Common Sense Oncology: Equity, Value, and Outcomes That Matter.

While some recent drug treatments have been transformative for patients with cancer, many treatments offer small benefits despite high clinical toxicity, time toxicity and financial toxicity. Moreover, treatments that do provide substantial clinical benefits are not available to many patients globally due to issues with availability and affordability. The Common Sense Oncology's vision is that patients will have access to treatments that provide meaningful improvements in outcomes that matter, regardless of where they live. In recognition of the growing challenges in the field of oncology, Common Sense Oncology seeks to achieve this vision by improving evidence generation, evidence interpretation and evidence communication.

Cost and value of cancer medicines in a single-payer public health system in Ontario, Canada: a cross-sectional study.

BACKGROUND: The financial impact of cancer medicines on health systems is not well known. We describe temporal trends in expenditure on cancer medicines within the single-payer health system of Ontario, Canada, and the extent of clinical benefit these treatments offer. METHODS: In this cross-sectional study, we identified cancer medicines and expenditures from formularies and costing databases (the New Drug Funding Program, Ontario Drug Benefit Program, and The High-Cost Therapy Funding Program) during 10 consecutive years (April 1, 2012, to March 31, 2022) in Ontario, Canada. For intravenous medicines, we applied the European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS) to identify expenditures associated with substantial clinical benefit. We also identified treatments associated with improved overall survival or quality of life. FINDINGS: 69 intravenous and 98 oral or injectable medicines were funded during 2012-22. Annual expenditure on cancer medicines increased by approximately 15% per year during 2012-22; the increase was more rapid in the most recent 4 years. Total expenditure on cancer medicines in the 2021-22 financial year was CA$1·7 billion. Immune checkpoint inhibitors were the single biggest expense by class ($284 million), representing 17% of the entire cancer medicine annual budget. Drugs with the highest individual costs were lenalidomide ($178 million) and pembrolizumab ($163 million), each accounting for around 10% of the entire budget. 29 (76%) of 38 indications eligible for ESMO-MCBS scoring met the threshold for substantial clinical benefit. Eight (21%) indications had no randomised trial evidence of improved overall survival, and only four (11%) were associated with improved QOL. $346 million (67% of the expenditure on intravenous cancer medicines) was spent on drugs that improved median overall survival by more than 6 months, $82 million (16%) was spent on medicines with overall survival gains of 3-6 months, and $32 million (6%) was spent on medicines with overall survival gains of less than 3 months. $53 million (10%) was spent on medicines with no established improvement in overall survival. INTERPRETATION: Costs of cancer medicines to the Canadian health system are increasing rapidly. Most funded indications met thresholds for substantial clinical benefit and two-thirds of the expenditure were for medicines that improve survival by more than 6 months. Whether this cost trajectory can be maintained in a sustainable, equitable, high-quality health system is unclear. Efforts are needed to ensure the price of medicines with substantial benefit is affordable and funding of treatments with very modest benefit might need to be re-assessed, particularly when alternative supportive and palliative therapies are available. FUNDING: None.

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).

Financial Toxicity: Unveiling the Burden of Cancer Care on Patients in Rwanda.

INTRODUCTION: Cancer is a major public health problem in Rwanda and other low- and middle-income countries (LMICs). While there have been some improvements in access to cancer treatment, the cost of care has increased, leading to financial toxicity and treatment barriers for many patients. This study explores the financial toxicity of cancer care in Rwanda. METHODS: This prospective cross-sectional study was conducted at 3 referral hospitals in Rwanda, which deliver most of the country's cancer care. Data were collected over 6 months from June 1 to December 1, 2022 by trained research assistants (RAs) using a modified validated data collection tool. RAs interviewed consecutive eligible patients with breast cancer, cervical cancer, colorectal cancer, Hodgkin's and non-Hodgkin's lymphoma who were on active systemic therapy. The study aimed to identify sources of financial burden. Data were analyzed using descriptive statistics. RESULTS: 239 patients were included; 75% (n = 180/239) were female and mean age was 51 years. Breast, cervix, and colorectal cancers were the most common diagnoses (42%, 100/239; 24%, 58/239; and 24%, 57/239, respectively) and 54% (n = 129/239) were diagnosed with advanced stage (stages III-IV). Financial burden was high; 44% (n = 106/239) of respondents sold property, 29% (n = 70/239) asked for charity from public, family, or friends, and 16% (n = 37/239) took loans with interest to fund cancer treatment. CONCLUSION: Despite health insurance which covers many elements of cancer care, a substantial proportion of patients on anti-cancer treatment in Rwanda experience major financial toxicity. Novel health financing solutions are needed to ensure accessible and affordable cancer care.

