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.

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.

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.

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.

"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.

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.

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.

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.

New Insights into the Epidemiology of Prostate Cancer in Ontario.

The epidemiology of prostate cancer (PC) continues to change. We evaluated the changes in incidence, in average age at diagnosis, and in survival from 1992 to 2015 in Ontario. We compared the cumulative incidence of PC-specific and non PC-specific mortality using two algorithms for cause of death: Method 1 assigned deaths from "other cancers" to non PC-specific causes, and Method 2 assigned these cases to PC-specific mortality. There were 188,714 cases diagnosed with PC between 1992 and 2015 in Ontario. The average age at diagnosis declined from 1992 to 2008 by 0.26 year (3.1 months) annually (p < 0.001) and increased by 0.15 year (1.8 months) thereafter (p > 0.05). Between 2010 and 2015, the proportion of patients diagnosed at stage IV increased, and the proportion diagnosed at stage I decreased (p-values for trends <0.001). Overall survival significantly improved over the years. The cumulative incidence of PC-specific mortality at 5 and 10 years was 6.8 and 9.8% using Method 1, and 10.2 and 16.8% using Method 2. We observed trends toward older age and more advanced stage at PC diagnosis in Ontario. Further studies are needed to validate algorithms for estimating PC-specific mortality from administrative databases.

The Bladder Utility Symptom Scale: A Novel Patient Reported Outcome Instrument for Bladder Cancer.

PURPOSE: Health related quality of life is important in bladder cancer care and clinical decision making because patients must choose between diverse treatment modalities with unique morbidities. A patient reported outcome measure of overall health related quality of life for bladder cancer regardless of disease severity and treatment could benefit clinical care and research. MATERIALS AND METHODS: Prospective questionnaire development was completed in 3 parts. In study 1 the BUSS (Bladder Utility Symptom Scale) questions were created by experts using a conceptual framework of bladder cancer health related quality of life generated through patient focus groups. In study 2 patients with bladder cancer, including those treated with surgery, radiation and chemotherapy, completed the BUSS and 5 health related quality of life instruments at baseline and 4 weeks to assess validity and test-retest reliability. External validity was then explored in study 3 by administering the BUSS to 578 patients online and at clinics. Construct validity was assessed by whole and subscale Spearman rank correlations, and by comparisons of BUSS scores across known groups. RESULTS: The BUSS had high whole scale correlation with the FACT-Bl (Functional Assessment of Cancer Therapy-Bladder) (rs = 0.82, p <0.0001) and substantial to high subscale correlations with the EQ-5D™-3L (EuroQol 5 Dimensions Questionnaire-3 Levels) (eg emotional well-being rs = 0.69, p <0.0001). BUSS scores were lower in patients with comorbidity and advanced disease. Cognitive debriefing and the 94% completion rate suggested good comprehensibility. There was excellent test-retest reliability (ICC = 0.79). Limitations included an extended time from diagnosis in many patients. CONCLUSIONS: The BUSS is a reliable and valid patient reported outcome instrument for health related quality of life in all patients with bladder cancer regardless of the treatment received or the stage of disease.

Costs for Childhood and Adolescent Cancer, 90 Days Prediagnosis and 1 Year Postdiagnosis: A Population-Based Study in Ontario, Canada.

BACKGROUND: Childhood and adolescent cancers are uncommon, but they have important economic and health impacts on patients, families, and health care systems. Few studies have measured the economic burden of care for childhood and adolescent cancers. OBJECTIVES: To estimate costs of cancer care in population-based cohorts of children and adolescents from the public payer perspective. METHODS: We identified patients with cancer, aged 91 days to 19 years, diagnosed from 1995 to 2009 using cancer registry data, and matched each to three noncancer controls. Using linked administrative health care records, we estimated total and net resource-specific costs (in 2012 Canadian dollars) during 90 days prediagnosis and 1 year postdiagnosis. RESULTS: Children (≤14 years old) numbered 4,396: 36% had leukemia, 21% central nervous system tumors, 10% lymphoma, and 33% other cancers. Adolescents (15-19 years old) numbered 2,329: 28.9% had lymphoma. Bone and soft tissue sarcoma, germ cell tumor, and thyroid carcinoma each comprised 12% to 13%. Mean net prediagnosis costs were $5,810 and $1,127 and mean net postdiagnosis costs were $136,413 and $62,326 for children and adolescents, respectively; the highest were for leukemia ($157,764 for children and $172,034 for adolescents). In both cohorts, costs were much higher for patients who died within 1 year of diagnosis. Inpatient hospitalization represented 69% to 74% of postdiagnosis costs. CONCLUSIONS: Treating children with cancer is costly, more costly than treating adolescents or adults. Substantial survival gains in children mean that treatment may still be very cost-effective. Comprehensive age-specific population-based cost estimates are essential to reliably assess the cost-effectiveness of cancer care for children and adolescents, and measure health system performance.

