A scoping review to create a framework for the steps in developing condition-specific preference-based instruments de novo or from an existing non-preference-based instrument: use of item response theory or Rasch analysis.

BACKGROUND: There is no widely accepted framework to guide the development of condition-specific preference-based instruments (CSPBIs) that includes both de novo and from existing non-preference-based instruments. The purpose of this study was to address this gap by reviewing the published literature on CSPBIs, with particular attention to the application of item response theory (IRT) and Rasch analysis in their development. METHODS: A scoping review of the literature covering the concepts of all phases of CSPBI development and evaluation was performed from MEDLINE, Embase, PsychInfo, CINAHL, and the Cochrane Library, from inception to December 30, 2022. RESULTS: The titles and abstracts of 1,967 unique references were reviewed. After retrieving and reviewing 154 full-text articles, data were extracted from 109 articles, representing 41 CSPBIs covering 21 diseases or conditions. The development of CSPBIs was conceptualized as a 15-step framework, covering four phases: 1) develop initial questionnaire items (when no suitable non-preference-based instrument exists), 2) establish the dimensional structure, 3) reduce items per dimension, 4) value and model health state utilities. Thirty-nine instruments used a type of Rasch model and two instruments used IRT models in phase 3. CONCLUSION: We present an expanded framework that outlines the development of CSPBIs, both from existing non-preference-based instruments and de novo when no suitable non-preference-based instrument exists, using IRT and Rasch analysis. For items that fit the Rasch model, developers selected one item per dimension and explored item response level reduction. This framework will guide researchers who are developing or assessing CSPBIs.

The impact of the early COVID-19 pandemic on healthcare system resource use and costs in two provinces in Canada: An interrupted time series analysis.

INTRODUCTION: The aim of our study was to assess the initial impact of COVID-19 on total publicly-funded direct healthcare costs and health services use in two Canadian provinces, Ontario and British Columbia (BC). METHODS: This retrospective repeated cross-sectional study used population-based administrative datasets, linked within each province, from January 1, 2018 to December 27, 2020. Interrupted time series analysis was used to estimate changes in the level and trends of weekly resource use and costs, with March 16-22, 2020 as the first pandemic week. Also, in each week of 2020, we identified cases with their first positive SARS-CoV-2 test and estimated their healthcare costs until death or December 27, 2020. RESULTS: The resources with the largest level declines (95% confidence interval) in use in the first pandemic week compared to the previous week were physician services [Ontario: -43% (-49%,-37%); BC: -24% (-30%,-19%) (both p<0.001)] and emergency department visits [Ontario: -41% (-47%,-35%); BC: -29% (-35%,-23%) (both p<0.001)]. Hospital admissions declined by 27% (-32%,-23%) in Ontario and 21% (-26%,-16%) in BC (both p<0.001). Resource use subsequently rose but did not return to pre-pandemic levels. Only home care and dialysis clinic visits did not significantly decrease compared to pre-pandemic. Costs for COVID-19 cases represented 1.3% and 0.7% of total direct healthcare costs in 2020 in Ontario and BC, respectively. CONCLUSIONS: Reduced utilization of healthcare services in the overall population outweighed utilization by COVID-19 patients in 2020. Meeting the needs of all patients across all services is essential to maintain resilient healthcare systems.

A province-by-province cost-effectiveness analysis and budget impact analysis of one-time birth cohort screening of hepatitis C virus (HCV) infection in Canada.

Managing chronic hepatitis C is challenging, as the majority of those infected are asymptomatic. Therefore, to ensure treatments are administered before the onset of severe complications, screening is important. In Canada, uncertainty regarding the cost-effectiveness and budget impact of screening has led to conflicting recommendations. The objective of this study is to estimate the cost-effectiveness and budget-impact of one-time HCV screening. A state-transition model was developed to evaluate the cost-effectiveness and budget-impact between a risk-based screening strategy (current-practice) and a one-time screening strategy on three different birth-cohorts. Cost and prevalence data were obtained from administrative data. Progression and utility data were based on recent systematic reviews. We used a provincial payer-perspective, life-time time-horizon and a 1.5% discount rate for the cost-effectiveness analysis, and used a 10-year time-horizon and no discounting for the budget-impact analysis. One-time screening strategy would cost more and provide more health benefits than the risk-based screening for all birth cohorts. For those born after 1964, the incremental-cost-effectiveness-ratio (ICER) per quality-adjusted-life-year (QALY) of screening versus current-practice varied from $27,422/QALY to $42,191/QALY across different provinces. One-time screening of the cohort would cost an additional $2 million to $236 million across different provinces. For those born 1945-1964, the ICER of screening versus current-practice varied from $35,217/QALY to $48,197/QALY across different provinces. For the cohort born before 1945, the ICER of screening versus current-practice was not cost-effective at a willingness-to-pay threshold of $50,000/QALY across all provinces. Our cost-effectiveness analysis suggests that a one-time HCV screening program for those born after 1945 is cost-effective. Considering the budget impact relative to other funded recommended health services and technologies, HCV screening could be considered affordable.

