Predicted long-term impact of COVID-19 pandemic-related care delays on cancer mortality in Canada.

The COVID-19 pandemic has affected cancer care worldwide. This study aimed to estimate the long-term impacts of cancer care disruptions on cancer mortality in Canada using a microsimulation model. The model simulates cancer incidence and survival using cancer incidence, stage at diagnosis and survival data from the Canadian Cancer Registry. We modeled reported declines in cancer diagnoses and treatments recorded in provincial administrative datasets in March 2020 to June 2021. Based on the literature, we assumed that diagnostic and treatment delays lead to a 6% higher rate of cancer death per 4-week delay. After June 2021, we assessed scenarios where cancer treatment capacity returned to prepandemic levels, or to 10% higher or lower than prepandemic levels. Results are the median predictions of 10 stochastic simulations. The model predicts that cancer care disruptions during the COVID-19 pandemic could lead to 21 247 (2.0%) more cancer deaths in Canada in 2020 to 2030, assuming treatment capacity is recovered to 2019 prepandemic levels in 2021. This represents 355 172 life years lost expected due to pandemic-related diagnostic and treatment delays. The largest number of expected excess cancer deaths was predicted for breast, lung and colorectal cancers, and in the provinces of Ontario, Québec and British Columbia. Diagnostic and treatment capacity in 2021 onward highly influenced the number of cancer deaths over the next decade. Cancer care disruptions during the COVID-19 pandemic could lead to significant life loss; however, most of these could be mitigated by increasing diagnostic and treatment capacity in the short-term to address the service backlog.

The impact of stratifying by family history in colorectal cancer screening programs.

In the province-wide colorectal cancer (CRC) screening program in Ontario, Canada, individuals with a family history of CRC are offered colonoscopy screening and those without are offered guaiac fecal occult blood testing (gFOBT, Hemoccult II). We used microsimulation modeling to estimate the cumulative number of CRC deaths prevented and colonoscopies performed between 2008 and 2038 with this family history-based screening program, compared to a regular gFOBT program. In both programs, we assumed screening uptake increased from 30% (participation level in 2008 before the program was launched) to 60%. We assumed that 11% of the population had a family history, defined as having at least one first-degree relative diagnosed with CRC. The programs offered screening between age 50 and 74 years, every two years for gFOBT, and every ten years for colonoscopy. Compared to opportunistic screening (2008 participation level kept constant at 30%), the gFOBT program cumulatively prevented 6,700 more CRC deaths and required 570,000 additional colonoscopies by 2038. The family history-based screening program increased these numbers to 9,300 and 1,100,000, a 40% and 93% increase, respectively. If biennial gFOBT was replaced with biennial fecal immunochemical test (FIT), annual Hemoccult Sensa or five-yearly sigmoidoscopy screening, both the added benefits and colonoscopies required would decrease. A biennial gFOBT screening program that identifies individuals with a family history of CRC and recommends them to undergo colonoscopy screening would prevent 40% (range in sensitivity analyses: 20-51%) additional deaths while requiring 93% (range: 43-116%) additional colonoscopies, compared to a regular gFOBT screening program.

The projected health and economic impact of increased colorectal cancer screening participation among Canadians by income quintile.

OBJECTIVES: Disparities in colorectal cancer (CRC) screening uptake by socioeconomic status have been observed in Canada. We used the OncoSim-Colorectal model to evaluate the health and economic outcomes associated with increasing the participation rates of CRC screening programs to 60% among Canadians in different income quintiles. METHODS: Baseline CRC screening participation rates were obtained from the 2017 Canadian Community Health Survey. The survey participants were categorized into income quintiles using their reported household income and 2016 Canadian Census income quintile thresholds. Within each quintile, the participation rate was the proportion of respondents aged 50-74 who reported having had a fecal test in the past two years. Using the OncoSim-Colorectal model, we simulated an increase in CRC screening uptake to 60% across income quintiles to assess the effects on CRC incidence, mortality, and associated economic costs from 2024 to 2073. RESULTS: Increasing CRC screening participation rates to 60% across all income quintiles would prevent 69,100 CRC cases and 36,600 CRC deaths over 50 years. The improvement of clinical outcomes would also translate to increased person-years and health-adjusted person-years. The largest impact was observed in the lowest income group, with 22,200 cases and 11,700 deaths prevented over 50 years. Increased participation could lead to higher screening costs ($121 million CAD more per year) and lower treatments costs ($95 million CAD less per year), averaged over the period 2024-2073. CONCLUSION: Increased screening participation will improve clinical outcomes across all income groups while alleviating associated treatment costs. The benefits of increased participation will be strongest among the lowest income quintile.

