The Impact of Model Assumptions on Personalized Lung Cancer Screening Recommendations.

BACKGROUND: Recommendations regarding personalized lung cancer screening are being informed by natural-history modeling. Therefore, understanding how differences in model assumptions affect model-based personalized screening recommendations is essential. DESIGN: Five Cancer Intervention and Surveillance Modeling Network (CISNET) models were evaluated. Lung cancer incidence, mortality, and stage distributions were compared across 4 theoretical scenarios to assess model assumptions regarding 1) sojourn times, 2) stage-specific sensitivities, and 3) screening-induced lung cancer mortality reductions. Analyses were stratified by sex and smoking behavior. RESULTS: Most cancers had sojourn times <5 y (model range [MR]; lowest to highest value across models: 83.5%-98.7% of cancers). However, cancer aggressiveness still varied across models, as demonstrated by differences in proportions of cancers with sojourn times <2 y (MR: 42.5%-64.6%) and 2 to 4 y (MR: 28.8%-43.6%). Stage-specific sensitivity varied, particularly for stage I (MR: 31.3%-91.5%). Screening reduced stage IV incidence in most models for 1 y postscreening; increased sensitivity prolonged this period to 2 to 5 y. Screening-induced lung cancer mortality reductions among lung cancers detected at screening ranged widely (MR: 14.6%-48.9%), demonstrating variations in modeled treatment effectiveness of screen-detected cases. All models assumed longer sojourn times and greater screening-induced lung cancer mortality reductions for women. Models assuming differences in cancer epidemiology by smoking behaviors assumed shorter sojourn times and lower screening-induced lung cancer mortality reductions for heavy smokers. CONCLUSIONS: Model-based personalized screening recommendations are primarily driven by assumptions regarding sojourn times (favoring longer intervals for groups more likely to develop less aggressive cancers), sensitivity (higher sensitivities favoring longer intervals), and screening-induced mortality reductions (greater reductions favoring shorter intervals). IMPLICATIONS: Models suggest longer screening intervals may be feasible and benefits may be greater for women and light smokers. HIGHLIGHTS: Natural-history models are increasingly used to inform lung cancer screening, but causes for variations between models are difficult to assess.This is the first evaluation of these causes and their impact on personalized screening recommendations through easily interpretable metrics.Models vary regarding sojourn times, stage-specific sensitivities, and screening-induced lung cancer mortality reductions.Model outcomes were similar in predicting greater screening benefits for women and potentially light smokers. Longer screening intervals may be feasible for women and light smokers.

COVID-related disruptions to colorectal cancer screening, diagnosis, and treatment could increase cancer Burden in Australia and Canada: A modelling study.

COVID-19 disrupted cancer control worldwide, impacting preventative screening, diagnoses, and treatment services. This modelling study estimates the impact of disruptions on colorectal cancer cases and deaths in Canada and Australia, informed by data on screening, diagnosis, and treatment procedures. Modelling was used to estimate short- and long-term effects on colorectal cancer incidence and mortality, including ongoing impact of patient backlogs. A hypothetical mitigation strategy was simulated, with diagnostic and treatment capacities increased by 5% from 2022 to address backlogs. Colorectal cancer screening dropped by 40% in Canada and 6.3% in Australia in 2020. Significant decreases to diagnostic and treatment procedures were also observed in Australia and Canada, which were estimated to lead to additional patient wait times. These changes would lead to an estimated increase of 255 colorectal cancer cases and 1,820 colorectal cancer deaths in Canada and 234 cases and 1,186 deaths in Australia over 2020-2030; a 1.9% and 2.4% increase in mortality, respectively, vs a scenario with no screening disruption or diagnostic/treatment delays. Diagnostic and treatment capacity mitigation would avert 789 and 350 deaths in Canada and Australia, respectively. COVID-related disruptions had a significant impact on colorectal cancer screening, diagnostic, and treatment procedures in Canada and Australia. Modelling demonstrates that downstream effects on disease burden could be substantial. However, backlogs can be managed and deaths averted with even small increases to diagnostic and treatment capacity. Careful management of resources can improve patient outcomes after any temporary disruption, and these results can inform targeted approaches early detection of cancers.

