Strategies to accelerate the elimination of cervical cancer in British Columbia, Canada: a modelling study.

BACKGROUND: To eliminate cervical cancer in Canada by 2040, defined as an annual age-standardized incidence rate (ASIR) lower than 4.0 per 100 000 women, the Canadian Partnership Against Cancer (CPAC) identified 3 priorities for action: increasing human papillomavirus (HPV) vaccine coverage, implementing HPV-based screening and increasing screening participation, and improving follow-up after abnormal screen results. Our objective was to explore the impact of these priorities on the projected time to elimination of cervical cancer in British Columbia. METHODS: We used OncoSim-Cervical, a microsimulation model led and supported by CPAC and developed by Statistics Canada that simulates HPV transmission and the natural history of cervical cancer for the Canadian population. We updated model parameters to reflect BC's historical participation rates and program design. We simulated the transition to HPV-based screening and developed scenarios to explore the additional impact of achieving 90% vaccination coverage, 95% screening recruitment, 90% ontime screening, and 95% follow-up compliance. We projected cervical cancer incidence, ASIR, and year of elimination for the population of BC for 2023-2050. RESULTS: HPV-based screening at current vaccination, participation, and follow-up rates can eliminate cervical cancer by 2034. Increasing on-time screening and follow-up compliance could achieve this target by 2031. Increasing vaccination coverage has a small impact over this time horizon. INTERPRETATION: With the implementation of HPV-based screening, cervical cancer can be eliminated in BC before 2040. Efforts to increase screening participation and follow-up through this transition could potentially accelerate this timeline, but the transition from cytology- to HPV-based screening is fundamental to achieving this goal.

"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.

Real-World Safety of Niraparib for Maintenance Treatment of Ovarian Cancer in Canada.

Niraparib was recently funded in Canada for the maintenance treatment of ovarian cancer following platinum-based chemotherapy. However, the drug's safety profile in the real world remains uncertain. We conducted a cohort study to describe the patient population using niraparib and the proportion that experienced adverse events between June 2019 and December 2022 in four Canadian provinces (Ontario, Alberta, British Columbia [BC], and Quebec). We used administrative data and electronic medical records from Ontario Health, Alberta Health Services, and BC Cancer, and registry data from Exactis Innovation. We summarized baseline characteristics using descriptive statistics and reported safety outcomes using cumulative incidence. We identified 514 patients receiving niraparib. Mean age was 67 years and most were initiated on a daily dose of 100 or 200 mg/day. Grade 3/4 anemia, neutropenia, and thrombocytopenia occurred in 11-16% of the cohort. In Ontario, the three-month cumulative incidence of grade 3/4 thrombocytopenia was 11.6% (95% CI, 8.3-15.4%), neutropenia was 7.1% (95% CI, 4.6-10.4%), and anemia was 11.3% (95% CI, 8.0-15.2%). Cumulative incidences in the remaining provinces were similar. Initial daily dose and proportions of hematological adverse events were low in the real world and may be related to cautious prescribing and close monitoring by clinicians.

Real-World Cost Effectiveness of a Policy of KRAS Testing to Inform Cetuximab or Panitumumab for Third-Line Therapy of Metastatic Colorectal Cancer in British Columbia, Canada.