Efficacy-effectiveness gaps in oncology: Looking beyond survival.

The efficacy-effectiveness (EE) gap describes the differences in survival seen in clinical trials and routine clinical practice, where patients in real-world practice often have inferior outcomes compared to trial populations. However, EE gaps may exist beyond survival outcomes, including gaps in quality of life, toxicity, cost-effectiveness, and patient time, and these EE gaps should also influence patient and clinician treatment decisions. Failure to clearly acknowledge these EE gaps may cause patients, clinicians, and health care systems to have unrealistic expectations of the benefits of therapy across a range of important clinical and economic domains. In this commentary, the authors review the evidence supporting the existence of EE gaps in quality of life, time toxicity, cost and toxicities, and urge for further research into this important topic.

Augmenting clinical trial economic analysis by linking cancer trial data to administrative data: current landscape and future opportunities.

BACKGROUND: Economic analyses based on clinical trial data are costly and time consuming, and alternative methods for performing economic analyses should be explored. OBJECTIVE AND METHODS: In this perspective, we examine the emerging role of administrative data for economic analyses in cancer. RESULTS: Compared with routinely collected clinical trial data, routinely collected administrative data have several strengths including high capture rates for healthcare encounters, less resource utilisation, low rates of misclassification, long follow-up periods and the opportunity to collect data points not traditionally captured in clinical trials. However, there are also limitations including the need for accurate data linkage across multiple databases and systems, the costs and time associated with data linkage, the potential time lag between trial data collection and the availability of administrative data, and limited data on quality of life, toxicity and indirect costs. In this perspective, we identify important barriers and potential solutions to performing economic analyses for oncology using administrative data, and outline strategies to increase research in this field. CONCLUSION: The use of routinely collected administrative data sets for economic analyses of clinical trials presents a unique opportunity that could complement and validate economic analyses based on trial-level data.

Global application of National Comprehensive Cancer Network resource-stratified guidelines for systemic treatment of colon cancer: a population-based, customisable model for cost, demand, and procurement.

BACKGROUND: Resource-stratified guidelines (RSGs) can inform systemic treatment decisions in the face of limited resources. The objective of this study was to develop a customisable modelling tool to predict the demand, cost, and drug procurement needs of delivering National Comprehensive Cancer Network (NCCN) RSG-based systemic treatment for colon cancer. METHODS: We developed decision trees for first-course systemic therapy for colon cancer based on the NCCN RSGs. Decision trees were merged with data from the Surveillance, Epidemiology, and End Results programme, the International Agency for Research on Cancer's GLOBOCAN 2020 national estimates for colon cancer incidence, country-level income data, and data on drug costs from Redbook (USA), the Pharmaceutical Benefits Scheme (Australia), and the Management Sciences for Health 2015 International Medical Products price guide to estimate global treatment needs and costs, and forecast drug procurement. Simulations and sensitivity analyses were used to explore the effect of scaling up services globally and the effect of alternative stage distributions on treatment demand and cost. We generated a customisable model, in which estimates can be tailored to local incidence, epidemiological, and costing data. FINDINGS: First-course systemic therapy is indicated in 608 314 (53·6%) of 1 135 864 colon cancer diagnoses in 2020. Indications for first-course systemic therapy are projected to rise to 926 653 in 2040; the indications in 2020 might be as high as 826 123 (72·7%), depending on stage distribution assumptions. Adhering to NCCN RSGs, patients with colon cancer in low-income and middle income countries (LMICs) would constitute 329 098 (54·1%) of 608 314 global systemic therapy demands, but only 10% of global expenditure on systemic therapies. The total cost of NCCN RSG-based first-course systemic therapy for colon cancer in 2020 would be between about US$4·2 and about $4·6 billion, depending on stage distribution. If all patients with colon cancer in 2020 were treated according to maximal resources, global expenditure on systemic therapy for colon cancer would rise to around $8·3 billion. INTERPRETATION: We have developed a customisable model that can be applied at global, national, and subnational levels to estimate systemic treatment needs, forecast drug procurement, and calculate expected drug costs on the basis of local data. This tool can be used to plan resource allocation for colon cancer globally. FUNDING: None.

