe symptom burden, and 1:5000 prevalence had 2.37-fold higher odds of being selected as important versus an equivalent disease with adult onset and no life expectancy reduction. CONCLUSIONS: Of disease attributes included in this DCE, respondents valued higher prevalence of disease, life expectancy and symptom burden as most important for prioritizing research and treatment. Based on expressed attribute preferences, a case study of an inherited pediatric disease involving substantial reductions to length and quality of life and requiring caregiver support has relatively high odds of being identified as important compared to diseases reflecting differing attribute profiles. These findings can help inform expansions of value frameworks by identifying important attributes from the societal perspective.
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Conducta de Elección , Calidad de Vida , Adulto , Humanos , Femenino , Niño , Masculino , Toma de Decisiones , Modelos Logísticos , Esperanza de Vida , Prioridad del Paciente , Encuestas y CuestionariosRESUMEN
OBJECTIVES: As the clinical course of autosomal recessive limb-girdle muscular dystrophy (LGMDR) is highly variable, this study characterized the frequency of loss of ambulation (LOA) among patients by subtype (LGMDR1, LGMDR2, LGMDR3-6, LGMDR9, LGMDR12) and progression to cardiac and respiratory involvement among those with and without LOA. METHODS: Systematic literature review. RESULTS: From 2929 abstracts screened, 418 patients were identified with ambulatory status data (LOA: 265 [63.4%]). Cardiac and/or respiratory function was reported for 142 patients (34.0%; all with LOA). Among these, respiratory involvement was most frequent in LGMDR3-6 (74.1%; mean [SD] age 23.9 [11.0] years) and cardiac in LGMDR9 (73.3%; mean [SD] age 23.7 [17.7] years). Involvement was less common in patients without LOA except in LGMDR9 (71.4% respiratory and 52.4% cardiac). CONCLUSIONS: This study described the co-occurrence of LOA, cardiac, and respiratory involvement in LGMDR and provides greater understanding of the clinical progression of LGMDR.
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Músculo Esquelético , Distrofia Muscular de Cinturas , Humanos , Adulto Joven , Adulto , Distrofia Muscular de Cinturas/genética , Progresión de la EnfermedadRESUMEN
BACKGROUND: The progression of Duchenne muscular dystrophy (DMD) is characterized by loss of ambulation, respiratory insufficiency, cardiomyopathy, and early mortality. DMD profoundly impacts health-related quality-of-life (HRQoL). However, few health state utility data exist; published utilities tend to be derived from small samples for a limited number of health states and are often based on caregiver-reported patient health status. This study estimated utility values for varied clinical and functional health states in DMD, based on patient-reported health status. METHODS: Individuals with DMD in the US aged 12-40 years completed the EQ-5D (5-level) and Health Utilities Index (HUI) preference-based instruments. Based on responses to a clinical questionnaire, participants self-classified into functional health states according to level of lower and upper limb function, use of respiratory support, and presence of cardiomyopathy. Mean [standard deviation (SD)] utility and EQ-5D visual analogue scale (VAS) scores were estimated according to health state; and median (interquartile range) attribute levels calculated to understand which domains of health are most severely affected in DMD. RESULTS: Of 63 males with DMD, mean (SD) age was 19.8 (6.1) years and 11 (17.5%) were ambulatory. Mean (SD) utility values were 0.92 (0.08; HUI2), 0.84 (0.20; HUI3), and 0.84 (0.13; EQ-5D) for ambulatory patients without cardiomyopathy (n = 10). For non-ambulatory patients with moderately impaired upper limb function, night and daytime ventilation without cardiomyopathy, mean (SD) utilities were 0.49 (0.07) for the HUI2, 0.16 (0.15) for the HUI3 and 025 (0.14) for the EQ-5D. Mean (SD) VAS scores for the same health states were 91 (9) and 83 (21), respectively. In addition to impairments in mobility/ambulation, and self-care, attributes like usual activities and pain also showed notable effects of DMD. CONCLUSIONS: In DMD, although a relationship between disease progression and HRQoL is observed, there is large variability in utility within functional health states, and across instruments. Utility values for less severe non-ambulatory health states described by level of upper limb function are novel. These utility values, derived based on direct patient feedback rather than from caregiver report, are relevant to individuals of varying functional statuses and augment scarce DMD-specific utility data.
