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

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

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

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

Impact of Frailty on Health Care Resource Utilization and Costs of Care in Myelodysplastic Syndromes.

PURPOSE: The role of frailty in affecting survival in myelodysplastic syndromes (MDS) is increasingly recognized. Despite this, a paucity of data exists on the association between frailty and other clinically meaningful outcomes including health care resource utilization and costs of care. METHODS: We linked the Ontario subset of the prospective Canadian MDS registry (including baseline patient/disease characteristics) to population-based health system administrative databases. Baseline frailty was calculated from the 15-item MDS-specific frailty scale (FS-15). Primary outcomes were public health care utilization and 30-day standardized costs of care (2019 Canadian dollars) determined for each phase of disease (initial, continuation, and terminal phases). Negative binomial regression was used to assess the association between frailty and health care costs with Poisson regression to explore predictors of hospitalization. RESULTS: Among 461 patients with complete FS-15 scores, 374 (81.1%) had a hospitalization with a mean length of stay of 10.6 days. Controlling for age, comorbidities, Revised International Prognostic Scoring System, and transfusion dependence, the FS-15 was independently associated with hospitalization during the initial (P = .02) and continuation (P = .01) phases but not the terminal disease phase (P = .09). The mean 30-day standardized cost per patient was $8,499 (median, $6,295; interquartile range, $2,798-$11,996), largely driven by cancer clinic visits and hospitalization. On multivariable analysis, the FS-15 was independently associated with costs of care during the initial disease phase (P = .02). CONCLUSION: We demonstrate an association between frailty and clinically meaningful outcomes including hospitalization and costs of care in patients with MDS. Our results suggest that baseline frailty may help to inform patients and physicians of expected outcomes.

The impact of routine Edmonton symptom assessment system use on receiving palliative care services: results of a population-based retrospective-matched cohort analysis.

BACKGROUND: In 2007, Cancer Care Ontario began standardised symptom assessment as part of routine care using the Edmonton Symptom Assessment System (ESAS). AIM: The purpose of this study was to evaluate the impact of ESAS on receipt of palliative care when compared with a matched group of unexposed patients. DESIGN: A retrospective-matched cohort study examined the impact of ESAS screening on initiation of palliative care services provided by physicians or homecare nurses. The study included adult patients diagnosed with cancer between 2007 and 2015. Exposure was defined as completing ≥1 ESAS during the study period. Using 4 hard and 14 propensity score-matched variables, patients with cancer exposed to ESAS were matched 1:1 to those who were not. Matched patients were followed from first ESAS until initiation of palliative care, death or end of study. RESULTS: The final cohort consisted of 204 688 matched patients with no prior palliative care consult. The pairs were well matched. The cumulative incidence of receiving palliative care within the first 5 years was higher among those exposed to ESAS compared with those who were not (27.9% (95% CI: 27.5% to 28.2%) versus 27.9% (95% CI: 27.5% to 28.2%)), when death is considered as a competing event. In the adjusted cause-specific Cox proportional hazards model, ESAS assessment was associated with a 6% increase in palliative care services (HR: 1.06, 95% CI: 1.04 to 1.08). CONCLUSION: We have demonstrated that patients exposed to ESAS were more likely to receive palliative care services compared with patients who were not exposed. This observation provides real-world data of the impact of routine assessment with a patient-reported outcome.

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

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

Cost-effectiveness Analysis of Pertuzumab With Trastuzumab in Patients With Metastatic Breast Cancer.

