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Purpose: This study has two aims: first, propose the use of the driver-pressure-state-impact-response (DPSIR) framework to expand the normal focus of impact pathways in social life cycle assessment (S-LCA) on endpoint impacts to a systematic analysis to find links between the main sources of social issues and impacts; second, develop a new impact assessment method to quantify the lifetime health and economic outcomes associated with social subcategories, for the first time, using decision analytic models. Methods: The DPSIR framework is mapped to the corresponding elements of the S-LCA context in relation to the social subcategories defined in the UNEP/SETAC methodological sheets. Next, a more robust approach is developed for cause-impact chains between social subcategories and impacts on human well-being based on decision-analytic models (decision trees and Markov models) using healthcare approaches and data. Finally, the health and economic consequences associated with social subcategories are quantified by using Quality Adjusted Life Years (QALYs) and costs based on medical literature and healthcare studies. Results and discussion: The method was applied to the "working hours" social subcategory in Canada. The cause-effect chain is built using DPSIR framework in relation to the current social issue in Canada of working more than standard hours. Results of the decision analytic model show that working standard hours is more effective and cost-saving than working more than standard hours from the Canadian healthcare perspective. Working standard hours compared to more than standard hours led to an increase of 0.73 QALY and decrease in cost of $6702 per worker. Based on an estimated 2.4 million Canadian workers working more than standard hours, this resulted in a total gain of 1.7 million QALYs and saving of $16 billion overall. Using cost-effectiveness analysis, possible interventions at multiple entry points of the cause-effect chain within DPSIR framework are proposed to reduce the negative health impacts and associated costs of working more than standard hours in Canada. Conclusions: Applying the method on other subcategories could help decision-makers establish the cause-effect aspects of the social performance of their product systems using a quantitative systematic analysis from a life cycle perspective. This approach supports corporate decision-makers to quantify social impacts associated with their product supply chains by calculating QALYs and healthcare costs of their socio-economic conditions enabling them to identify possible interventions to improve the social performance. [ABSTRACT FROM AUTHOR]

Background: Continuous oral targeted therapy (OTT) for chronic lymphocytic leukemia (CLL) represents an effective therapy but also a major economic burden on the healthcare system. This study aimed to estimate future direct costs, along with the prevalence, of CLL in the era of continuous OTT in Canada. Methods: The economic burden of OTT was modelled and compared to chemoimmunotherapy (CIT), for CLL treatment. The burden was assessed/projected from 2011 to 2025. For the OTT scenario, CIT was considered the standard of care before 2015, while OTT was considered standard of care for patients with either unmutated immunoglobulin heavy-chain variable (IGHV) or del(17p)/TP53 mutations starting in 2015 and, from 2020 onwards, for all first-line treatments except for patients with mutated IGHV. A Markov model was developed including four health states: watchful-waiting, first-line treatment, relapse and death. Costs of therapy, follow-up/monitoring and adverse events were included. Key clinical parameters were extracted from pivotal clinical trials. Results: As incidence rates and rate of survival are increasing, the prevalence of CLL in Canada is projected to increase 1.8-fold, from 8301 patients in 2011 to 14,654 by 2025. Correspondingly, the total annual costs of CLL management are predicted to increase 15.7-fold, from $60.8 million to $957.5 million during that same period. Conclusions: Although OTT enhances survival for patients with CLL, it is nonetheless associated with an important economic burden due to the projected vast increase in costs from 2011 to 2025. Changes in clinical strategies, such as implementation of a fixed OTT treatment duration, could help alleviate financial burden. [ABSTRACT FROM AUTHOR]

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Purpose: Despite the success of provincial screening programs, colorectal cancer (CRC) is still the third most common cancer in Canada and the second most common cause of cancer-related death. Fecal-based tests, such as fecal occult blood test (FOBT) and fecal immunochemical test (FIT), form the foundation of the provincial CRC screening programs in Canada. However, those tests have low sensitivity for CRC precursors, adenomatous polyps and have low adherence. This study evaluated the effectiveness and cost-effectiveness of a new urine metabolomic-based test (UMT) that detects adenomatous polyps and CRC. Methods: A Markov model was designed using data from the literature and provincial healthcare databases for Canadian at average risk for CRC; calibration was performed against statistics data. Screening strategies included the following: FOBT every year, FIT every year, colonoscopy every 10 years, and UMT every year. The costs, quality adjusted life years (QALY) gained, and incremental cost-effectiveness ratios (ICERs) for each strategy were estimated and compared. Results: Compared with no screening, a UMT strategy reduced CRC mortality by 49.9% and gained 0.15 life years per person at $42,325/life year gained in the base case analysis. FOBT reduced CRC mortality by 14.9% and gained 0.04 life years per person at $25,011/life year gained. FIT reduced CRC mortality by 35.8% and gained 0.11 life years per person at $25,500/life year while colonoscopy reduced CRC mortality by 24.7% and gained 0.08 life years per person at $50,875/life year. Conclusions: A UMT strategy might be a cost-effective strategy when used in programmatic CRC screening programs. [ABSTRACT FROM AUTHOR]