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Cardiomiopatías , Distrofia Muscular de Duchenne , Masculino , Humanos , Distrofia Muscular de Duchenne/terapia , Dolor , Calidad de Vida , RespiraciónRESUMEN
PURPOSE: Under a societal perspective, disease and treatment attributes that the general public deem important should be considered within value frameworks. The objective was to investigate how members of the general public value attributes beyond health gains and healthcare system expenditures; and better understand their perspectives regarding the importance of attributes typically characterizing rare genetic diseases like Duchenne muscular dystrophy (DMD). METHODS: Qualitative interviews were conducted to elicit feedback on the importance of disease and treatment attributes from general public participants from three US cities. Participants ranked attributes (scale, 1-10) in terms of importance for future research, reported their rationale for ranking, and provided feedback specific to rare diseases. Interview transcripts were coded using NVivo for thematic analysis. RESULTS: The 33 participants (median age, 51 years; 48.5% male) ranked disease severity (mean [median] ranking, 8.7 [9.0]), treatment availability (8.7 [9.0]), and impact on life expectancy (8.4 [9.0]), as most important. The impact on the family, need for equity, and intrinsic value of life were frequently provided rationales. While rare disease as an attribute received a relatively low ranking (6.1 [7.0]), 88% of participants prioritized disease profiles including attributes of severity, health related quality of life (HRQoL) impact, limited lifespan and young age at onset. CONCLUSION: Attributes including disease severity, impact on life expectancy and HRQoL, and treatment availability were all highly important to members of the general public. These findings support the growing evidence regarding the importance of expanding value assessments to include attributes considered important from a societal perspective.
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BackgroundThe impact of age at autosomal recessive limb girdle muscular dystrophy (LGMDR) onset on progression to loss of ambulation (LOA) has not been well established, particularly by subtype. OBJECTIVES: To describe the characteristics of patients with adult-, late childhood-, and early childhood-onset LGMDR by subtype and characterize the frequency and timing of LOA. METHODS: A systematic review was conducted in MEDLINE, Embase and the Cochrane library. Frequency and timing of LOA in patients with LGMDR1, LGMDR2/Miyoshi myopathy (MM), LGMDR3-6, LGMDR9, and LGMDR12 were synthesized from published data. RESULTS: In 195 studies, 695 (43.4%) patients had adult-, 532 (33.2%) had late childhood-, and 376 (23.5%) had early childhood-onset of disease across subtypes among those with a reported age at onset (nâ=â1,603); distribution of age at onset varied between subtypes. Among patients with LOA (nâ=â228), adult-onset disease was uncommon in LGMDR3-6 (14%) and frequent in LGMDR2/MM (42%); LGMDR3-6 cases with LOA primarily had early childhood-onset (74%). Mean (standard deviation [SD]) time to LOA varied between subtypes and was shortest for patients with early childhood-onset LGMDR9 (12.0 [4.9] years, nâ=â19) and LGMDR3-6 (12.3 [10.7], nâ=â56) and longest for those with late childhood-onset LGMDR2/MM (21.4 [11.5], nâ=â36). CONCLUSIONS: This review illustrated that patients with early childhood-onset disease tend to have faster progression to LOA than those with late childhood- or adult-onset disease, particularly in LGMDR9. These findings provide a greater understanding of progression to LOA by LGMDR subtype, which may help inform clinical trial design and provide a basis for natural history studies.