IMPORTANCE: The initial assessment of pertuzumab use for treatment of metastatic breast cancer by health technology assessment agencies suggested that pertuzumab was not cost-effective. In Ontario, Canada, pertuzumab became funded in November 2013 based on the substantial clinical benefit. To date, there is a paucity of analysis of pertuzumab using real-world data for cost-effectiveness. OBJECTIVE: To assess the cost-effectiveness of pertuzumab, trastuzumab, and chemotherapy vs trastuzumab and chemotherapy for patients with metastatic breast cancer. DESIGN, SETTING, AND PARTICIPANTS: A population-based retrospective economic evaluation was conducted in Ontario, Canada. Patients who received first-line treatments for metastatic breast cancer from January 1, 2008, to March 31, 2018, were identified. Patients were followed up from the start of treatment up to 5 years, with maximum follow-up to March 31, 2019. Patients were identified from the Ontario Cancer Registry and linked to the New Drug Funding Program database to identify receipt of first-line treatment (N = 1158). INTERVENTIONS: Treatment with pertuzumab, trastuzumab, and chemotherapy after public funding (November 25, 2013) compared with treatment with trastuzumab and chemotherapy before funding. MAIN OUTCOMES AND MEASURES: Cost-effectiveness, from a public payer perspective, was estimated from administrative data with a 5-year time horizon, adjusted for censoring, and discounted (1.5%). Incremental cost-effectiveness ratios for life-years gained and quality-adjusted life year (QALY) with bootstrapped 95% CIs were calculated. Sensitivity analysis with price reduction of pertuzumab alone or in combination with trastuzumab was conducted. RESULTS: A total of 579 pairs of matched patients receiving pertuzumab and controls were included. The mean (SD) age of the matched study cohort was 58 (12.97) years; 1151 were women (99.4%). Pertuzumab resulted in 0.61 life-years gained and 0.44 QALYs gained at an incremental cost of $192 139 (all costs measured in Canadian dollar values, CAD) with an incremental cost-effectiveness ratio of $316 203 per life-year gained and $436 679 per QALY. The main factors associated with cost included the cost of pertuzumab (60%), outpatient cancer treatment delivery (24%), and trastuzumab (15%). With 100% price reduction of pertuzumab, the incremental cost-effectiveness ratio was $174 027 per QALY. When the price of pertuzumab and trastuzumab were both reduced by more than 71%, the incremental cost-effectiveness ratio decreased below $100 000 per QALY. CONCLUSIONS AND RELEVANCE: The findings of this population-based study suggest that pertuzumab may increase survival for patients with metastatic breast cancer but would not be considered cost-effective, even after 100% price reduction, under conventional thresholds.

Building a National Reassessment Process for Oncology Drugs: Lessons Learned by the Canadian Real-World Evidence for Value of Cancer Drugs (CanREValue) Collaboration through a Simulated Reassessment Exercise.

The CanREValue Collaboration established the Reassessment & Uptake Working Group to develop a preliminary process to reassess funded cancer drugs in Canada. A simulated exercise was conducted to evaluate the proposed reassessment process using a real-world case. We invited 32 attendees including representatives from Health Canada and Health Technology Assessment (HTA) agencies, along with payers, clinicians, academics, and patient representatives. A case was developed using a real-world study on a publicly funded cancer drug. In facilitated group sessions, participants were asked to deliberate upon the evidence presented in the case to issue reassessment recommendations. Several themes were identified through the deliberation discussions. While the generalizability of real-world evidence (RWE) is perceived as a strength, trust in the RWE depends largely on the source of the real-world data. The attendees suggested several improvements to the proposed reassessment process including evidence requirement for reassessment, recommendation categories, and a priori study protocols. This exercise generated important insights on the evidence required for conducting reassessment and considerations for improvements of the proposed reassessment process. Building upon lessons from this exercise, future work would continue to refine the reassessment process as part of the overall CanREValue framework.

The Association of Drug-Funding Reimbursement With Survival Outcomes and Use of New Systemic Therapies Among Patients With Advanced Pancreatic Cancer.

