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.

Home-based versus supervised group exercise in men with prostate cancer on androgen deprivation therapy: A randomized controlled trial and economic analysis.

INTRODUCTION: Differences between health outcomes, participation/adoption, and cost-effectiveness of home-based (HOME) interventions and supervised group-based training (GROUP) in men with prostate cancer (PC) on androgen deprivation therapy (ADT) are currently unknown. The objective of this study was to assess the clinical efficacy, adherence, and cost-effectiveness of HOME versus GROUP in men on ADT for PC. MATERIALS AND METHODS: This was a multicentre, 2-arm non-inferiority randomized controlled trial and companion cost-effectiveness analysis. Men with PC on ADT were recruited from August 2016 to March 2020 from four Canadian centres and randomized 1:1 to GROUP or HOME. All study participants engaged in aerobic and resistance training four to five days weekly for six months. Fatigue [Functional Assessment of Cancer Therapy-Fatigue (FACT-F)] and functional endurance [6-min walk test (6MWT)] at six months were the co-primary outcomes. Secondary outcomes included quality of life, physical fitness, body composition, blood markers, sedentary behaviour, and adherence. Between-group differences in primary outcomes were compared to margins of 3 points for FACT-F and 40 m for 6MWT using a Bayesian analysis of covariance (ANCOVA). Secondary outcomes were compared with ANCOVA, Costs included Ministry of Health costs, program costs, patient out-of-pocket, and time costs. TRIAL REGISTRATION: #NCT02834416. RESULTS: Thirty-eight participants (mean [standard deviation (SD)] age, 70 [9.0] years) were enrolled (GROUP n = 20; HOME n = 18). There was an 89.8% probability that HOME was non-inferior to GROUP for both fatigue and functional endurance and a 9.5% probability that HOME reduced fatigue compared to GROUP (mean [SD] change, 12.1 [8.1] vs 3.6 [6.1]; p = 0.040) at six months. Adherence was similar among study arms. HOME was cost-saving (mean difference: -$4122) relative to GROUP. DISCUSSION: A HOME exercise intervention appears non-inferior to GROUP for fatigue and functional endurance and requires fewer resources to implement. HOME appears to ameliorate fatigue more than GROUP, but has comparable effects on other clinically relevant outcomes. Although limited by sample size and attrition, these results support further assessment of home-based programs.

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.

Characterizing the cascade of care for hepatitis C virus infection among Status First Nations peoples in Ontario: a retrospective cohort study.

BACKGROUND: As First Nations Peoples are a priority focus of Canada's commitment to eliminating hepatitis C virus (HCV) as a public health threat, understanding individuals' progression from diagnosis to cure can guide prioritization of elimination efforts. We sought to characterize and identify gaps in the HCV care cascade for Status First Nations peoples in Ontario. METHODS: In this retrospective cohort study, a partnership between the Ontario First Nations HIV/AIDS Education Circle and academic researchers, HCV testing records (1999-2018) for Status First Nations peoples in Ontario were linked to health administrative data. We defined the cascade of care as 6 stages, as follows: tested positive for HCV antibody, tested for HCV RNA, tested positive for HCV RNA, HCV genotyped, initiated treatment and achieved sustained viral response (SVR). We mapped the care cascade from 1999 to 2018, and estimated the number and proportion of people at each stage. We stratified analyses by sex, diagnosis date and location of residence. We used Cox regression to analyze the secondary outcomes, namely the associations between undergoing HCV RNA testing and initiating treatment, and demographic and clinical predictors. RESULTS: By Dec. 31, 2018, 4962 people tested positive for HCV antibody. Of those testing positive, 4118 (83.0%) were tested for HCV RNA, with 2480 (60.2%) testing positive. Genotyping was completed in 2374 (95.7%) of those who tested positive for HCV RNA, with 1002 (42.2%) initiating treatment. Nearly 80% (n = 801, 79.9%) of treated people achieved SVR, with 34 (4.2%) experiencing reinfection or relapse. Undergoing testing for HCV RNA was more likely among people in older age categories (within 1 yr of antibody test; adjusted hazard ratio [HR] 1.30, 95% confidence interval [CI] 1.19-1.41, among people aged 41-60 yr; adjusted HR 1.47, 95% CI 1.18-1.81, among people aged > 60 yr), those living in rural areas (adjusted HR 1.20, 95% CI 1.10-1.30), those with an index date after Dec. 31, 2013 (era of treatment with direct-acting antiviral regimens) (adjusted HR 1.99, 95% CI 1.85-2.15) and those with a record of substance use or addictive disorders (> 1 yr after antibody test; adjusted HR 1.38, 95% CI 1.18-1.60). Treatment initiation was more likely among people in older age categories at index date (adjusted HR 1.32, 95% CI 1.15-1.50, among people aged 41-60 yr; adjusted HR 2.62, 95% CI 1.80-3.82, among people aged > 60 yr) and those with a later diagnosis year (adjusted HR 2.71, 95% CI 2.29-3.22). INTERPRETATION: In comparison with HCV testing and diagnosis, a substantial gap in treatment initiation remains among Status First Nations populations in Ontario. Elimination efforts that prioritize linkage to care and integration with harm reduction and substance use services are needed to close gaps in HCV care among First Nations populations in Ontario.