The impact on clinical outcomes and healthcare resources from discontinuing colonoscopy surveillance subsequent to low-risk adenoma removal: A simulation study using the OncoSim-Colorectal model.

OBJECTIVE: To estimate the impact on clinical outcomes and healthcare resource use from recommending that patients with 1-2 low-risk adenomas (LRAs) return to routine fecal immunochemical test (FIT) screening instead of surveillance colonoscopy, from a Canadian provincial healthcare system perspective. METHODS: The OncoSim-Colorectal microsimulation model simulated average-risk individuals eligible for FIT-based colorectal cancer (CRC) screening in Alberta, Canada. We simulated two surveillance strategies that applied to individuals with 1-2 LRAs (<10 mm) removed as part of the average risk CRC screening program: (a) Surveillance colonoscopy (status quo) and (b) return to FIT screening (new strategy); both at 5 years after polypectomy. A 75 ng/mL FIT positivity threshold was used in the base case. The simulations projected average annual CRC outcomes and healthcare resource use from 2023 to 2042. We conducted alternative scenarios and sensitivity analyses on key variables. RESULTS: Returning to FIT screening (versus surveillance colonoscopy) after polypectomy was projected to have minimal impact on long-term CRC incidence and deaths (not statistically significant). There was a projected decrease of one (4%) major bleeding event and seven (5%) perforation events per year. There was a projected increase of 4800 (1.5%) FIT screens, decrease of 3900 (5.1%) colonoscopies, and a decrease of $3.4 million (1.2%) in total healthcare costs per year, on average. The annual colonoscopies averted and healthcare cost savings increased over time. Results were similar in the alternative scenarios and sensitivity analyses. CONCLUSIONS: Returning to FIT screening would have similar clinical outcomes as surveillance colonoscopy but could reduce colonoscopy demand and healthcare costs.

Potential global loss of life expected due to COVID-19 disruptions to organised colorectal cancer screening.

Background: Screening for colorectal cancer (CRC) decreases cancer burden through removal of precancerous lesions and early detection of cancer. The COVID-19 pandemic has disrupted organised CRC screening programs worldwide, with some programs completely suspending screening and others experiencing significant decreases in participation and diagnostic follow-up. This study estimated the global impact of screening disruptions on CRC outcomes, and potential effects of catch-up screening. Methods: Organised screening programs were identified in 29 countries, and data on participation rates and COVID-related changes to screening in 2020 were extracted where available. Four independent microsimulation models (ASCCA, MISCAN-Colon, OncoSim, and Policy1-Bowel) were used to estimate the long-term impact on CRC cases and deaths, based on decreases to screening participation in 2020. For countries where 2020 participation data were not available, changes to screening were approximated based on excess mortality rates. Catch-up strategies involving additional screening in 2021 were also simulated. Findings: In countries for which direct data were available, organised CRC screening volumes at a country level decreased by an estimated 1.3-40.5% in 2020. Globally, it is estimated that COVID-related screening decreases led to a deficit of 7.4 million fewer faecal screens performed in 2020. In the absence of any organised catch-up screening, this would lead to an estimated 13,000 additional CRC cases and 7,900 deaths globally from 2020 to 2050; 79% of the additional cases and 85% of additional deaths could have been prevented with catch-up screening, respectively. Interpretation: COVID-19-related disruptions to screening will cause excess CRC cases and deaths, but appropriately implemented catch-up screening could have reduced the burden by over 80%. Careful management of any disruption is key to improving the resilience of colorectal cancer screening programs. Funding: The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by Cancer Council New South Wales, Health Canada, and Dutch National Institute for Public Health and Environment.

Long-term projections of cancer incidence and mortality in Canada: The OncoSim All Cancers Model.

