Impact on costs and outcomes of multi-gene panel testing for advanced solid malignancies: a cost-consequence analysis using linked administrative data.

Background: To date, economic analyses of tissue-based next generation sequencing genomic profiling (NGS) for advanced solid tumors have typically required models with assumptions, with little real-world evidence on overall survival (OS), clinical trial enrollment or end-of-life quality of care. Methods: Cost consequence analysis of NGS testing (555 or 161-gene panels) for advanced solid tumors through the OCTANE clinical trial (NCT02906943). This is a longitudinal, propensity score-matched retrospective cohort study in Ontario, Canada using linked administrative data. Patients enrolled in OCTANE at Princess Margaret Cancer Centre from August 2016 until March 2019 were matched with contemporary patients without large gene panel testing from across Ontario not enrolled in OCTANE. Patients were matched according to 19 patient, disease and treatment variables. Full 2-year follow-up data was available. Sensitivity analyses considered alternative matched cohorts. Main Outcomes were mean per capita costs (2019 Canadian dollars) from a public payer's perspective, OS, clinical trial enrollment and end-of-life quality metrics. Findings: There were 782 OCTANE patients with 782 matched controls. Variables were balanced after matching (standardized difference <0.10). There were higher mean health-care costs with OCTANE ($79,702 vs. $59,550), mainly due to outpatient and specialist visits. Publicly funded drug costs were less with OCTANE ($20,015 vs. $24,465). OCTANE enrollment was not associated with improved OS (restricted mean survival time [standard error]: 1.50 (±0.03) vs. 1.44 (±0.03) years, log-rank p = 0.153), varying by tumor type. In five tumor types with ≥35 OCTANE patients, OS was similar in three (breast, colon, uterus, all p > 0.40), and greater in two (ovary, biliary, both p < 0.05). OCTANE was associated with greater clinical trial enrollment (25.4% vs. 9.5%, p < 0.001) and better end-of-life quality due to less death in hospital (10.2% vs. 16.4%, p = 0.003). Results were robust in sensitivity analysis. Interpretation: We found an increase in healthcare costs associated with multi-gene panel testing for advanced cancer treatment. The impact on OS was not significant, but varied across tumor types. OCTANE was associated with greater trial enrollment, lower publicly funded drug costs and fewer in-hospital deaths suggesting important considerations in determining the value of NGS panel testing for advanced cancers. Funding: T.P H holds a research grant provided by the Ontario Institute for Cancer Research through funding provided by the Government of Ontario (#IA-035 and P.HSR.158) and through funding of the Canadian Network for Learning Healthcare Systems and Cost-Effective 'Omics Innovation (CLEO) via Genome Canada (G05CHS).

Expanding access to high-cost medicines under the Universal Health Coverage scheme in Thailand: review of current practices and recommendations.

BACKGROUND: There has been an increasing demand to reimburse high-cost medicines, through public health insurance schemes in Thailand. METHODS: A mixed method approach was employed. First, a rapid review of select high-income countries was conducted, followed by expert consultations and an in-depth review of three countries: Australia, England and Republic of Korea to understand reimbursement mechanisms of high-cost medicines. In Thailand, current pathways for reimbursing high-cost medicines reviewed, the potential opportunity cost estimated, and stakeholder consultations were conducted to identify context specific considerations. RESULTS: High-income countries reviewed have implemented a variety of pathways and mechanisms for reimbursing high-cost medicines under specific eligibility criteria, listing processes, varying cost-effectiveness thresholds and special funding arrangements. In Thailand, high-cost medicines that do not offer good value-for-money are excluded from the reimbursement process. A framework for reimbursing high-cost medicines that are not cost-effective at the current willingness-to-pay threshold was proposed for Thailand. Under this framework, specific criteria are proposed to determine their eligibility for reimbursement such life-saving nature, treatment of conditions with no alternative treatment options, and affordability. CONCLUSION: High-cost medicines may become eligible for reimbursement through alternative mechanisms based on specific criteria which depend on each context. The application of HTA methods and processes is important in guiding these decisions to support sustainable access to affordable healthcare in pursuit of Universal Health Coverage (UHC).

Cost-effectiveness of second-line ipilimumab for metastatic melanoma: A real-world population-based cohort study of resource utilization.