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.

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.

Time Costs and Out-of-Pocket Costs in Patients With Chronic Hepatitis C in a Publicly Funded Health System.

OBJECTIVES: Chronic hepatitis C (CHC) infection affects more than 70 million people worldwide and imposes considerable health and economic burdens on patients and society. This study estimated 2 understudied components of the economic burden, patient out-of-pocket (OOP) costs and time costs, in patients with CHC in a tertiary hospital clinic setting and a community clinic setting. METHODS: This was a multicenter, cross-sectional study with hospital-based (n = 174) and community-based (n = 101) cohorts. We used a standardized instrument to collect healthcare resource use, time, and OOP costs. OOP costs included patient-borne costs for medical services, nonprescription drugs, and nonmedical expenses related to healthcare visits. Patient and caregiver time costs were estimated using an hourly wage value derived from patient-reported employment income and, where missing, derived from the Canadian census. Sensitivity analysis explored alternative methods of valuing time. Costs were reported in 2020 Canadian dollars. RESULTS: The mean 3-month OOP cost was $55 (95% confidence interval [CI] $21-$89) and $299 (95% CI $170-$427) for the community and hospital cohorts, respectively. The mean 3-month patient time cost was $743 (95% CI $485-$1002) (community) and $465 (95% CI $248-$682) (hospital). The mean 3-month caregiver time cost was $31 (95% CI $0-$63) (community) and $277 (95% CI $174-$380) (hospital). Patients with decompensated cirrhosis bore the highest costs. CONCLUSIONS: OOP costs and patient and caregiver time costs represent a considerable economic burden to patient with CHC, equivalent to 14% and 21% of the reported total 3-month income for the hospital-based and community-based cohorts, respectively.

Health care costs associated with hepatitis C virus infection in First Nations populations in Ontario: a retrospective matched cohort study.

BACKGROUND: Colonization and marginalization have affected the risk for and experience of hepatitis C virus (HCV) infection for First Nations people in Canada. In partnership with the Ontario First Nations HIV/AIDS Education Circle, we estimated the publicly borne health care costs associated with HCV infection among Status First Nations people in Ontario. METHODS: In this retrospective matched cohort study, we used linked health administrative databases to identify Status First Nations people in Ontario who tested positive for HCV antibodies or RNA between 2004 and 2014, and Status First Nations people who had no HCV testing records or only a negative test result (control group, matched 2:1 to case participants). We estimated total and net costs (difference between case and control participants) for 4 phases of care: prediagnosis (6 mo before HCV infection diagnosis), initial (after diagnosis), late (liver disease) and terminal (6 mo before death), until death or Dec. 31, 2017, whichever occurred first. We stratified costs by sex and residence within or outside of First Nations communities. All costs were measured in 2018 Canadian dollars. RESULTS: From 2004 to 2014, 2197 people were diagnosed with HCV infection. The mean net total costs per 30 days of HCV infection were $348 (95% confidence interval [CI] $277 to $427) for the prediagnosis phase, $377 (95% CI $288 to $470) for the initial phase, $1768 (95% CI $1153 to $2427) for the late phase and $893 (95% CI -$1114 to $3149) for the terminal phase. After diagnosis of HCV infection, net costs varied considerably among those who resided within compared to outside of First Nations communities. Net costs were higher for females than for males except in the terminal phase. INTERPRETATION: The costs per 30 days of HCV infection among Status First Nations people in Ontario increased substantially with progression to advanced liver disease and finally to death. These estimates will allow for planning and evaluation of provincial and territorial population-specific hepatitis C control efforts.