Importance: Gemcitabine-nab-paclitaxel (GEMNAB) and fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX) both improve survival of patients with advanced pancreatic cancer when compared with single-agent gemcitabine in clinical trials. Objective: To describe changes in the survival of patients with advanced pancreatic cancer associated with sequential drug-funding approvals and to determine if there exist distinct patient populations for whom GEMNAB and FOLFIRINOX are associated with survival benefit. Design, Setting, and Participants: This population-based, retrospective cohort study examined all incident cases of advanced pancreatic cancer treated with first-line chemotherapy in Ontario, Canada (2008-2018) that were identified from the Cancer Care Ontario (Ontario Health) New Drug Funding Program database. Statistical analysis was performed from October 2020 to January 2021. Exposures: First-line chemotherapy for advanced pancreatic cancer. Main Outcomes and Measures: The main outcomes were the proportion of patients treated with each chemotherapy regimen over time and overall survival for each regimen. Cox proportional hazards regression models were used to compare overall survival between treatment regimens after adjustment for confounding variables, inverse probability of treatment weighting, and matching. Results: From 2008 to 2018, 5465 patients with advanced pancreatic cancer were treated with first-line chemotherapy in Ontario, Canada. The median (range) age of patients was 66.9 (27.8-93.4) years; 2447 (45%) were female; 878 (16%) had prior pancreatic resection, and 328 (6%) had prior adjuvant gemcitabine. During the time period when only gemcitabine and FOLFIRINOX were funded (2011-2015), 49% (929 of 1887) received FOLFIRINOX. When GEMNAB was subsequently funded (2015-2018), 9% (206 of 2347) received gemcitabine, 44% (1034 of 2347) received FOLFIRINOX, and 47% (1107 of 2347) received GEMNAB. The median overall survival increased from 5.6 months (95% CI, 5.1-6.0 months) in 2008 to 2011 to 6.9 months (95% CI, 6.5-7.4 months) in 2011 to 2015 to 7.6 months (95% CI, 7.1-8.0 months) in 2015 to 2018. Patients receiving FOLFIRINOX were younger and healthier than patients receiving GEMNAB. After adjustment and weighting, FOLFIRINOX was associated with better overall survival than GEMNAB (hazard ratio [HR], 0.75 [95% CI, 0.69-0.81]). In analyses comparing patients treated with GEMNAB and gemcitabine, GEMNAB was associated with better overall survival (HR, 0.86 [95% CI, 0.78-0.94]). Conclusions and Relevance: This cohort study of patients with advanced pancreatic cancer receiving first-line palliative chemotherapy within a universal health care system found that drug funding decisions were associated with increased uptake of new treatment options over time and improved survival. Both FOLFIRINOX and GEMNAB were associated with survival benefits in distinct patient populations.

Transforming Canada's role in global cancer control.

Cancer has not been an explicit priority of Canada's international health and development agenda, but it is key to realising the country's Sustainable Development Goal commitments. Multiple converging political, health, and social forces could now drive support for a more integrated Canadian approach to global cancer control. Success will depend on the extent to which Canadian leaders and institutions can build consensus as a community and agree to work together. Collaboration should include agreement on the framing and prioritisation of the core issues, building a broad coalition base, aligning with priorities of international partners, and on a governance structure that reflects the principles of equity, diversity, and inclusion. This Series paper will discuss global cancer control within Canada's global health agenda, how Canada can address its history of colonisation and present-day disparities in its global work, and the challenges and opportunities of creating a Canadian global cancer control network.

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.

The cost of chemotherapy administration: a systematic review and meta-analysis.

PURPOSE: Cancer treatment is a significant driver of healthcare costs worldwide, however, the economic impact of treating patients with anti-neoplastic agents is poorly elucidated. We conducted a systematic review and meta-analysis to estimate the direct costs associated with administering intravenous chemotherapy in an outpatient setting. METHODS: We systematically searched four databases from 2010 to present and extracted hourly administration costs and the respective components of each estimate. Separate analyses were conducted of Canadian and United States (US) studies, respectively, to address a priori hypotheses regarding heterogeneity amongst estimates. The Drummond checklist was used to assess risk-of-bias. Data were summarized using medians with interquartile ranges and five outliers were identified; costs were presented in 2019 USD. RESULTS: Forty-four studies were analyzed, including sub-analyses of 19 US and seven Canadian studies. 26/44 studies were of moderate-high quality. When components of administration cost were evaluated, physician costs were reported most frequently (24 studies), followed by lab tests (13) and overhead costs (9). The median estimate (excluding outliers) was $142/hour (IQR = $103-166). The median administration cost in the US was $149/hour (IQR = $118-158), and was $128/hour (IQR = $102-137) in Canada. CONCLUSIONS: There is currently a paucity of literature addressing the costs of chemotherapy administration, and existing studies utilize a patchwork of reporting methodologies which renders direct comparison challenging. Our results demonstrate that the cost of administering chemotherapy is approximately $125-150/hour, globally. This value is dependent upon the region of analysis, inclusiveness of cost subcomponents as well as the methodology used to estimate unit prices, as described here.