BACKGROUND: The efficacy-effectiveness gap between randomized trial and real-world evidence regarding the clinical benefit of ipilimumab for metastatic melanoma (MM) has been well characterized by previous literature, consistent with initial concerns raised by health technology assessment agencies (HTAs). As these differences can significantly impact cost-effectiveness, it is critical to assess the real-world cost-effectiveness of second-line ipilimumab versus non-ipilimumab treatments for MM. METHODS: This was a population-based retrospective cohort study of patients who received second-line non-ipilimumab therapies between 2008 and 2012 versus ipilimumab treatment between 2012 and 2015 (after public reimbursement) for MM in Ontario. Using a 5-year time horizon, censor-adjusted and discounted (1.5%) costs (from the public payer's perspective in Canadian dollars) and effectiveness were used to calculate incremental cost-effectiveness ratios (ICERs) in life-years gained (LYGs) and quality-adjusted life years (QALYs), with bootstrapping to capture uncertainty. Varying the discount rate and reducing the price of ipilimumab were done as sensitivity analyses. RESULTS: In total, 329 MM were identified (Treated: 189; Controls: 140). Ipilimumab was associated with an incremental effectiveness of 0.59 LYG, incremental cost of $91,233, and ICER of $153,778/LYG. ICERs were not sensitive to discounting rate. Adjusting for quality of life using utility weights resulted in an ICER of $225,885/QALY, confirming the original HTA estimate prior to public reimbursement. Reducing the price of ipilimumab by 100% resulted in an ICER of $111,728/QALY. CONCLUSION: Despite its clinical benefit, ipilimumab as second-line monotherapy for MM patients is not cost-effective in the real world as projected by HTA under conventional willingness-to-pay thresholds.

Real-World Cost-Effectiveness of First-Line Gemcitabine Plus Nab-Paclitaxel vs FOLFIRINOX in Patients With Advanced Pancreatic Cancer.

BACKGROUND: There are no randomized control trials (RCTs) comparing gemcitabine and nab-paclitaxel (Gem-Nab) and fluorouracil, folinic acid, irinotecan, oxaliplatin (FOLFIRINOX) for advanced pancreatic cancer (APC). Although it is well known that RCT-based efficacy often does not translate to real-world effectiveness, there is limited literature investigating comparative cost-effectiveness of Gem-Nab vs FOLFIRINOX for APC. We aimed to examine the real-world cost-effectiveness of Gem-Nab vs FOLFIRINOX for APC in Ontario, Canada. METHODS: This study compared patients treated with first-line Gem-Nab or FOLFIRINOX for APC in Ontario from April 2015 to March 2019. Patients were linked to administrative databases. Using propensity scores and a stabilizing weights method, an inverse probability of treatment weighted cohort was developed. Mean survival and total costs were calculated over a 5-year time horizon, adjusted for censoring, and discounted at 1.5%. Incremental cost-effectiveness ratio and net monetary benefit were computed to estimate cost-effectiveness from the public health-care payer's perspective. Sensitivity analysis was conducted using the propensity score matching method. RESULTS: A total of 1988 patients were identified (Gem-Nab: n = 928; FOLFIRINOX: n = 1060). Mean survival was lower for patients in the Gem-Nab than the FOLFIRINOX group (0.98 vs 1.26 life-years; incremental effectiveness = -0.28 life-years [95% confidence interval = -0.47 to -0.13]). Patients in the Gem-Nab group incurred greater mean 5-year total costs (Gem-Nab: $103 884; FOLFIRINOX: $101 518). Key cost contributors include ambulatory cancer care, acute inpatient hospitalization, and systemic therapy drug acquisition. Gem-Nab was dominated by FOLFIRINOX, as it was less effective and more costly. Results from the sensitivity analysis were similar. CONCLUSIONS: Gem-Nab is likely more costly and less effective than FOLFIRINOX and therefore not considered cost-effective at commonly accepted willingness-to-pay thresholds.

Cancer treatment-related financial toxicity experienced by patients in low- and middle-income countries: a scoping review.

PURPOSE: In the past decade, literature has called attention to financial toxicities experienced by cancer patients. Though studies have addressed research questions in high-income countries, there remains a paucity of in-depth reviews regarding low- and middle-income countries (LMICs). Our scoping review provides an overview of treatment-related financial toxicities experienced by cancer patients in LMICs. METHODS: A systematic search was conducted in MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials. English peer-reviewed articles that (a) explored patients' experience with financial toxicity due to cancer treatment (b) were specific to LMICs as defined by the World Bank and (c) focused on qualitative data were included. Details regarding participants and main findings were extracted and synthesized. RESULTS: The search yielded 6290 citations, and 42 studies across 3 low-income, 9 lower-middle-income and 8 upper-middle-income countries. Main themes identified included cancer patients encountered various material hardships, managed costs with different coping behaviours and experienced negative psychological responses to their financial burden. Higher levels of financial toxicities were associated with patient characteristics such as lower socio-economic status and lack of insurance, as well as patient outcomes such as lower quality of life. CONCLUSION: Cancer patients in LMIC experience deleterious financial toxicities as a result of treatment. This comprehensive characterization of financial toxicities will better allow health systems to adopt evidence-based mitigation strategies to reduce the financial burden on patients.

Multi-use physical activity trails in an urban setting and cardiovascular disease: a difference-in-differences analysis of a natural experiment in Winnipeg, Manitoba, Canada.