Background: Islet cell transplantation is a method to stabilize type 1 diabetes patients with hypoglycemia unawareness and unstable blood glucose levels by reducing insulin dependency and protecting against severe hypoglycemia through restoring endogenous insulin secretion. This study analyses the current cost-effectiveness of this technology and estimates the value of further research to reduce uncertainty around cost-effectiveness. Methods: We performed a cost-utility analysis using a Markov cohort model with a mean patient age of 49 to simulate costs and health outcomes over a life-time horizon. Our analysis used intensive insulin therapy (IIT) as comparator and took the provincial healthcare provider perspective. Cost and effectiveness data for up to four transplantations per patient came from the University of Alberta hospital. Costs are expressed in 2012 Canadian dollars and effectiveness in quality-adjusted life-years (QALYs) and life years. To characterize the uncertainty around expected outcomes, we carried out a probabilistic sensitivity analysis within the Bayesian decision-analytic framework. We performed a value-of-information analysis to identify priority areas for future research under various scenarios. We applied a structural sensitivity analysis to assess the dependence of outcomes on model characteristics. Results: Compared to IIT, islet cell transplantation using non-generic (generic) immunosuppression had additional costs of $150,006 ($112,023) per additional QALY, an average gain of 3.3 life years, and a probability of being cost-effective of 0.5 % (28.3 %) at a willingness-to-pay threshold of $100,000 per QALY. At this threshold the non-generic technology has an expected value of perfect information (EVPI) of $260,744 for Alberta. This increases substantially in cost-reduction scenarios. The research areas with the highest partial EVPI are costs, followed by natural history, and effectiveness and safety. Conclusions: Current transplantation technology provides substantial improvements in health outcomes over conventional therapy for highly selected patients with 'unstable' type 1 diabetes. However, it is much more costly and so is not cost-effective. The value of further research into the cost-effectiveness is dependent upon treatment costs. Further, we suggest the value of information should not only be derived from current data alone when knowing that this data will most likely change in the future. [ABSTRACT FROM AUTHOR]

Immigrants with chronic hepatitis C ( CHC) in Canada have doubled risk of hepatocellular carcinoma. To measure the burden of CHC among immigrants in Canada. A decision analytic model was developed to compare immigrants with CHC and age-matched immigrants without CHC for survival years, quality-adjusted life-years ( QALYs) and medical costs per life year. Hepatitis C epidemiology among immigrants was based on hepatitis C prevalence in their home countries. A cohort of immigrant patients was retrospectively followed up to estimate fibrosis stage distribution, treatment patterns and prognosis of compensated cirrhosis. Other model variables were based on published sources. Base case analysis, one-way sensitivity analysis and probabilistic sensitivity analysis were performed to measure the burden of CHC and assess the impact of uncertainty associated with model variables on the burden of CHC. CHC could reduce survival by 9.6 years [95% credible interval ( CI): 8.0-10.9 years], reduce QALYs by 9.5 years (95% CI: 6.0-13.8 years) and increase medical costs per life year by $1950 (95% CI: $1518 to $2486, 2006 Canadian dollars). Because nearly half of immigrants with CHC were not diagnosed until the development of cirrhosis, the burden of CHC was highly sensitive to the risks of liver-related complications and mortality but insensitive to pegylated interferon plus ribavirin. The burden of CHC among immigrants in Canada is substantial mainly due to liver-related complications and mortality. The delay in diagnosis was another important contributor to the burden of CHC among immigrants. [ABSTRACT FROM AUTHOR]

