CAR T-cell Therapy for Diffuse Large B-cell Lymphoma in Canada: A Cost-Utility Analysis.

BACKGROUND: Chimeric antigen receptor (CAR) T-cell therapy is a novel cell therapy for treating non-Hodgkin lymphoma. The development of CAR T-cell therapy has transformed oncology treatment by offering a potential cure. However, due to the high cost of these therapies, and the large number of eligible patients, decision makers are faced with difficult funding decisions. Our objective was to assess the cost-effectiveness of tisagenlecleucel for adults with relapsed/refractory diffuse large B-cell lymphoma in Canada using updated survival data from the recent JULIET trial. METHODS: We developed an individual-simulated discrete event simulation model to assess the costs and quality-adjusted life-years (QALY) of tisagenlecleucel compared with salvage chemotherapy. Survival estimates were obtained from a published clinical trial and retrospective analysis. If patients remained progression free for 5 y, they were assumed to be in long-term remission. Costing and utility data were obtained from reports and published sources. A Canadian health care payer perspective was used, and outcomes were modeled over a lifetime horizon. Costs and outcomes were discounted at 1.5% annually, with costs reported in 2021 Canadian dollars. A probabilistic analysis was used, and model parameters were varied in 1-way sensitivity analyses and scenario analyses. RESULTS: After we incorporated the latest clinical evidence, tisagenlecleucel led to an additional cost of $503,417 and additional effectiveness of 2.48 QALYs, with an incremental cost-effectiveness ratio of $202,991 compared with salvage chemotherapy. At a willingness-to-pay threshold of $100,000/QALY, tisagenlecleucel had a 0% likelihood of being cost-effective. CONCLUSIONS: At the current drug price, tisagenlecleucel was not found to be a cost-effective option. These results heavily depend on assumptions regarding long-term survival and the price of CAR T. Real-world evidence is needed to reduce uncertainty. HIGHLIGHTS: For patients with diffuse large B-cell lymphoma who failed 2 or more lines of systemic therapy, CAR T was not found to be a cost-effective treatment option at a willingness-to-pay threshold of $100,000.These results heavily depend on the expected long-term survival. The uncertainty in the model may be improved using real-world evidence reported in the future.

Hepatitis C Attributable Healthcare Costs and Mortality among Immigrants: A Population-Based Matched Cohort Study.

Background: Data on the economic burden of chronic hepatitis C (CHC) among immigrants are limited. Our objective was to estimate the CHC-attributable mortality and healthcare costs among immigrants in Ontario, Canada. Methods: We conducted a population-based matched cohort study among immigrants diagnosed with CHC between May 31, 2003, and December 31, 2018, using linked health administrative data. Immigrants with CHC (exposed) were matched 1 : 1 to immigrants without CHC (unexposed) using a combination of hard (index date, sex, and age) and propensity-score matching. Net costs (2020 Canadian dollars) collected from the healthcare payer perspective were calculated using a phase-of-care approach and used to estimate long-term costs adjusted for survival. Results: We matched 5,575 exposed individuals with unexposed controls, achieving a balanced match. The mean age was 47 years, and 52% was male. On average, 10.5% of exposed and 3.5% of unexposed individuals died 15 years postindex (relative risk = 2.9; 95% confidence interval (CI): 2.6-3.5). The net 30-day costs per person were $88 (95% CI: 55 to 122) for the prediagnosis, $324 (95% CI: 291 to 356) for the initial phase, $1,016 (95% CI: 900 to 1,132) for the late phase, and $975 (95% CI: -25 to 1,974) for the terminal phase. The mean net healthcare cost adjusted for survival at 15 years was $90,448. Conclusions: Compared to unexposed immigrants, immigrants infected with CHC have higher mortality rates and greater healthcare costs. These findings will support the planning of HCV elimination efforts among key risk groups in the province.

An economic evaluation of community pharmacy-dispensed naloxone in Canada.

