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.

Financial Conflicts of Interest: Payment at the Expense of Patients?

This provocative editorial proposes four steps that can be immediately implemented to reduce the impact of financial conflicts of interest in oncology without stifling collaboration.

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).

Breast Cancer-Related Financial Toxicity in Sri Lanka: Insights From a Lower Middle-Income Country With Free Universal Public Healthcare.

Financial toxicity (FT) describes either objective or perceived excess financial strain due to a cancer diagnosis on the well-being of patients, families, and society. The consequences of FT have been shown to span countries of varied economic tiers and diverse healthcare models. This study attempts to describe FT and its effects in a lower- to middle-income country delivering predominantly public nonfee-levying healthcare. This was a cross-sectional study involving 210 patients with breast cancer of any stage (I to IV), interviewed between 6 and 18 months from the date of diagnosis. Financial toxicity was highly prevalent with 81% reporting 3 or more on a scale of 1 to 5. Costs incurred for travelling (94%), out-of-hospital investigations (87%), and consultation fees outside the public system (81%) were the most common contributors to FT. Daily compromises for food and education were made by 30% and 20%, respectively, with loss of work seen in over one-third. Greater FT was seen with advanced cancer stage and increasing distance to the nearest radiotherapy unit (P = .008 and .01, respectively). Family and relatives were the most common form of financial support (77.6%). In conclusion, FT is substantial in our group, with many having to make daily compromises for basic needs. Many opt to visit the fee-levying private sector for at least some part of their care, despite the availability of an established public nonfee-levying healthcare.

Surrogate endpoints for HTA decisions of breast cancer drugs: utility and pitfalls.

PURPOSE OF REVIEW: Health technology assessment (HTA) of cancer drugs is important to identify whether drugs should be publicly funded. With increasing use of surrogate end points in clinical trials including breast cancer, a review of literature was done to synthesize evidence for validation of these surrogate end points and their potential role in HTA decisions pertaining to breast cancer. FINDINGS: Disease free survival (DFS) in human epidermal receptor 2 (HER2) positive early breast cancer remains the only validated surrogate end point. Other surrogate end points like pathological complete response (pCR) and event free survival (EFS) in early breast cancer (EBC) and objective response rate (ORR) and progression free survival (PFS) in advanced disease have not been validated for overall survival (OS). Moreover, surrogate end points for quality of life (QOL) have not been established and drugs that improve PFS can have detrimental effect on QOL. End points like pCR have excellent prognostic utility in individual patients but have weak correlation with survival at trial level. SUMMARY: Most surrogate end points used in breast cancer do not predict OS or QOL which makes it challenging to use them for decisions regarding public funding of cancer drugs. These findings are relevant to HTA agencies prior to making drug reimbursement decisions.

Association between nutritional status and socio-economic status among school children aged 9-17 years in a semi-urban area of Nepal.

BACKGROUND: In many low-and middle-income countries (LMICs), childhood overweight is increasing, while underweight remains a problem. This study aimed to investigate the association between socio-economic status (SES) and nutritional status among Nepalese school children. METHODS: This cross-sectional study used a multistage random cluster sampling method and included 868 students aged 9-17 years from both public and private schools located in a semi-urban area of Pokhara Metropolitan City, Nepal. SES was determined based on a self-reported questionnaire. Body weight and height were measured by health professionals and body mass index (BMI) was categorized based on the World Health Organization BMI-for-age cut-offs. The association between Lower and Upper SES and BMI was assessed using mixed-effects logistic regression model estimating the adjusted odds ratio (aOR) with a corresponding 95% confidence interval (CI) and compared to Middle SES. RESULTS: The proportion of obesity, overweight, underweight, and stunting among school children was 4%, 12%, 7%, and 17%, respectively. More girls were overweight/obese compared with boys (20% vs. 13%). The mixed-effects logistic regression model showed that both participants from Lower SES households and Upper SES households had a higher tendency to be overweight compared to participants from Middle SES; aOR = 1.4; 95% CI 0.7-3.1 and aOR = 1.1; 95% CI 0.6-2.1, respectively. Furthermore, stunting and overweight occurred simultaneously. CONCLUSIONS: This study found that about one out of four children and adolescents in the study setting was malnourished. There was a tendency that both participants from Lower SES and Upper SES had higher odds of being overweight compared to participants from Middle SES. Furthermore, both stunting and overweight were present simultaneously in some individuals. This emphasizes the complexity and importance of awareness of childhood malnutrition in LMICs like Nepal.