Using the OncoSim All Cancers Model, we estimated the annual cancer incidence, mortality and cancer management costs in Canada from 2020 to 2040. Incidence for each cancer type was estimated from logistic regression analyses of the Canadian Cancer Registry (1992-2017), with province/territory, sex, five-year age groups and year as covariates. Deaths were estimated by sex and tumour site for cancers diagnosed between 2000 and 2017 (deaths to the end of 2017). The total cost of a cancer type was the sum of costs for individuals across four phases of cancer care. The projections presented in this study were generated based on a simulation of 32 million cases. The OncoSim All Cancers Model projects a 40% increase in the overall number of incident cancer cases from 2020 to 2040. The number of the four most commonly diagnosed cancers in Canada (breast, colorectal, lung, and prostate) are projected to increase annually. The overall number of cancer deaths is projected to increase by 44% from 2020 to 2040. More cancer deaths are projected in males than in females. The age-standardized mortality rate is expected to remain relatively stable over time. Overall cancer management costs are projected to increase from $20.6B in 2020 to $31.4B in 2040. Due mainly to an aging population and population growth in Canada, we estimate that cancer incidence, mortality and cancer management costs will increase considerably between 2020 and 2040. These results highlight the importance of planning for increasing investment and capacity in cancer control.

The Burden of Health-Related Out-of-Pocket Cancer Costs in Canada: A Case-Control Study Using Linked Data.

BACKGROUND: The burden of out-of-pocket costs among cancer patients/survivors in Canada is not well understood. The objective of this study was to examine the health-related out-of-pocket cost burden experienced by households with a cancer patient/survivor compared to those without, examine the components of health-related costs and determine who experiences a greater burden. DATA AND METHODS: This study used a data linkage between the Survey of Household Spending and the Canadian Cancer Registry to identify households with a cancer patient/survivor (cases) and those without (controls). The out-of-pocket burden (out-of-pocket costs measured relative to household income) and mean costs were described and regression analyses examined the characteristics associated with the household out-of-pocket burden and annual out-of-pocket costs. RESULTS: The health-related out-of-pocket cost burden and annual costs measured in households with a cancer patient/survivor were 3.08% (95% CI: 2.55-3.62%) and CAD 1600 (95% CI: 1456-1759), respectively, compared to a burden of 2.84% (95% CI: 2.31-3.38) and annual costs of CAD 1511 (95% CI: 1377-1659) measured in control households, respectively. Households with a colorectal cancer patient/survivor had a significantly higher out-of-pocket burden compared to controls (mean difference: 1.0%, 95% CI: 0.18, 0.46). Among both cases and controls, the lowest income quintile households experienced the highest health-related out-of-pocket cost burden. INTERPRETATION: Within a universal health care system, it is still relevant to monitor health-related out-of-pocket spending that is not covered by existing insurance mechanisms; however, this is not routinely assessed in Canada. We demonstrate the feasibility of measuring such costs in households with a cancer patient/survivor using routinely collected data. While the burden and annual health-related out-of-pocket costs of households with a cancer patient/survivor were not significantly higher than control households in this study, the routine measurement of out-of-pocket costs in Canada could be systemized, providing a novel, system-level, equity-informed performance indicator, which is relevant for monitoring inequities in the burden of out-of-pocket costs.

Efficacy of Risk Prediction Models and Thresholds to Select Patients for Lung Cancer Screening.

PurposeScreening for lung cancer is recommended to reduce lung cancer mortality, but there is no consensus on patient selection for screening in Canada. Risk prediction models are more efficacious than the screening recommendations of the Canadian Task Force on Preventive Health Care (CTFPHC), but it remains to be determined which model and threshold are optimal. MethodsWe retrospectively applied the PLCOm2012, PLCOall2014 and LLPv2 risk prediction models to 120 lung cancer patients from a Canadian province, at risk thresholds of ≥ 1.51% and ≥ 2.00%, to determine screening eligibility at time of diagnosis. OncoSim modelling was used to compare these risk thresholds. ResultsSensitivities of the risk prediction models at a threshold of ≥ 1.51% were similar with 93 (77.5%), 96 (80.0%), and 97 (80.8%) patients selected for screening, respectively. The PLCOm2012 and PLCOall2014 models selected significantly more patients for screening at a ≥ 1.51% threshold. The OncoSim simulation model estimated that the ≥ 1.51% threshold would detect 4 more cancers per 100 000 people than the ≥ 2.00% threshold. All risk prediction models, at both thresholds, achieved greater sensitivity than CTFPHC recommendations, which selected 56 (46.7%) patients for screening. ConclusionCommonly considered lung cancer screening risk thresholds (≥1.51% and ≥2.00%) are more sensitive than the CTFPHC 30-pack-years criterion to detect lung cancer. A lower risk threshold would achieve a larger population impact of lung cancer screening but would require more resources. Patients with limited or no smoking history, young patients, and patients with no history of COPD may be missed regardless of the model chosen.