Costs of cancer care in children and adolescents in Ontario, Canada.

BACKGROUND: Cancer in children and adolescents presents unique issues regarding treatment and survivorship, but few studies have measured economic burden. We estimated health care costs by phase of cancer care, from the public payer perspective, in population-based cohorts. METHODS: Children newly diagnosed at ages 0 days-14.9 years and adolescents newly diagnosed at 15-19.9 years, from January 1, 1995 to June 30, 2010, were identified from Ontario cancer registries, and each matched to three noncancer controls. Data were linked with administrative records describing resource use for cancer and other health care. Total and net (patients minus controls) resource-specific costs ($CAD2012) were estimated using generalized estimating equations for four phases of care: prediagnosis (60 days), initial (360 days), continuing (variable), final (360 days). RESULTS: Mean ages at diagnosis were 6 years for children (N = 4,606) and 17 years for adolescents (N = 2,443). Mean net prediagnosis phase 60-day costs were $6,177 for children and $1,018 for adolescents. Costs for initial, continuing, and final phases were $138,161, $15,756, and $316,303 per 360 days for children, and $62,919, $7,071, and $242,008 for adolescents. The highest initial phase costs were for leukemia patients ($156,225 per 360 days for children and $171,275 for adolescents). The final phase was the most costly ($316,303 per 360 days for children and $242,008 for adolescents). CONCLUSIONS: Costs for children with cancer are much higher than for adolescents and much higher than those reported in adults. Comprehensive population-based long-term estimates of cancer costs are useful for health services planning and cost-effectiveness analysis.

Benefits and harms of prostate cancer screening - predictions of the ONCOTYROL prostate cancer outcome and policy model.

BACKGROUND: A recent recalibration of the ONCOTYROL Prostate Cancer Outcome and Policy (PCOP) Model, assuming that latent prostate cancer (PCa) detectable at autopsy might be detectable by screening as well, resulted in considerable worsening of the benefit-harm balance of screening. In this study, we used the recalibrated model to assess the effects of familial risk, quality of life (QoL) preferences, age, and active surveillance. METHODS: Men with average and elevated familial PCa risk were simulated in separate models, differing in familial risk parameters. Familial risk was assumed to affect PCa onset and progression simultaneously in the base-case, and separately in scenario analyses. Evaluated screening strategies included one-time screening at different ages, and screening at different intervals and age ranges. Optimal screening strategies were identified depending on age and individual QoL preferences. Strategies were additionally evaluated with active surveillance by biennial re-biopsy delaying treatment of localized cancer until grade progression to Gleason score ≥ 7. RESULTS: Screening men with average PCa risk reduced quality-adjusted life expectancy (QALE) even under favorable assumptions. Men with elevated familial risk, depending on age and disutilities, gained QALE. While for men with familial risk aged 55 and 60 years annual screening to age 69 was the optimal strategy over most disutility ranges, no screening was the preferred option for 65 year-old men with average and above disutilities. Active surveillance greatly reduced overtreatment, but QALE gains by averted adverse events were opposed by losses due to delayed treatment and additional biopsies. The effect of active surveillance on the benefit-harm balance of screening differed between populations, as net losses and gains in QALE predicted for screening without active surveillance in men with average and familial PCa risk, respectively, were both reduced. CONCLUSIONS: Assumptions about PCa risk and screen-detectable prevalence significantly affect the benefit-harm balance of screening. Based on the assumptions of our model, PCa screening should focus on candidates with familial predisposition with consideration of individual QoL preferences and age. Active surveillance may require treatment initiation before Gleason score progression to 7. Alternative active surveillance strategies should be evaluated in further modeling studies.

Phase-specific and lifetime costs of cancer care in Ontario, Canada.

