Discriminatory Properties of Quality-Adjusted Life Year Based Cost-Effectiveness Analyses for Patients With Disabilities: A Duchenne Muscular Dystrophy Case Study.

OBJECTIVES: Quality-adjusted life years (QALYs) have been challenged as a measure of benefit for people with disabilities, particularly for those in low-utility health states or with irreversible disability. This study examined the impact of a QALY-based assessment on the price for a hypothetical treatment for Duchenne muscular dystrophy (DMD), a progressive, genetic neuromuscular disease. METHODS: A previously published, 5-state model, which analyzed treatments for early ambulatory (EA) DMD patients, was replicated, validated, and adapted to include early nonambulatory (ENA) DMD patients. The model was used to assess a QALY-based threshold price (maximum cost-effective price) for a hypothetical treatment for 13-year-old ENA and 5-year-old EA patients (initial health states with lower and higher utility, respectively). All inputs were replicated including willingness-to-pay thresholds of $50 000 to $200 000/QALY. RESULTS: In contrast to EA patients, ENA patients had a 98% modeled decline in QALY-based threshold price at a willingness-to-pay of $150 000/QALY or higher, despite equal treatment benefit (delayed progression/death). At $100 000/QALY or lower, net nontreatment costs exceeded health benefits, implying any treatment for ENA patients would not be considered cost-effective, even at $0 price, including an indefinite pause in disease progression. CONCLUSIONS: For certain severe, disabling conditions, traditional approaches are likely to conclude that treatments are not cost-effective at any price once a patient progresses to a disabled health state with low utility value. These findings elucidate theoretical/ethical concerns regarding potential discriminatory properties of traditional QALY assessments for people with disabilities, particularly those who have lost ambulation or have other physical limitations.

Exploring the relationship between North Star Ambulatory Assessment and Health Utilities Index scores in Duchenne muscular dystrophy.

BACKGROUND: The North Star Ambulatory Assessment (NSAA) documents motor performance in ambulatory individuals with Duchenne muscular dystrophy (DMD). Health Utilities Index (HUI) scores, reflecting preferences for health-related quality-of-life (HRQoL) implications of health states, are commonly estimated within trials. This study sought to characterize the relationship between the NSAA score and utility in DMD. METHODS: Family members serving as proxy respondents for placebo-treated ambulatory individuals with DMD (NCT01254019; BioMarin Pharmaceuticals Inc) completed the HUI and the NSAA (score range, 0-34). Mean change over time on these measures was estimated, and the correlation between changes in NSAA score and a) HUI utility; b) HUI3 ambulation and HUI2 mobility attribute scores, over 48 weeks was calculated. RESULTS: Baseline mean (range) age was 8.0 years (5-16; n = 61) and mean (standard deviation [SD]) scores were 0.87 (0.13; HUI2), 0.82 (0.19; HUI3), and 21.0 (8.1; NSAA). Mean (SD) change over 48 weeks was -0.05 (0.14; HUI2), -0.06 (0.19; HUI3), and -2.9 (4.7; NSAA). Weak positive correlations were observed between baseline NSAA score and HUI utility (HUI2: r = 0.29; HUI3: r = 0.17) and for change over 48 weeks (HUI2: r = 0.16; HUI3: r = 0.15). Stronger correlations were observed between change in NSAA score and the HUI3 ambulation (r = 0.41) and HUI2 mobility (r = 0.41) attributes. CONCLUSIONS: Among ambulatory individuals with DMD, NSAA score is weakly correlated with HUI utility, suggesting that motor performance alone does not fully explain HRQoL. Stronger relationships were observed between HUI ambulation and mobility attributes, and NSAA. Although unidimensional measures like the NSAA are informative for documenting disease-specific health impacts, they may not correlate well with measures of overall health status; requiring use in conjunction with other patient-reported and preference-based outcomes.

The impact of genotype on outcomes in individuals with Duchenne muscular dystrophy: A systematic review.