Lessons from First Nations partnerships in hepatitis C research and the co-creation of knowledge.

BACKGROUND: Administrative health data provide a rich and powerful tool for health services research. Partnership between researchers and the Ontario First Nations HIV/AIDS Education Circle (OFNHAEC) allowed for comprehensive analyses of the health and economic impacts of hepatitis C virus (HCV) infection in First Nations populations across Ontario, using administrative data. Examples of meaningful involvement of First Nations partners in research using secondary data sources demonstrate how community-based participatory research principles can be adapted to empower First Nations stakeholders and decision-makers. The aim of this review is to summarize and reflect on lessons learned in producing meaningful and actionable First Nations HCV research using health administrative data, from the perspective of health services researchers who collaborated for the first time with First Nations partners. METHODS: We discuss how our relationship with OFNHAEC formed and how engagement contextualized findings and provided opportunities for fostering trust and mutual capacity building. Methods included adherence to data governance principles, agreements outlining ethical conduct, and establishing commitment between partners. RESULTS: Engagement with OFNHAEC enhanced cultural understandings in study conception, design, and analysis, and enabled meaningful lessons for both parties through contextualizing findings together. Partnership ensured attention to factors, such as strength-based approaches and limitations of administrative data in their representation of First Nations peoples, that are not considered in standard HCV health services research using administrative health data. CONCLUSIONS: Collaboration throughout the HCV research provided first-hand experience of the relevance, representation, and importance of incorporating First Nations perspectives in health services research using administrative data.

Disparities in health utilities among hepatitis C patients receiving care in different settings.

BACKGROUND: Although chronic hepatitis C (CHC) disproportionately affects marginalized individuals, most health utility studies are conducted in hospital settings which are difficult for marginalized patients to access. We compared health utilities in CHC patients receiving care at hospital-based clinics and socio-economically marginalized CHC patients receiving care through a community-based program. METHODS: We recruited CHC patients from hospital-based clinics at the University Health Network and community-based sites of the Toronto Community Hep C Program, which provides treatment, support, and education to patients who have difficulty accessing mainstream health care. We elicited utilities using six standardized instruments (EuroQol-5D-3L [EQ-5D], Health Utilities Index Mark 2/Mark 3 [HUI2/HUI3], Short Form-6D [SF-6D], time trade-off [TTO], and Visual Analogue Scale [VAS]). Multivariable regression analysis was performed to examine factors associated with differences in health utility. RESULTS: Compared with patients recruited from the hospital setting (n = 190), patients recruited from the community setting (n = 101) had higher unemployment (87% versus 67%), history of injection drug use (88% versus 42%), and history of mental health issue(s) (79% versus 46%). Unadjusted health utilities were lower in community than hospital patients (e.g., EQ-5D: 0.722 [SD 0.209] versus 0.806 [SD 0.195]). Unemployment and a history of mental health issue(s) were significant predictors of low health utility. CONCLUSIONS: Socio-economically marginalized CHC patients have lower health utilities than patients typically represented in the CHC utility literature. Their utilities should be incorporated into future cost-utility analyses to better represent the population living with CHC in health policy decisions.

Impact of direct-acting antiviral treatment on health utility in patients with chronic hepatitis C in hospital and community settings.