Aims: To determine the cost-effectiveness of pharmacy-based intranasal (IN) and intramuscular (IM) naloxone distribution in Canada. Methods: We developed a state-transition model for pharmacy-based naloxone distribution, every 3 years, to illicit, prescription, opioid-agonist therapy and nonopioid use populations compared to no naloxone distribution. We used a monthly cycle length, lifetime horizon and a Canadian provincial Ministry of Health perspective. Transition probabilities, cost and utility data were retrieved from the literature. Costs (2020) and quality-adjusted life years (QALY) were discounted 1.5% annually. Microsimulation, 1-way and probabilistic sensitivity analyses were conducted. Results: Distribution of naloxone to all Canadians compared to no distribution prevented 151 additional overdose deaths per 10,000 persons, with an incremental cost-effectiveness ratio (ICER) of $50,984 per QALY for IM naloxone and an ICER of $126,060 per QALY for IN naloxone. Distribution of any naloxone to only illicit opioid users was the most cost-effective. One-way sensitivity analysis showed that survival rates for illicit opioid users were most influenced by the availability of either emergency medical services or naloxone. Conclusion: Distribution of IM and IN naloxone to all Canadians every 3 years is likely cost-effective at a willingness-to-pay threshold of $140,000 Canadian dollars/QALY (~3 × gross domestic product from the World Health Organization). Distribution to people who use illicit opioids was most cost-effective and prevented the most deaths. This is important, as more overdose deaths could be prevented through nationwide public funding of IN naloxone kits through pharmacies, since individuals report a preference for IN naloxone and these formulations are easier to use, save lives and are cost-effective. Can Pharm J (Ott) 2024;157:xx-xx.

Characterising the effectiveness of social determinants of health-focused hepatitis B interventions: a systematic review.

Social determinants of health are important in designing effective interventions for hepatitis B virus (HBV) infection. This systematic review characterises equity-oriented, social determinants of health-focused HBV interventions, and describes their effectiveness in terms of the prevention, care, or treatment of HBV in high-income countries. We searched electronic databases for central concepts of 'HBV', 'equity', 'social determinants of health', 'intervention', and 'Organization for Economic Co-operation and Development (OECD) countries'. Screening and data abstraction were conducted independently by two reviewers. Data were abstracted from 66 studies; articles with a comparative study design (n=36) were included in the narrative synthesis, highlighting social determinants of health domains of interventions, HBV-relevant health outcomes, and extra-health social determinants of health effects (ie, those effects that extend beyond health outcomes). Synthesis aligned with six emergent themes corresponding to HBV prevention and care: knowledge and education, diagnosis and screening, immunisation, care initiation, engagement with clinical care and treatment, and upstream prevention. Studies presented a heterogeneous array of HBV-relevant health outcomes. Most interventions were tailored for social determinants of health domains of race, ethnicity, culture, and language; drug use; and socioeconomic status. Across the themes, at least two-thirds of interventions showed comparative effectiveness for addressing HBV. Extra-health social determinants of health outcomes were observed for two studies. Considerable diversity in population-level approaches was observed regarding intervention goals and effectiveness; most interventions were effective at enhancing the prevention, care, or treatment of HBV.

Modelling small block aperture in an in-house developed GPU-accelerated Monte Carlo-based dose engine for pencil beam scanning proton therapy.

Purpose. To enhance an in-house graphic-processing-unit accelerated virtual particle (VP)-based Monte Carlo (MC) proton dose engine (VPMC) to model aperture blocks in both dose calculation and optimization for pencil beam scanning proton therapy (PBSPT)-based stereotactic radiosurgery (SRS).Methods and materials. A module to simulate VPs passing through patient-specific aperture blocks was developed and integrated in VPMC based on simulation results of realistic particles (primary protons and their secondaries). To validate the aperture block module, VPMC was first validated by an opensource MC code, MCsquare, in eight water phantom simulations with 3 cm thick brass apertures: four were with aperture openings of 1, 2, 3, and 4 cm without a range shifter, while the other four were with same aperture opening configurations with a range shifter of 45 mm water equivalent thickness. Then, VPMC was benchmarked with MCsquare and RayStation MC for 10 patients with small targets (average volume 8.4 c.c. with range of 0.4-43.3 c.c.). Finally, 3 typical patients were selected for robust optimization with aperture blocks using VPMC.Results. In the water phantoms, 3D gamma passing rate (2%/2 mm/10%) between VPMC and MCsquare was 99.71 ± 0.23%. In the patient geometries, 3D gamma passing rates (3%/2 mm/10%) between VPMC/MCsquare and RayStation MC were 97.79 ± 2.21%/97.78 ± 1.97%, respectively. Meanwhile, the calculation time was drastically decreased from 112.45 ± 114.08 s (MCsquare) to 8.20 ± 6.42 s (VPMC) with the same statistical uncertainties of ~0.5%. The robustly optimized plans met all the dose-volume-constraints (DVCs) for the targets and OARs per our institutional protocols. The mean calculation time for 13 influence matrices in robust optimization by VPMC was 41.6 s and the subsequent on-the-fly 'trial-and-error' optimization procedure took only 71.4 s on average for the selected three patients.Conclusion. VPMC has been successfully enhanced to model aperture blocks in dose calculation and optimization for the PBSPT-based SRS.

An Exploratory Analysis of the Cost-Effectiveness of a Multi-cancer Early Detection Blood Test Compared with Standard of Care Screening in Ontario, Canada.