Duchenne muscular dystrophy (DMD) is associated with progressive muscle weakness, loss of ambulation (LOA), and early mortality. In this review we have synthesized published data on the clinical course of DMD by genotype. Using a systematic search implemented in Medline and Embase, 53 articles were identified that describe the clinical course of DMD, with pathogenic variants categorizable by exon skip or stop-codon readthrough amenability and outcomes presented by age. Outcomes described included those related to ambulatory, cardiac, pulmonary, or cognitive function. Estimates of the mean (95% confidence interval) age at LOA ranged from 9.1 (8.7-9.6) years among 90 patients amenable to skipping exon 53 to 11.5 (9.5-13.5) years among three patients amenable to skipping exon 8. Although function worsened with age, the impact of genotype was less clear for other outcomes (eg, forced vital capacity and left ventricular ejection fraction). Understanding the distribution of pathogenic variants is important for studies in DMD, as this research suggests major differences in the natural history of disease. In addition, specific details of the use of key medications, including corticosteroids, antisense oligonucleotides, and cardiac medications, should be reported.

Factors associated with the health-related quality of life among people with Duchenne muscular dystrophy: a study using the Health Utilities Index (HUI).

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.

Characterizing health state utilities associated with Duchenne muscular dystrophy: a systematic review.

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.

The economic burden of overactive bladder in the United States: A systematic literature review.

AIMS: Overactive bladder (OAB) affects up to 17% of the United States (US) population. This study aimed to synthesize estimates of direct and indirect costs of OAB in the US and compare costs among those with and without OAB. METHODS: A systematic review was performed using MEDLINE/PubMed and Embase, from 2003 to 2016, following PRISMA guidelines. The target population was adults with idiopathic OAB or urge urinary incontinence from the US. Data were extracted on study and patient characteristics, all-cause and OAB-specific direct costs, resource use, and indirect costs. Costs were inflated to a common price year of 2016 USD. RESULTS: Eighteen studies were included. Mean insurer paid all-cause total direct healthcare costs ranged from 8168 to 15 569 USD, and OAB-specific costs ranged from 656 to 860 USD per-patient annually. Estimates of the incremental costs for OAB patients compared to non-OAB comparators ranged from 43% to 117%. One study estimated total annual indirect costs of OAB at 11 134 USD per-patient. CONCLUSIONS: The range of direct healthcare costs reported for managing patients with OAB varied, but was relatively small given the differing contributing data sources, study designs, and cost definitions. Direct costs were consistently higher among patients with OAB versus non-OAB comparisons, from a 1.4- to >2-fold increase annually. OAB-specific costs made up a small proportion of all-cause costs, highlighting the clinical and economic impact of OAB-related conditions such as falls, urinary tract infection, and depression. Few studies were identified that examined the indirect costs of OAB in the US.

The economic burden of overactive bladder (OAB) and its effects on the costs associated with other chronic, age-related comorbidities in the United States.

AIMS: The prevalence of OAB increases with age and is associated with several chronic comorbidities. However, the impact of OAB on the healthcare costs of patients with such comorbidities is not well-understood. This study aimed to quantify the impact of OAB on healthcare costs and assess the potential moderating effects of OAB on the costs of patients with chronic comorbidities. METHODS: Adults with evidence of OAB/OAB-related therapy between 1/1/2008-12/31/2013 were identified from two large, administrative claims databases. Per-patient-per-month (PPPM) expenditures for OAB cases were estimated and compared to those of propensity score-matched subjects without OAB. Costs were modeled using ordinary least squares regression including main effects and interactions of chronic depression, dementia, diabetes, hypertension, and osteoporosis with OAB. Values for the comparisons were calculated on the original dollar scale using smearing estimators. RESULTS: A total of 110 059 pairs of OAB cases and matched non-OAB controls were identified. The mean, multivariable-adjusted, PPPM all-cause costs of OAB cases from the model without interactions were $3003, compared to $1123 for matched controls (P < 0.0001). In the model assessing the interactions of chronic comorbidities with OAB, those OAB patients with comorbid depression, dementia, diabetes, hypertension, and osteoporosis incurred significantly higher costs than controls with these comorbidities. The synergistic effect of these interactions was estimated to be $95-$574 PPPM. CONCLUSIONS: Within this US-based population, the healthcare costs of OAB patients were more than 2.5 times those of similar patients without OAB. Additionally, patients with OAB and chronic, age-related comorbidities incurred higher healthcare costs than non-OAB controls with the same comorbidities.