Health technology assessment for cancer medicines across the G7 countries and Oceania: an international, cross-sectional study.

BACKGROUND: Criticisms have emerged that cancer medicines offer modest benefits at increasingly high prices. Reimbursement decisions made by health technology assessment (HTA) agencies have become a complex endeavour for cancer medicines. Most high-income countries (HICs) use HTA criteria to identify high-value medicines for reimbursement under public drug coverage plans. We compared HTA criteria specific for cancer medicines in economically similar HICs, to understand how these criteria contribute to reimbursement decisions. METHODS: We did an international, cross-sectional analysis in collaboration with author investigators across eight HICs, from the Group of Seven (known as G7; Canada, England, France, Germany, Italy, and Japan) and Oceania (Australia and New Zealand). Publicly available data from HTA agency reports and official documentation were extracted and analysed between Aug 15, 2021, and July 31, 2022. We collected data pertaining to the decision-making criteria used by the national HTA agency; HTA reimbursement status for 34 medicine-indication pairs corresponding to 15 unique US top-selling cancer medicines; and HTA reimbursement status for 18 cancer medicine-indication pairs (13 unique medicines) with minimal clinical benefit (score of 1 on the European Society of Medical Oncology Magnitude of Clinical Benefit Scale). Descriptive statistics were used to compare HTA decision criteria and drug reimbursement recommendations (or for Germany and Japan, final reimbursement status) across the eight countries. FINDINGS: Therapeutic impact related to clinical outcomes of the new medicine was a uniform criterion across the eight countries, whereas quality of evidence (under the remit of therapeutic impact assessment) and equity were infrequently cited criteria. Only the German HTA agency mandated that surrogate endpoints be validated in therapeutic impact assessment. All countries except Germany included formal cost-effectiveness analyses within HTA reports. England and Japan were the only countries that specified a cost-effectiveness threshold. Of the 34 medicine-indication pairs corresponding to US top-selling cancer medicines, Germany reimbursed the maximum (34 [100%]), followed by Italy (32 [94%] recommended for reimbursement), Japan (28 [82%] reimbursed), Australia, Canada, England, and France (27 [79%] recommended for reimbursement), and New Zealand (12 [35%] recommended for reimbursement). Of the 18 cancer medicine-indication pairs with marginal clinical benefit, Germany reimbursed 15 (83%) and Japan reimbursed 12 (67%). France recommended nine (50%) for reimbursement, followed by Italy (seven [39%]), Canada (five [28%]), and Australia and England (three [17%] each). New Zealand did not recommend any medicine-indications with marginal clinical benefit for reimbursement. Considering the overall cumulative proportion across the eight countries, 58 (21%) of 272 indications for the US top-selling medicines and 90 (63%) of 144 marginally beneficial medicine-indications were not recommended for reimbursement or reimbursed. INTERPRETATION: Our findings indicate discordance in public reimbursement decisions across economically similar countries, despite overlapping HTA decision criteria. This suggests a need for improved transparency around the nuances of the criteria to ensure improved access to high-value cancer medicines, and deprioritisation of low-value cancer medicines. Health systems have opportunities to improve their HTA decision-making processes by learning from the systems in other countries. FUNDING: None.

Expensive Drug Prices for Rare Cancers: Are Patients Truly Benefitting?