BACKGROUND: Direct-acting antiviral agents (DAAs) have transformed chronic hepatitis C (CHC) treatment. Continued affordable access to DAAs requires updated cost-effectiveness analyses (CEA). Utility is a preference-based measure of health-related quality of life (HRQoL) used in CEA. This study evaluated the impact of DAAs on utilities for patients with CHC in two clinical settings. METHODS: This prospective longitudinal study included patients aged ≥18 years, diagnosed with CHC and scheduled to begin DAA treatment, from two tertiary care hospital clinics and four community clinics in Toronto, Calgary, and Montreal. Patients completed two utility instruments (EQ-5D-5L and Health Utilities Index 2/3 (HUI2/3)) before treatment, 6 weeks after treatment initiation, and 12 weeks and 1 year after treatment completion. We measured utilities for all patients, and for hospital-based and community-based groups. RESULTS: Between 2017 and 2020, 209 patients (126 hospital-based, 83 community-based; average age 53 years; 65% male) were recruited, and 143 completed the 1-year post-treatment assessment. Pre-treatment, utilities were (mean ± standard deviation) 0.77 ± 0.21 (EQ-5D-5L), 0.69 ± 0.24 (HUI2) and 0.58 ± 0.34 (HUI3). The mean changes at 1-year post-treatment were 0.035, 0.038 and 0.071, respectively. While utilities for hospital-based patients steadily improved, utilities for the community-based cohort improved between baseline and 12-weeks post-treatment, but decreased thereafter. DISCUSSION: This study suggests that utilities improve after DAA treatment in patients with CHC in a variety of settings. However, community-based patients may face challenges related to comorbid health and social conditions that are not meaningfully addressed by treatment. Our study is essential for valuing health outcomes in CHC-related CEA.

Developing the Breast Utility Instrument to Measure Health-Related Quality-of-Life Preferences in Patients with Breast Cancer: Selecting the Item for Each Dimension.

Introduction. Generic preference-based instruments inadequately measure breast cancer (BrC) health-related quality-of-life preferences given advances in therapy. Our overall purpose is to develop the Breast Utility Instrument (BUI), a BrC-specific preference-based instrument. This study describes the selection of the BUI items. Methods. A total of 408 patients from diverse BrC health states completed the EORTC QLQ-C30 and BR45 (breast module). For each of 10 dimensions previously assessed with confirmatory factor analysis, we evaluated data fit to the Rasch model based on global model and item fit, including threshold ordering, item residuals, infit and outfit, differential item functioning (age), and unidimensionality. Misfitting items were removed iteratively, and the model fit was reassessed. From items fitting the Rasch model, we selected 1 item per dimension based on high patient- and clinician-rated item importance, breadth of item thresholds, and clinical relevance. Results. Global model fit was good in 7 and borderline in 3 dimensions. Separation index was acceptable in 4 dimensions. Item selection criteria were maximized for the following items: 1) physical functioning (trouble taking a long walk), 2) emotional functioning (worry), 3) social functioning (interfering with social activities), 4) pain (having pain), 5) fatigue (tired), 6) body image (dissatisfied with your body), 7) systemic therapy side effects (hair loss), 8) sexual functioning (interest in sex), 9) breast symptoms (oversensitive breast), and 10) endocrine therapy symptoms (problems with your joints). Conclusions. We propose 10 items for the BUI. Our next steps include assessing the measurement properties prior to eliciting preference weights of the BUI. Highlights: A previous confirmatory factor analysis established 10 dimensions of the European Organisation for Research and Treatment of Cancer (EORTC) core quality of life questionnaire (QLQ-C30) and its breast module (BR45).In this study, we selected 1 item per dimension based on fit to the Rasch model, patient- and clinician-rated item importance, breadth of item thresholds, and clinical relevance.These items form the core of the future Breast Utility Instrument (BUI).The future BUI will be a novel breast cancer-specific preference-based instrument that potentially will better reflect women's preferences in clinical decision making and cost utility analyses.

Initial health care costs for COVID-19 in British Columbia and Ontario, Canada: an interprovincial population-based cohort study.