Patient-reported outcomes in patients with overactive bladder treated with mirabegron and tolterodine in a prospective, double-blind, randomized, two-period crossover, multicenter study (PREFER).

BACKGROUND: The PREFER study was an assessment of medication tolerability, treatment preference and symptom improvement during treatment with mirabegron (M) and tolterodine (T) extended release (ER) in patients with overactive bladder (OAB). In this analysis of PREFER, patient-reported outcomes (PROs) were assessed during treatment. METHODS: PREFER was a two-period, 8-week crossover, double-blind, phase IV study (NCT02138747) of treatment-naïve adults with OAB ≥3 months randomized to 1 of 4 treatment sequences (M/T; T/M; M/M; T/T), separated by a 2-week washout. Tolterodine ER was dosed at 4 mg for 8 weeks and mirabegron was dosed at 25 mg for 4 weeks then increased to 50 mg for the next 4 weeks. At each visit, PROs related to treatment satisfaction, quality of life and symptom bother were assessed using the OAB Satisfaction (OAB-S; 3 independent scales/5 single-item overall assessments), OAB-q (total health-related QoL [HRQoL] and subscales [Sleep, Social, Coping, Concern] and Symptom Bother scale) and Patient Perception of Bladder Condition (PPBC) questionnaires. Responder rates were reported for OAB-q subscales based on a minimal important difference (MID; ≥ 10-point improvement) and OAB-S Medication Tolerability score ≥ 90. RESULTS: In total, 358 randomized patients received ≥1 dose of double-blind study medication and completed ≥1 post-baseline value (OAB-S scale, OAB-q, PPBC): M/T (n = 154), T/M (n = 144), M/M (n = 30) or T/T (n = 30). At end of treatment (EoT), mirabegron and tolterodine ER were associated with similar mean improvements in 7 of the 8 OAB-S scores investigated, OAB-q scales and PPBC. A higher percentage of patients achieved clinically relevant improvements (MID) in OAB-q scales and OAB-S Medication Tolerability score during treatment with mirabegron than tolterodine ER. CONCLUSIONS: On average, patients with OAB experienced improvements in treatment satisfaction, HRQoL and symptom bother that were of a similar magnitude during treatment with mirabegron or tolterodine ER. However, during mirabegron treatment, patients were more likely to achieve clinically relevant improvements in tolerability and HRQoL (as measured by the MID for the OAB-q or an OAB-S Medication Tolerability score ≥ 90) than during tolterodine ER treatment. TRIAL REGISTRATION: NCT02138747 ; registered May 13, 2014.

Liver-specific case fatality due to chronic hepatitis C virus infection: a systematic review.

Despite reports that mortality is increasing, overall case fatality due to hepatitis C virus (HCV) is thought to be low. Given the variability in published rates, we aimed to synthesize estimates of liver-specific case fatality and all-cause mortality in chronic HCV according to follow-up duration, sustained viral response (SVR) to treatment, and liver disease severity. A systematic review was conducted of studies published in English from 2003 to 2013, reporting liver-specific case fatality estimates from HCV-infected samples. Thirty-five eligible articles were identified; 26 also presented estimates of all-cause mortality. Among community-based samples, liver-specific case fatality ranged from 0.3% over 5.7 years to 9.2% over 8.2 years of follow-up; and of all-cause mortality, from 4.0% over 5.7 years, to 23.0% over 8.2 years of follow-up. Estimates were higher among clinic-based samples and those with more severe liver disease. Among treated patients achieving SVR, liver-specific case fatality was low: up to 1.4% over 11.5 years of follow-up among samples with any severity of liver disease. Estimates were higher among those without SVR: up to 14.0% over 10 years of followup among samples with any severity of liver disease, and higher still among samples with more severe liver disease. The proportion of deaths attributable to liver-specific causes ranged from 55 to 85% among those with severe liver disease. Published estimates of fatality are high among certain populations of chronic HCV patients, with liver-specific causes being an important contributor. Understanding current HCV mortality rates is important for quantifying the total burden of HCV disease.