Hepatitis C virus infection in First Nations populations in Ontario from 2006 to 2014: a population-based retrospective cohort analysis.

BACKGROUND: Hepatitis C virus (HCV) infection causes substantial morbidity and mortality in Canada and is of concern among First Nations communities. In partnership with the Ontario First Nations HIV/AIDS Education Circle, we described trends in HCV testing and epidemiologic features among Status First Nations people in Ontario. METHODS: In this retrospective study, we used health administrative databases for 2006-2014 in Ontario with 3 cohorts of Status First Nations people: those tested for HCV for the first time, those who tested positive for HCV antibodies or RNA, and those with no HCV laboratory or testing records. We examined cohort characteristics, and the annual prevalence and incidence of testing and diagnosis of HCV infection. Outcomes were stratified by region, sex and residence within or outside of First Nations communities. RESULTS: During the study period, 2423 Status First Nations people were diagnosed with HCV infection, 20 481 received their first test, and 135 185 had no test record. The point prevalence of ever having been tested increased from 6.3 (95% confidence interval [CI] 6.2-6.5) per 100 people in 2006 to 16.2 (95% CI 16.0-16.4) per 100 people in 2014. The point prevalence of diagnosed HCV infection increased from 0.9 (95% CI 0.9-1.0) to 2.0 (95% CI 1.9-2.0) per 100 people. The incidence of first test and of diagnosis increased from 12.1 (95% CI 11.5-12.6) to 21.3 (95% CI 20.5-22.1) per 1000 person-years and from 1.3 (95% CI 1.1-1.5) to 2.3 (95% CI 2.1-2.6) per 1000 person-years, respectively. Testing, diagnosis and prevalence of HCV infection were consistently higher among people living outside of versus within First Nations communities, but larger increases over time were observed among those living within First Nations communities. INTERPRETATION: Testing and diagnosis of HCV infection increased from 2006 to 2014 among Status First Nations people in Ontario. Our findings indicate the need for population-level efforts to eliminate hepatitis C in First Nations communities.

Review and estimation of disutility for joint health states of severe and nonsevere hypoglycemic events in diabetes.

Aim: Many economic evaluations used linear or log-transformed additive methods to estimate the disutility of hypoglycemic events in diabetes, both nonsevere (NSHEs) and severe (SHEs). Methods: We conducted a literature search for studies of disutility for hypoglycemia. We used additive, minimum and multiplicative methods, and the adjusted decrement estimator to estimate the disutilities of joint health states with both NSHEs and SHEs in six scenarios. Results: Twenty-four studies reported disutilities for hypoglycemia in diabetes. Based on construct validity, the adjusted decrement estimator method likely provides less biased estimates, predicting that when SHEs occur, the additional impact from NSHEs is marginal. Conclusion: Our proposed new method provides a different perspective on the estimation of quality-adjusted life-years in economic evaluations of hypoglycemic treatments.

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.

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.

Exploring the Benefits of Transformations in Health Utility Mapping.

Background. Quality-of-life research and cost-effectiveness analyses frequently require data on health utility, a global measure of health-related quality of life. When utilities are unavailable, researchers have "mapped" descriptive instruments to utility instruments, using samples of responses to both instruments. Health utilities have an idiosyncratic distribution, with upper bound and probability mass at 1, left skewness, and kurtosis. Estimation of mean utility values conditional on covariates is of interest, particularly in health utility mapping applications. Traditional linear regression may be unsuitable because fundamental assumptions are violated. Complex statistical methods come with deficiencies that may outweigh their benefits. Aim. To investigate the benefits of transforming the health utility response variable before fitting a linear regression model. Methods. We compared log, logit, arcsin, and Box-Cox transformations with an untransformed model, using several measures of model accuracy. We made our evaluation by designing and conducting a simulation study and reanalyzing data from 2 published studies, which "mapped" a psychometric descriptive instrument to a utility instrument. Results. In the simulation study, log transformation with smearing estimator had in most cases the lowest bias but one of the highest variances, especially for estimating low utility values under small sample size. The untransformed model was outperformed by the transformed models. Findings were inconclusive for the analysis of real data, where arcsin gave the lowest error for one of the data sets, while the untransformed model had the best performance for the other. Conclusions. We identified the benefits of transformations and offered suggestions for future modeling of health utilities. However, the benefits were moderate and no single transformation appeared to be universally optimal, suggesting that selection requires examination on a case-by-case basis.