Real-World Costs of Azacitidine Treatment in Patients With Higher-Risk Myelodysplastic Syndromes/Low Blast-Count Acute Myeloid Leukemia.

PURPOSE: Azacitidine (AZA) is a standard of care for higher-risk myelodysplastic syndrome (MDS)/low blast-count acute myeloid leukemia (AML). Despite this, there is a paucity of data on the real-world health care resource utilization costs of AZA in this population. METHODS: We linked the Ontario AZA MDS registry-higher-risk MDS/low blast-count AML-to population-based health system administrative databases. Patients were observed for 24 months after first AZA and censored at the earliest of 90 days after last AZA, date of death, time of AML induction/stem-cell transplantation, or March 31, 2016. Costs (2015 Canadian dollars) were expressed as standardized mean and median 28-day costs. Univariable quantile regression was used to explore the association of baseline patient and disease characteristics and median cost. Multivariable quantile regression was used to explore predictors of median costs. RESULTS: Among 877 patients in the registry, mean standardized 28-day cost per patient was $17,638 (median, $15,272; interquartile range [IQR], $11,869-$19,580) and $13,450 (median, $11,043; IQR, $7,981-$14,882) excluding the cost of AZA. Major nondrug drivers of cost were cancer clinic visits and inpatient care (mean standardized 28-day cost, $4,631; median, $1,558; IQR, $238-$4,961). Transfusion dependence at AZA initiation (P = .001) and greater comorbid disease burden (P = .009) were independently associated with increased cost. CONCLUSION: Our cohort of patients with uniformly higher-risk MDS/low blast-count AML treated with AZA demonstrates substantial costs of care above and beyond the cost of AZA alone. These results provide insight into the costs of AZA in the real world with implications for resource allocation.

The impact of routine Edmonton Symptom Assessment System (ESAS) use on overall survival in cancer patients: Results of a population-based retrospective matched cohort analysis.

BACKGROUND: The Edmonton Symptom Assessment System (ESAS) is a validated instrument whose use has been standardized in the Ontario cancer system to measure symptoms among ambulatory cancer patients. The objective was to examine the effect of ESAS exposure on overall survival. We hypothesized, a priori, that patients exposed to ESAS would have higher rates of overall survival than those who were not exposed. METHODS: This was a retrospective matched cohort study of adults diagnosed with cancer between 2007 and 2015. Patients were considered exposed if they were screened with ESAS at least once during the study period. Their first ESAS screening date defined the index date. Each exposed patient was matched randomly to a cancer patient without ESAS using a combination of hard matching (4 variables) and propensity score matching (14 variables). Kaplan-Meier curves and multivariable Cox regression were used to evaluate the impact of ESAS exposure on survival. RESULTS: There were 128,893 pairs well matched on all baseline characteristics. The probability of survival within the first 5 years was higher among those exposed to ESAS compared to those who were not (81.9% vs. 76.4% at 1 year, 68.3% vs. 66.1% at 3 years, 61.9% vs. 61.4% at 5 years, P-value < .0001). In the multivariable Cox regression model, ESAS was significantly associated with a decreased mortality risk (HR: 0.48, 95% CI: 0.47-0.49). CONCLUSIONS: Our results show that ESAS exposure is associated with improved survival in cancer patients. This provides real world evidence of the impact of routine symptom assessment in cancer care.

Impact of Standardized Edmonton Symptom Assessment System Use on Emergency Department Visits and Hospitalization: Results of a Population-Based Retrospective Matched Cohort Analysis.