OBJECTIVE: To determine if expansion of multi-use physical activity trails in an urban centre is associated with reduced rates of cardiovascular disease (CVD). METHODS: This was a natural experiment with a difference in differences analysis using administrative health records and trail-based cycling data in Winnipeg, Canada. Prior to the intervention, each year, 314,595 (IQR: 309,044 to 319,860) persons over 30 years without CVD were in the comparison group and 37,901 residents (IQR: 37,213 to 38,488) were in the intervention group. Following the intervention, each year, 303,853 (IQR: 302,843 to 304,465) persons were in the comparison group and 35,778 (IQR: 35,551 to 36,053) in the intervention group. The natural experiment was the construction of four multi-use trails, 4-7 km in length, between 2010 and 2012. Intervention and comparison areas were based on buffers of 400 m, 800 m and 1200 m from a new multi-use trail. Bicycle counts were obtained from electromagnetic counters embedded in the trail. The primary outcome was a composite of incident CVD events: CVD-related mortality, ischemic heart disease, cerebrovascular events and congestive heart failure. The secondary outcome was a composite of incident CVD risk factors: hypertension, diabetes and dyslipidemia. RESULTS: Between 2014 and 2018, 1,681,125 cyclists were recorded on the trails, which varied ~ 2.0-fold across the four trails (2358 vs 4264 counts/week in summer months). Between 2000 and 2018, there were 82,632 CVD events and 201,058 CVD risk events. In propensity score matched Poisson regression models, the incident rate ratio (IRR) was 1.06 (95% CI: 0.90 to 1.24) for CVD events and 0.95 (95%CI: 0.88 to 1.02) for CVD risk factors for areas within 400 m of a trail, relative to comparison areas. Sensitivity analyses indicated this effect was greatest among households adjacent to the trail with highest cycling counts (IRR = 0.85; 95% CI: 0.75 to 0.96). CONCLUSIONS: The addition of multi-use trails was not associated with differences in CVD events or CVD risk factors, however the differences in CVD risk may depend on the level of trail use. TRIAL REGISTRATION: Trial registration number: NCT04057417 .

Building the health-economic case for scaling up the WHO-HEARTS hypertension control package in low- and middle-income countries / Argumentos de la economía de la salud para ampliar las medidas de control de la hipertensión de la iniciativa HEARTS de la OMS en los países de ingresos medianos y bajos / Ampliação do pacote de controle da hipertensão OMS-HEARTS em países de baixa e média renda: argumentos a partir da perspectiva da economia em saúde

ABSTRACT Generally, hypertension control programs are cost-effective, including in low- and middle-income countries, but country governments and civil society are not likely to support hypertension control programs unless value is demonstrated in terms of public health benefits, budget impact, and value-for-investment for the individual country context. The World Health Organization (WHO) and the Pan American Health Organization (PAHO) established a standard, simplified Global HEARTS approach to hypertension control, including preferred antihypertensive medicines and blood pressure measurement devices. The objective of this study is to report on health economic studies of HEARTS hypertension control package cost (especially medication costs), cost-effectiveness, and budget impact and describe mathematical models designed to translate hypertension control program data into the optimal approach to hypertension care service delivery and financing, especially in low- and middle-income countries. Early results suggest that HEARTS hypertension control interventions are either cost-saving or cost-effective, that the HEARTS package is affordable at between US$ 18-44 per person treated per year, and that antihypertensive medicines could be priced low enough to reach a global standard of an average <US$ 5 per patient per year in the public sector. This health economic evidence will make a compelling case for government ownership and financial support for national scale hypertension control programs.

RESUMEN En general, los programas de control de la hipertensión son costo-eficaces, incluso en los países de ingresos bajos y medios. Aun así, es poco probable que los gobiernos nacionales y la sociedad civil apoyen los programas de control de la hipertensión a menos que se demuestre su valor en términos de beneficios para la salud pública, impacto presupuestario y valor de la inversión para el contexto individual del país. La Organización Mundial de la Salud (OMS) y la Organización Panamericana de la Salud (OPS) implementaron la iniciativa HEARTS, un enfoque mundial estandarizado y simplificado para el control de la hipertensión, que incluye los medicamentos antihipertensivos y los dispositivos de medición de la presión arterial de preferencia. El objetivo de este estudio es informar sobre los estudios en el ámbito de la economía de la salud relativos al costo de las medidas de control de la hipertensión previstas en HEARTS (especialmente, de los medicamentos), la costo-efectividad y el impacto presupuestario, así como describir los modelos matemáticos diseñados para traducir los datos de este programa en un enfoque óptimo para la prestación y el financiamiento de los servicios de atención de la hipertensión, especialmente en países de ingresos medianos y bajos. Los primeros resultados indican que las intervenciones de HEARTS para el control de la hipertensión son de bajo costo o costo-eficaces, que el conjunto de medidas HEARTS es asequible, a un precio que oscila entre US$ 18 y US$ 44 al año por paciente tratado, y que los medicamentos antihipertensivos podrían tener un precio lo suficientemente bajo como para alcanzar un estándar medio mundial de <US$ 5 por paciente al año en el sector público. Estos datos del ámbito de la economía de la salud serán argumentos convincentes para que los gobiernos se involucren en los programas de control de la hipertensión a escala nacional y les brinden apoyo financiero.