RéSUMé: OBJECTIFS: Des disparités dans le recours au dépistage du cancer colorectal (CCR) selon le statut socioéconomique sont observées au Canada. Nous avons utilisé le modèle OncoSim-Colorectal pour évaluer les résultats cliniques et économiques associés à une augmentation à 60 % des taux de participation aux programmes de dépistage du CCR chez les Canadiennes et les Canadiens appartenant à différents quintiles de revenu. MéTHODE: Les taux de participation de référence au dépistage du CCR provenaient de l'Enquête sur la santé dans les collectivités canadiennes de 2017. Nous avons catégorisé les participantes et les participants de l'enquête en quintiles de revenu à l'aide du revenu du ménage déclaré et des seuils de quintiles de revenu du Recensement du Canada de 2016. Dans chaque quintile, le taux de participation était la proportion des répondantes et des répondants de 50 à 74 ans ayant dit avoir subi un test fécal au cours des deux années antérieures. À l'aide du modèle OncoSim-Colorectal, nous avons simulé une augmentation à 60 % du recours au dépistage du CCR dans tous les quintiles de revenu pour en évaluer les effets sur l'incidence, la mortalité et les coûts économiques associés du CCR entre 2024 et 2073. RéSULTATS: L'augmentation des taux de participation au dépistage du CCR à 60 % dans tous les quintiles de revenu préviendrait 69 100 cas de CCR et 36 600 décès dus au CCR sur 50 ans. L'amélioration des résultats cliniques se traduirait aussi par une augmentation des personnes-années et des personnes-années corrigées en fonction de la santé. Nous avons observé l'effet le plus marquant dans la catégorie de revenu inférieure, avec la prévention de 22 200 cas et de 11 700 décès sur 50 ans. La participation accrue pourrait entraîner une hausse des coûts de dépistage (121 millions de dollars canadiens de plus par année) et une baisse des coûts de traitement (95 millions de dollars canadiens de moins par année), en moyenne, sur la période de 2024 à 2073. CONCLUSION: La participation accrue au dépistage améliorera les résultats cliniques dans toutes les catégories de revenu tout en réduisant les coûts de traitement associés. Les avantages d'une participation accrue seront les plus marquants dans le quintile de revenu inférieur.

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.

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.

Prioritisation of colonoscopy services in colorectal cancer screening programmes to minimise impact of COVID-19 pandemic on predicted cancer burden: A comparative modelling study.

OBJECTIVES: Colorectal cancer (CRC) screening with a faecal immunochemical test (FIT) has been disrupted in many countries during the COVID-19 pandemic. Performing catch-up of missed screens while maintaining regular screening services requires additional colonoscopy capacity that may not be available. This study aimed to compare strategies that clear the screening backlog using limited colonoscopy resources. METHODS: A range of strategies were simulated using four country-specific CRC natural-history models: Adenoma and Serrated pathway to Colorectal CAncer (ASCCA) and MIcrosimulation SCreening ANalysis for CRC (MISCAN-Colon) (both in the Netherlands), Policy1-Bowel (Australia) and OncoSim (Canada). Strategies assumed a 3-month screening disruption with varying recovery period lengths (6, 12, and 24 months) and varying FIT thresholds for diagnostic colonoscopy. Increasing the FIT threshold reduces the number of referrals to diagnostic colonoscopy. Outcomes for each strategy were colonoscopy demand and excess CRC-related deaths due to the disruption. RESULTS: Performing catch-up using the regular FIT threshold in 6, 12 and 24 months could prevent most excess CRC-related deaths, but required 50%, 25% and 12.5% additional colonoscopy demand, respectively. Without exceeding usual colonoscopy demand, up to 60% of excess CRC-related deaths can be prevented by increasing the FIT threshold for 12 or 24 months. Large increases in FIT threshold could lead to additional deaths rather than preventing them. CONCLUSIONS: Clearing the screening backlog in 24 months could avert most excess CRC-related deaths due to a 3-month disruption but would require a small increase in colonoscopy demand. Increasing the FIT threshold slightly over 24 months could ease the pressure on colonoscopy resources.