BACKGROUND: COVID-19 imposed substantial health and economic burdens. Comprehensive population-based estimates of health care costs for COVID-19 are essential for planning and policy evaluation. We estimated publicly funded health care costs in 2 Canadian provinces during the pandemic's first wave. METHODS: In this historical cohort study, we linked patients with their first positive SARS-CoV-2 test result by June 30, 2020, in 2 Canadian provinces (British Columbia and Ontario) to health care administrative databases and matched to negative or untested controls. We stratified patients by highest level of initial care: community, long-term care, hospital (without admission to the intensive care unit [ICU]) and ICU. Mean publicly funded health care costs for patients and controls, mean net (attributable to COVID-19) costs and total costs were estimated from 30 days before to 120 days after the index date, or to July 31, 2020, in 30-day periods for patients still being followed by the start of each period. RESULTS: We identified 2465 matched people with a positive test result for SARS-CoV-2 in BC and 28 893 in Ontario. Mean age was 53.4 (standard deviation [SD] 21.8) years (BC) and 53.7 (SD 22.7) years (Ontario); 55.7% (BC) and 56.1% (Ontario) were female. Net costs in the first 30 days after the index date were $22 010 (95% confidence interval [CI] 19 512 to 24 509) and $15 750 (95% CI 15 354 to 16 147) for patients admitted to hospital, and $65 828 (95% CI 58 535 to 73 122) and $56 088 (95% CI 53 721 to 58 455) for ICU patients in BC and Ontario, respectively. In the community and long-term care settings, net costs were near 0. Total costs for all people, from 30 days before to 30 days after the index date, were $22 128 330 (BC) and $175 778 210 (Ontario). INTERPRETATION: During the first wave, we found that mean costs attributable to COVID-19 were highest for patients with ICU admission and higher in BC than Ontario. Reducing the number of people who acquire COVID-19 and severity of illness are required to mitigate the economic impact of COVID-19.

"Bring the Hoses to Where the Fire Is!": Differential Impacts of Marginalization and Socioeconomic Status on COVID-19 Case Counts and Healthcare Costs.

OBJECTIVES: Local health leaders and the Director General of the World Health Organization alike have observed that COVID-19 "does not discriminate." Nevertheless, the disproportionate representation of people of low socioeconomic status among those infected resembles discrimination. This population-based retrospective cohort study examined COVID-19 case counts and publicly funded healthcare costs in Ontario, Canada, with a focus on marginalization. METHODS: Individuals with their first positive severe acute respiratory syndrome coronavirus 2 test from January 1, 2020 to June 30, 2020, were linked to administrative databases and matched to negative/untested controls. Mean net (COVID-19-attributable) costs were estimated for 30 days before and after diagnosis, and differences among strata of age, sex, comorbidity, and measures of marginalization were assessed using analysis of variance tests. RESULTS: We included 28 893 COVID-19 cases (mean age 54 years, 56% female). Most cases remained in the community (20 545, 71.1%) or in long-term care facilities (4478, 15.5%), whereas 944 (3.3%) and 2926 (10.1%) were hospitalized, with and without intensive care unit, respectively. Case counts were skewed across marginalization strata with 2 to 7 times more cases in neighborhoods with low income, high material deprivation, and highest ethnic concentration. Mean net costs after diagnosis were higher for males ($4752 vs $2520 for females) and for cases with higher comorbidity ($1394-$7751) (both P < .001) but were similar across levels of most marginalization dimensions (range $3232-$3737, all P ≥ .19). CONCLUSIONS: This study suggests that allocating resources unequally to marginalized individuals may improve equality in outcomes. It highlights the importance of reducing risk of COVID-19 infection among marginalized individuals to reduce overall costs and increase system capacity.

Developing the Breast Utility Instrument, a preference-based instrument to measure health-related quality of life in women with breast cancer: Confirmatory factor analysis of the EORTC QLQ-C30 and BR45 to establish dimensions.

OBJECTIVES: Breast cancer (BrC) and its treatments impair health-related quality of life (HRQoL). Utility is a measure of HRQoL that includes preferences for health outcomes, used in treatment decision-making. Generic preference-based instruments lack BrC-specific concerns, indicating the need for a BrC-specific preference-based instrument. Our objective was to determine dimensions of the European Organisation for Research and Treatment of Cancer (EORTC) general cancer (QLQ-C30) and breast module (BR45) instruments, the first step in our development of the novel Breast Utility Instrument (BUI). METHODS: Patients (n = 408) attending outpatient BrC clinics at an urban cancer centre, and representing a spectrum of BrC health states, completed the QLQ-C30 and BR45. We performed confirmatory factor analysis of the combined QLQ-C30 and BR45 using mean-and variance-adjusted unweighted least squares estimation. The hypothesized factor model was based on clinical relevance, item distributions, missing data, item-importance, and internal reliability of dimensions. Models were evaluated based on global and item fit, local areas of strain, and likelihood ratio tests of nested models. RESULTS: Our final model had 10 dimensions: physical and role functioning, emotional functioning, social functioning, body image, pain, fatigue, systemic therapy side effects, sexual functioning and enjoyment, arm and breast symptoms, and endocrine therapy symptoms. Good overall model fit was achieved: χ2/df: 1.45, Tucker-Lewis index: 0.946, comparative fit index: 0.951, standardized root-mean-square residual: 0.069, root-mean-square error of approximation: 0.033 (0.030-0.037). All items had salient factor loadings (λ>0.4, p<0.001). CONCLUSIONS: We identified important BrC HRQoL dimensions to develop the BUI, a BrC-specific preference-based instrument.