BACKGROUND: Determining whether multi-cancer early detection (MCED) tests are cost effective is important in deciding whether they should be included in the clinical path of cancer care, especially for cancers where screening tools do not exist. RESEARCH OBJECTIVE: The main objective of this study is to determine the cost effectiveness of including a MCED screening regimen together with existing provincial screening protocols for selected cancers that are prevalent in Ontario, Canada, among average risk persons aged 50-75 years. The selected cancers include breast, colorectal, lung, esophageal, liver, pancreatic, stomach, and ovarian. METHODS: Cost effectiveness was estimated from a provincial Ministry of Health perspective. A state-transition Markov model representing the decision path of both the proposed and existing screening strategies along the natural history of the selected types of cancers was implemented. The incremental cost-effectiveness ratio (ICER) was calculated using data from available literature and the guidelines published by the Canadian Agency for Drugs and Technologies in Health (CADTH) for conducting a cost-effectiveness analysis, which included a discount rate of 1.5% applied to all costs and outcomes. Costs were also converted to 2022 Canadian dollars. To test the robustness of the model, both univariate and probabilistic sensitivity analyses were conducted. RESULTS: MCED screening resulted in more diagnosed cases of each type of cancer, even at an earlier stage of disease. This was also associated with fewer related deaths compared with standard of care. Notwithstanding, the analysis revealed that the MCED intervention was not cost effective [ICER: CAD$143,369 per quality-adjusted life year (QALY)], given a willingness to pay (WTP) threshold of $100,000 per QALY. The probabilistic sensitivity analyses revealed that the MCED intervention strategy was preferred to standard of care no more than 2% of the time at this WTP for both males and females. The model was most sensitive to the cost of MCED screening, and the levels of specificity of the MCED and colorectal cancer screening tests. CONCLUSION: The main contribution of the study is to present and execute a methodological approach that can be adopted to test the cost effectiveness of an MCED tool in the Canadian setting. The model is also sufficiently generic that it could be adapted to other jurisdictions, and with consideration for increasing the WTP threshold beyond the common $100,000 per QALY limit, given the life-threatening nature of cancer, to ensure that MCED interventions are cost-effective.

The impact of the early COVID-19 pandemic on healthcare system resource use and costs in two provinces in Canada: An interrupted time series analysis.

INTRODUCTION: The aim of our study was to assess the initial impact of COVID-19 on total publicly-funded direct healthcare costs and health services use in two Canadian provinces, Ontario and British Columbia (BC). METHODS: This retrospective repeated cross-sectional study used population-based administrative datasets, linked within each province, from January 1, 2018 to December 27, 2020. Interrupted time series analysis was used to estimate changes in the level and trends of weekly resource use and costs, with March 16-22, 2020 as the first pandemic week. Also, in each week of 2020, we identified cases with their first positive SARS-CoV-2 test and estimated their healthcare costs until death or December 27, 2020. RESULTS: The resources with the largest level declines (95% confidence interval) in use in the first pandemic week compared to the previous week were physician services [Ontario: -43% (-49%,-37%); BC: -24% (-30%,-19%) (both p<0.001)] and emergency department visits [Ontario: -41% (-47%,-35%); BC: -29% (-35%,-23%) (both p<0.001)]. Hospital admissions declined by 27% (-32%,-23%) in Ontario and 21% (-26%,-16%) in BC (both p<0.001). Resource use subsequently rose but did not return to pre-pandemic levels. Only home care and dialysis clinic visits did not significantly decrease compared to pre-pandemic. Costs for COVID-19 cases represented 1.3% and 0.7% of total direct healthcare costs in 2020 in Ontario and BC, respectively. CONCLUSIONS: Reduced utilization of healthcare services in the overall population outweighed utilization by COVID-19 patients in 2020. Meeting the needs of all patients across all services is essential to maintain resilient healthcare systems.

A province-by-province cost-effectiveness analysis and budget impact analysis of one-time birth cohort screening of hepatitis C virus (HCV) infection in Canada.