The Economic Burden of Cancer in Canada from a Societal Perspective.

Cancer patients and their families experience considerable financial hardship; however, the current published literature on the economic burden of cancer at the population level has typically focused on the costs from the health system's perspective. This study aims to estimate the economic burden of cancer in Canada from a societal perspective. The analysis was conducted using the OncoSim-All Cancers model, a Canadian cancer microsimulation model. OncoSim simulates cancer incidence and deaths using incidence and mortality data from the Canadian Cancer Registry and demography projections from Statistics Canada. Using a phase-based costing framework, we estimated the economic burden of cancer in Canada in 2021 by incorporating published direct health system costs and patients' and families' costs (out-of-pocket costs, time costs, indirect costs). From a societal perspective, cancer-related costs were CAD 26.2 billion in Canada in 2021; 30% of costs were borne by patients and their families. The economic burden was the highest in the first year after cancer was diagnosed (i.e., initial care). During this time, patients and families' costs amounted to almost CAD 4.8 billion in 2021. This study provides a comprehensive estimate of the economic burden of cancer, which could inform cost-benefit analyses of proposed cancer prevention interventions.

A Cost Analysis of Pulse Oximetry as a Determinant in the Decision to Admit Infants With Mild to Moderate Bronchiolitis.

OBJECTIVES: A previous randomized controlled trial showed that artificially elevating the pulse oximetry display resulted in fewer hospitalizations with no worse outcomes. This suggests that management decisions based mainly on pulse oximetry may unnecessarily increase health care costs. This study assessed the incremental cost of altered relative to true oximetry in infants with mild to moderate bronchiolitis. METHODS: A cost analysis was undertaken from the health care system and societal perspectives using patient-level data from the randomized controlled trial, with a 5-day time horizon after emergency department visit. Infants aged 4 weeks to 12 months with mild to moderate bronchiolitis were randomized to pulse oximetry measurements with true or altered saturation values displayed by artificially increasing saturation 3% points above true values. Direct and indirect health care costs were measured. Sensitivity analyses were performed to assess parameter uncertainty. RESULTS: From the health care system perspective, the average cost per patient was Can $1155 for altered oximetry and $1967 for true oximetry, with a net savings of $812. From a societal perspective, the average cost per patient was $1559 for altered oximetry and $2473 for true oximetry, with a net savings of $914. Probabilistic analyses demonstrated that altered oximetry remained the less costly study group, with an average savings of $810 (95% confidence interval, $748-$872) from the health care system perspective and $910 (95% confidence interval, $848-$973) from the societal system perspective. CONCLUSIONS: Reliance on oximetry as a major determinant in the decision to hospitalize infants with mild to moderate bronchiolitis is associated with significantly greater costs.

Temporal trends in place of death for end-of-life patients: Evidence from Toronto, Canada.

Understanding the temporal trends in the place of death among patients in receipt of home-based palliative care can help direct health policies and planning of health resources. This paper aims to assess the temporal trends in place of death and its determinants over the past decade for patients receiving home-based palliative care. This paper also examines the impact of early referral to home-based palliative care services on patient's place of death. Survey data collected in a home-based end-of-life care program in Toronto, Canada from 2005 to 2015 were analysed using a multivariate logistic model. The results suggest that the place of death for patients in receipt of home-based palliative care has changed over time, with more patients dying at home over 2006-2015 when compared to 2005. Also, early referral to home-based palliative care services may not increase a patient's likelihood of home death. Understanding the temporal shifts of place of death and the associated factors is essential for effective improvements in home-based palliative care programs and the development of end-of-life care policies.

Does informal care impact utilisation of home-based formal care services among end-of-life patients? A decade of evidence from Ontario, Canada.