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Distrofia Muscular de Cinturas , Adulto , Niño , Preescolar , Miopatías Distales , Humanos , Atrofia Muscular , Distrofia Muscular de Cinturas/genética , CaminataRESUMEN
BACKGROUND: Providing caregiving support to people with Duchenne muscular dystrophy (DMD) is challenging, beginning in early childhood, and continuing through the progression of multidimensional disability. This study addressed the interplay between caregiver impact, out-of-pocket expenditures, and DMD disability. To examine these interconnections, we investigated the association between caregiver impact domains and out-of-pocket expenditures; and the presence of clusters in caregivers on the basis of DMD-related disability domains in the patients for whom they provided caregiving support. METHODS: This web-based study recruited 566 DMD caregivers (140 males, 426 females; mean age 41.6 years, SD 8.8, range 21-72), examining caregiver impact using the DMD Caregiver Impact Measure, PROMIS-derived parent-proxy (PPP) measures of their child's disability, and items tapping out-of-pocket expenditures related to home and vehicle accommodations and assistive devices. T-tests compared caregiver impact scores by out-of-pocket expenditures incurred. Latent Profile Analyses (LPA) were conducted to generate impact profiles related to child's disability as reported by caregiver proxies. RESULTS: Higher out-of-pocket expenditures were generally associated with worse impact on the subscales, but several expenditures (e.g., kitchen, bathroom, scooter) were associated with lower impact. LPA indicated that the four-group solution provided the best relative fit and yielded good profile separation (entropy = 0.91). Caregivers with lowest impact reported the highest mobility, cognitive, and upper extremity functioning of their DMD care recipients, whereas the highest caregiver impact was driven by their care recipient's negative affect and fatigue. The upper-middle impact group showed great variability in proxy-disability domains, whereas the lower-middle group had similar levels of disability across domains. Profiles were represented across all child ages. CONCLUSION: Out-of-pocket expenditures were often associated with worse caregiver impact, but some associated with milder impact (i.e., bathroom or kitchen modification, investing in a ceiling lift or medical scooter). While their son's level of disability and age were related to impact on the DMD caregiver, the domains giving rise to highest caregiver impact were not the most visible aspects of disability, such as mobility, but rather negative affect and fatigue. Other contextual attributes are likely implicated, and will be addressed in the companion paper.
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BACKGROUND: This research aimed to review the theoretical and methodological aspects of the quality-adjusted life year (QALY) which give rise to potential for bias against certain patient populations, including those with problems with walking or an inability to walk (ambulatory disabilities), when health technology assessment decisions rely on QALY gain to show cost-effectiveness. Societal preferences for treating ambulatory versus non-ambulatory patients were also investigated. METHODS: We reviewed published literature to identify information on theoretical underpinnings of the QALY, measurement of utilities for QALY assessment, and empirical evidence of societal preferences for the treatment of ambulatory and non-ambulatory patients. RESULTS AND DISCUSSION: Health states which represent mobility impairment and the inability to walk receive low valuation from general public preferences. Non-ambulatory patients, for example those with advanced neuromuscular disease, have lower utilities determined by standardized preference-based measurement (PBM) tools. Any treatment that increases survival but could not restore ambulation would result in lower lifetime QALY gains for non-ambulatory versus ambulatory patients. Treatments could therefore potentially be deemed less cost-effective, or not cost-effective at all for this patient population.Empirical research indicates a societal preference for equal treatment of patients regardless of ambulatory status. The main limitation of our review was the non-systematic approach to evidence search and review, however, given the broad scope of content required to meet the aims of the review, we believe that the targeted approach was appropriate. The evidence presented in this article highlights the need for alternatives to strict QALY-based approaches to prevent avoidable health inequities when determining cost-effectiveness of healthcare interventions for non-ambulatory populations against fixed cost-effectiveness thresholds. An alternative metric, the Equal Value of Life Years Gained (evLYG), has been proposed as a supplementary measure for use alongside the QALY for its potential to alleviate bias against disabled patient populations during the assessment of healthcare treatments.