BACKGROUND: Cancer is a major public health issue and represents a significant economic burden to health care systems worldwide. The objective of this analysis was to estimate phase-specific, 5-year and lifetime net costs for the 21 most prevalent cancer sites, and remaining tumour sites combined, in Ontario, Canada. METHODS: We selected all adult patients diagnosed with a primary cancer between 1997 and 2007, with valid ICD-O site and histology codes, and who survived 30 days or more after diagnosis, from the Ontario Cancer Registry (N = 394,092). Patients were linked to treatment data from Cancer Care Ontario and administrative health care databases at the Institute for Clinical and Evaluative Sciences. Net costs (i.e., cost difference between patients and matched non-cancer control subjects) were estimated by phase of care and sex, and used to estimate 5-year and lifetime costs. RESULTS: Mean net costs of care (2009 CAD) were highest in the initial (6 months post-diagnosis) and terminal (12 months pre-death) phases, and lowest in the (3 months) pre-diagnosis and continuing phases of care. Phase-specific net costs were generally lowest for melanoma and highest for brain cancer. Mean 5-year net costs varied from less than $25,000 for melanoma, thyroid and testicular cancers to more than $60,000 for multiple myeloma and leukemia. Lifetime costs ranged from less than $55,000 for lung and liver cancers to over $110,000 for leukemia, multiple myeloma, lymphoma and breast cancer. CONCLUSIONS: Costs of cancer care are substantial and vary by cancer site, phase of care and time horizon analyzed. These cost estimates are valuable to decision makers to understand the economic burden of cancer care and may be useful inputs to researchers undertaking cancer-related economic evaluations.

An international comparison of costs of end-of-life care for advanced lung cancer patients using health administrative data.

BACKGROUND: Patterns of end-of-life cancer care differ in Canada and the United States; yet little is known about differences in service-specific and overall costs. AIM: The aim of this study was to compare end-of-life costs in Ontario, Canada, and the United States, using administrative health data. DESIGN: Advanced-stage nonsmall cell lung cancer patients who died from cancer at age ⩾ 65.5 years in 2001-2005 were selected from the US Surveillance, Epidemiology, and End Results-Medicare database (N = 16,858) and the Ontario Cancer Registry (N = 8643). We estimated total and service-specific costs (2009 US dollars) in each of the last 6 months of life from the public payer perspectives for short-term and long-term survivors (lived < 180 and ⩾ 180 days post-diagnosis, respectively). Services were defined for comparisons between systems. RESULTS: Mean monthly costs increased as death approached, were higher in short-term than long-term survivors, and were generally higher in the United States than in Ontario until the month before death, when they were similar (long-term survivors: US$10,464 and US$10,094 (p = 0.53), short-term survivors US$14,455 and US$12,836 (p = 0.11), in Surveillance, Epidemiology, and End Results-Medicare and Ontario, respectively). Costs for Medicare hospice and Ontario's palliative care components were similar and increased closer to death. Inpatient hospitalization was the main cost driver with similar costs in both cohorts, despite lower utilization in the United States. The compositions of many services and costs differed. CONCLUSION: Costs for nonsmall cell lung cancer patients were slightly higher in the United States than Ontario until 1 month before death. Administrative data allow exploration and international comparisons of reimbursement policies, health-care delivery, and costs at the end of life.

Real world costs and cost-effectiveness of Rituximab for diffuse large B-cell lymphoma patients: a population-based analysis.

