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.

"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.

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.

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.

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.

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.

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.

Pharmacotherapy vs surgery as initial therapy for patients with moderate-to-severe benign prostate hyperplasia: a cost-effectiveness analysis.

OBJECTIVE: To evaluate the cost-effectiveness of using a surgery, such as transurethral resection of the prostate (TURP) or photoselective vaporisation of the prostate using greenlight laser (GL-PVP), as initial treatment for men with moderate-to-severe benign prostate hyperplasia (BPH) compared to the standard practice of using pharmacotherapy as initial treatment followed by surgery if symptoms do not resolve. PATIENTS AND METHODS: We compared a combination of eight strategies involving upfront pharmacotherapy (i.e., α-blocker, 5α-reductase inhibitor, or combination) followed by surgery (e.g. TURP or GL-PVP) upon failure vs TURP or GL-PVP as initial treatment, for a target population of men with moderate-to-severe BPH symptoms, with a mean age of 65 years and no contraindications for treatment. A microsimulation decision-analytic model was developed to project the costs and quality-adjusted life years (QALYs) of the target population over the lifetime. The model was populated and validated using published literature. Incremental cost-effectiveness ratios (ICERs) were determined. Cost-effectiveness was evaluated using a public payer perspective, a lifetime horizon, a discount rate of 1.5%, and a cost-effectiveness threshold of $50 000 (Canadian dollars)/QALY. Sensitivity and probabilistic analyses were performed. RESULTS: All options involving an upfront pharmacotherapy followed by TURP for those who fail were economically unattractive compared to strategies involving a GL-PVP for those who fail, and compared to using either BPH surgery as initial treatment. Overall, upfront TURP was the most costly and effective option, followed closely by upfront GL-PVP. On average, upfront TURP costs $1015 more and resulted in a small gain of 0.03 QALYs compared to upfront GL-PVP, translating to an incremental cost per QALY gained of $29 066. Results were robust to probabilistic analysis. CONCLUSIONS: Surgery is cost-effective as initial therapy for BPH. However, the health and economic evidence should be considered concurrently with patient preferences and risk attitudes towards different therapy options.

Effects of long-term androgen deprivation therapy on cognitive function over 36 months in men with prostate cancer.

BACKGROUND: Many men with prostate cancer (PC) require long-term androgen deprivation therapy (ADT), but to the authors' knowledge, its effects on cognitive function beyond 1 year are not described. METHODS: Three groups of men aged ≥50 years who were matched based on age and education were enrolled: 77 patients with nonmetastatic PC who initiated continuous ADT, 82 patients with PC who were not receiving ADT (PC controls), and 82 healthy controls. A battery of 14 neuropsychological tests, examining 8 cognitive domains, was administered on 5 occasions over 36 months. Changes in cognitive scores over time were analyzed using 3 approaches: linear mixed effects regression, the percentage of participants per group with declines in ≥1/2 cognitive tests, and a global summary of cognitive change. RESULTS: The mean age of the study subjects was 68.9 years, with a median of 16 years of education. In mixed effects models adjusted for age and education, ADT use was not found to be associated with significant changes over time in any cognitive test compared with healthy controls. The percentage of participants declining by ≥1.5 standard deviations in ≥2 tests or ≥2 standard deviations in ≥1 tests was similar across groups. A global summary of cognitive change found no statistically significant worsening of cognitive function among ADT users compared with controls. Sensitivity analyses adjusting for duration of ADT and using multiple imputation for missing data did not materially alter the study findings. CONCLUSIONS: The ongoing use of ADT for up to 36 months does not appear to be associated with cognitive decline. Cancer 2017;123:237-244. © 2016 American Cancer Society.

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.

Long-term cardiovascular outcomes and overall survival of early-stage breast cancer patients with early discontinuation of trastuzumab: a population-based study.

We critically examined long-term cardiovascular (CV) outcomes and overall survival (OS) of breast cancer (BC) patients who had cardiotoxicity during adjuvant trastuzumab treatment requiring discontinuation in a population-based sample. This was a retrospective cohort of early-stage BC patients diagnosed before 2010 and treated with trastuzumab in Ontario. Patients were stratified based on trastuzumab doses received: 1-8, 9-15, ≥16 (therapy completion). Time-dependent multivariable Cox models were used to analyze primary endpoint OS, and the following composite endpoints: hospitalization/emergency room visit for heart failure (HF) or death; non-HF CV (myocardial infarction, stroke) or death; and clinically significant relapse (palliative systemic therapy initiation >90 days after last trastuzumab dose) or death. Of the 3134 women, 6, 10, and 85 % received 1-8, 9-15, and ≥16 doses, respectively. Over 5-year median follow-up, early trastuzumab discontinuation was associated with more HF/death [1-8 doses hazard ratio (HR) 4.0, 95 % confidence interval (CI) 2.7-6.0; 9-15 doses HR 2.97, 95 % CI 2.1-4.3], non-HF/death (1-8 doses HR 4.3, 95 % CI 3.0-6.1; 9-15 doses HR 3.1, 95 % CI 2.2-4.4), clinically significant relapse/death (1-8 doses HR 3.1, 95 % CI 2.2-4.4; 9-15 doses HR 2.4, 95 % CI 1.8-3.3), and importantly lower OS (77, 80, 93 %; P < 0.001). Early discontinuation (1-8 doses HR 2.41, 95 % CI 1.5-3.8; 9-15 doses HR 2.9, 95 % CI 2.0-4.1) and clinically significant relapse (HR 34.0, 95 % CI 24.9-46.6) were both independent predictors of mortality. Of note, early discontinuation remained a critical independent predictor of OS even after adjusting for incident HF. Early trastuzumab discontinuation is a powerful independent predictor of cardiac events and clinically significant relapse, and both may contribute to poor survival. Both adequate cancer control and optimal CV management are required to improve long-term outcomes.