Reliability and validity of using EQ-5D-5L among healthy and adolescents with major mental health disorders in Ethiopia.

BACKGROUND: The EQ-5D is a validated and widely used generic measure of health-related quality of life (HRQoL) in both healthy individuals and those with various medical conditions. The objective of this study was to test whether EQ-5D-5L is reliable and valid for use among school sample adolescents and those with major mental health disorders in Ethiopia. METHODS: Participants were recruited from ten sub-districts comprising the Butajira Rural Health Programme (BRHP) and Butajira major mental health disorders center. Data were collected using an Amharic (Ethiopia) EQ-5D-5L self-complete-paper and the questionnaire was administered 10 days after the first completion for test-retest procedures. Two-way mixed-effects models absolute intraclass correlation coefficient (ICC) was used to test reliability of the instrument while Kruskal-Wallis rank test with pairwise comparison was used to assess the known group validity of the instrument. RESULTS: There were 501 (201 school sample and 300 adolescents with major mental health disorders) participants recruited and 497 were included in the sample for analysis. The ICC was high (ICC > 0.7, p < 0.001) for all EQ-5D-5L dimensions, EQ-5D-5L utility index and EQ-VAS scores. The findings revealed that the Amharic EQ-5D-5L has significant known group validity as shown by the difference in scores among various disease group (depression, schizophrenia, and bipolar) and experience of chronic illness. CONCLUSIONS: The results shows that the Amharic EQ-5D-5L is reliable and valid instrument for the measurement of HRQoL among adolescent populations in Ethiopia.

Health care costs associated with chronic hepatitis C virus infection in Ontario, Canada: a retrospective cohort study.

BACKGROUND: High-quality estimates of health care costs are required to understand the burden of illness and to inform economic models. We estimated the costs associated with hepatitis C virus (HCV) infection from the public payer perspective in Ontario, Canada. METHODS: In this population-based retrospective cohort study, we identified patients aged 18-105 years diagnosed with chronic HCV infection in Ontario from 2003 to 2014 using linked administrative data. We allocated the time from diagnosis until death or the end of follow-up (Dec. 31, 2016) to 9 mutually exclusive health states using validated algorithms: no cirrhosis, no cirrhosis (RNA negative) (i.e., cured HCV infection), compensated cirrhosis, decompensated cirrhosis, hepatocellular carcinoma, both decompensated cirrhosis and hepatocellular carcinoma, liver transplantation, terminal (liver-related) and terminal (non-liver-related). We estimated direct medical costs (in 2018 Canadian dollars) per 30 days per health state and used regression models to identify predictors of the costs. RESULTS: We identified 48 239 patients with chronic hepatitis C, of whom 30 763 (63.8%) were men and 35 891 (74.4%) were aged 30-59 years at diagnosis. The mean 30-day costs were $798 (95% confidence interval [CI] $780-$816) (n = 43 568) for no cirrhosis, $661 (95% CI $630-$692) (n = 6422) for no cirrhosis (RNA negative), $1487 (95% CI $1375-$1599) (n = 4970) for compensated cirrhosis, $3659 (95% CI $3279-$4039) (n = 3151) for decompensated cirrhosis, $4238 (95% CI $3480-$4996) (n = 550) for hepatocellular carcinoma, $8753 (95% CI $7130-$10 377) (n = 485) for both decompensated cirrhosis and hepatocellular carcinoma, $4539 (95% CI $3746-$5333) (n = 372) for liver transplantation, $11 202 (95% CI $10 645-$11 760) (n = 3201) for terminal (liver-related) and $8801 (95% CI $8331-$9271) (n = 5278) for terminal (non-liver-related) health states. Comorbidity was the most significant predictor of total costs for all health states. INTERPRETATION: Our findings suggest that the financial burden of HCV infection is substantially higher than previously estimated in Canada. Our comprehensive, up-to-date cost estimates for clinically defined health states of HCV infection should be useful for future economic evaluations related to this disorder.