RESUMO Geralmente, os programas de controle de hipertensão são custo-efetivos, inclusive em países de baixa e média renda, mas os governos dos países e a sociedade civil provavelmente não apoiarão tais programas a menos que demonstrem valor em termos de benefícios à saúde pública, impacto orçamentário e retorno sobre o investimento no contexto individual do país. A Organização Mundial da Saúde (OMS) e a Organização Pan-Americana da Saúde (OPAS) criaram a Global HEARTS, uma abordagem padrão e simplificada ao controle da hipertensão arterial, que inclui medicamentos anti-hipertensivos preferidos e dispositivos para aferição da pressão arterial preferidos. O objetivo deste estudo é relatar os estudos de economia em saúde que analisaram o custo (especialmente custos de medicamentos), custo-benefício e impacto orçamentário do pacote HEARTS para controle da hipertensão e descrever modelos matemáticos elaborados para traduzir os dados do programa de controle de hipertensão em uma abordagem ideal para a prestação e financiamento de serviços de atenção às pessoas com hipertensão, especialmente em países de baixa e média renda. Os primeiros resultados sugerem que as intervenções HEARTS para controle da hipertensão são de baixo custo ou custo-efetivas, que o pacote HEARTS é acessível (custando de US$ 18 a 44 por pessoa tratada por ano) e que o preço dos medicamentos anti-hipertensivos poderia ser baixo o suficiente para atingir uma média global de <US$ 18 por paciente por ano no setor público. Estas evidências do campo da economia em saúde serão um argumento convincente para que os governos se responsabilizem por programas de controle de hipertensão em escala nacional e os dotem de recursos financeiros.

Real-World Cost-Effectiveness of Bevacizumab With First-Line Combination Chemotherapy in Patients With Metastatic Colorectal Cancer: Population-Based Retrospective Cohort Studies in Three Canadian Provinces.

Background. Real-world evidence can be a valuable tool when clinical trial data are incomplete or uncertain. Bevacizumab was adopted as first-line therapy for metastatic colorectal cancer (mCRC) based on significant survival improvements in initial clinical trials; however, survival benefit diminished in subsequent analyses. Consequently, there is uncertainty surrounding the cost-effectiveness of bevacizumab therapy achieved in practice. Objective. To assess real-world cost-effectiveness of first-line bevacizumab with irinotecan-based chemotherapy versus irinotecan-based chemotherapy alone for mCRC in British Columbia (BC), Saskatchewan, and Ontario, Canada. Methods. Using provincial cancer registries and linked administrative databases, we identified mCRC patients who initiated publicly funded irinotecan-based chemotherapy, with or without bevacizumab, in 2000 to 2015. We compared bevacizumab-treated patients to historical controls (treated before bevacizumab funding) and contemporaneous controls (receiving chemotherapy without bevacizumab), using inverse-probability-of-treatment weighting with propensity scores to balance baseline covariates. We calculated incremental cost-effectiveness ratios (ICER) using 5-year cost and survival adjusted for censoring, with bootstrapping to characterize uncertainty. We also conducted one-way sensitivity analysis for key drivers of cost-effectiveness. Results. The cohorts included 12,112 (Ontario), 1,161 (Saskatchewan), and 2,977 (BC) patients. Bevacizumab significantly increased treatment costs, with mean ICERs between $78,000 and $84,000/LYG (life-year gained) in the contemporaneous comparisons and $75,000 and $101,000/LYG in the historical comparisons. Reducing the cost of bevacizumab by 50% brought ICERs in all comparisons below $61,000/LYG. Limitations. Residual confounding in observational data may bias results, while the use of original list prices overestimates current bevacizumab cost. Conclusion. The addition of bevacizumab to irinotecan-based chemotherapy extended survival for mCRC patients but at significant cost. At original list prices bevacizumab can only be considered cost-effective with certainty at a willingness-to-pay threshold over $100,000/LYG, but price reductions or discounts have a significant impact on cost-effectiveness.

Cost-Utility Analysis of the Ontario Fracture Screening and Prevention Program.

BACKGROUND: The Fracture Screening and Prevention Program (FSPP), a fracture liaison service (FLS), was implemented in the province of Ontario, Canada, in 2007 to prevent recurrent fragility fractures and to improve post-fracture care. The objective of this analysis was to determine the cost-effectiveness of the current model of the FSPP compared with usual care (no program) from the perspective of the universal public health-care payer (Ontario Ministry of Health and Long-Term Care [MOHLTC]), over the lifetime of older adults who presented with a fragility fracture of the proximal part of the femur, the proximal part of the humerus, or the distal part of the radius and were not taking medications to prevent or slow bone loss and reduce the risk of fracture (bone active medications). METHODS: We developed a state-transition (Markov) model to conduct a cost-effectiveness analysis of the FSPP in comparison with usual care. The model simulated a cohort of patients with a fragility fracture starting at 71 years of age. Model parameters were obtained from published literature and from the FSPP. Quality-adjusted life-years (QALYs) and costs in 2018 Canadian dollars were predicted over a lifetime horizon using a 1.5% annual discount rate. Health outcomes included subsequent proximal femoral, vertebral, proximal humeral, and distal radial fractures. Scenario and subgroup analyses were reported. RESULTS: The FSPP had lower expected costs ($277 less) and higher expected effectiveness (by 0.018 QALY) than usual care over the lifetime horizon. Ninety-four percent of the 10,000 Monte Carlo simulated incremental cost-effectiveness ratios (ICERs) demonstrated lower costs and higher effectiveness of the FSPP. CONCLUSIONS: The FSPP appears to be cost-effective compared with usual care over a lifetime for patients with fragility fracture. This information may help to quantify the value of the FSPP and to assist policy-makers in deciding whether to expand the FSPP to additional hospitals or to initiate similar programs where none exist. LEVEL OF EVIDENCE: Economic and Decision Analysis Level II. See Instructions for Authors for a complete description of levels of evidence.