Managing chronic hepatitis C is challenging, as the majority of those infected are asymptomatic. Therefore, to ensure treatments are administered before the onset of severe complications, screening is important. In Canada, uncertainty regarding the cost-effectiveness and budget impact of screening has led to conflicting recommendations. The objective of this study is to estimate the cost-effectiveness and budget-impact of one-time HCV screening. A state-transition model was developed to evaluate the cost-effectiveness and budget-impact between a risk-based screening strategy (current-practice) and a one-time screening strategy on three different birth-cohorts. Cost and prevalence data were obtained from administrative data. Progression and utility data were based on recent systematic reviews. We used a provincial payer-perspective, life-time time-horizon and a 1.5% discount rate for the cost-effectiveness analysis, and used a 10-year time-horizon and no discounting for the budget-impact analysis. One-time screening strategy would cost more and provide more health benefits than the risk-based screening for all birth cohorts. For those born after 1964, the incremental-cost-effectiveness-ratio (ICER) per quality-adjusted-life-year (QALY) of screening versus current-practice varied from $27,422/QALY to $42,191/QALY across different provinces. One-time screening of the cohort would cost an additional $2 million to $236 million across different provinces. For those born 1945-1964, the ICER of screening versus current-practice varied from $35,217/QALY to $48,197/QALY across different provinces. For the cohort born before 1945, the ICER of screening versus current-practice was not cost-effective at a willingness-to-pay threshold of $50,000/QALY across all provinces. Our cost-effectiveness analysis suggests that a one-time HCV screening program for those born after 1945 is cost-effective. Considering the budget impact relative to other funded recommended health services and technologies, HCV screening could be considered affordable.

Modelling small block aperture in an in-house developed GPU-accelerated Monte Carlo-based dose engine for pencil beam scanning proton therapy.

Purpose: To enhance an in-house graphic-processing-unit (GPU) accelerated virtual particle (VP)-based Monte Carlo (MC) proton dose engine (VPMC) to model aperture blocks in both dose calculation and optimization for pencil beam scanning proton therapy (PBSPT)-based stereotactic radiosurgery (SRS). Methods and Materials: A module to simulate VPs passing through patient-specific aperture blocks was developed and integrated in VPMC based on simulation results of realistic particles (primary protons and their secondaries). To validate the aperture block module, VPMC was first validated by an opensource MC code, MCsquare, in eight water phantom simulations with 3cm thick brass apertures: four were with aperture openings of 1, 2, 3, and 4cm without a range shifter, while the other four were with same aperture opening configurations with a range shifter of 45mm water equivalent thickness. Then, VPMC was benchmarked with MCsquare and RayStation MC for 10 patients with small targets (average volume 8.4 cc with range of 0.4 - 43.3 cc). Finally, 3 typical patients were selected for robust optimization with aperture blocks using VPMC. Results: In the water phantoms, 3D gamma passing rate (2%/2mm/10%) between VPMC and MCsquare was 99.71±0.23%. In the patient geometries, 3D gamma passing rates (3%/2mm/10%) between VPMC/MCsquare and RayStation MC were 97.79±2.21%/97.78±1.97%, respectively. Meanwhile, the calculation time was drastically decreased from 112.45±114.08 seconds (MCsquare) to 8.20±6.42 seconds (VPMC) with the same statistical uncertainties of ~0.5%. The robustly optimized plans met all the dose-volume-constraints (DVCs) for the targets and OARs per our institutional protocols. The mean calculation time for 13 influence matrices in robust optimization by VPMC was 41.6 seconds and the subsequent on-the-fly "trial-and-error" optimization procedure took only 71.4 seconds on average for the selected three patients. Conclusion: VPMC has been successfully enhanced to model aperture blocks in dose calculation and optimization for the PBSPT-based SRS.

A Systematic Review of the Cost-Effectiveness Analyses of Anaplastic Lymphoma Kinase (ALK) Inhibitors in Patients with Locally Advanced or Metastatic Non-small Cell Lung Cancer (NSCLC).