The OncoSim-Breast Cancer Microsimulation Model.

BACKGROUND: OncoSim-Breast is a Canadian breast cancer simulation model to evaluate breast cancer interventions. This paper aims to describe the OncoSim-Breast model and how well it reproduces observed breast cancer trends. METHODS: The OncoSim-Breast model simulates the onset, growth, and spread of invasive and ductal carcinoma in situ tumours. It combines Canadian cancer incidence, mortality, screening program, and cost data to project population-level outcomes. Users can change the model input to answer specific questions. Here, we compared its projections with observed data. First, we compared the model's projected breast cancer trends with the observed data in the Canadian Cancer Registry and from Vital Statistics. Next, we replicated a screening trial to compare the model's projections with the trial's observed screening effects. RESULTS: OncoSim-Breast's projected incidence, mortality, and stage distribution of breast cancer were close to the observed data in the Canadian Cancer Registry and from Vital Statistics. OncoSim-Breast also reproduced the breast cancer screening effects observed in the UK Age trial. CONCLUSIONS: OncoSim-Breast's ability to reproduce the observed population-level breast cancer trends and the screening effects in a randomized trial increases the confidence of using its results to inform policy decisions related to early detection of breast cancer.

Impact of the COVID-19 pandemic on faecal immunochemical test-based colorectal cancer screening programmes in Australia, Canada, and the Netherlands: a comparative modelling study.

BACKGROUND: Colorectal cancer screening programmes worldwide have been disrupted during the COVID-19 pandemic. We aimed to estimate the impact of hypothetical disruptions to organised faecal immunochemical test-based colorectal cancer screening programmes on short-term and long-term colorectal cancer incidence and mortality in three countries using microsimulation modelling. METHODS: In this modelling study, we used four country-specific colorectal cancer microsimulation models-Policy1-Bowel (Australia), OncoSim (Canada), and ASCCA and MISCAN-Colon (the Netherlands)-to estimate the potential impact of COVID-19-related disruptions to screening on colorectal cancer incidence and mortality in Australia, Canada, and the Netherlands annually for the period 2020-24 and cumulatively for the period 2020-50. Modelled scenarios varied by duration of disruption (3, 6, and 12 months), decreases in screening participation after the period of disruption (0%, 25%, or 50% reduction), and catch-up screening strategies (within 6 months after the disruption period or all screening delayed by 6 months). FINDINGS: Without catch-up screening, our analysis predicted that colorectal cancer deaths among individuals aged 50 years and older, a 3-month disruption would result in 414-902 additional new colorectal cancer diagnoses (relative increase 0·1-0·2%) and 324-440 additional deaths (relative increase 0·2-0·3%) in the Netherlands, 1672 additional diagnoses (relative increase 0·3%) and 979 additional deaths (relative increase 0·5%) in Australia, and 1671 additional diagnoses (relative increase 0·2%) and 799 additional deaths (relative increase 0·3%) in Canada between 2020 and 2050, compared with undisrupted screening. A 6-month disruption would result in 803-1803 additional diagnoses (relative increase 0·2-0·4%) and 678-881 additional deaths (relative increase 0·4-0·6%) in the Netherlands, 3552 additional diagnoses (relative increase 0·6%) and 1961 additional deaths (relative increase 1·0%) in Australia, and 2844 additional diagnoses (relative increase 0·3%) and 1319 additional deaths (relative increase 0·4%) in Canada between 2020 and 2050, compared with undisrupted screening. A 12-month disruption would result in 1619-3615 additional diagnoses (relative increase 0·4-0·9%) and 1360-1762 additional deaths (relative increase 0·8-1·2%) in the Netherlands, 7140 additional diagnoses (relative increase 1·2%) and 3968 additional deaths (relative increase 2·0%) in Australia, and 5212 additional diagnoses (relative increase 0·6%) and 2366 additional deaths (relative increase 0·8%) in Canada between 2020 and 2050, compared with undisrupted screening. Providing immediate catch-up screening could minimise the impact of the disruption, restricting the relative increase in colorectal cancer incidence and deaths between 2020 and 2050 to less than 0·1% in all countries. A post-disruption decrease in participation could increase colorectal cancer incidence by 0·2-0·9% and deaths by 0·6-1·6% between 2020 and 2050, compared with undisrupted screening. INTERPRETATION: Although the projected effect of short-term disruption to colorectal cancer screening is modest, such disruption will have a marked impact on colorectal cancer incidence and deaths between 2020 and 2050 attributable to missed screening. Thus, it is crucial that, if disrupted, screening programmes ensure participation rates return to previously observed rates and provide catch-up screening wherever possible, since this could mitigate the impact on colorectal cancer deaths. FUNDING: Cancer Council New South Wales, Health Canada, and Dutch National Institute for Public Health and Environment.