BACKGROUND: Current treatment of diffuse-large-B-cell lymphoma (DLBCL) includes rituximab, an expensive drug, combined with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy. Economic models have predicted rituximab plus CHOP (RCHOP) to be a cost-effective alternative to CHOP alone as first-line treatment of DLBCL, but it remains unclear what its real-world costs and cost-effectiveness are in routine clinical practice. METHODS: We performed a population-based retrospective cohort study from 1997 to 2007, using linked administrative databases in Ontario, Canada, to evaluate the costs and cost-effectiveness of RCHOP compared to CHOP alone. A historical control cohort (n = 1,099) with DLBCL who received CHOP before rituximab approval was hard-matched on age and treatment intensity and then propensity-score matched on sex, comorbidity, and histology to 1,099 RCHOP patients. All costs and outcomes were adjusted for censoring using the inverse probability weighting method. The main outcome measure was incremental cost per life-year gained (LYG). RESULTS: Rituximab was associated with a life expectancy increase of 3.2 months over 5 years at an additional cost of $16,298, corresponding to an incremental cost-effectiveness ratio of $61,984 (95% CI $34,087-$135,890) per LYG. The probability of being cost-effective was 90% if the willingness-to-pay threshold was $100,000/LYG. The cost-effectiveness ratio was most favourable for patients less than 60 years old ($31,800/LYG) but increased to $80,600/LYG for patients 60-79 years old and $110,100/LYG for patients ≥ 80 years old. We found that post-market survival benefits of rituximab are similar to or lower than those reported in clinical trials, while the costs, incremental costs and cost-effectiveness ratios are higher than in published economic models and differ by age. CONCLUSIONS: Our results showed that the addition of rituximab to standard CHOP chemotherapy was associated with improvement in survival but at a higher cost, and was potentially cost-effective by standard thresholds for patients <60 years old. However, cost-effectiveness decreased significantly with age, suggesting that rituximab may be not as economically attractive in the very elderly on average. This has important clinical implications regarding age-related use and funding decisions on this drug.

Conceptualizing global health-related quality of life in bladder cancer.

PURPOSE: Patients' values for health outcomes are central to treatment decisions in bladder cancer (BCa). An instrument incorporating the expressed preferences of BCa patients, as measured by utility, can inform clinical guidelines, resource allocation and policy decisions. Developing this instrument requires a formal conceptual framework summarizing the important domains comprising global health-related quality of life (HRQOL) in BCa. METHODS: We performed a systematic literature search on the HRQOL effects of BCa and its treatments to generate initial items in Medline, Embase, CINAHL and PsychInfo up to January 2013. Thematic synthesis was used to group related items into overarching themes (domains) and create a provisional conceptual framework. In focus groups, 12 BCa experts and 47 BCa patients with diverse clinical histories generated further items to inform the final conceptual framework. RESULTS: We retrieved 1,275 citations and reviewed 170 full-text publications. One hundred and sixty-nine items were extracted into 12 domains. Study investigators used the findings from the focus groups to confirm the domains and condense the list to 83 clinically important items. Functional limitations in work, travel, social interaction and sleep lowered HRQOL in many domains. The final conceptual framework included BCa-specific (urinary, sexual, bowel, body image) and generic domains (pain, vigor, social, psychological, sleep, functional, family relationship, medical care relationship). CONCLUSIONS: A conceptual framework including 12 domains can serve as the foundation for the development of an instruments measuring global HRQOL in BCa and in particular, one that can measure patient preferences and generate utilities.

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.

A reference set of health utilities for long-term survivors of prostate cancer: population-based data from Ontario, Canada.

PURPOSE: To measure quality of life (QOL) and utilities for prostate cancer (PC) patients and determine their predictors. METHODS: A population-based, community-dwelling, geographically diverse sample of long-term PC survivors in Ontario, Canada, was identified from the Ontario Cancer Registry and contacted through their referring physician. Consenting patients completed questionnaires by mail: Health Utilities Index (HUI 2/3), Patient Oriented Prostate Utility Scale PORPUS-U (utility), PORPUS-P (health profile), Functional Assessment of Cancer Therapy-Prostate (FACT-P), and Prostate Cancer Index (PCI). Clinical data were obtained from chart reviews. Regression models determined the effects of a series of variables on QOL and utility. RESULTS: We received questionnaires and reviewed charts for 585 patients (mean age 72.6, 2-13 years postdiagnosis). Mean utility scores were as follows: PORPUS-U = 0.92, HUI2 = 0.85, and HUI3 = 0.78. Mean health profile scores were as follows: PORPUS-P = 71.7, PCI sexual, urinary, and bowel function = 23.7, 79.1, and 84.6, respectively (0 = worst, 100 = best), and FACT-P = 125.1 (0 = worst, 156 = best). In multiple regression analyses, comorbidity and PCI urinary, sexual, and bowel function were significant predictors of other QOL measures. With all variables, 32-50 % of the variance in utilities was explained. CONCLUSIONS: Many variables affect global QOL of PC survivors; only prostate symptoms and comorbidity have independent effects. Our model allows estimation of the effects of multiple factors on utilities. These utilities for long-term outcomes of PC and its treatment are valuable for decision/cost-effectiveness models of PC treatment.

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.