BACKGROUND: The anaplastic lymphoma kinase (ALK) inhibitor treatment landscape is rapidly evolving, providing patients with ALK-positive (+) non-small cell lung cancer (NSCLC) with multiple therapy options, multiple lines of treatments, and prolonged survival. However, these recent treatment advances have resulted in additional increases in treatment costs. The objective of this article is to review the economic evidence of ALK inhibitors in patients with ALK+ NSCLC. METHODS: The systematic review was conducted in accordance with the Joanna Briggs Institute (JBI) systematic reviews of economic evaluation. The population included adult patients with locally advanced (stage IIIb/c) or metastatic (stage IV) NSCLC cancer with confirmed ALK fusions. The interventions included the ALK inhibitors alectinib, brigatinib, ceritinib, crizotinib, ensartinib, or lorlatinib. The comparators included the listed ALK inhibitors, chemotherapy, or best supportive care. The review considered cost-effectiveness analysis studies (CEAs) that reported incremental cost-effectiveness ratio in quality-adjusted life years and/or in life years gained. Published literature was searched in Medline (via Ovid) by 4 January 2023, in Embase (via Ovid) by 4 January 2023, in International Pharmaceutical Abstracts (via Ovid) by 4 January 2023, and in Cochrane library (via Wiley) by 11 January 2023. Preliminary screening of titles and abstracts was conducted against the inclusion criteria by two independent researchers followed by a full text of selected citations. Search results are presented in a Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) flow diagram. Critical appraisal was conducted using the validated Consolidated Health Economic Evaluation Reporting Standards 2022 (CHEERS) tool as well as the Phillips et al. 2004 appraisal tool to assess the reporting and quality of the economic evaluations. Data were extracted from the final set of articles and presented in a table of characteristics of included studies, an overview of study methods of included studies, and a summarization of outcomes of included studies. RESULTS: A total of 19 studies met all inclusion criteria. The majority of the studies were in the first-line treatment setting (n = 15). Included CEAs varied in the interventions and comparators being evaluated and were conducted from different country perspectives, limiting their comparability. Outcomes from the included CEAs showed that ALK inhibitors may be considered a cost-effective treatment option for patients with ALK+ NSCLC in the first-line and subsequent lines of treatment setting. However, the probability of cost effectiveness of ALK inhibitors ranged from 46 to 100% and were mostly achieved at willingness-to-pay thresholds of $100,000 USD or higher (> $30,000 or higher in China) in the first-line treatment setting and at thresholds of $50,000 USD or higher in subsequent lines of treatment setting. The number of published full-text CEAs is low and the studies represent a handful of country perspectives. The source of survival data was dependent on data from randomized controlled trials (RCTs). Where RCT data were not available, indirect treatment comparisons or matched adjusted indirect comparisons were performed using efficacy data from different clinical studies. Real world evidence was rarely used for efficacy and costing data inputs. CONCLUSION: The findings summarized available evidence on cost effectiveness of ALK inhibitors for the treatment of patients with locally advanced or metastatic ALK+ NSCLC across lines of treatment settings and generated a valuable overview of analytical approaches utilized to support future economic analyses. To help further inform treatment and policy decisions, this review emphasizes the need for comparative cost effectiveness of multiple ALK inhibitors simultaneously using real-world data sources with broad representation of settings.

Cost-utility analysis of a multispecialty interprofessional team dementia care model in Ontario, Canada.

OBJECTIVES: To examine the cost-effectiveness of Multi-specialty INterprofessional Team (MINT) Memory Clinic care in comparison to the provision of usual care. DESIGN: Using a Markov-based state transition model, we performed a cost-utility (costs and quality-adjusted life years, QALY) analysis of MINT Memory Clinic care and usual care not involving MINT Memory Clinics. SETTING: A primary care-based Memory Clinic in Ontario, Canada. PARTICIPANTS: The analysis included data from a sample of 229 patients assessed in the MINT Memory Clinic between January 2019 and January 2021. PRIMARY OUTCOME MEASURES: Effectiveness as measured in QALY, costs (in Canadian dollars) and the incremental cost-effectiveness ratio calculated as the incremental cost per QALY gained between MINT Memory Clinics versus usual care. RESULTS: MINT Memory Clinics were found to be less expensive ($C51 496 (95% Crl $C4806 to $C119 367) while slightly improving quality of life (+0.43 (95 Crl 0.01 to 1.24) QALY) compared with usual care. The probabilistic analysis showed that MINT Memory Clinics were the superior treatment compared with usual care 98% of the time. Variation in age was found to have the greatest impact on cost-effectiveness as patients may benefit from the MINT Memory Clinics more if they receive care beginning at a younger age. CONCLUSION: Multispecialty interprofessional memory clinic care is less costly and more effective compared with usual care and early access to care significantly reduces care costs over time. The results of this economic evaluation can inform decision-making and improvements to health system design, resource allocation and care experience for persons living with dementia. Specifically, widespread scaling of MINT Memory Clinics into existing primary care systems may assist with improving quality and access to memory care services while decreasing the growing economic and social burden of dementia.

First Report On Physician Assessment and Clinical Acceptability of Custom-Retrained Artificial Intelligence Models for Clinical Target Volume and Organs-at-Risk Auto-Delineation for Postprostatectomy Patients.

PURPOSE: To assess the clinical acceptability of a commercial deep-learning-based auto-segmentation (DLAS) prostate model that was retrained using institutional data for delineation of the clinical target volume (CTV) and organs-at-risk (OARs) for postprostatectomy patients, accounting for clinical and imaging protocol variations. METHODS AND MATERIALS: CTV and OARs of 109 prostate-bed patients were used to evaluate the performance of the vendor-trained model and custom retrained DLAS models using different training quantities. Two new models for OAR structures were retrained (n = 30, 60 data sets), while separate models were trained for a new CTV structure (n = 30, 60, 90 data sets), with the remaining data sets used for testing (n = 49, 19). The dice similarity coefficient (DSC), Hausdorff distance, and mean surface distance were evaluated. Six radiation oncologists performed a qualitative evaluation scoring both preference and clinical utility for blinded structure sets. Physician consensus data sets identified from the qualitative evaluation were used toward a separate CTV model. RESULTS: Both the 30- and 60-case retrained OAR models had median DSC values between 0.91 to 0.97, improving significantly over the vendor-trained model for all OARs except the penile bulb. The brand new 60-case CTV model had a median DSC of 0.70 improving significantly over the 30-case model. DLAS (60-case model) and manual contours were blinded and evaluated by physicians with contours deemed acceptable or precise for 87% and 94% of cases for DLAS and manual delineations, respectively. DLAS-generated CTVs were scored precise or acceptable in 54% of cases, compared with the manual delineation value of 73%. The 30-case physician consensus CTV model did not show a significant difference compared with the randomly selected models. CONCLUSIONS: Custom retraining using institutional data leads to performance improvement in the clinical utility and accuracy of DLAS for postprostatectomy patients. A small number of data sets are sufficient for building an institutional site-specific DLAS OAR model, as well as for training new structures. Data indicates the workload for identifying training data sets could be shared among groups for the male pelvic region, making it accessible to clinics of all sizes.