BACKGROUND: Cetuximab and panitumumab, two anti-EGFR therapies, are widely used for third-line therapy of metastatic colorectal cancer (mCRC) with wild-type KRAS, but there remains uncertainty around their cost effectiveness. The objective of this analysis was to conduct a real-world cost-effectiveness analysis of the policy change introducing KRAS testing and third-line anti-EGFR therapy mCRC in British Columbia (BC), Canada. METHODS: We conducted secondary analysis of administrative data for a cohort of mCRC patients treated in BC in 2006-2015. Patients potentially eligible for KRAS testing and third-line therapy after the policy change (July 2009) were matched 2:1 to pre-policy patients using genetic matching on propensity score and baseline covariates. Costs and survival time were calculated over an 8-year time horizon, with bootstrapping to characterize uncertainty around endpoints. Cost effectiveness was expressed using incremental cost-effectiveness ratios (ICER) and the probability of cost effectiveness at a range of thresholds. RESULTS: The cohort included 1757 mCRC patients (n = 456 pre-policy and n = 1304 post-policy; of those, n = 420 received cetuximab or panitumumab). There was a significant increase in survival and cost following the policy change. Adoption of KRAS testing and anti-EGFR therapy had an ICER of CA$73,759 per life-year gained (LYG) (95% CI 46,133-186,446). In scenario analysis, a reduction in cetuximab and panitumumab cost of at least 50% was required to make the policy change cost effective at a threshold of CA$50,000/LYG. CONCLUSION: A policy of third-line anti-EGFR therapy informed by KRAS testing may be considered cost effective at thresholds above CA$70,000/LYG. Reduction in drug costs, through price discounts or potential future biosimilars, would make anti-EGFR therapy considerably more cost effective. By using real-world data for a large cohort with long follow-up we can assess the value of a policy of KRAS testing and anti-EGFR therapy achieved in practice.

Health Care Costs Attributable to Prostate Cancer in British Columbia, Canada: A Population-Based Cohort Study.

We aimed to estimate the total health care costs attributable to prostate cancer (PCa) during care phases by age, cancer stage, tumor grade, and primary treatment in the first year in British Columbia (BC), Canada. Using linked administrative health data, we followed a cohort of men aged ≥ 50 years at diagnosis with PCa between 2010 and 2017 (Cohort 1) from the diagnosis date until the date of death, the last date of observation, or 31 December 2019. Patients who died from PCa after 1 January 2010, were selected for Cohort 2. PCa attributable costs were estimated by comparing costs in patients to matched controls. Cohort 1 (n = 22,672) had a mean age of 69.9 years (SD = 8.9) and a median follow-up time of 5.2 years. Cohort 2 included 6942 patients. Mean PCa attributable costs were the highest during the first year after diagnosis ($14,307.9 [95% CI: $13,970.0, $14,645.8]) and the year before death ($9959.7 [$8738.8, $11,181.0]). Primary treatment with radiation therapy had significantly higher costs each year after diagnosis than a radical prostatectomy or other surgeries in advanced-stage PCa. Androgen deprivation therapy (and/or chemotherapy) had the highest cost for high-grade and early-stage cancer during the three years after diagnosis. No treatment group had the lowest cost. Updated cost estimates could inform economic evaluations and decision-making.

Economic evaluation of prostate cancer risk assessment methods: A cost-effectiveness analysis using population data.

BACKGROUND: The current prostate cancer (PCa) screening standard of care (SOC) leads to unnecessary biopsies and overtreatment because decisions are guided by prostate-specific antigen (PSA) levels, which have low specificity in the gray zone (3-10 ng/mL). New risk assessment tools (RATs) aim to improve biopsy decision-making. We constructed a modeling framework to assess new RATs in men with gray zone PSA from the British Columbia healthcare system's perspective. METHODS: We evaluated the cost-effectiveness of a new RAT used in biopsy-naïve men aged 50+ with a PSA of 3-10 ng/mL using a time-dependent state-transition model. The model was informed by engaging patient partners and using linked administrative health data, supplemented with published literature. The incremental cost-effectiveness ratio and the probability of the RAT being cost-effective were calculated. Probabilistic analysis was used to assess parameter uncertainty. RESULTS: In the base case, a RAT based on an existing biomarker's characteristics was a dominant strategy associated with a cost savings of $44 and a quality-adjusted life years (QALY) gain of 0.00253 over 18 years of follow-up. At a cost-effectiveness threshold of $50,000/QALY, the probability that using a RAT is cost-effective relative to the SOC was 73%. Outcomes were sensitive to RAT costs and accuracy, especially the detection rate of high-grade PCa. Results were also impacted by PCa prevalence and assumptions about undetected PCa survival. CONCLUSIONS: Our findings showed that a more accurate RAT to guide biopsy can be cost-effective. Our proposed general model can be used to analyze the cost-effectiveness of any novel RAT.