Are NCCN Resource-Stratified Guidelines for Breast Cancer Systemic Therapy Achievable? A Population-Based Study of Global Need and Economic Impact.

PURPOSE: Resource-stratified guidelines (RSG) for cancer provide a hierarchy of interventions, based on resource availability. We quantify treatment need and cost if National Comprehensive Cancer Network (NCCN) RSGs for breast cancer (BC) are adopted globally. METHODS: We developed decision trees for first-course systemic therapy, merged with SEER and Global Cancer Observatory 2018 incidence data to estimate treatment need and cost if NCCN RSG are implemented globally based on country-level income. Simulations were used to quantify need and cost of globally scaling up services to Maximal. RESULTS: Based on NCCN RSG, first-course chemotherapy is indicated in 0% (Basic), 87% (Core), and 86% (Enhanced) but declined to 50% (Maximal) because of incorporation of genomic profiling. First-course endocrine therapy (ET) is indicated in 80% in all settings. In 2018, treatment need was 1.4 million people for chemotherapy, 183,943 for human epidermal growth factor receptor 2 (HER2) therapies and 1.6 million for ET. The cost per person for chemotherapy or HER2 or immunotherapy increased by 17-fold from Core to Maximal ($1,278-$22,313 Australian dollars [AUD]). The cost of ET per person rose eight-fold from Basic to Maximal ($1,236-$9,809 AUD). If all patients with BC globally were treated with Maximal resources, the need for chemotherapy would decline by 28%, whereas cost of first-course treatment would rise by 1.8-fold ($21-$37 billion AUD) because of more costly therapies. CONCLUSION: NCCN RSGs for BC could result in chemotherapy overtreatment in Core and Enhanced settings. The absence of chemotherapy in Basic settings should be reconsidered, and future iterations of RSG should perform cross-tumor comparisons to ensure equitable resource distribution and maximize population-level outcomes. Our model is flexible and can be tailored to the costs, population attributes, and resource availability of any institution or country for health-services planning.

Global demand for cancer surgery and an estimate of the optimal surgical and anaesthesia workforce between 2018 and 2040: a population-based modelling study.

BACKGROUND: The growing demand for cancer surgery has placed a global strain on health systems. In-depth analyses of the global demand for cancer surgery and optimal workforce requirements are needed to plan service provision. We estimated the global demand for cancer surgery and the requirements for an optimal surgical and anaesthesia workforce, using benchmarks based on clinical guidelines. METHODS: Using models of benchmark surgical use based on clinical guidelines, we estimated the proportion of cancer cases with an indication for surgery across 183 countries, stratified by income group. These proportions were multiplied by age-adjusted national estimates of new cancer cases using GLOBOCAN 2018 data and then aggregated to obtain the estimated number of surgical procedures required globally. The numbers of cancer surgical procedures in 44 high-income countries were divided by the actual number of surgeons and anaesthetists in the respective countries to calculate cancer procedures per surgeon and anaesthetist ratios. Using the median (IQR) of these ratios as benchmarks, we developed a three-tiered optimal surgical and anaesthesia workforce matrix, and the predictions were extrapolated up to 2040. FINDINGS: Our model estimates that the number of cancer cases globally with an indication for surgery will increase by 5 million procedures (52%) between 2018 (9 065 000) and 2040 (13 821 000). The greatest relative increase in surgical demand will occur in 34 low-income countries, where we also observed the largest gaps in workforce requirements. To match the median benchmark for high-income countries, the surgical workforce in these countries would need to increase by almost four times and the anaesthesia workforce by nearly 5·5 times. The greatest increase in optimal workforce requirements from 2018 to 2040 will occur in low-income countries (from 28 000 surgeons to 58 000 surgeons; 107% increase), followed by lower-middle-income countries (from 166 000 surgeons to 277 000 surgeons; 67% increase). INTERPRETATION: The global demand for cancer surgery and the optimal workforce are predicted to increase over the next two decades and disproportionately affect low-income countries. These estimates provide an appropriate framework for planning the provision of surgical services for cancer worldwide. FUNDING: University of New South Wales Scientia Scholarship and UK Research and Innovation Global Challenges Research Fund.