Cost Effectiveness of Implementing a Universal Birth Hepatitis B Vaccination Program in Ontario.

BACKGROUND AND OBJECTIVE: The World Health Organization recommends a universal hepatitis B vaccination within the first 24 h of birth. However, hepatitis B vaccines are given during adolescence in many jurisdictions including in Ontario, Canada. The objective of this study was to assess the cost effectiveness of shifting the hepatitis B vaccination timing from adolescence to birth. METHODS: A state-transition model of 18 health states representing the natural history of acute and chronic hepatitis B was developed to conduct a cost-utility analysis. Most input parameters were obtained from the Canadian literature or publicly available provincial data. The model followed a lifetime model time horizon with health outcomes and costs being discounted at 1.5% annually. Deterministic and probabilistic sensitivity analyses were performed to test the robustness of the model. Analyses were conducted from a public-payer perspective with all costs adjusted to 2021 Canadian dollars. RESULTS: Hepatitis B vaccination in newborns dominated the current strategy of adolescent vaccination. The probabilistic analysis showed that the newborn strategy was cost effective in 100% of the iterations at a willingness-to-pay threshold of $50,000/quality-adjusted life-year and cost saving in 79.39% of the iterations. A microsimulation projected that a newborn vaccination may lead to reductions in cases by 16.1% in acute hepatitis B, 43.2% in chronic hepatitis B, 48.2% in hepatocellular carcinoma, and 51.9% in hepatitis B liver-related death. CONCLUSIONS: Our analysis suggests that changing the age of the hepatitis B vaccination recommendation from adolescent to newborn is cost effective and mostly a cost-saving strategy. Newborn vaccination may lead to cost and health benefits while aligning with best available evidence and guidance from the World Health Organization.

Cost-utility analysis of emicizumab for the treatment of severe hemophilia A patients in Canada.

INTRODUCTION: EHL FVIII products and emicizumab provide clinicians with other prophylactic options for treating hemophilia A, however, it is unclear if emicizumab is a cost-saving option. The objective of this study is to estimate the health and economic effects of using prophylactic EHL FVIII, SHL FVIII, and emicizumab in severe haemophilia A patients. MATERIALS AND METHODS: A state-transition Markov model evaluated the cost-effectiveness of prophylactic SHL FVIII, EHL FVIII, and emicizumab in a cohort of 2-year-old male patients over a lifetime horizon in the form of a cost-utility analysis using a Canadian provincial ministry of health payer perspective. The transition probabilities, costs, and utilities were obtained from literature and the Canadian Bleeding Disorders Registry. Probabilistic sensitivity and scenario analyses were performed to test the robustness of the model. RESULTS: The base-case analysis, over a lifetime horizon, resulted in a total cost and utilities per person for SHL FVIII, EHL FVIII, and emicizumab of $27.2 million (M), $36.7 M, and $26.2 M, respectively, and 31.30, 31.16, and 31.61 quality-adjusted life years, respectively. Emicizumab treatment resulted in 29 and 16 less bleeds in a lifetime compared to SHL FVIII and EHL FVIII, respectively. Probabilistic sensitivity analysis showed that emicizumab was cost-saving 100% of the time compared to SHL FVIII and EHL FVIII. CONCLUSION: The cost-utility analysis showed that emicizumab is more effective and may be less costly than FVIII for Canadian haemophilia A patients, conditional on drug cost assumptions. Our model indicates that emicizumab may be a potentially favourable treatment option for minimising healthcare costs and providing higher effectiveness.

Cost effectiveness of treatment strategies for high risk prostate cancer.