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.

Hepatitis B virus screening before adjuvant chemotherapy in patients with early-stage breast cancer: a cost-effectiveness analysis.

Most patients with hepatitis B virus (HBV) have no symptoms, and many are unaware of the infection. However, HBV can reactivate with immunosuppression; chemotherapy causes reactivation in 22 % of hepatitis B surface antigen-positive patients. HBV reactivation can be fatal. HBV reactivation can be prevented, provided that HBV is recognized prior to chemotherapy. The objective of this study is to estimate the health and economic effects of HBV screening strategies in patients receiving adjuvant chemotherapy for breast cancer. We developed a state-transition microsimulation model to examine the cost-effectiveness of three HBV screening strategies: (1) "No screening"; (2) "Screen-and-Treat to prevent reactivation" (screen-all) with either lamivudine/tenofovir (LAM/TDF) or entecavir (ETV); and (3) "Screen-and-Treat high-risk only" (screen-HR) and treat with either LAM/TDF or ETV. Model data were obtained from the published literature. We used a payer's perspective, a lifetime horizon, and a 5 % discount rate for the analysis. "Screen-all" would prevent at least 38 severe reactivations per 100,000 persons screened over the lifetime of the cohort. "Screen-all" was associated with an increase of 0.0034-0.0035 QALYs and an additional cost of C$164-C$266 per person, which translated into an incremental cost-effectiveness ratio of C$47,808/QALY-C$76,527/QALY gained compared with "No screening" depending on the antiviral therapy received. "Screen-all" was the most cost-effective strategy, while "Screen-HR" was inferior in all scenarios tested. HBV screening before adjuvant chemotherapy for breast cancer patients would prevent a significant number of reactivations, would likely be moderately cost-effective, and may extend the lives of breast cancer patients.

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.

Use of forecasted assessment of quality of life to validate time-trade-off utilities and a prostate cancer screening decision-analytic model.

PURPOSE: To determine whether the forecasted assessment of how someone would feel in a future health state can be predictive of utilities (e.g. as elicited by the time-trade-off method) and also predictive of optimal decisions as determined by a decision-analytic model. METHODS: We elicited time-trade-off utilities for prostate cancer treatment outcomes from 168 men. We also elicited forecasted assessments, that is, an informal, non-quantitative, descriptive evaluation, of impotence and incontinence from these men. We used multivariate regression analysis to explore the relationship between forecasted assessment and reluctance to trade length for improved quality of life, that is, the unwillingness to trade length of life for improved quality of life in the time-trade-off utility assessment and the relationship between the forecasted assessments and the optimal decision of whether to undergo screening for prostate cancer as determined from a previously published decision-analytic model. RESULTS: Importance of sexual function was strongly related to impotence utilities (P < 0.05). Based on the multivariate analysis, significant predictors for the utility of severe incontinence were family income, family history of prostate cancer, work status and attitude towards needing to wear an incontinence pad. However, no variables were statistically significant predictors for the utility of complete impotence. The importance of sexual functioning was a significant predictor of the optimal decision. CONCLUSION: Anticipated difficulty adjusting to adverse health effects were highly related to preferences and could be used as a proxy measure of utility. Similarly, the importance of sexual functioning, a future preference, was highly related to the optimal decision, which validates our previously published decision-analytic model.

A multi-level qualitative analysis of Telehomecare in Ontario: challenges and opportunities.

BACKGROUND: Despite research demonstrating the potential effectiveness of Telehomecare for people with Chronic Obstructive Pulmonary Disease and Heart Failure, broad-scale comprehensive evaluations are lacking. This article discusses the qualitative component of a mixed-method program evaluation of Telehomecare in Ontario, Canada. The objective of the qualitative component was to explore the multi-level factors and processes which facilitate or impede the implementation and adoption of the program across three regions where it was first implemented. METHODS: The study employs a multi-level framework as a conceptual guide to explore the facilitators and barriers to Telehomecare implementation and adoption across five levels: technology, patients, providers, organizations, and structures. In-depth semi-structured interviews and ethnographic observations with program stakeholders, as well as a Telehomecare document review were used to elicit key themes. Study participants (n = 89) included patients and/or informal caregivers (n = 39), health care providers (n = 23), technicians (n = 2), administrators (n = 12), and decision makers (n = 13) across three different Local Health Integration Networks in Ontario. RESULTS: Key facilitators to Telehomecare implementation and adoption at each level of the multi-level framework included: user-friendliness of Telehomecare technology, patient motivation to participate in the program, support for Telehomecare providers, the integration of Telehomecare into broader health service provision, and comprehensive program evaluation. Key barriers included: access-related issues to using the technology, patient language (if not English or French), Telehomecare provider time limitations, gaps in health care provision for patients, and structural barriers to patient participation related to geography and social location. CONCLUSIONS: Though Telehomecare has the potential to positively impact patient lives and strengthen models of health care provision, a number of key challenges remain. As such, further implementation and expansion of Telehomecare must involve continuous assessments of what is working and not working with all stakeholders. Increased dialogue, evaluation, and knowledge translation within and across regions to understand the contextual factors influencing Telehomecare implementation and adoption is required. This can inform decision-making that better reflects and addresses the needs of all program stakeholders.