Effectiveness of an eHealth self-management tool for older adults with multimorbidity (KeepWell): protocol for a hybrid effectiveness-implementation randomised controlled trial.

INTRODUCTION: In response to the burden of chronic disease among older adults, different chronic disease self-management tools have been created to optimise disease management. However, these seldom consider all aspects of disease management are not usually developed specifically for seniors or created for sustained use and are primarily focused on a single disease. We created an eHealth self-management application called 'KeepWell' that supports seniors with complex care needs in their homes. It incorporates the care for two or more chronic conditions from among the most prevalent high-burden chronic diseases. METHODS AND ANALYSIS: We will evaluate the effectiveness, cost and uptake of KeepWell in a 6-month, pragmatic, hybrid effectiveness-implementation randomised controlled trial. Older adults age ≥65 years with one or more chronic conditions who are English speaking are able to consent and have access to a computer or tablet device, internet and an email address will be eligible. All consenting participants will be randomly assigned to KeepWell or control. The allocation sequence will be determined using a random number generator.Primary outcome is perceived self-efficacy at 6 months. Secondary outcomes include quality of life, health background/status, lifestyle (nutrition, physical activity, caffeine, alcohol, smoking and bladder health), social engagement and connections, eHealth literacy; all collected via a Health Risk Questionnaire embedded within KeepWell (intervention) or a survey platform (control). Implementation outcomes will include reach, effectiveness, adoption, fidelity, implementation cost and sustainability. ETHICS AND DISSEMINATION: Ethics approval has been received from the North York General Hospital Research and Ethics Board. The study is funded by the Canadian Institutes of Health Research and the Ontario Ministry of Health. We will work with our team to develop a dissemination strategy which will include publications, presentations, plain language summaries and an end-of-grant meeting. TRIAL REGISTRATION NUMBER: NCT04437238.

Real-world, population-based cohort study of toxicity and resource utilization of second-line ipilimumab for metastatic melanoma in Ontario, Canada.

Second-line ipilimumab has been publicly funded in Ontario for metastatic melanoma (MM) since September 2012. We examined real-world toxicity of second-line ipilimumab compared to standard second-line treatments prior to funding. MM patients who received systemic treatment from April 2005 to March 2015 were included. Patients receiving second-line ipilimumab after September 2012 were considered as cases, and those who received second-line treatment prior to the funding date were included as historical controls. Outcomes assessed include treatment-related mortality, any-cause hospital visits, ipilimumab-related hospital visits and specialist visits (eg, endocrinologists, ophthalmologists, gastroenterologists, rheumatologists and respirologists), which were captured from up to 30 and/or 90 days after end of second-line treatment. Inverse probability of treatment weighting was used to adjust for baseline differences between groups. Odds ratios (ORs) from logistic regressions and rate ratios (RRs) from rate regressions were used to assess differences between groups. We identified 329 MM patients who received second-line treatments (ipilimumab: 189; controls: 140). Ipilimumab was associated greater any-cause (60.1% vs 45.7%; OR = 1.81; P value = .019) and ipilimumab-related (47.2% vs 31.9%; OR = 1.91; P value = .011) hospital visits. Adjusting for different follow-up days, ipilimumab was associated with higher rates of all-cause (RR = 1.56 [95%CI: 1.12-2.16]), and ipilimumab-related (RR = 2.18 [95% CI: 1.45-3.27]) hospital visits. Patients receiving ipilimumab were more likely to visit specialist involved in immunotherapy toxicity management (23.5% vs 13.7%; P value = .04). Compared to historical second-line treatments, second-line ipilimumab was associated with more health service utilization (specifically hospital visits and specialist visits), suggestive of potentially increased toxicity in the real world.

Use of real-world evidence in cancer drug funding decisions in Canada: a qualitative study of stakeholders' perspectives.