A population-based study of childhood respiratory morbidity after severe lower respiratory tract infections in early childhood.

OBJECTIVES: To estimate the risk of childhood chronic respiratory morbidity among those hospitalized for severe lower respiratory tract infection (LRTI) in early childhood, and to determine whether severe LRTI is an independent predictor. STUDY DESIGN: The population-based Régie de l'Assurance Maladie du Québec datasets were used to identify LRTI hospitalizations before age 2 years in a birth cohort from 1996-1997 and a comparison cohort of children without an LRTI hospitalization. The incidence rate and incidence rate ratio of chronic respiratory morbidity before age 10 years were calculated, and multivariable logistic regression was performed to estimate the impact of LRTI hospitalization on chronic respiratory morbidity. Population-attributable risks of chronic respiratory morbidity due to severe LRTI were estimated, and similar analyses were performed for respiratory syncytial virus LRTI. RESULTS: Among the birth cohort, 7104 patients (4.9%) were hospitalized for LRTI before age 2 years. By age 10 years, 52.5% of the LRTI cohort and 27.9% of the nonhospitalized cohort had developed chronic respiratory morbidity; the incidence rate ratio was 1.81 (95% CI, 1.76-1.86) for males and 1.91 (95% CI, 1.84-1.99) for females. The OR for chronic respiratory morbidity based on LRTI hospitalization before age 2 years was 2.79 (95% CI, 2.66-2.93). The population-attributable risk of chronic respiratory morbidity due to any LRTI was approximately 25%, and that for respiratory syncytial virus LRTI was similar. CONCLUSIONS: Hospitalization of young children for LRTIs is associated with two-fold increased risk of childhood chronic respiratory morbidity, demonstrating the ongoing impact of LRTI in infancy.

Psychometric evaluation of the hepatitis C virus patient-reported outcomes (HCV-PRO) instrument: validity, responsiveness, and identification of the minimally important difference in a phase 2 clinical trial.

PURPOSE: To describe the psychometric properties and identify the minimally important difference (MID) of the hepatitis C virus patient-reported outcomes (HCV-PRO) instrument. Chronic HCV infection and associated treatments negatively affect PROs of function and well-being. METHODS: In a phase 2 trial, HCV-infected patients received direct-acting antivirals (DAAs) for 12 weeks with peg-interferon/ribavirin (peg-IFN/RBV) for 48 weeks, or placebo plus peg-IFN/RBV. The HCV-PRO total score, SF-36 PCS and MCS scores, EQ-5D-3L, and EQ VAS were measured at baseline, week 8, end of DAA treatment (EODT), end of peg-IFN/RBV treatment (EOT), and posttreatment week 24 (SVR24). Convergent validity of the HCV-PRO was assessed by Pearson's correlation coefficients. Discriminant validity was assessed by analyzing mean HCV-PRO total scores by EQ-5D anxiety/depression and pain/discomfort domain scores (none vs. some) and presence/absence of depression or fatigue adverse events. MID was identified through effect size (ES) and receiver-operating characteristic (ROC) curve analyses (HCV-PRO response vs. SF-36 PCS/MCS and EQ VAS MID thresholds). RESULTS: In 74 patients (22 % female; 81 % White; 51 % ≥50 years), correlations (0.64-0.96) between HCV-PRO total scores, SF-36 PCS/MCS scores, and EQ VAS scores at all time points supported convergent validity. HCV-PRO total scores were reduced to 10-30 points in patients impaired by depression, pain, or fatigue symptoms. Impact of peg-IFN/RBV regimen on HCV-PRO ES increased over time (EODT -0.76; EOT -0.93). ES and ROC curve analyses indicated an MID of -10 points. CONCLUSION: The HCV-PRO was valid and responsive in the population studied. An MID of -10 points represented a threshold of clinical significance for the HCV-PRO.

The economic burden of prematurity in Canada.