Impact of direct-acting antiviral regimens on mortality and morbidity outcomes in patients with chronic hepatitis c: Systematic review and meta-analysis.

The long-term effects of direct-acting antiviral therapies (DAAs) for chronic hepatitis C (CHC) remain uncertain. The objective of this systematic review and meta-analysis was to assess the impact of DAAs on CHC progression and mortality. We searched Ovid MEDLINE, Ovid EMBASE and PubMed databases (January 2011 to March 2020) for studies that compared the efficacy of DAAs to a non-DAA control in patients with CHC. Main outcomes were the adjusted hazard ratios (HRs) for mortality, liver decompensation, HCC occurrence and recurrence. Pooled estimates of HRs were determined using random-effects meta-analyses with inverse variance weighting, with sensitivity analyses and meta-regression to explore the effects of clinical factors. We identified 39 articles for the primary analysis. Compared with unexposed individuals, patients treated with DAA had a reduced risk of death (HR; CI = 0.44; 0.38-0.52), decompensation (HR; CI = 0.54; 0.38- 0.76) and HCC occurrence (HR; CI = 0.72; 0.61- 0.86). The protective effect of DAA on HCC recurrence was less clear (HR; CI = 0.72; 0.44-1.16). Sustained virologic response (SVR) attainment was a significant predictor of reduced mortality (HR; CI = 0.33; 0.23-0.46), decompensation (HR; CI = 0.11; 0.05-0.24), HCC occurrence (HR; CI = 0.31; 0.27-0.37) and HCC recurrence (HR; CI = 0.32; 0.20-0.51). Meta-regression showed no evidence of effect modification by patient age, sex, presence of cirrhosis or length of follow-up. In conclusion, our findings show protective effects of DAA treatment and DAA-related SVR on CHC progression and mortality.

Pharmacological Acromegaly Treatment: Cost-Utility and Value of Information Analysis.

OBJECTIVES: To conduct a cost-utility analysis comparing drug strategies involving octreotide, lanreotide, pasireotide, and pegvisomant for the treatment of patients with acromegaly who have failed surgery, from a Brazilian public payer perspective. METHODS: A probabilistic cohort Markov model was developed. One-year cycles were employed. The patients started at 45 years of age and were followed lifelong. Costs, efficacy, and quality of life parameters were retrieved from the literature. A discount rate (5%) was applied to both costs and efficacy. The results were reported as costs per quality-adjusted life year (QALY), and incremental cost-effectiveness ratios (ICERs) were calculated when applicable. Scenario analyses considered alternative dosages, discount rate, tax exemption, and continued use of treatment despite lack of response. Value of information (VOI) analysis was conducted to explore uncertainty and to estimate the costs to be spent in future research. RESULTS: Only lanreotide showed an ICER reasonable for having its use considered in clinical practice (R$ 112,138/US$ 28,389 per QALY compared to no treatment). Scenario analyses corroborated the base-case result. VOI analysis showed that much uncertainty surrounds the parameters, and future clinical research should cost less than R$ 43,230,000/US$ 10,944,304 per year. VOI also showed that almost all uncertainty that precludes an optimal strategy choice involves quality of life. CONCLUSIONS: With current information, the only strategy that can be considered cost-effective in Brazil is lanreotide treatment. No second-line treatment is recommended. Significant uncertainty of parameters impairs optimal decision-making, and this conclusion can be generalized to other countries. Future research should focus on acquiring utility data.

Health-Related Quality of Life Changes Associated With Hearing Loss.