Cancer medicines comprise the largest proportion of expensive drugs for rare diseases (EDRDs). The US Orphan Drug Act (ODA) (Office of Inspector General, Department of Health and Human Services 2001) encourages pharmaceutical manufacturers to develop medicines for rare diseases through a range of financial incentives, which has shifted the development of cancer medicines to rare cancer subtypes. Although certain medicines approved through the ODA have revolutionized cancer treatment, only half demonstrate added therapeutic benefit compared to existing alternatives. Canadian regulators should ensure that cancer medicines that receive fast-track approval through the Health Canada Notice of Compliance with conditions offer benefit to Canadian patients. Furthermore, payers might engage in methods for reassessment and renegotiations over the medicines' lifespan.

Assessment of Price and Clinical Benefit of Cancer Drugs in Canada, 2011-2020.

This cohort study examines the association between approval characteristics, clinical benefit, and prices of cancer drugs recommended for reimbursement by the Canadian Agency for Drug and Technology in Health.

The Impact of Artificial Intelligence on Health Equity in Oncology: Scoping Review.

BACKGROUND: The field of oncology is at the forefront of advances in artificial intelligence (AI) in health care, providing an opportunity to examine the early integration of these technologies in clinical research and patient care. Hope that AI will revolutionize health care delivery and improve clinical outcomes has been accompanied by concerns about the impact of these technologies on health equity. OBJECTIVE: We aimed to conduct a scoping review of the literature to address the question, "What are the current and potential impacts of AI technologies on health equity in oncology?" METHODS: Following PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews) guidelines for scoping reviews, we systematically searched MEDLINE and Embase electronic databases from January 2000 to August 2021 for records engaging with key concepts of AI, health equity, and oncology. We included all English-language articles that engaged with the 3 key concepts. Articles were analyzed qualitatively for themes pertaining to the influence of AI on health equity in oncology. RESULTS: Of the 14,011 records, 133 (0.95%) identified from our review were included. We identified 3 general themes in the literature: the use of AI to reduce health care disparities (58/133, 43.6%), concerns surrounding AI technologies and bias (16/133, 12.1%), and the use of AI to examine biological and social determinants of health (55/133, 41.4%). A total of 3% (4/133) of articles focused on many of these themes. CONCLUSIONS: Our scoping review revealed 3 main themes on the impact of AI on health equity in oncology, which relate to AI's ability to help address health disparities, its potential to mitigate or exacerbate bias, and its capability to help elucidate determinants of health. Gaps in the literature included a lack of discussion of ethical challenges with the application of AI technologies in low- and middle-income countries, lack of discussion of problems of bias in AI algorithms, and a lack of justification for the use of AI technologies over traditional statistical methods to address specific research questions in oncology. Our review highlights a need to address these gaps to ensure a more equitable integration of AI in cancer research and clinical practice. The limitations of our study include its exploratory nature, its focus on oncology as opposed to all health care sectors, and its analysis of solely English-language articles.

Cancer Medicines: What Is Essential and Affordable in India?

PURPOSE: The WHO essential medicines list (EML) guides selection of drugs for national formularies. Here, we evaluate which medicines are considered highest priority by Indian oncologists and the extent to which they are available in routine practice. METHODS: This is a secondary analysis of an electronic survey developed by the WHO EML Cancer Medicine Working Group. The survey was distributed globally using a hierarchical snowball method to physicians who prescribe systemic anticancer therapy. The survey captured the 10 medicines oncologists considered highest priority for population health and their availability in routine practice. RESULTS: The global study cohort included 948 respondents from 82 countries; 98 were from India and 67 were from other low- and middle-income countries. Compared with other low- and middle-income countries, the Indian cohort was more likely to be medical oncologist (70% v 31%, P < .001) and work exclusively in the private health system (52% v 17%, P < .001). 14/20 most commonly selected medicines were conventional cytotoxic drugs. Universal access to these medicines was reported by a minority of oncologists; risks of significant out-of-pocket expenditures for each medicine were reported by 19%-58% of oncologists. Risk of catastrophic expenditure was reported by 58%-67% of oncologists for rituximab and trastuzumab. Risks of financial toxicity were substantially higher within the private health system compared with the public system. CONCLUSION: Most high-priority cancer medicines identified by Indian oncologists are generic chemotherapy agents that provide substantial improvements in survival and are already included in WHO EML. Access to these treatments remains limited by major financial burdens experienced by patients. This is particularly acute within the private health system. Strategies are urgently needed to ensure that high-quality cancer care is affordable and accessible to all patients in India.