BACKGROUND: Preterm birth is a major risk factor for morbidity and mortality among infants worldwide, and imposes considerable burden on health, education and social services, as well as on families and caregivers. Morbidity and mortality resulting from preterm birth is highest among early (< 28 weeks gestational age) and moderate (28-32 weeks) preterm infants, relative to late preterm infants (33-36 weeks). However, substantial societal burden is associated with late prematurity due to the larger number of late preterm infants relative to early and moderate preterm infants. METHODS: The aim in this study was to characterize the burden of premature birth in Canada for early, moderate, and late premature infants, including resource utilization, direct medical costs, parental out-of-pocket costs, education costs, and mortality, using a validated and published decision model from the UK, and adapting it to a Canadian setting based on analysis of administrative, population-based data from Québec. RESULTS: Two-year survival was estimated at 56.0% for early preterm infants, 92.8% for moderate preterm infants, and 98.4% for late preterm infants. Per infant resource utilization consistently decreased with age. For moderately preterm infants, hospital days ranged from 1.6 at age two to 0.09 at age ten. Cost per infant over the first ten years of life was estimated to be $67,467 for early preterm infants, $52,796 for moderate preterm infants, and $10,010 for late preterm infants. Based on population sizes this corresponds to total national costs of $123.3 million for early preterm infants, $255.6 million for moderate preterm infants, $208.2 million for late preterm infants, and $587.1 million for all infants. CONCLUSION: Premature birth results in significant infant morbidity, mortality, healthcare utilization and costs in Canada. A comprehensive decision-model based on analysis of a Canadian population-based administrative data source suggested that the greatest national-level burden is associated with moderate preterm infants due to both a large cost per infant and population size while the highest individual-level burden is in early preterm infants and the largest total population size is in late preterm infants. Although the highest medical costs are incurred during the neonatal period, greater resource utilization and costs extend into childhood.

Current Challenges of Using Patient-Level Claims and Electronic Health Record Data for the Longitudinal Evaluation of Duchenne Muscular Dystrophy Outcomes.

INTRODUCTION: Insurance claims data and electronic health records (EHRs) have been used to characterize Duchenne muscular dystrophy (DMD) in real-world populations. The ability to assess patient-level DMD disease progression within insurance claims or EHR data infrastructures is unknown. Insurance claims and EHR data were comprehensively examined for availability and reliability of DMD outcomes that describe functional status and disease progression at the individual patient level over time. METHODS: MarketScan Commercial and Medicaid claims, and EHR-linked Clarivate open claims datasets were examined for data measuring 54 previously identified DMD-relevant outcomes in patients with DMD. Each outcome was assigned to one of five categories: functional and clinical events, clinical measures, biomarkers, functional measures, or patient-reported outcomes (PROs). Patients were identified using published coding algorithms. Annual 5-year attrition and data availability for each outcome was determined. The ability to distinguish disease severity and identify test results was also considered where applicable. RESULTS: A total of 1964 (MarketScan Commercial), 2007 (MarketScan Medicaid), and 10,639 (Clarivate) patients were identified. At 5 years, 31.7%, 35.1%, and 59.1% of patients remained in MarketScan Commercial, MarketScan Medicaid, and Clarivate, respectively. Claims were available for five of six functional and clinical events, with 45.5% (MarketScan Commercial), 48.0% (Clarivate), and 48.5% (MarketScan Medicaid) of patients with ≥ 1 claim for the most frequently identified clinical event (cardiomyopathy diagnosis). No data were available to describe frequency of wheelchair use or loss of ambulation. Very limited EHR data (≤ 2% of patients) were available to indicate tests were ordered for clinical measures, biomarkers, or functional assessments. No PRO notes or scores were observed. Data existed for inferring disease severity (e.g., hospitalization for cardiomyopathy); however, it was not apparent whether these events were incident. CONCLUSION: Insurance claims and EHR-linked open claims data are of limited utility for holistically evaluating the progression and burden of DMD in individual patients.