PURPOSE: The Edmonton Symptom Assessment System (ESAS) is a validated instrument whose use has been standardized in the Ontario cancer system to measure symptoms among ambulatory patients with cancer. The objective was to examine the effect of ESAS exposure on visits to the emergency department (ED) and hospitalizations. METHODS: This was a retrospective matched cohort study conducted in Ontario, Canada. The study included patients ≥ 18 years of age diagnosed with cancer between 2007 and 2015. Patients were considered exposed if they were screened with ESAS at least once during the study period, and their first ESAS screening date was defined as the index date. Each exposed patient was matched randomly to a patient with cancer without ESAS assessment using a combination of hard matching (birth year ± 2 years, cancer diagnosis date ± 1 year, cancer type, and sex) and propensity score matching (14 variables, including cancer stage, treatments received, and comorbidities). A multivariable Andersen-Gill recurrent event model was used to evaluate the effect of ESAS on the rate of health care use. RESULTS: The analysis included 128,893 matched pairs that were well balanced on baseline measures. After adjusting for other variables, patients with ESAS had lower rates of both ED visits (relative rate [RR], 0.92; 95% CI, 0.91 to 0.93) and hospitalizations (RR, 0.86; 95% CI, 0.85 to 0.87) compared with patients without ESAS. CONCLUSION: ESAS exposure is independently associated with decreased rates of ED visits and hospitalizations. This provides real-world evidence of one potential positive impact of standardized symptom assessment in cancer care.

Health system costs for cancer medications and radiation treatment in Ontario for the 4 most common cancers: a retrospective cohort study.

BACKGROUND: Previous costing and resource estimates for cancer have not been complete owing to lack of comprehensive data on cancer-related medication and radiation treatment. Our objective was to calculate the mean overall costs per patient of cancer-related medications and radiation, as well as by disease subtype and stage, in the first year after diagnosis for the 4 most prevalent cancers in Ontario. METHODS: We conducted a retrospective cohort study using provincial health administrative databases to identify population health system resources and costs for all patients diagnosed with breast, colorectal, lung or prostate cancer between Jan. 1, 2010, and Dec. 31, 2015 in Ontario. The primary outcome measure was the overall average cost per patient in the 365 days after diagnosis for cancer-related medications and radiation treatment, calculated with the use of 2 novel costing algorithms. We determined the cost by disease, disease subtype and stage as secondary outcomes. RESULTS: There were 168 316 Ontarians diagnosed with cancer during the study period, 50 141 with breast cancer, 38 108 with colorectal cancer, 34 809 with lung cancer and 45 258 with prostate cancer. The mean per-patient cost for cancer-related medications was $8167 (95% confidence interval [CI] $8023-$8311), $6568 (95% CI $6446-$6691), $2900 (95% CI $2816-$2984) and $1211 (95% CI $1175-$1247) for breast, colorectal, lung and prostate cancer, respectively. The corresponding mean radiation treatment costs were $18 529 (95% CI $18 415-$18 643), $15 177 (95% CI $14 899-$15 456), $10 818 (95% CI $10 669-$10 966) and $16 887 (95% CI $16 648-$17 125). In general, stage III and IV cancers were the most expensive stages for both medications and radiation across all 4 disease sites. INTERPRETATION: Our work updates previous costing estimates to help understand costs and resources critical to health care system planning in a single-payer system. More refined costing estimates are useful as inputs to allow for more robust health economic modelling and health care system planning.

Assessing the Impact of Early Identification of Patients Appropriate for Palliative Care on Resource Use and Costs in the Final Month of Life.