Association between air travel and importation of chikungunya into the USA.

Background: During infectious disease outbreaks with pandemic potential, the number of air passengers travelling from the outbreak source to international destinations has been used as a proxy for disease importation risk to new locations. However, evaluations of the validity of this approach are limited. We sought to quantify the association between international air travel and disease importation using the 2014-2016 chikungunya outbreak in the Americas as a case study.Methods: We used country-level chikungunya case data to define a time period of epidemic activity for each of the 45 countries and territories in the Americas reporting outbreaks between 2014 and 2016. For each country, we identified airports within or proximate to areas considered suitable for chikungunya transmission and summed the number of commercial air passengers departing from these airports during the epidemic period to each US state. We used negative binomial models to quantify the association between the number of incoming air passengers from countries experiencing chikungunya epidemics and the annual rate of chikungunya importation into the USA at the state level.Results: We found a statistically significant positive association between passenger flows via airline travel from countries experiencing chikungunya epidemics and the number of imported cases in the USA at the state level (P < 0.0001). Additionally, we found that as the number of arriving airline passengers increased by 10%, the estimated number of imported cases increased by 5.2% (95% CI: 3.0-7.6).Conclusion: This validation study demonstrated that air travel was strongly associated with observed importation of chikungunya cases in the USA and can be a useful proxy for identifying areas at increased risk for disease importation. This approach may be useful for understanding exportation risk of other arboviruses.

Infectious disease implications of large-scale migration of Venezuelan nationals.

Background: The ongoing economic and political crisis in Venezuela has resulted in a collapse of the healthcare system and the re-emergence of previously controlled or eliminated infectious diseases. There has also been an exodus of Venezuelan international migrants in response to the crisis. We sought to describe the infectious disease risks faced by Venezuelan nationals and assess the international mobility patterns of the migrant population. Methods: We synthesized data on recent infectious disease events in Venezuela and among international migrants from Venezuela, as well as on current country of residence among the migrant population. We used passenger-level itinerary data from the International Air Transport Association to evaluate trends in outbound air travel from Venezuela over time. We used two parameter-free mobility models, the radiation and impedance models, to estimate the expected population flows from Venezuelan cities to other major Latin American and Caribbean cities. Results: Outbreaks of measles, diphtheria and malaria have been reported across Venezuela and other diseases, such as HIV and tuberculosis, are resurgent. Changes in migration in response to the crisis are apparent, with an increase in Venezuelan nationals living abroad, despite an overall decline in the number of outbound air passengers. The two models predicted different mobility patterns, but both highlighted the importance of Colombian cities as destinations for migrants and also showed that some migrants are expected to travel large distances. Despite the large distances that migrants may travel internationally, outbreaks associated with Venezuelan migrants have occurred primarily in countries proximate to Venezuela. Conclusions: Understanding where international migrants are relocating is critical, given the association between human mobility and the spread of infectious diseases. In data-limited situations, simple models can be useful for providing insights into population mobility and may help identify areas likely to receive a large number of migrants.