Abstract: Objective: A head-to-head comparator study has shown that the clinical efficacy of ustekinumab is superior to that of etanercept over a 12-week period in patients with psoriasis. Economic models are often hindered by the lack of trials directly comparing outcomes between relevant alternative therapies. The aim of this analysis was to evaluate the cost-effectiveness of ustekinumab versus etanercept among adults with moderate-to-severe plaque psoriasis based on a Phase 3 head-to-head trial. Methods: The Markov model incorporates trial data from the Active Comparator (CNTO 1275/Enbrel) Psoriasis Trial study (ustekinumab 45 mg at Weeks 0 and 4; etanercept 50 mg biweekly) to follow patient response to initial treatment using the modeling approach developed by the Centre for Reviews and Dissemination, University of York, and often cited by others conducting economic analyses of psoriasis. Beyond the initial trial period, the Canadian model extrapolates results up to 10 years. Results: Over the 10-year time horizon of the model, the mean annual costs were $16,807 for ustekinumab (45 mg) and $19,525 for etanercept (50 mg). The incremental difference in costs and utilities remained in favour of ustekinumab across a range of sensitivity analyses. Conclusions: This model highlights the advantage of having head-to-head comparative trial data relevant to the at-risk population. Our model shows that ustekinumab is more cost-effective than etanercept for patients with moderate-to-severe plaque psoriasis. [Copyright &y& Elsevier]

Objectives: The primary risk of abdominal aortic aneurysms (AAAs) is rupture, which is associated with a high mortality rate. Elective surgical options for AAA include open repair (OR) and endovascular aneurysm repair (EVAR). EVAR is less invasive than OR, and therefore may have less surgical risk than OR. However, the graft used for EVAR is much more expensive then the graft used for OR. Methods: A decision model with a 10-year time horizon was used to assess the cost-effectiveness of EVAR versus OR. The primary outcome measure was quality-adjusted life-years (QALYs). The model incorporated the costs and benefits of both perioperative outcomes and postoperative outcomes. A systematic review was conducted to derive clinical outcome rates. Cost and utility model variables were based on various literature sources and data from a recent Canadian observational study. Parameter uncertainty was assessed using probabilistic sensitivity analysis. Results: In the base-case model, the incremental cost per QALY of EVAR was estimated to be $268,337, whereas the incremental cost per life-year was found to be $444,129. The incremental cost per QALY of EVAR remained above $295,715 under different assumptions of cohort age and model time horizon. Conclusions: Based on commonly quoted willingness-to-pay thresholds, EVAR was not found to be cost-effective compared to OR. [ABSTRACT FROM AUTHOR]

This Canadian hepatitis C model estimates economic burden of disease using Markov modeling to predict progression over 11 health states annually from 2001 to 2040. Incidence-based estimates help demonstrate the capability to determine cost-effectiveness of programs to prevent different proportions of incident cases. Benefits of prevention increase linearly with the number of incident cases prevented. The model forecasts annual health care costs for the treatment of HCV-related disease ranging from $103 to $158 million over time. Health care costs attributable to 2001 incidence cohort are forecast at $14.6 million for prevention. The increasing cost of HCV provides a framework for further analysis and implementation of long-term policies aimed at appropriate allocation of resources for health in Canada. [ABSTRACT FROM AUTHOR]

Introduction : Balancing the high cost of treatment brought about by new therapies has become a problem that needs to be considered. Cost-effectiveness analysis (CEA) is a commonly used method that provides information on the potential value of new cancer treatments. The Markov and partitioned survival (PS) models are commonly used. Whether the results differ between the models in empirical research and the methodological differences remain unclear. Areas covered : A review was conducted to identify Canadian Agency for Drugs and Technologies in Health (CADTH) reports and papers published during the past 5 years that reported full economic evaluations of cancer treatments and used both models. In the included studies, most results except one obtained using the two models did not significantly differ. Expert opinion : Not enough evidence could support that there existed relevant bias in empirical studies about the PS model, and more methodological research and application of empirical research should be performed. We recommended that when individual data are available and the model structure is not complicated, the PS model is more appropriate. Both the PS and Markov models are recommended to assess model structure uncertainty.