Understanding how informal care impacts formal care utilisation for home-based end-of-life patients is an important policy- and practice-relevant question. This paper aims to assess the relationship between informal and formal home care among home-based end-of-life patients and how this relationship has changed over the last decade and over the end-of-life trajectory. We focus on informal care provided by family members or friends, and three types of home-based formal care services: care by personal support workers, physician visits, and nurse visits. Using survey data collected in a home-based end-of-life care programme in Ontario, Canada from 2005 to 2016, we build a two-part utilisation model analysing both the propensity to use each type of formal care and the amount of formal care received by patients. The results suggest that informal care is a substitute for care by personal support workers, but a complement to physician visits and nurse visits. In the case of nurse visits, an increased complementary effect is observed in more recent years. For home-based physician and nurse visits, the complementary effect grows with patient's proximity to death. These results highlight the complexity of the relationship between informal and formal care among home-based end-of-life patients. Decision-makers need to take into account the relationship between informal care and different types of formal services when introducing future policies.

Nivolumab in the Treatment of Metastatic Renal Cell Carcinoma: A Cost-Utility Analysis.

INTRODUCTION: Nivolumab improves overall survival and health-related quality of life compared with everolimus in metastatic renal cell carcinoma (mRCC). This study assesses the cost-utility of nivolumab from the Canadian health care payer perspective. MATERIALS AND METHODS: To evaluate the cost-utility of nivolumab, a Markov cohort model that incorporated data from the phase 3 CheckMate-025 trial and other sources was developed. The incremental cost per quality-adjusted life month (QALM) gained for nivolumab was calculated. A lifetime horizon was used in the base-case with costs and outcomes discounted 3% annually. The probabilities of progression and death from cancer and utility values were captured from the CheckMate-025 trial. Expected costs were based on Ontario fees and other sources. Scenario and sensitivity analyses were conducted to assess uncertainty. RESULTS: Compared with everolimus, nivolumab provided an additional 4.2 QALM at an incremental cost of $34,153. The resulting incremental cost-effectiveness ratio was $8138/QALM gained. Assuming a willingness to pay (WTP) threshold of $4167/QALM ($50,000/quality-adjusted life-year [QALY]), nivolumab was not cost-effective. In 1-way sensitivity analyses, nivolumab cost, median overall survival, and median treatment duration were sensitive to changes. Furthermore, the results were sensitive to the WTP threshold and nivolumab became a cost-effective strategy with a WTP of $8333/QALM ($100,000/QALY). CONCLUSIONS: Compared with everolimus, nivolumab is unlikely to be cost-effective for the treatment of mRCC from a Canadian health care perspective with its current price assuming a WTP of $50,000/QALY. Although mRCC patients derive a meaningful clinical benefit from nivolumab, considerations should be given to avoid drug wastage and increase the WTP threshold to render this strategy more affordable.

Biomarkers of Secondhand Smoke Exposure in Waterpipe Tobacco Venue Employees in Istanbul, Moscow, and Cairo.

Background: Most smoke-free legislation to reduce secondhand smoke (SHS) exposure exempts waterpipe (hookah) smoking venues. Few studies have examined SHS exposure in waterpipe venues and their employees. Methods: We surveyed 276 employees of 46 waterpipe tobacco venues in Istanbul, Moscow, and Cairo. We interviewed venue managers and employees and collected biological samples from employees to measure exhaled carbon monoxide (CO), hair nicotine, saliva cotinine, urine cotinine, urine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), and urine 1-hydroxypyrene glucuronide (1-OHPG). We estimated adjusted geometric mean ratios (GMR) of each SHS biomarker by employee characteristics and indoor air SHS measures. Results: There were 73 nonsmoking employees and 203 current smokers of cigarettes or waterpipe. In nonsmokers, the median (interquartile) range concentrations of SHS biomarkers were 1.1 (0.2, 40.9) µg/g creatinine urine cotinine, 5.5 (2, 15) ng/mL saliva cotinine, 0.95 (0.36, 5.02) ng/mg hair nicotine, 1.48 (0.98, 3.97) pg/mg creatinine urine NNAL, 0.54 (0.25, 0.97) pmol/mg creatinine urine 1-OHPG, and 1.67 (1.33, 2.33) ppm exhaled CO. An 8-hour increase in work hours was associated with higher urine cotinine (GMR: 1.68, 95% CI: 1.20, 2.37) and hair nicotine (GMR: 1.22, 95% CI: 1.05, 1.43). Lighting waterpipes was associated with higher saliva cotinine (GMR: 2.83, 95% CI: 1.05, 7.62). Conclusions: Nonsmoking employees of waterpipe tobacco venues were exposed to high levels of SHS, including measurable levels of carcinogenic biomarkers (tobacco-specific nitrosamines and PAHs). Implications: Smoke-free regulation should be extended to waterpipe venues to protect nonsmoking employees and patrons from the adverse health effects of SHS.