BACKGROUND: Real-world evidence (RWE) can provide postmarket data to inform whether funded cancer drugs yield expected outcomes and value for money, but it is unclear how to incorporate RWE into Canadian cancer drug funding decisions. As part of the Canadian Real-World Evidence Value for Cancer Drugs (CanREValue) Collaboration, this study aimed to explore stakeholder perspectives on the current state of RWE in Canada to inform a Canadian framework for use of RWE in cancer drug funding decisions. METHODS: This was a qualitative descriptive study. Qualitative semistructured interviews were conducted from April to July 2018. Participants were Canadian and international stakeholders who had experience with RWE and drug funding decision-making. Thematic analysis was used to analyze data. RESULTS: Thirty stakeholders participated in the study. Five themes were identified. Stakeholders indicated that RWE had value in cancer drug funding decisions. However, a cultural shift is needed to adopt RWE in decision-making. Further, the Canadian infrastructure for real-world data is currently inadequate for decision-making, and there is a need for committed investment in building capacity to collect and analyze RWE. Finally, there is a need for increased collaboration among key stakeholders. INTERPRETATION: The findings of this study suggest that if RWE is to be used in drug funding decisions, there is a need for a cultural shift, improved data infrastructure, committed investment in capacity building and increased stakeholder collaboration. Together with local stakeholder engagement, application of these findings may contribute to optimizing implementation of RWE.

The effectiveness of rituximab and HIV on the survival of Ontario patients with diffuse large B-cell lymphoma.

INTRODUCTION: For patients with diffuse large B-cell lymphoma (DLBCL), standard-care is rituximab administered with CHOP or CHOP-like chemotherapy (R-CHOP). However, the effectiveness and safety of R-CHOP among DLBCL patients with human immunodeficiency virus (HIV) infection is less clear, as HIV+ patients were omitted from most clinical trials and population-level data from unselected patients are limited. R-CHOP was funded for HIV-associated DLBCL patients with CD4 >50/mm3 in Ontario in February 2015. METHODS: Patients with a new diagnosis of DLBCL were identified from the Ontario Cancer Registry between April 2010 and March 2018. HIV diagnosis and chemotherapy regimen were ascertained using administrative databases at Ontario Health. The effect of rituximab and HIV on overall survival was assessed in the HIV+ subgroup (R-CHOP vs CHOP) and in the R-CHOP subgroup (HIV+ vs HIV-). RESULTS: Among HIV+ patients, receipt of R-CHOP was associated with a fivefold improvement in overall survival (hazard ratio [HR] 0.29 (0.13-0.66) compared with CHOP), after adjustment. Among patients who received R-CHOP (n = 6106), older age, male sex, lower neighborhood income, and higher comorbidity were associated with worse overall survival, after adjustment (P < .001 for all), but HIV positivity was not prognostic (HR 1.12 (0.60-2.10)). Within 1-year after diagnosis, HIV+ patients receiving R-CHOP had a similar proportion of patients who visited the emergency department (67% vs 66% P = .43) or admitted to hospital (58% vs 52%, P = .43) and as HIV- patients receiving R-CHOP. CONCLUSION: HIV status did not affect prognosis for patients with DLBCL receiving R-CHOP in an unselected general population when rituximab was used according to funding criteria. R-CHOP was safe and effective for DLBCL treatment, regardless of HIV status.

The emergency department as a setting-specific opportunity for population-based hepatitis C screening: An economic evaluation.

BACKGROUND AND AIMS: The World Health Organization's hepatitis C virus (HCV) elimination strategy recognizes the need for interventions that identify populations most affected by infection. The emergency department (ED) has been suggested as a setting for HCV screening. The study objective was to explore the health and economic impact of HCV screening in the ED setting. METHODS: We used a microsimulation model to conduct a cost-utility analysis evaluating two ED setting-specific strategies: no screening, and screening and subsequent treatment. Strategies were examined for two populations: (a) the general ED patient population; and (b) ED patients born between 1945 and 1975. The analysis was conducted from a healthcare payer perspective over a lifetime time horizon. A reference and high ED HCV seroprevalence measure were examined in the Canadian healthcare setting.US costs of chronic infection were used for a scenario analysis of screening in the US healthcare setting. RESULTS: For birth cohort screening, in comparison to no screening, one liver-related death was averted for every 760 and 123 persons screened for the reference and high seroprevalence measures. For general population screening, one liver-related death was averted for every 831 and 147 persons screened for the reference and high seroprevalence measures. In comparison to no screening, birth cohort screening was cost-effective at CAN$25,584/quality-adjusted life year (QALY) and US$42,615/QALY. General population screening was cost-effective at CAN$19,733/QALY and US$32,187/QALY. CONCLUSIONS: ED screening may represent a cost-effective component of population-based strategies to eliminate HCV. Further studies are warranted to explore the feasibility and acceptability of this approach.

A Cost-Utility Analysis of Magnetic Resonance (MR) Guided Brachytherapy Versus Two-Dimensional and Computed Tomography (CT) Guided Brachytherapy for Locally Advanced Cervical Cancer.