Objectives: The current screening method for diabetic nephropathy (DN) is based on detection of albumin in the urine and decline of glomerular filtration rate. The latter usually occurs relatively late in the course of the disease. A polygenic risk score (PRS) was recently developed for early prediction of the risk for patients with type 2 diabetes (T2D) to develop DN. The aim of this study was to assess the economic impact of the implementation of the PRS for early prediction of DN in patients with T2D compared with usual screening methods in Canada., Methods: A cost-utility analysis was developed using a Markov model. Health states include pre-end-stage renal disease (ESRD), ESRD and death. Model efficacy parameters were based on prediction of outcome data by polygenic risk testing of the genotyped participants in the Action in Diabetes and Vascular Disease PreterAx and DiamicronN Controlled Evaluation trial. Analyses were conducted from Canadian health-care and societal perspectives. Deterministic and probabilistic sensitivity analyses were conducted to assess results robustness., Results: Over a lifetime horizon, the PRS was a dominant strategy, from both a health-care system and societal perspective. The PRS was less expensive and more efficacious in terms of quality-adjusted life-years compared with usual screening technics. Deterministic and probabilistic sensitivity analyses showed that results remained dominant in most simulations., Conclusions: This economic evaluation demonstrates that the PRS is a dominant option compared with usual screening methods for the prevention of DN in patients with T2D. Adoption of the PRS would reduce costs saving but would also help prevent ESRD and improve patients' quality of life., (Copyright © 2020 Canadian Diabetes Association. Published by Elsevier Inc. All rights reserved.)

Rationale & Objective: On account of the high prevalence of cardiovascular disease in patients with kidney failure, clinical practice guidelines recommend regular screening for asymptomatic coronary artery disease (CAD) in patients on the kidney transplant waitlist. To date, the cost-effectiveness of such screening has not been evaluated. A Canadian-Australasian randomized controlled trial of screening kidney transplant candidates for CAD (CARSK) is currently is being conducted to answer this question. We conducted a cost-utility analysis to determine, before completion of the trial, the cost-effectiveness of no further screening versus regular screening for asymptomatic CAD and to evaluate potential influential variables that may affect results of the economic evaluation., Study Design: A modeled cost-utility analysis., Setting & Population: A theoretical cohort of adult Australian and New Zealand kidney transplant candidates on the waitlist., Intervention: No further screening for asymptomatic CAD versus regular protocolized screening (annual or second yearly) for CAD after kidney transplant waitlisting., Outcomes: Incremental cost-effectiveness ratio, reported as cost per quality-adjusted life-year (QALY)., Model, Perspectives, & Timeframe: Markov microsimulation model, health system perspective and over a lifetime horizon., Results: In the base case, the incremental cost-effectiveness ratio of no further screening was $11,122 per QALY gained when compared with regular screening. No further screening increased survival by 0.49 life-year or 0.35 QALY. One-way sensitivity analyses identified the costs of transplantation in the first year and CAD prevalence as the most influential variables. Probabilistic sensitivity analyses showed that 94% of the simulations were cost-effective below a willingness-to-pay threshold of $50,000 per QALY gained., Limitations: Rates of cardiovascular events in waitlisted candidates and transplant recipients are limited in the contemporary era. The results may not be generalizable to populations outside Australia and New Zealand., Conclusions: No further screening for CAD after waitlisting is likely to be cost-effective and may improve survival. Precision around CAD prevalence estimates and health care resource use will reduce existing uncertainty., (Copyright © 2019 National Kidney Foundation, Inc. All rights reserved.)

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., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Stroke is often a severe and debilitating event that requires ongoing rehabilitation. The Community Stroke Rehabilitation Teams (CSRTs) offer home-based stroke rehabilitation to individuals for whom further therapy is unavailable or inaccessible. The objective of this study was to evaluate the cost-effectiveness of the CSRT programme compared with a "Usual Care" cohort. Methods: We collected data on CSRT clients from January 2012 to February 2013. Comparator data were derived from a study of stroke survivors with limited access to specialised stroke rehabilitation. Literature-derived values were used to inform a long-term projection. Using Markov modelling, we projected the model for 35 years in six-month cycles. One-way, two-way, and probabilistic sensitivity analyses were performed. Results were discounted at 3% per year. Results: Results demonstrated that the CSRT programme has a net monetary benefit (NMB) of $43,655 over Usual Care, and is both less costly and more effective (incremental cost = -$17,255; incremental effect = 1.65 Quality Adjusted Life Years [QALYs]). Results of the probabilistic sensitivity analysis revealed that incremental cost-effectiveness of the CSRT programme is superior in 100% of iterations when compared to Usual Care. Conclusions: The study shows that CSRT model of care is cost-effective, and should be considered when evaluating potential stroke rehabilitation delivery methods. Implications for Rehabilitation Ongoing rehabilitation following stroke is imperative for optimal recovery. Home-based specialised stroke rehabilitation may be an option for individuals for whom ongoing rehabilitation is unavailable or inaccessible. The results of this study demonstrated that home-based rehabilitation is a cost-effective means of providing ongoing rehabilitation to individuals who have experienced a stroke.