Utilisation of home-based physician, nurse and personal support worker services within a palliative care programme in Ontario, Canada: trends over 2005-2015.

With health system restructuring in Canada and a general preference by care recipients and their families to receive palliative care at home, attention to home-based palliative care continues to increase. A multidisciplinary team of health professionals is the most common delivery model for home-based palliative care in Canada. However, little is known about the changing temporal trends in the propensity and intensity of home-based palliative care. The purpose of this study was to assess the propensity to use home-based palliative care services, and once used, the intensity of that use for three main service categories: physician visits, nurse visits and care by personal support workers (PSWs) over the last decade. Three prospective cohort data sets were used to track changes in service use over the period 2005 to 2015. Service use for each category was assessed using a two-part model, and a Heckit regression was performed to assess the presence of selectivity bias. Service propensity was modelled using multivariate logistic regression analysis and service intensity was modelled using log-transformed ordinary least squares regression analysis. Both the propensity and intensity to use home-based physician visits and PSWs increased over the last decade, while service propensity and the intensity of nurse visits decreased. Meanwhile, there was a general tendency for service propensity and intensity to increase as the end of life approached. These findings demonstrate temporal changes towards increased use of home-based palliative care, and a shift to substitute care away from nursing to less expensive forms of care, specifically PSWs. These findings may provide a general idea of the types of services that are used more intensely and require more resources from multidisciplinary teams, as increased use of home-based palliative care has placed dramatic pressures on the budgets of local home and community care organisations.

Secondhand smoke in waterpipe tobacco venues in Istanbul, Moscow, and Cairo.

OBJECTIVE: The prevalence of waterpipe tobacco smoking has risen in recent decades. Controlled studies suggest that waterpipe secondhand smoke (SHS) contains similar or greater quantities of toxicants than cigarette SHS, which causes significant morbidity and mortality. Few studies have examined SHS from waterpipe tobacco in real-world settings. The purpose of this study was to quantify SHS exposure levels and describe the characteristics of waterpipe tobacco venues. METHODS: In 2012-2014, we conducted cross-sectional surveys of 46 waterpipe tobacco venues (9 in Istanbul, 17 in Moscow, and 20 in Cairo). We administered venue questionnaires, conducted venue observations, and sampled indoor air particulate matter (PM2.5) (N=35), carbon monoxide (CO) (N=23), particle-bound polycyclic aromatic hydrocarbons (p-PAHs) (N=31), 4-methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) (N=43), and air nicotine (N=46). RESULTS: Venue characteristics and SHS concentrations were highly variable within and between cities. Overall, we observed a mean (standard deviation (SD)) of 5 (5) waterpipe smokers and 5 (3) cigarette smokers per venue. The overall median (25th percentile, 75th percentile) of venue mean air concentrations was 136 (82, 213) µg/m(3) for PM2.5, 3.9 (1.7, 22) ppm for CO, 68 (33, 121) ng/m(3) for p-PAHs, 1.0 (0.5, 1.9) ng/m(3) for NNK, and 5.3 (0.7, 14) µg/m(3) for nicotine. PM2.5, CO, and p-PAHs concentrations were generally higher in venues with more waterpipe smokers and cigarette smokers, although associations were not statistically significant. CONCLUSION: High concentrations of SHS constituents known to cause health effects indicate that indoor air quality in waterpipe tobacco venues may adversely affect the health of employees and customers.