Harms, benefits and costs of fecal immunochemical testing versus guaiac fecal occult blood testing for colorectal cancer screening.

BACKGROUND: The ColonCancerCheck screening program for colorectal cancer (CRC) in Ontario, Canada, is considering switching from biennial guaiac fecal occult blood test (gFOBT) screening between age 50-74 years to the more sensitive, but also less specific fecal immunochemical test (FIT). The aim of this study is to estimate whether the additional benefits of FIT screening compared to gFOBT outweigh the additional costs and harms. METHODS: We used microsimulation modeling to estimate quality adjusted life years (QALYs) gained and costs of gFOBT and FIT, compared to no screening, in a cohort of screening participants. We compared strategies with various age ranges, screening intervals, and cut-off levels for FIT. Cost-efficient strategies were determined for various levels of available colonoscopy capacity. RESULTS: Compared to no screening, biennial gFOBT screening between age 50-74 years provided 20 QALYs at a cost of CAN$200,900 per 1,000 participants, and required 17 colonoscopies per 1,000 participants per year. FIT screening was more effective and less costly. For the same level of colonoscopy requirement, biennial FIT (with a high cut-off level of 200 ng Hb/ml) between age 50-74 years provided 11 extra QALYs gained while saving CAN$333,300 per 1000 participants, compared to gFOBT. Without restrictions in colonoscopy capacity, FIT (with a low cut-off level of 50 ng Hb/ml) every year between age 45-80 years was the most cost-effective strategy providing 27 extra QALYs gained per 1000 participants, while saving CAN$448,300. INTERPRETATION: Compared to gFOBT screening, switching to FIT at a high cut-off level could increase the health benefits of a CRC screening program without considerably increasing colonoscopy demand.

The evaluation and use of economic evidence to inform cancer drug reimbursement decisions in Canada.

BACKGROUND: Cost-effectiveness evidence is increasingly considered in the reimbursement decisions of pharmaceuticals. In some jurisdictions such as the UK and Canada, pharmaceutical manufacturers are required to submit economic evaluations when seeking reimbursement. OBJECTIVES: Our objectives were to describe the role of economic evidence in the cancer drug review process in Canada, and to investigate the nature of problems encountered in the review and interpretation of economic evidence used in the process. DESIGN: We conducted a retrospective review of cancer drug review meeting minutes and reviewers' comments on pharmacoeconomic studies submitted to the oncology drug review process in Canada. DATA SOURCES: We used pharmacoeconomic reviewers' reports and relevant cancer drug review expert advisory committee meeting minutes during the first year of the review process (April 2007 to March 2008). RESULTS: Fifteen economic submissions were reviewed. One-third of the studies had flaws significant enough that the advisory committee could not determine the cost effectiveness of the drugs from the results. The common issues outlined by the reviewers and committee were related to the uncertainty of comparative clinical benefits, quality of life and costs. The reviewers felt that few analyses provided sufficient sensitivity analyses around key variables to assess the robustness of results. Most problems identified by reviewers are simple to fix and do not involve advanced methods. CONCLUSIONS: Canada has a separate review process for making cancer drug funding recommendations, and this process uses both clinical and economic evidence. The committee could not determine the value for money of the drugs from several of the submitted pharmacoeconomic analyses. Transparent analyses and detailed critique of evidence are crucial to the use of economic evidence in reimbursement decisions. Rigorous evaluation is resource intensive and may benefit from a shared drug review process among several jurisdictions.