Importance: Utility is a single-value, preference-based measure of health-related quality of life that represents the desirability of a health state relative to being dead or in perfect health. Clinical, funding, and policy decisions rely on measured changes in utility. The benefit of hearing loss treatments may be underestimated because existing utility measures fail to capture important changes in quality of life associated with hearing loss. Objective: To develop a comprehensive profile of items that describe how quality of life is associated with hearing loss and its treatments that can be used to generate hearing-related quality of life measures, including a novel utility measure. Design, Setting, and Participants: This qualitative study, performed from August 1, 2018, to August 1, 2019, in tertiary referral centers, comprised a systematic literature review, focus groups, and semistructured interviews. The systematic review evaluated studies published from 1982 to August 1, 2018. Focus groups included 8 clinical experts experienced in the measurement, diagnosis, treatment, and rehabilitation of hearing loss. Semistructured interviews included 26 adults with hearing loss recruited from an institutional data set and outpatient hearing aid and otology clinics using stratified convenience sampling to include individuals of diverse ages, urban and rural residency, causes of hearing loss, severity of hearing loss, and treatment experience. Main Outcomes and Measures: A set of items and subdomains that collectively describe the association of hearing loss with health-related quality of life. Results: The literature search yielded 2779 articles from the MEDLINE, Embase, Cochrane, PsycINFO, and CINAHL databases. Forty-five studies including 1036 individuals (age range, 18-84 years) were included. The focus group included 4 audiologists and 4 otologists. Hour-long semistructured interviews were conducted with 26 individuals (13 women; median age, 54 years; range, 25-83 years) with a broad range of hearing loss causes, configurations, and severities. From all 3 sources, a total of 125 items were generated and organized into 29 subdomains derived from the World Health Organization's International Classification of Functioning, Disability and Health. Conclusions and Relevance: The association of hearing loss with quality of life is multidimensional and includes subdomains that are not considered in the estimation of health utility by existing utility measures. The presented comprehensive profile of items can be used to generate or evaluate measures of hearing-related quality of life, including utility measures.

Comparing Childhood Cancer Care Costs in Two Canadian Provinces.

BACKGROUND: Cancer in children presents unique issues for diagnosis, treatment and survivorship care. Phase-specific comparative cost estimates are important for informing healthcare planning. OBJECTIVE: The aim of this paper is to compare direct medical costs of childhood cancer by phase of care in British Columbia (BC) and Ontario (ON). METHODS: For cancer patients diagnosed at <15 years of age and propensity-score-matched non-cancer controls, we applied standard costing methodology using population-based healthcare administrative data to estimate and compare phase-based costs by province. RESULTS: Phase-specific cancer-attributable costs were 2%-39% higher for ON than for BC. Leukemia pre-diagnosis costs and annual lymphoma continuing care costs were >50% higher in ON. Phase-specific in-patient hospital costs (the major cost category) represented 63%-82% of ON costs, versus 43%-73% of BC costs. Phase-specific diagnostic tests and procedures accounted for 1.0%-3.4% of ON costs and 2.8%-13.0% of BC costs. CONCLUSION: There are substantial cost differences between these two Canadian provinces, BC and ON, possibly identifying opportunities for healthcare planning improvement.

The health impact of delaying direct-acting antiviral treatment for chronic hepatitis C: A decision-analytic approach.

BACKGROUND & AIMS: Direct-acting antivirals (DAAs) are highly effective, but expensive treatments for chronic hepatitis C (CHC). To manage costs, drug plans worldwide have rationed access to DAAs in a variety of ways. This study quantifies the health impact of formulary restrictions and presents a clinical decision tool for informing treatment timing decisions. METHODS: A decision-analytic model was developed to quantify the health impact of delaying DAAs for subpopulations stratified by age, fibrosis level, viral genotype, and injection drug use over their lifetime. The health impact was quantified in terms of quality-adjusted life expectancy (quality-adjusted life years, or QALYs) and life expectancy (years). RESULTS: Deferring DAAs for patients with no or mild fibrosis (F0/F1) for 1-5 years is unlikely to result in life expectancy losses and leads only to marginal losses of 0.02-0.06 QALYs per year of delay. However, for 30-50-year-olds with advanced fibrosis (≥F3) delays as short as a year results in a considerable health loss (0.25-1.04 QALYs and 0.19-1.53 years). Reimbursement limits for those with substance use are associated with large health losses. People who actively inject drugs with advanced fibrosis (≥F3) may lose 0.18-1.05 QALYs and 0.13-1.16 years per year of delay, despite the risk of reinfection and competing mortality. Results are robust to parameter uncertainty and key assumptions. CONCLUSIONS: We present a clinical decision tool for informing treatment timing for various CHC subpopulations. In general, findings suggest that patients with at least moderate fibrosis should be treated promptly regardless of active drug use.

Long-term morbidity and mortality in a Canadian post-transfusion hepatitis C cohort: Over 15 years of follow-up.