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.

Tools for the Economic Evaluation of Precision Medicine: A Scoping Review of Frameworks for Valuing Heterogeneity-Informed Decisions.

BACKGROUND AND OBJECTIVE: Precision medicine highlights the importance of exploring heterogeneity in the effectiveness and costs of interventions. Our objective was to identify and compare frameworks for valuing heterogeneity-informed decisions, and consider their strengths and weaknesses for application to precision medicine. METHODS: We conducted a scoping review to identify papers that proposed an analytical framework to place a value, in terms of costs and health benefits, on using heterogeneity to inform treatment selection. The search included English-language papers indexed in MEDLINE, Embase or EconLit, and a manual review of references and citations. We compared the frameworks qualitatively considering: the purpose and setting of the analysis; the types of precision medicine interventions where the framework could be applied; and the framework's ability to address the methodological challenges of evaluating precision medicine. RESULTS: Four analytical frameworks were identified: value of stratification, value of heterogeneity, expected value of individualised care and loss with respect to efficient diffusion. Each framework is suited to slightly different settings and research questions. All focus on maximising net benefit, and quantify the opportunity cost of ignoring heterogeneity by comparing individualised or stratified decisions to a means-based population-wide decision. Where the frameworks differ is in their approaches to uncertainty, and in the additional metrics they consider. CONCLUSIONS: Identifying and utilising heterogeneity is at the core of precision medicine, and the ability to quantify the value of heterogeneity-informed decisions is critical. Using an analytical framework to value heterogeneity will help provide evidence to inform investment in precision medicine interventions, appropriately capturing the value of targeted health interventions.

Mapping Canadian Data Assets to Generate Real-World Evidence: Lessons Learned from Canadian Real-World Evidence for Value of Cancer Drugs (CanREValue) Collaboration's RWE Data Working Group.

Canadian provinces routinely collect patient-level data for administrative purposes. These real-world data (RWD) can be used to generate real-world evidence (RWE) to inform clinical care and healthcare policy. The CanREValue Collaboration is developing a framework for the use of RWE in cancer drug funding decisions. A Data Working Group (WG) was established to identify data assets across Canada for generating RWE of oncology drugs. The mapping exercise was conducted using an iterative scan with informant surveys and teleconference. Data experts from ten provinces convened for a total of three teleconferences and two in-person meetings from March 2018 to September 2019. Following each meeting, surveys were developed and shared with the data experts which focused on identifying databases and data elements, as well as a feasibility assessment of conducting RWE studies using existing data elements and resources. Survey responses were compiled into an interim data report, which was used for public stakeholder consultation. The feedback from the public consultation was used to update the interim data report. We found that databases required to conduct real-world studies are often held by multiple different data custodians. Ninety-seven databases were identified across Canada. Provinces held on average 9 distinct databases (range: 8-11). An Essential RWD Table was compiled that contains data elements that are necessary, at a minimal, to conduct an RWE study. An Expanded RWD Table that contains a more comprehensive list of potentially relevant data elements was also compiled and the availabilities of these data elements were mapped. While most provinces have data on patient demographics (e.g., age, sex) and cancer-related variables (e.g., morphology, topography), the availability and linkability of data on cancer treatment, clinical characteristics (e.g., morphology and topography), and drug costs vary among provinces. Based on current resources, data availability, and access processes, data experts in most provinces noted that more than 12 months would be required to complete an RWE study. The CanREValue Collaboration's Data WG identified key data holdings, access considerations, as well as gaps in oncology treatment-specific data. This data catalogue can be used to facilitate future oncology-specific RWE analyses across Canada.

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.

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

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