Industry Relationships With Medical Oncologists: Who Are the High-Payment Physicians?

PURPOSE: Many oncologists have relationships with industry. Previous work has shown that these payments are usually modest; however, there exist a subset of medical oncologists who receive more than $100,000 US dollars (USD) annually. Here, we describe the characteristics of these physicians. METHODS: This retrospective cohort study used the Open Payments data set to identify all US-based medical oncologists/hematologists who received $100,000+ USD in general payments linked to cancer medications in 2018. Open Payments and a web-based search were used to identify physician characteristics, demographics, research profile, and leadership positions. RESULTS: One hundred thirty-nine medical oncologists received > $100,000 USD in general payments. The median payment was $154,613 USD, and the total payment was $24.2 million USD. These high-payment physicians represent 1% of all US medical oncologists (N = 10,620) yet account for 37% of all industry payments in 2018. Sixty percent (84 of 139) and 21% (29 of 139) of these high-payment physicians hold hospital and specialty association leadership roles, respectively. One quarter (24%, 33 of 139) serve on journal editorial boards, and 10% (14 of 139) have authored clinical practice guidelines; 72% (100 of 139) hold faculty appointments. CONCLUSION: A small number of medical oncologists receive very high payments from the pharmaceutical industry. These physicians hold major leadership roles within oncology. Further work is needed to understand the extent to which these conflicts of interest may shape clinical practice and policy.

Training General Practitioners in Oncology: A Needs Assessment Survey From Nepal.

PURPOSE: Nepal lacks enough cancer care providers to address the growing burden of cancer in the country. One way of addressing this issue is to train general practitioners (GPs) in oncology (GPOs) so that they can task-share and task-shift oncology care. However, limited information is available regarding the current level of oncology expertise of Nepali GPs and whether they perceive a need for, and have an interest in, such a GPO training program if available in Nepal. METHODS: A survey was distributed to GPs in Nepal to collect data on current oncology training and clinical practice and evaluate levels of interest and need for a GPO training program. The survey was distributed electronically from February to July 2021. RESULTS: The survey obtained 71 individual responses from GPs in Nepal. The majority of respondents were male (87%), and most worked as consultants or senior consultants (63%). Only 6% of respondents had a mandatory oncology rotation during their GP training, and only 15% indicated that their GP training had adequately prepared them to care for patients with cancer. Ninety-six percent of respondents perceived a need for a GPO training program in Nepal, with 94% indicating an interest in enrolling in such a program and 71% indicating that they were very interested. CONCLUSION: The findings indicate an urgent need for and an encouraging interest in establishing a GPO training program in Nepal. These findings will be used to guide the development and implementation of this type of program.

Trends in drug revenue among major pharmaceutical companies: A 2010-2019 cohort study.

BACKGROUND: Over the past 2 decades there has been a substantial increase in the number of new cancer medicines; this has been accompanied by a dramatic rise in drug costs. It is unknown how these trends impact the revenue of the pharmaceutical sector. METHODS: Retrospective cohort study to characterize temporal trends of revenue generated from cancer medicines as a proportion of total drug revenue among 10 large pharmaceutical companies from 2010 to 2019. Itemized product-sales data publicly available through company websites or annual filings were used to identify annual drug revenue. Revenue data were adjusted for inflation and converted to 2019 US dollars. RESULTS: During the study period, cumulative annual revenue generated from cancer drugs increased by 70%: from $55.8 billion to $95.1 billion, while cumulative revenue from nononcology drugs decreased 18%: from $342.2 billion to $281.5 billion. The proportion of total drug revenue generated from oncology drugs increased substantially over the study period: from 14% in 2010 to 25% in 2019 (τ = 1.0, P < .001). CONCLUSIONS: Among 10 of the world's largest pharmaceutical companies, revenues generated from the sale of cancer drugs have increased by 70% over the past decade, while revenues from other medicines have decreased by 18%. Revenues from cancer drugs now account for one-quarter of the net revenues from these companies. Further work is needed to understand if this increase in sales revenue reflects industry profit, and to what extent increased spending has translated into improvements in patient and population outcomes.