The value of first-line chemotherapy and targeted therapy in the treatment of breast cancer.

OBJECTIVE: To investigate the value (survival benefit and cost) of first-line chemotherapy and targeted therapy in breast cancer at a population level. METHODS: Based on guideline recommendations, a model of optimal utilisation was constructed for first-line chemotherapy and targeted therapy in breast cancer, calculating the survival benefit and average cost of all regimens recommended for each treatment indication at 5 years and at 10 years. RESULTS: Survival benefits from chemotherapy and targeted therapy differ markedly depending on the treatment indications. The cost per life-year gained at 5 years is $38,044 for stages I and II, $33,749 for stage III and $ 151,668 for patients presenting with stage IV breast cancer. The cost per life-year gained at 10 years is $ 13,587 for early breast cancer. The most expensive chemotherapy indication in breast cancer is the treatment of metastatic HER2-positive breast cancer costing $330,978 per LYG for a survival benefit of 11% at 5 years falling to zero survival benefit at 10 years. CONCLUSION: There are large differences in value between the different indications for first-course chemotherapy and targeted therapy in the treatment of breast cancer that should be considered when pricing cancer drugs.

Estimates of global chemotherapy demands and corresponding physician workforce requirements for 2018 and 2040: a population-based study.

BACKGROUND: The incidence of cancer (excluding non-melanomatous skin cancers) is projected to rise from 17·0 million to 26·0 million between 2018 and 2040. A large proportion of these patients would be likely to derive benefit from chemotherapy, but no studies so far have quantified current and projected global chemotherapy demands. We aimed to estimate changes in national, regional, and global demands for first-course chemotherapy and the cancer physician workforce between 2018 and 2040 if all patients were treated according to best-practice evidence-based guidelines. METHODS: Data for the incidence of 29 types of cancer in 183 countries in 2018, and projections of incidence in 2040, were obtained from GLOBOCAN 2018. Optimal chemotherapy utilisation from evidence-based guidelines was applied to these incidence data to generate the number of new patients requiring first-course chemotherapy in 2018 and 2040. We then estimated the corresponding cancer physician workforce required to deliver this chemotherapy (on the basis of physicians seeing 150 new patients requiring chemotherapy per year). We did sensitivity analyses to investigate how cancer stage at presentation affected chemotherapy demands. We also did sensitivity analyses to explore changes to workforce requirements if each physician was seeing 100 new patients requiring chemotherapy per year or 300 new patients requiring chemotherapy per year. FINDINGS: Between 2018 and 2040, the number of patients requiring first-course chemotherapy annually will increase from 9·8 million to 15·0 million, a relative increase of 53%. The estimated proportion of patients needing chemotherapy who reside in low-income or middle-income countries was 63% (6 162 240 of 9 782 783) in 2018, and will be 67% (10 071 049 of 14 984 560) in 2040. The most common indications for chemotherapy worldwide in 2040 will be lung cancer (accounting for 2 455 137 [16·4%] of 14 984 560 cases eligible for chemotherapy), breast cancer (1 898 740 [12·7%]), and colorectal cancer (1 678 153 [11·1%]). We estimated that, in 2018, 65 000 cancer physicians were required worldwide to deliver optimal chemotherapy-a figure that we estimate will rise to 100 000 by 2040 (with estimates ranging from from 50 000 to 150 000, depending on workload). INTERPRETATION: Strategic investments in chemotherapy service provision and cancer physicians are needed to meet the projected increased demand for chemotherapy in 2040. FUNDING: None.