Duchenne muscular dystrophy is a fatal disease that weakens muscles and causes loss of function over time. The timing of symptoms varies across individuals, making it important for doctors to closely monitor them. Although billing data from medical practices have been used to understand how Duchenne muscular dystrophy progresses at the population level, how well these data can document disease progression over time in individuals is unclear. This study examined data submitted by healthcare providers to insurers and electronic health records used to track patients' medical histories to see what information is available about known clinical and functional outcomes for Duchenne muscular dystrophy. Some information was available about major events experienced by patients with Duchenne muscular dystrophy, like heart problems and breathing difficulties. However, these data were limited to more advanced stages of Duchenne muscular dystrophy and did not reveal when these events first occurred or how severe they were. Information about whether ordered tests were performed was limited, with even less information available for test results. There were no data reported by patients themselves available in the datasets. The limitations of data submitted to insurers and from electronic health records in describing the clinical and functional outcomes of Duchenne muscular dystrophy make it difficult to understand individuals' medical history. Other data sources, particularly from tests measuring patient function done in the doctor's office or patient-reported outcomes, may exist but are not transferred to insurer data infrastructures.

Observing the Clinical Course of Duchenne Muscular Dystrophy in Medicaid Real-World Healthcare Data.

INTRODUCTION: Duchenne muscular dystrophy (DMD) is a rare, severe progressive neuromuscular disease. Health insurance claims allow characterization of population-level real-world outcomes, based on observed healthcare resource use. An analysis of data specific to those with Medicaid insurance is presently unavailable. The objective was to describe the real-world clinical course of DMD based on claims data from Medicaid-insured individuals in the USA. METHODS: Individuals with DMD were identified from the MarketScan Multi-State Medicaid datasets (2013-2018). Diagnosis and procedure codes from healthcare claims were used to characterize the occurrence of DMD-relevant clinical observations; categories were scoliosis, cardiovascular-related, respiratory and severe respiratory-related, and neurologic/neuropsychiatric. Age-restricted analyses were conducted to focus on the ages at which DMD-relevant clinical observations were more likely to be captured, and to better understand the impact of both age and follow-up time. RESULTS: Of 2007 patients with DMD identified, median (interquartile range) age at index was 14 (9-20) years, and median follow-up was 3.1 (1.6-4.7) years. Neurologic and neuropsychiatric observations were most frequently identified, among 49.3% of the cohort; followed by cardiovascular (48.5%), respiratory (38.1%), scoliosis (36.3%), and severe respiratory (25.0%). Prevalence estimates for each category were higher when analyzed within age-restricted subgroups; and increased as follow-up time increased. CONCLUSIONS: This study is the first to use diagnosis and procedure codes from real-world Medicaid claims to document the clinical course in DMD. Findings were consistent with previously published estimates from commercially insured populations and clinical registries; and contribute to the expanding body of real-world evidence around clinical progression of patients with DMD.

"You Take This Day by Day, Come What May": A Qualitative Study of the Psychosocial Impacts of Living with Duchenne Muscular Dystrophy.

INTRODUCTION: Studies have reported health-related quality-of-life impacts of Duchenne muscular dystrophy (DMD); however, further research is needed to understand how those with DMD experience their condition and how psychosocial impacts evolve over time in response to disease progression. This qualitative study explores the social and emotional implications of key transitions, challenges and adaptations throughout the disease course from the perspective of patients and family caregivers. METHODS: Semi-structured interviews were conducted with men and boys with DMD, and/or their caregivers, in the USA. Thematic analysis was used to examine patterns in data collected across the interviews. RESULTS: Nineteen participants were included. Three major themes were identified: (1) barriers to participation are multifaceted; (2) an emotional journey shaped by 'inevitable progression;' (3) family provides critical tangible and emotional support. This study illustrates that psychosocial impacts of DMD are shaped by knowledge of the condition's natural history alongside other factors including the extent of social barriers, personal growth and adaptation, and family support. CONCLUSIONS: Findings provide insight into the strength and resilience with which individuals and their families respond to daily challenges and major clinical milestones and highlight the relative importance of loss of upper limb function as a transition in DMD affecting health-related quality-of-life.

Comparing Preferences for Disease Profiles: A Discrete Choice Experiment from a US Societal Perspective.

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.

Elevated risk of asthma after hospitalization for respiratory syncytial virus infection in infancy.