The Federal Government of Canada established a $1.1 billion compensation programme in 1999 to support individuals who acquired hepatitis C virus (HCV) through blood products between January 1986 and July 1990. We aimed to describe the morbidity and mortality of this unique post-transfusion cohort (n = 4550) followed for over 15 years from 2000 to 2016. The age-standardized mortality rates were compared with that of the Canadian general population and HCV cohorts from other countries. We evaluated all-cause mortality using Kaplan-Meier survival curves and HCV-related and unrelated mortality using competing risk models. The age-standardized all-cause and HCV-related mortality rates per 10 000 person-years were 127 (95% CI: 117-138) and 76 (95% CI: 69-85) for males, and 77 (95% CI: 69-87) and 43 (95% CI: 37-51) for females, respectively. The risk of death of the post-transfusion cohort was almost twice as high as the Canadian general population (rate ratio = 1.8; 95% CI: 1.7-1.9). All-cause, HCV-related and HCV-unrelated mortality were 20%, 12% and 8%, respectively at 15 years of follow-up. By comparison, HCV-related mortality rates per 10 000 person-years for population-based HCV cohorts varied from 18 and 11 in Australia to 65 and 43 in Scotland for males and females, respectively. We reported long-term follow-up data for the largest post-transfusion cohort in the literature. The all-cause mortality rates were markedly higher than that of the Canadian general population. We also showed that HCV-related mortality were greater compared to other HCV cohorts. This suggests that continued efforts to identify and treat post-transfusion HCV are warranted.

Picturing ELSI+: a visual representation of ethical, legal, and social issues, and patient experiences in Health Technology Assessment in Canada.

OBJECTIVES: Consideration of ethical, legal, and social issues plus patient values (ELSI+) in health technology assessment (HTA) is challenging because of a lack of conceptual clarity and the multi-disciplinary nature of ELSI+. We used concept mapping to identify key concepts and inter-relationships in the ELSI+ domain and provide a conceptual framework for consideration of ELSI+ in HTA. METHODS: We conducted a scoping review (Medline and EMBASE, 2000-2016) to identify ELSI+ issues in the HTA literature. Items from the scoping review and an expert brainstorming session were consolidated into eighty ELSI+-related statements, which were entered into Concept Systems® Global MAX™ software. Participants (N = 38; 36 percent worked as researchers, 21 percent as academics; 42 percent self-identified as HTA experts) sorted the statements into thematic groups, and rated them on importance in making decisions about adopting technologies in Canada, from 1 (not at all important) to 5 (extremely important). We used Concept Systems® Global MAX™ software to create and analyze concept maps with four to sixteen clusters. RESULTS: Our final ELSI+ map consisted of five clusters, with each cluster representing a different concept and the statements within each cluster representing the same concept. Based on the concepts, we named these clusters: patient preferences/experiences, patient quality of life/function, patient burden/harm, fairness, and organizational. The highest mean importance ratings were for the statements in the patient burden/harm (3.82) and organizational (3.92) clusters. CONCLUSIONS: This study suggests an alternative approach to ELSI+, based on conceptual coherence rather than academic disciplines. This will provide a foundation for incorporating ELSI+ into HTA.

Valuing Health State: An EQ-5D-5L Value Set for Ethiopians.

OBJECTIVES: There is a growing interest in health technology assessment and economic evaluations in developing countries such as Ethiopia. The objective of this study was to derive an EQ-5D-5L value set from the Ethiopian general population to facilitate cost utility analysis. METHODS: A nationally representative sample (N = 1050) was recruited using a stratified multistage quota sampling technique. Face-to-face, computer-assisted interviews using the EuroQol Portable Valuation Technology (EQ-PVT) protocol of composite time trade-off (c-TTO) and discrete choice experiments (DCEs) were undertaken to elicit preference scores. The feasibility of the EQ-PVT protocol was pilot tested in a sample of the population (n = 110). A hybrid regression model combining c-TTO and DCE data was used to estimate the final value set. RESULTS: In the pilot study, the acceptability of the tasks was good, and there were no special concerns with undertaking the c-TTO and DCE tasks. The coefficients generated from a hybrid model were logically consistent. The predicted values for the EQ-5D-5L ranged from -0.718 to 1. Level 5 anxiety/depression had the largest impact on utility decrement (-0.458), whereas level 5 self-care had the least impact (-0.222). The maximum predicted value beyond full health was 0.974 for the 11112 health state. CONCLUSIONS: This is the first EQ-5D-5L valuation study in Africa using international valuation methods (c-TTO and DCE) and also the first using the EQ-PVT protocol to derive a value set. We expect that the availability of this value set will facilitate health technology assessment and health-related quality-of-life research and inform policy decision making in Ethiopia.