BACKGROUND: Patients with high-risk prostate cancer (HRPC) have multiple accepted treatment options. Because there is no overall survival benefit of one option over another, appropriate treatment must consider patient life expectancy, quality of life, and cost. METHODS: The authors compared quality-adjusted life years (QALYs) and cost effectiveness among treatment options for HRPC using a Markov model with three treatment arms: (1) external-beam radiotherapy (EBRT) delivered with 20 fractions, (2) EBRT with 23 fractions followed by low-dose-rate (LDR) brachytherapy boost, or (3) radical prostatectomy alone. An exploratory analysis considered a simultaneous integrated boost according to the FLAME trial (ClinicalTrials.gov identifier NCT01168479). RESULTS: Treatment strategies were compared using the incremental cost-effectiveness ratio (ICER). EBRT with LDR brachytherapy boost was a cost-effective strategy (ICER, $20,929 per QALY gained). These results were most sensitive to variations in the biochemical failure rate. However, the results still demonstrated cost effectiveness for the brachytherapy boost paradigm, regardless of any tested parameter ranges. Probabilistic sensitivity analysis demonstrated that EBRT with LDR brachytherapy was favored in 52% of 100,000 Monte Carlo iterations. In an exploratory analysis, EBRT with a simultaneous integrated boost was also a cost-effective strategy, resulting in an ICER of $62,607 per QALY gained; however, it was not cost effective compared with EBRT plus LDR brachytherapy boost. CONCLUSIONS: EBRT with LDR brachytherapy boost may be a cost-effective treatment strategy compared with EBRT alone and radical prostatectomy for HRPC, demonstrating high-value care. The current analysis suggests that a reduction in biochemical failure alone can result in cost-effective care, despite no change in overall survival.

External validation of a prediction model for estimating fat mass in children and adolescents in 19 countries: individual participant data meta-analysis.

OBJECTIVE: To evaluate the performance of a UK based prediction model for estimating fat-free mass (and indirectly fat mass) in children and adolescents in non-UK settings. DESIGN: Individual participant data meta-analysis. SETTING: 19 countries. PARTICIPANTS: 5693 children and adolescents (49.7% boys) aged 4 to 15 years with complete data on the predictors included in the UK based model (weight, height, age, sex, and ethnicity) and on the independently assessed outcome measure (fat-free mass determined by deuterium dilution assessment). MAIN OUTCOME MEASURES: The outcome of the UK based prediction model was natural log transformed fat-free mass (lnFFM). Predictive performance statistics of R2, calibration slope, calibration-in-the-large, and root mean square error were assessed in each of the 19 countries and then pooled through random effects meta-analysis. Calibration plots were also derived for each country, including flexible calibration curves. RESULTS: The model showed good predictive ability in non-UK populations of children and adolescents, providing R2 values of >75% in all countries and >90% in 11 of the 19 countries, and with good calibration (ie, agreement) of observed and predicted values. Root mean square error values (on fat-free mass scale) were <4 kg in 17 of the 19 settings. Pooled values (95% confidence intervals) of R2, calibration slope, and calibration-in-the-large were 88.7% (85.9% to 91.4%), 0.98 (0.97 to 1.00), and 0.01 (-0.02 to 0.04), respectively. Heterogeneity was evident in the R2 and calibration-in-the-large values across settings, but not in the calibration slope. Model performance did not vary markedly between boys and girls, age, ethnicity, and national income groups. To further improve the accuracy of the predictions, the model equation was recalibrated for the intercept in each setting so that country specific equations are available for future use. CONCLUSION: The UK based prediction model, which is based on readily available measures, provides predictions of childhood fat-free mass, and hence fat mass, in a range of non-UK settings that explain a large proportion of the variability in observed fat-free mass, and exhibit good calibration performance, especially after recalibration of the intercept for each population. The model demonstrates good generalisability in both low-middle income and high income populations of healthy children and adolescents aged 4-15 years.

Initial health care costs for COVID-19 in British Columbia and Ontario, Canada: an interprovincial population-based cohort study.