Severe respiratory syncytial virus (RSV) infection in infancy is associated with substantial morbidity worldwide; whether it is a risk factor for childhood asthma is contentious. A systematic review of 28 articles was conducted, summarizing estimates of asthma risk after RSV hospitalization during infancy. Prevalence estimates of asthma, among those hospitalized for RSV in infancy, were from 8% to 63%, 10% to 92%, and 37%, at ages <5, 5 to 11, and ≥ 12 years, respectively. These rates were higher than those among non-hospitalized comparisons. The attributable risk of asthma due to RSV ranged from 13% to 22% and from 11% to 27% among children aged ≤ 5 and aged 5 to 11, respectively, and was 32% among children ≥ 12 years of age. Overall, 59% of asthma prevalence estimates from those previously hospitalized for RSV exceeded 20%, compared to only 6% of non-hospitalized comparison estimates. Despite variability in asthma prevalence estimates after RSV-related hospitalization, available data suggest a link between severe RSV infection in infancy and childhood asthma.

The risk of mortality among young children hospitalized for severe respiratory syncytial virus infection.

Respiratory syncytial virus (RSV) lower respiratory tract infection (LRTI) is the leading cause of childhood morbidity. Although also an important cause of childhood mortality worldwide, the impact of key risk factors has not been established. A systematic review of 34 articles reporting case fatality rates in young children hospitalized for severe RSV LRTI, according to the presence of underlying RSV risk factors, was conducted. The weighted mean case fatality rate was 1.2% (range, 0-8.3%; median, 0%; n = 10) among preterm infants; 5.2% (range, 2.0-37.0%; median, 5.9%; n = 7) among children with CHD; and 4.1% (range, 0-10.5%; median, 7.0%; n = 6) among children with BPD. Case fatality estimates among children not at high risk (n = 6) ranged from 0% to 1.5% (weighted mean, 0.2%; median, 0.0%). Fatality during hospitalization for severe RSV LRTI is rare among children not at high risk, but occurs more commonly among children at higher risk of RSV LRTI.

A model of the costs of community and nosocomial pediatric respiratory syncytial virus infections in Canadian hospitals.

BACKGROUND: Approximately one in 10 hospitalized patients will acquire a nosocomial infection (NI) after admission to hospital, of which 71% are due to respiratory viruses, including the respiratory syncytial virus (RSV). NIs are concerning and lead to prolonged hospitalizations. The economics of NIs are typically described in generalized terms and specific cost data are lacking. OBJECTIVE: To develop an evidence-based model for predicting the risk and cost of nosocomial RSV infection in pediatric settings. METHODS: A model was developed, from a Canadian perspective, to capture all costs related to an RSV infection hospitalization, including the risk and cost of an NI, diagnostic testing and infection control. All data inputs were derived from published literature. Deterministic sensitivity analyses were performed to evaluate the uncertainty associated with the estimates and to explore the impact of changes to key variables. A probabilistic sensitivity analysis was performed to estimate a confidence interval for the overall cost estimate. RESULTS: The estimated cost of nosocomial RSV infection adds approximately 30.5% to the hospitalization costs for the treatment of community-acquired severe RSV infection. The net benefits of the prevention activities were estimated to be equivalent to 9% of the total RSV-related costs. Changes in the estimated hospital infection transmission rates did not have a significant impact on the base-case estimate. CONCLUSIONS: The risk and cost of nosocomial RSV infection contributes to the overall burden of RSV. The present model, which was developed to estimate this burden, can be adapted to other countries with different disease epidemiology, costs and hospital infection transmission rates.