PURPOSE: This study evaluates whether an intervention to identify Canadian patients eligible for a palliative approach changes the use of health care resources and costs within the final month of life. METHODS: Between 2014 and 2017, physicians identified 1,187 patients in family practice units and cancer centers who were likely to die within 1 year based on diagnosis, symptom assessment, and performance status. A multidisciplinary intervention that included activation of community resources and initiation of palliative planning was started. By using propensity-score matching, patients in the intervention group were matched 1:1 with nonintervention controls selected from provincial administrative data. We compared health care use and costs (using 2017 Canadian dollars) for 30 days before death between patients who died within the 1-year follow-up and matched controls. RESULTS: Groups (n = 629 in each group) were well-balanced in sociodemographic characteristics, comorbidities, and previous health care use. In the last 30 days, there was no differences in proportions between the two groups of patients regarding emergency department visits, intensive care unit admissions, or inpatient hospitalizations. However, patients in the intervention group had greater use of palliative physician encounters, community home care visits, and/or physician home visits (92.8% v 88.4%; P = .007). In the 507 pairs with cancer, more patients in the intervention group underwent chemotherapy (44% v 33%; P < .001) and radiation (18.7% v 3.2%; P = .043) in the last 30 days. Mean cost per patient was similar for the intervention group (mean, $17,231; 95% CI, $16,027 to $18,436) and for the control group (mean, $16,951; 95% CI, $15,899 to $18,004). CONCLUSION: Even with the limitations in our observational study design, identification of palliative patients did not significantly change overall costs but may shift resources toward palliative services.

High-Cost Patients and Preventable Spending: A Population-Based Study.

BACKGROUND: Although high-cost (HC) patients make up a small proportion of patients, they account for most health system costs. However, little is known about HC patients with cancer or whether some of their care could potentially be prevented. This analysis sought to characterize HC patients with cancer and quantify the costs of preventable acute care (emergency department visits and inpatient hospitalizations). METHODS: This analysis examined a population-based sample of all HC patients in Ontario in 2013. HC patients were defined as those above the 90th percentile of the cost distribution; all other patients were defined as non-high-cost (NHC). Patients with cancer were identified through the Ontario Cancer Registry. Sociodemographic and clinical characteristics were examined and the costs of preventable acute care for both groups by category of visit/condition were estimated using validated algorithms. RESULTS: Compared with NHC patients with cancer (n=369,422), HC patients with cancer (n=187,770) were older (mean age 70 vs 65 years), more likely to live in low-income neighborhoods (19% vs 16%), sicker, and more likely to live in long-term care homes (8% vs 0%). Although most patients from both cohorts tended to be diagnosed with breast, prostate, or colorectal cancer, those with multiple myeloma or pancreatic or liver cancers were overrepresented among the HC group. Moreover, HC patients were more likely to have advanced cancer at diagnosis and be in the initial or terminal phase of treatment compared with NHC patients. Among HC patients with cancer, 9% of spending stemmed from potentially preventable/avoidable acute care, whereas for NHC patients, this spending was approximately 30%. CONCLUSIONS: HC patients with cancer are a unique subpopulation. Given the type of care they receive, there seems to be limited scope to prevent acute care spending among this patient group. To reduce costs, other strategies, such as making hospital care more efficient and generating less costly encounters involving chemotherapy, should be explored.

Value assessment of oncology drugs using a weighted criterion-based approach.

BACKGROUND: Globally, the rising cost of anticancer therapy has motivated efforts to quantify the overall value of new cancer treatments. Multicriteria decision analysis offers a novel approach to incorporate multiple criteria and perspectives into value assessment. METHODS: The authors recruited a diverse, multistakeholder group who identified and weighted key criteria to establish the drug assessment framework (DAF). Construct validity assessed the degree to which DAF scores were associated with past pan-Canadian Oncology Drug Review (pCODR) funding recommendations and European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS; version 1.1) scores. RESULTS: The final DAF included 10 criteria: overall survival, progression-free survival, response rate, quality of life, toxicity, unmet need, equity, feasibility, disease severity, and caregiver well-being. The first 5 clinical benefit criteria represent approximately 64% of the total weight. DAF scores ranged from 0 to 300, reflecting both the expected impact of the drug and the quality of supporting evidence. When the DAF was applied to the last 60 drugs (with reviewers blinded) reviewed by pCODR (2015-2018), those drugs with positive pCODR funding recommendations were found to have higher DAF scores compared with drugs not recommended (103 vs 63; Student t test P = .0007). DAF clinical benefit criteria mildly correlated with ESMO-MCBS scores (correlation coefficient, 0.33; 95% CI, 0.009-0.59). Sensitivity analyses that varied the criteria scores did not change the results. CONCLUSIONS: Using a structured and explicit approach, a criterion-based valuation framework was designed to provide a transparent and consistent method with which to value and prioritize cancer drugs to facilitate the delivery of affordable cancer care.