A Systematic Review and Meta-Analysis of Health Utilities in Patients With Chronic Hepatitis C.

BACKGROUND: Chronic hepatitis C (CHC) is among the most burdensome infectious diseases in the world. Health utilities are a valuable tool for quantifying this burden and conducting cost-utility analysis. OBJECTIVE: Our study summarizes the available data on utilities in CHC patients. This will facilitate analyses of CHC treatment and elimination strategies. METHODS: We searched MEDLINE, Embase, and the Cochrane Library for studies measuring utilities in CHC patients. Utilities were pooled by health state and utility instrument using meta-analysis. A further analysis used meta-regression to adjust for the effects of clinical status and methodological variation. RESULTS: Fifty-one clinical studies comprising 15 053 patients were included. Based on the meta-regression, patients' utilities were lower for more severe health states (predicted mean EuroQol-5D-3L utility for mild/moderate CHC: 0.751; compensated cirrhosis: 0.671; hepatocellular carcinoma: 0.662; decompensated cirrhosis: 0.602). Patients receiving interferon-based treatment had lower utilities than those on interferon-free treatment (0.647 vs 0.733). Patients who achieved sustained virologic response (0.786) had higher utilities than those with mild to moderate CHC. Utilities were substantially higher for patients in experimental studies compared to observational studies (coefficient: +0.074, P < .05). The time tradeoff instrument was associated with the highest utilities, and the Health Utilities Index 3 was associated with the lowest utilities. CONCLUSION: Chronic hepatitis C is associated with a significant impairment in global health status, as measured by health utility instruments. Impairment is greater in advanced disease. Experimental study designs yield higher utilities-an effect not previously documented. Curative therapy can alleviate the burden of CHC, although further research is needed in certain areas, such as the long-term impacts of treatment on utilities.

Patterns of Care and Costs for Older Patients With Colorectal Cancer at the End of Life: Descriptive Study of the United States and Canada.

PURPOSE: End-of-life (EOL) cancer care is costly, with challenges regarding intensity and place of care. We described EOL care and costs for patients with colorectal cancer (CRC) in the United States and the province of Ontario, Canada, to inform better care delivery. METHODS: Patients diagnosed with CRC from 2007 to 2013, who died of any cancer from 2007 to 2013 at age ≥ 66 years, were selected from the US SEER cancer registries linked to Medicare claims (n = 16,565) and the Ontario Cancer Registry linked to administrative health data (n = 6,587). We estimated total and resource-specific costs (2015 US dollars) from public payer perspectives over the last 360 days of life by 30-day periods, by stage at diagnosis (0-II, III, IV). RESULTS: In all months, especially 30 days before death, higher percentages of SEER-Medicare than Ontario patients received chemotherapy (15.7% v 8.0%), and imaging tests (39.4% v 31.1%). A higher percentage of Ontario patients were hospitalized (62.5% v 51.0%), but 43.2% of hospitalized SEER-Medicare patients had intensive care unit (ICU) admissions versus 17.9% of hospitalized Ontario patients. Cost differences between cohorts were greater for patients with stage IV disease. In the last 30 days, mean total costs for patients with stage IV disease were $15,881 (SEER-Medicare) and $12,034 (Ontario) versus $19,354 and $17,312 for stage 0-II. Hospitalization costs were higher for SEER-Medicare patients ($11,180 v $9,434), with lower daily hospital costs in Ontario ($1,067 v $2,004). CONCLUSION: These findings suggest opportunities for reducing chemotherapy and ICU use in the United States and hospitalizations in Ontario.