BACKGROUND: COVID-19 imposed substantial health and economic burdens. Comprehensive population-based estimates of health care costs for COVID-19 are essential for planning and policy evaluation. We estimated publicly funded health care costs in 2 Canadian provinces during the pandemic's first wave. METHODS: In this historical cohort study, we linked patients with their first positive SARS-CoV-2 test result by June 30, 2020, in 2 Canadian provinces (British Columbia and Ontario) to health care administrative databases and matched to negative or untested controls. We stratified patients by highest level of initial care: community, long-term care, hospital (without admission to the intensive care unit [ICU]) and ICU. Mean publicly funded health care costs for patients and controls, mean net (attributable to COVID-19) costs and total costs were estimated from 30 days before to 120 days after the index date, or to July 31, 2020, in 30-day periods for patients still being followed by the start of each period. RESULTS: We identified 2465 matched people with a positive test result for SARS-CoV-2 in BC and 28 893 in Ontario. Mean age was 53.4 (standard deviation [SD] 21.8) years (BC) and 53.7 (SD 22.7) years (Ontario); 55.7% (BC) and 56.1% (Ontario) were female. Net costs in the first 30 days after the index date were $22 010 (95% confidence interval [CI] 19 512 to 24 509) and $15 750 (95% CI 15 354 to 16 147) for patients admitted to hospital, and $65 828 (95% CI 58 535 to 73 122) and $56 088 (95% CI 53 721 to 58 455) for ICU patients in BC and Ontario, respectively. In the community and long-term care settings, net costs were near 0. Total costs for all people, from 30 days before to 30 days after the index date, were $22 128 330 (BC) and $175 778 210 (Ontario). INTERPRETATION: During the first wave, we found that mean costs attributable to COVID-19 were highest for patients with ICU admission and higher in BC than Ontario. Reducing the number of people who acquire COVID-19 and severity of illness are required to mitigate the economic impact of COVID-19.

Virtual particle Monte Carlo: A new concept to avoid simulating secondary particles in proton therapy dose calculation.

BACKGROUND: In proton therapy dose calculation, Monte Carlo (MC) simulations are superior in accuracy but more time consuming, compared to analytical calculations. Graphic processing units (GPUs) are effective in accelerating MC simulations but may suffer thread divergence and racing condition in GPU threads that degrades the computing performance due to the generation of secondary particles during nuclear reactions. PURPOSE: A novel concept of virtual particle (VP) MC (VPMC) is proposed to avoid simulating secondary particles in GPU-accelerated proton MC dose calculation and take full advantage of the computing power of GPU. METHODS: Neutrons and gamma rays were ignored as escaping from the human body; doses of electrons, heavy ions, and nuclear fragments were locally deposited; the tracks of deuterons were converted into tracks of protons. These particles, together with primary and secondary protons, are considered to be the realistic particles. Histories of primary and secondary protons were replaced by histories of multiple VPs. Each VP corresponded to one proton (either primary or secondary). A continuous-slowing-down-approximation model, an ionization model, and a large angle scattering event model corresponding to nuclear interactions were developed for VPs by generating probability distribution functions (PDFs) based on simulation results of realistic particles using MCsquare. For efficient calculations, these PDFs were stored in the Compute Unified Device Architecture textures. VPMC was benchmarked with TOPAS and MCsquare in phantoms and with MCsquare in 13 representative patient geometries. Comparisons between the VPMC calculated dose and dose measured in water during patient-specific quality assurance (PSQA) of the selected 13 patients were also carried out. Gamma analysis was used to compare the doses derived from different methods and calculation efficiencies were also compared. RESULTS: Integrated depth dose and lateral dose profiles in both homogeneous and inhomogeneous phantoms all matched well among VPMC, TOPAS, and MCsquare calculations. The 3D-3D gamma passing rates with a criterion of 2%/2 mm and a threshold of 10% was 98.49% between MCsquare and TOPAS and 98.31% between VPMC and TOPAS in homogeneous phantoms, and 99.18% between MCsquare and TOPAS and 98.49% between VPMC and TOPAS in inhomogeneous phantoms, respectively. In patient geometries, the 3D-3D gamma passing rates with 2%/2 mm/10% between dose distributions from VPMC and MCsquare were 98.56 ± 1.09% in patient geometries. The 2D-3D gamma analysis with 3%/2 mm/10% between the VPMC calculated dose distributions and the 2D measured planar dose distributions during PSQA was 98.91 ± 0.88%. VPMC calculation was highly efficient and took 2.84 ± 2.44 s to finish for the selected 13 patients running on four NVIDIA Ampere GPUs in patient geometries. CONCLUSION: VPMC was found to achieve high accuracy and efficiency in proton therapy dose calculation.

Human total, basal and activity energy expenditures are independent of ambient environmental temperature.

Lower ambient temperature (Ta) requires greater energy expenditure to sustain body temperature. However, effects of Ta on human energetics may be buffered by environmental modification and behavioral compensation. We used the IAEA DLW database for adults in the USA (n = 3213) to determine the effect of Ta (-10 to +30°C) on TEE, basal (BEE) and activity energy expenditure (AEE) and physical activity level (PAL). There were no significant relationships (p > 0.05) between maximum, minimum and average Ta and TEE, BEE, AEE and PAL. After adjustment for fat-free mass, fat mass and age, statistically significant (p < 0.01) relationships between TEE, BEE and Ta emerged in females but the effect sizes were not biologically meaningful. Temperatures inside buildings are regulated at 18-25°C independent of latitude. Hence, adults in the US modify their environments to keep TEE constant across a wide range of external ambient temperatures.

"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.