Reviewing the Reviewers Potential Financial Conflicts of Interest in Editorial Boards of Surgery Journals.

OBJECTIVE: To assess the prevalence, magnitude, and disclosure status of industry funding in editorial boards of surgery journals. SUMMARY OF BACKGROUND DATA: Financial COI can bias research. Although authors seeking to publish in peer-reviewed surgery journals are required to provide COI disclosures, editorial board members' COI disclosures are generally not disclosed to readers. METHODS: We present a cross-sectional analysis of industry funding to editorial board members of high-impact surgery journals. We reviewed top US-based surgery journals by impact factor to determine the presence of financial COI in members of each journal's editorial board. The prevalence and magnitude of COI was determined using 2018 industry reported payments found in the Centers for Medicare and Medicaid Services Open Payments database. Journal websites were also reviewed looking for the presence of editorial board disclosure statements. RESULTS: A total of 1002 names of editorial board members from the top 10 high-impact American surgery journals were identified. Of 688 individual physicians based in the USA, 452 (65.7%) were found to have received industry payments in 2018, totaling $21,916,503 with a median funding amount per physician of $1253 (interquartile range $156-$10,769). Funding levels varied by surgical specialty and journal. Editorial board disclosure information was found in only 3.3% of physicians. CONCLUSIONS: Industry funding to editorial board members of high impact surgery journals is prevalent and underreported. Mechanisms of disclosure for COI are needed at the editorial board level to provide readers full transparency. This would acknowledge this COI of editorial board members, and thereby attempt to potentially further reduce the risk of bias in editorial decisions.

Real-world Use of and Spending on New Oral Targeted Cancer Drugs in the US, 2011-2018.

Importance: Launch prices of new cancer drugs in the US have substantially increased in recent years despite growing concerns about the quantity and quality of evidence supporting their approval by the US Food and Drug Administration (FDA). Objective: To assess the use of and spending on new oral targeted cancer drugs among US residents with employer-sponsored insurance between 2011 and 2018, stratified by the strength of available evidence of benefit. Design, Setting, and Participants: In this cross-sectional study, dispensing claims for oral targeted cancer drugs first approved by the FDA between January 1, 2011, and December 31, 2018, were analyzed. The number of patients with drugs dispensed and the total payment for all claims were aggregated by calendar year, and these outcomes were arrayed according to evidence underlying FDA approvals, including pivotal study design (availability of randomized clinical trials) and overall survival (OS) benefit, as documented in drug labels. This study was conducted from July 17, 2019, to July 23, 2021. Main Outcomes and Measures: Annual and cumulative numbers of patients who had dispensing events, and annual and cumulative sums of payment for eligible drugs. Results: Of 37 348 patients who had at least 1 of the 44 new oral targeted drugs dispensed between 2011 and 2018, 21 324 were men (57.1%); mean (SD) age was 64.1 (13.1) years. Most individuals (36 246 [97.0%]) received drugs for which evidence from randomized clinical trials existed; however, a growing share of patients received drugs without documented OS benefit during the study period: from 12.7% in 2011 to 58.8% in 2018. Cumulative spending on all sample drugs totaled $3.5 billion by the end of 2018, of which 96.8% was spent on drugs that were approved based on a pivotal randomized clinical trial. Cumulative spending on drugs without documented OS benefit ($1.8 billion [51.6%]) surpassed that on drugs with documented OS benefit ($1.7 billion [48.4%]) by the end of 2018. Conclusions and Relevance: The findings of this cross-sectional study suggest that drugs used for treatment of cancer without documented OS benefits are adopted in the health system and account for substantial spending.