PURPOSE: The standard treatment for locally advanced cervical cancer is external beam radiation therapy and concurrent cisplatin followed by brachytherapy. Traditionally, 2-dimensional brachytherapy (2DBT) or computed tomography guided brachytherapy (CTgBT) has been used, but magnetic resonance guided brachytherapy (MRgBT) improves clinical outcomes and has become the new standard of care. This cost-utility analysis was undertaken to compare MRgBT to CTgBT and 2DBT. METHODS AND MATERIALS: A Markov model was constructed to evaluate the cost-utility from the perspective of the public health care payer in Ontario. Treatment effectiveness, expressed as quality-adjusted life years, and costs, expressed in 2016 Canadian dollars, were evaluated for MRgBT, CTgBT, and 2DBT. Results were reported as incremental cost-effectiveness ratios for all patients and separately for low and high-risk subgroups. Sensitivity analyses were performed to assess the impact of uncertainty in model parameters. RESULTS: MRgBT improved tumor control, reduced side effects, and was less costly compared with either CTgBT or 2DBT for all patients and in low- and high-risk prognostic subgroups separately. Sensitivity analysis supported the robustness of the findings and identified the cost of treating cancer recurrence to be the single most influential model parameter. CONCLUSIONS: MRgBT is more effective and less costly than CTgBT or 2DBT by avoiding downstream costs of treating cancer recurrence and managing side effects. These findings will assist health care providers and policymakers with future infrastructure and human resource planning to ensure optimal care of women with this disease.

Assessing the efficacy-effectiveness gap for cancer therapies: A comparison of overall survival and toxicity between clinical trial and population-based, real-world data for contemporary parenteral cancer therapeutics.

BACKGROUND: Although increasing evidence has suggested that an efficacy-effectiveness gap exists between clinical trial (CT) and real-world evidence (RWE), to the authors' knowledge, the magnitude of this difference remains undercharacterized. The objective of the current study was to quantify the magnitude of survival and toxicity differences between CT and RWE for contemporary cancer systemic therapies. METHODS: Patients receiving cancer therapies funded under Cancer Care Ontario's New Drug Funding Program (NDFP) were identified. Landmark CTs with data regarding survival and adverse events (AEs) for each drug indication were identified. RWE for survival and hospitalization rates during treatment were ascertained through Canadian population-based databases. The efficacy-effectiveness gap for each drug indication was calculated as the difference between RWE and CT data for median overall survival (OS), 1-year OS, and generated hazard ratios (HRs) with 95% CIs from Kaplan-Meier OS curves. Toxicity differences were calculated as the difference between RWE of hospitalization rates and CT serious AE rates. RESULTS: Twenty-nine indications from 20 systemic therapies were included. Twenty-eight of 29 indications (97%) demonstrated worse survival in RWE, with a median OS difference of 5.2 months (interquartile range, 3.0-12.1 months). Lower effectiveness in RWE also was demonstrated through a meta-analysis of an OS hazard ratio of 1.58 (95% CI, 1.39-1.80). The median difference between RWE for hospitalization rates and CT serious AEs was 14% (95% CI, 9%-22%). CONCLUSIONS: An efficacy-effectiveness gap exists for contemporary cancer systemic therapies, with a 5.2-month lower median OS observed in RWE compared with CT data. These data supports the use of RWE to better inform real-world decision making regarding the use of cancer systemic therapies.

Developing a framework to incorporate real-world evidence in cancer drug funding decisions: the Canadian Real-world Evidence for Value of Cancer Drugs (CanREValue) collaboration.

BACKGROUND: Oncology therapy is becoming increasingly more expensive and challenging the affordability and sustainability of drug programmes around the world. When new drugs are evaluated, health technology assessment organisations rely on clinical trials to inform funding decisions. However, clinical trials are not able to assess overall survival and generalises evidence in a real-world setting. As a result, policy makers have little information on whether drug funding decisions based on clinical trials ultimately yield the outcomes and value for money that might be expected. OBJECTIVE: The Canadian Real-world Evidence for Value of Cancer Drugs (CanREValue) collaboration, consisting of researchers, recommendation-makers, decision makers, payers, patients and caregivers, are developing and testing a framework for Canadian provinces to generate and use real-world evidence (RWE) for cancer drug funding in a consistent and integrated manner. STRATEGY: The CanREValue collaboration has established five formal working groups (WGs) to focus on specific processes in the generation and use of RWE for cancer drug funding decisions in Canada. The different RWE WGs are: (1) Planning and Drug Selection; (2) Methods; (3) Data; (4) Reassessment and Uptake; (5) Engagement. These WGs are acting collaboratively to develop a framework for RWE evaluation, validate the framework through the multiprovince RWE projects and help to integrate the final RWE framework into the Canadian healthcare system. OUTCOMES: The framework will enable the reassessment of cancer drugs, refinement of funding recommendations and use of novel funding mechanisms by decision-makers/payers across Canada to ensure the healthcare system is providing clinical benefits and value for money.

Real-world outcomes of FOLFIRINOX vs gemcitabine and nab-paclitaxel in advanced pancreatic cancer: A population-based propensity score-weighted analysis.