Economic impacts of care by high-volume providers for non-curative esophagogastric cancer: a population-based analysis.

BACKGROUND: Esophagogastric cancer (EGC) is one of the deadliest and costliest malignancies to treat. Care by high-volume providers can provide better outcomes for patients with EGC. Cost implications of volume-based cancer care are unclear. We examined the cost-effectiveness of care by high-volume medical oncology providers for non-curative management of EGC. METHODS: We conducted a population-based cohort study of non-curative EGC over 2005-2017 by linking administrative datasets. High-volume was defined as ≥ 11 patients/provider/year. Healthcare costs ($USD/patient/month-survived) were computed from diagnosis to death or end of follow-up from the perspective of the healthcare system. Multivariable quantile regression examined the association between care by high-volume providers and costs. Sensitivity analyses were conducted by varying costing horizons and high-volume definitions. RESULTS: Among 7011 non-curative EGC patients, median overall survival was superior with care by high-volume providers with 7.0 (IQR 3.3-13.3) compared to 5.9 (IQR 2.6-12.1) months (p < 0.001) for low-volume providers. Median costs/patient/month-lived were lower for high-volume providers ($5518 vs. $5911; p < 0.001), owing to lower inpatient acute care costs, despite higher medication-associated and radiotherapy costs. Care by high-volume providers was independently associated with a reduction of $599 per patient/month-lived (95% confidence interval - 966 to - 331) compared to low-volume providers. The incremental cost-effectiveness ratio was - 393. Care by high-volume providers remained the dominant strategy when varying the costing horizon and the high-volume definition. CONCLUSION: Care by high-volume providers for non-curative EGC is associated with superior survival and lower healthcare costs, indicating a dominant strategy that may provide an opportunity to improve cost-effectiveness of care delivery.

Variation in receipt of therapy and survival with provider volume for medical oncology in non-curative esophago-gastric cancer: a population-based analysis.

BACKGROUND: While surgical care by high-volume providers for esophago-gastric cancer (EGC) yields better outcomes, volume-outcome relationships are unknown for systemic therapy. We examined receipt of therapy and outcomes in the non-curative management of EGC based on medical oncology provider volume. METHODS: We conducted a population based retrospective cohort study of non-curative EGC over 2005-2017 by linking administrative healthcare datasets. The volume of new EGC consultations per medical oncology provider per year was calculated and divided into quintiles. High-volume (HV) medical oncologists were defined as the 4-5th quintiles. Outcomes were receipt of chemotherapy and overall survival (OS). Multivariate logistic and Cox-proportional hazards regressions examined the association between management by HV medical oncologist, receipt of systemic therapy, and OS. RESULTS: 7011 EGC patients with non-curative management consulted with medical oncology. 1-year OS was superior for HV medical oncologists (> 11 patients/year), with 28.4% (95% CI 26.7-30.2%) compared to 25.1% (95% CI 23.8-26.3%) for low volume (p < 0.001). After adjusting for age, sex, comorbidity burden, rurality, income quintile, and diagnosis year, HV medical oncologist was independently associated with higher odds of receiving chemotherapy (OR 1.13, 95% CI 1.01-1.26), and independently associated with superior OS (HR 0.89, 95% CI 0.84-0.93). CONCLUSIONS: Medical oncology provider volume was associated with variation in non-curative management and outcomes of EGC. Care by an HV medical oncologist was independently associated with higher odds of receiving chemotherapy and superior OS, after adjusting for case mix. This information is important to inform disease care pathways and care organization; an increase in the number of HV medical oncologists may reduce variation and improve outcomes.