HISTORIQUE: Environ un patient hospitalisé sur dix contractera une infection d'origine nosocomiale (ION) après son hospitalisation, dont 71 % sont imputables à des virus respiratoires, y compris le virus respiratoire syncytial (VRS). Les ION sont inquiétantes et provoquent des hospitalisations prolongées. En général, les aspects économiques des ION sont décrits en termes généraux, et on ne possède pas de données précises sur leurs coûts. OBJECTIF: Élaborer un modèle fondé sur des données probantes pour prédire le risque et le coût des infections à VRS d'origine nosocomiale en milieu pédiatrique. MÉTHODOLOGIE: Les chercheurs ont élaboré un modèle, d'après une perspective canadienne, afin de saisir tous les coûts liés à une hospitalisation découlant d'une infection à VRS, y compris le risque et le coût d'une ION, les tests diagnostiques et le contrôle de l'infection. Toutes les données saisies étaient dérivées des publications. Les chercheurs ont effectué des analyses de sensibilité déterministe pour évaluer l'incertitude associée aux évaluations et pour explorer les répercussions de changements aux variables clés. Ils ont effectué une analyse de sensibilité probabiliste pour évaluer l'intervalle de confiance de l'évaluation globale des coûts. RÉSULTATS: Les coûts estimatifs de l'infection à VRS d'origine nosocomiale ajoutent environ 30,5 % aux frais d'hospitalisation pour traiter l'infection à VRS grave d'origine non nosocomiale. Les chercheurs ont évalué que les bénéfices nets des activités de prévention équivalaient à 9 % des coûts totaux liés au VRS. Les modifications aux taux estimatifs de transmission de l'infection en milieu hospitalier n'avaient pas de répercussions significatives sur l'évaluation des cas de base. CONCLUSIONS: Le risque et le coût de l'infection à VRS d'origine nosocomiale contribuent au fardeau global du VRS. Le présent modèle, qui a été élaboré pour évaluer ce fardeau, peut être adapté à d'autres pays selon d'autres épidémiologies de maladies, coûts et taux de transmission de l'infection en milieu hospitalier.

A qualitative study to understand the Duchenne muscular dystrophy experience from the parent/patient perspective.

BACKGROUND: Duchenne muscular dystrophy (DMD) is a rare, severe, fatal neuromuscular disease characterized by progressive atrophy and muscle weakness, resulting in loss of ambulation, decreased upper body function, and impaired cardiorespiratory function. This study aimed to generate qualitative evidence to describe the primary symptoms and impacts of DMD in ambulatory and non-ambulatory patients as reported by patient/caregiver dyads. Information was also gathered on expectations for future DMD treatments. METHODS: Forty-six dyads (caregiver and patients with DMD aged 4 to 22 years) participated in 60-min semi-structured video interviews. Interview transcripts were analyzed using thematic analysis. Differences in experiences with DMD by ambulation status were examined. RESULTS: Mean ages of ambulatory (n = 28) and non-ambulatory participants (n = 18) were 8.7 and 11.3 years, respectively, with an average age of diagnosis of 3.7 years (SD = 2.3). The primary symptoms reported by both groups were lack of strength (ambulatory: n = 28, 100.0%; non-ambulatory: n = 17, 94.4%) and fatigue (ambulatory: n = 24, 85.7%; non-ambulatory: n = 14, 77.8%). Physical function was the domain that was most impacted by DMD, with participants describing progressive decline of physical function due to loss of physical strength as the primary defining feature of the disease across all stages of ambulatory ability. For those who maintained ambulatory ability at the time of the interview, physical function impacts described impaired mobility (e.g., climbing stairs: n = 16, 57.1%; running: n = 13, 46.4%), impaired upper body function, in particular fine motor skills like holding a pen/pencil or buttoning clothes (n = 17, 60.7%), problem with transfers (e.g., getting off the floor: n = 10, 35.7%), and activities of daily living (ADLs; n = 15, 53.6%). For non-ambulatory participants, the functional impacts most frequently described were problems with transfers (e.g., getting in/out of bed: n = 13, 72.2%; getting in/out of chair or position in bed: both n = 10, 55.6%), impaired upper body function (reaching: n = 14, 77.8%), and ADLs (n = 15, 83.3%). Meaningful treatment goals differed by ambulatory status; for ambulatory participants, goals included maintaining current functioning (n = 20, 71.4%), improving muscle strength (n = 7, 25.9%), and reducing fatigue (n = 6, 22.2%). For non-ambulatory participants, these included increased upper body strength (n = 8, 42.1%) and greater independence in ADLs (n = 6, 31.6%). A preliminary conceptual model was developed to illustrate the primary symptoms and physical function impacts of DMD and capture their relationship to disease progression. CONCLUSION: This study contributes to the limited qualitative literature by characterizing impacts of physical limitations and symptoms of DMD on disease progression and thus providing insights into the lived experience with DMD. Differences in treatment goals were also identified based on ambulatory status. Taken together, these findings can help inform patient-centered measurement strategies for evaluating outcomes in DMD clinical research.