BACKGROUND: In Ontario, FOLFIRINOX (FFX) and gemcitabine + nab-paclitaxel (GnP) have been publicly funded for first-line unresectable locally advanced pancreatic cancer (uLAPC) or metastatic pancreatic cancer (mPC) since April 2015. We examined the real-world effectiveness and safety of FFX vs GnP for advanced pancreatic cancer, and in uLAPC and mPC. METHODS: Patients receiving first-line FFX or GnP from April 2015 to March 2017 were identified in the New Drug Funding Program database. Baseline characteristics and outcomes were obtained through the Ontario Cancer Registry and other population-based databases. Overall survival (OS) was assessed using Kaplan-Meier and weighted Cox proportional hazard models, weighted by the inverse propensity score adjusting for baseline characteristics. Weighted odds ratio (OR) for hospitalization and emergency department visits (EDV) were estimated from weighted logistic regression models. RESULTS: For 1130 patients (632 FFX, 498 GnP), crude median OS was 9.6 and 6.1 months for FFX and GnP, respectively. Weighted OS was improved for FFX vs GnP (HR = 0.77, 0.70-0.85). Less frequent EDV and hospitalization were observed in FFX (EDV: 67.8%; Hospitalization: 49.2%) than GnP (EDV: 77.7%; Hospitalization: 59.3%). More frequent febrile neutropenia-related hospitalization was observed in FFX (5.8%) than GnP (3.3%). Risk of EDV and hospitalization were significantly lower for FFX vs GnP (EDV: OR = 0.68, P = .0001; Hospitalization: OR = 0.76, P = .002), whereas the risk of febrile neutropenia-related hospitalization was significantly higher (OR = 2.12, P = .001). Outcomes for uLAPC and mPC were similar. CONCLUSION: In the real world, FFX had longer OS, less frequent all-cause EDV and all-cause hospitalization, but more febrile neutropenia-related hospitalization compared to GnP.

Health outcomes, utility and costs of returning incidental results from genomic sequencing in a Canadian cancer population: protocol for a mixed-methods randomised controlled trial.

INTRODUCTION: Genomic sequencing has rapidly transitioned into clinical practice, improving diagnosis and treatment options for patients with hereditary disorders. However, large-scale implementation of genomic sequencing faces challenges, especially with regard to the return of incidental results, which refer to genetic variants uncovered during testing that are unrelated to the primary disease under investigation, but of potential clinical significance. High-quality evidence evaluating health outcomes and costs of receiving incidental results is critical for the adoption of genomic sequencing into clinical care and to understand the unintended consequences of adoption of genomic sequencing. We aim to evaluate the health outcomes and costs of receiving incidental results for patients undergoing genomic sequencing. METHODS AND ANALYSIS: We will compare health outcomes and costs of receiving, versus not receiving, incidental results for adult patients with cancer undergoing genomic sequencing in a mixed-methods randomised controlled trial. Two hundred and sixty patients who have previously undergone first or second-tier genetic testing for cancer and received uninformative results will be recruited from familial cancer clinics in Toronto, Ontario. Participants in both arms will receive cancer-related results. Participants in the intervention arm have the option to receive incidental results. Our primary outcome is psychological distress at 2 weeks following return of results. Secondary outcomes include behavioural consequences, clinical and personal utility assessed over the 12 months after results are returned and health service use and costs at 12 months and 5 years. A subset of participants and providers will complete qualitative interviews about utility of incidental results. ETHICS AND DISSEMINATION: This study has been approved by Clinical Trials Ontario Streamlined Research Ethics Review System that provides ethical review and oversight for multiple sites participating in the same clinical trial in Ontario.Results from the trial will be shared through stakeholder workshops, national and international conferences, and peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT03597165.

Impact of smoking on health system costs among cancer patients in a retrospective cohort study in Ontario, Canada.

OBJECTIVE: Smoking is the main modifiable cancer risk factor. The objective of this study was to examine the impact of smoking on health system costs among newly diagnosed adult patients with cancer. Specifically, costs of patients with cancer who were current smokers were compared with those of non-smokers from a publicly funded health system perspective. METHODS: This population-based cohort study of patients with cancer used administrative databases to identify smokers and non-smokers (1 April 2014-31 March 2016) and their healthcare costs in the 12-24 months following a cancer diagnosis. The health services included were hospitalisations, emergency room visits, drugs, home care services and physician services (from the time of diagnosis onwards). The difference in cost (ie, incremental cost) between patients with cancer who were smokers and those who were non-smokers was estimated using a generalised linear model (with log link and gamma distribution), and adjusted for age, sex, neighbourhood income, rurality, cancer site, cancer stage, geographical region and comorbidities. RESULTS: This study identified 3606 smokers and 14 911 non-smokers. Smokers were significantly younger (61 vs 65 years), more likely to be male (53%), lived in poorer neighbourhoods, had more advanced cancer stage,and were more likely to die within 1 year of diagnosis, compared with non-smokers. The regression model revealed that, on average, smokers had significantly higher monthly healthcare costs ($5091) than non-smokers ($4847), p<0.05. CONCLUSIONS: Smoking status has a significant impact on healthcare costs among patients with cancer. On average, smokers incurred higher healthcare costs than non-smokers. These findings provide a further rationale for efforts to introduce evidence-based smoking cessation programmes as a standard of care for patients with cancer as they have the potential not only to improve patients' outcomes but also to reduce the economic burden of smoking on the healthcare system.