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Atención a la Salud , Evaluación de la Tecnología Biomédica , Análisis Costo-Beneficio , Toma de Decisiones , Humanos , Años de Vida Ajustados por Calidad de VidaRESUMEN
BACKGROUND: This study examined the impact of Duchenne muscular dystrophy (DMD) on family-member caregivers in terms of quality of life, life stress, and indirect costs, as compared to a stratified comparison group of parents of similar-age children without DMD. METHODS: A web-based survey included DMD caregivers and a nationally representative comparison group of parents of children without DMD stratified by Child Age Group. Outcomes included quality of life, resilience, caregiver impact, stressful life events, financial strain, out-of-pocket expenditures, work productivity and unrealized ambitions. General linear models assessed the main effect of Caregiver Group and the interaction of Caregiver Group with Child-Age-Group, after adjusting for demographic covariates. RESULTS: Compared to parents without a DMD child, DMD Caregivers reported better physical health but worse mental health, positive affect/well-being, environmental mastery, difficulty paying bills, and more hours missed from work. Providing caregiving support for DMD teenagers was the most challenging. DMD caregivers curtailed their educational and professional ambitions, and modified their homes to accommodate the disability associated with DMD. Their non-DMD children had to make sacrifices as well. Nonetheless, in resilience and life stress, DMD caregivers were comparable to the comparison group, and showed consistent levels of positive emotions across the age of their DMD child. CONCLUSION: DMD caregivers fared worse on most outcomes and faced more hurdles in work life. They face constraints and hidden costs that impact their health and financial well-being. Caregivers of teenagers with DMD reported higher impact. Nonetheless, parents of DMD children of all ages maintained notable resilience and positivity.
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BACKGROUND: Person-reported outcomes measurement development for rare diseases has lagged behind that of more common diseases. In studies of caregivers of patients with rare diseases, one relies on proxy report to characterize this disability. It is important to measure the child's disability accurately and comprehensively because it affects caregiver burden. We aimed to create a condition-specific caregiver proxy-report measure for Duchenne Muscular Dystrophy (DMD) in order to understand the impact of DMD on the caregiver. Drawing on relevant item banks from the Patient-Reported Outcome Measurement Information System (PROMIS), we sought to confirm their reliability and validity in the target sample of DMD caregivers. METHODS: This web-based study recruited DMD caregivers via Rare Patient Voice, patient-advocacy groups, and word of mouth. Recruitment was stratified by age of the caregiver's child with DMD, which broadly represents stages of DMD progression: 2-7, 8-12, 13-17, and > 18. Telephone interviews with DMD parent-caregivers pretested possible measures for content validity. The web-based study utilized an algorithm to categorize respondents' ambulatory status for tailored administration of PROMIS Parent-Proxy items as well as some new items developed based on caregiver interviews. Item response theory analyses were implemented. RESULTS: The study sample included 521 DMD caregivers representing equally the four age strata. The proxy-report measure included the following domains: fatigue impact, strength impact, cognitive function, upper extremity function, positive affect, negative affect, sleep-device symptoms, and mobility. The first five domains had strong psychometric characteristics (unidimensionality; acceptable model fit; strong standardized factor loadings; high marginal reliability). Negative Affect, covering anger, anxiety, depressive symptoms, and psychological stress, fit a bifactor model with good model fit, high marginal reliability, and strong factor loadings. The Sleep-device symptoms domain was not unidimensional, and the mobility domain did not have a simple structure due to residual correlations among items at opposite end of the mobility-disability continuum. These two domain scores were retained as clinimetric indices (i.e., uncalibrated scales), to achieve the overall goal of having a content-valid DMD-specific measure across all stages of disease severity. CONCLUSIONS: The present study derived a DMD-specific proxy-report measure from PROMIS item banks and supplemental items that could potentially be utilized in caregiver research across all stages of the care recipient's DMD. Future research will focus on assessing the responsiveness and validity of the measure over time and its comparison to DMD patient self-report.