Access to cancer medicines deemed essential by oncologists in 82 countries: an international, cross-sectional survey.

BACKGROUND: The WHO Essential Medicines List (EML) identifies priority medicines that are most important to public health. Over time, the EML has included an increasing number of cancer medicines. We aimed to investigate whether the cancer medicines in the EML are aligned with the priority medicines of frontline oncologists worldwide, and the extent to which these medicines are accessible in routine clinical practice. METHODS: This international, cross-sectional survey was developed by investigators from a range of clinical practice settings across low-income to high-income countries, including members of the WHO Essential Medicines Cancer Working Group. A 28-question electronic survey was developed and disseminated to a global network of oncologists in 89 countries and regions by use of a hierarchical snowball method; each primary contact distributed the survey through their national and regional oncology associations or personal networks. The survey was open from Oct 15 to Dec 7, 2020. Fully qualified physicians who prescribe systemic anticancer therapy to adults were eligible to participate in the survey. The primary question asked respondents to select the ten cancer medicines that would provide the greatest public health benefit to their country; subsequent questions explored availability and cost of cancer medicines. Descriptive statistics were used to compare access to medicines between low-income and lower-middle-income countries, upper-middle-income countries, and high-income countries. FINDINGS: 87 country-level contacts and two regional networks were invited to participate in the survey; 46 (52%) accepted the invitation and distributed the survey. 1697 respondents opened the survey link; 423 were excluded as they did not answer the primary study question and 326 were excluded because of ineligibility. 948 eligible oncologists from 82 countries completed the survey (165 [17%] in low-income and lower-middle-income countries, 165 [17%] in upper-middle-income countries, and 618 [65%] in high-income countries). The most commonly selected medicines were doxorubicin (by 499 [53%] of 948 respondents), cisplatin (by 470 [50%]), paclitaxel (by 423 [45%]), pembrolizumab (by 414 [44%]), trastuzumab (by 402 [42%]), carboplatin (by 390 [41%]), and 5-fluorouracil (by 386 [41%]). Of the 20 most frequently selected high-priority cancer medicines, 19 (95%) are currently on the WHO EML; 12 (60%) were cytotoxic agents and 13 (65%) were granted US Food and Drug Administration regulatory approval before 2000. The proportion of respondents indicating universal availability of each top 20 medication was 9-54% in low-income and lower-middle-income countries, 13-90% in upper-middle-income countries, and 68-94% in high-income countries. The risk of catastrophic expenditure (spending >40% of total consumption net of spending on food) was more common in low-income and lower-middle-income countries, with 13-68% of respondents indicating a substantial risk of catastrophic expenditures for each of the top 20 medications in lower-middle-income countries versus 2-41% of respondents in upper-middle-income countries and 0-9% in high-income countries. INTERPRETATION: These data demonstrate major barriers in access to core cancer medicines worldwide. These findings challenge the feasibility of adding additional expensive cancer medicines to the EML. There is an urgent need for global and country-level policy action to ensure patients with cancer globally have access to high priority medicines. FUNDING: None.

Assessing the benefit of cancer drugs approved by the European Medicines Agency using the European Society for Medical Oncology Magnitude of Clinical Benefit Scale over time.

BACKGROUND: Increasingly, cancer drugs are being approved based on surrogate measurements of efficacy. Clinically meaningful data, such as overall survival (OS) and quality of life, are often only presented in subsequent publications. We examined if the clinical benefit of cancer drugs, as measured by the European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS), improves post-European Medicines Agency (EMA) approval as more data emerges. METHODS: Cancer drug indications approved by the EMA from January 2006 to December 2016 were reviewed and trials cited for efficacy were identified. Primary and subsequent publications (up to December 2019) of scorable trials were included. Changes in benefit over time were measured using ESMO-MCBS thresholds for non-curative (≥4 for substantial, =3 for intermediate and ≤2 for low benefit) and curative intent (A or B for major benefit) scoring. RESULTS: Fifty-five non-curative and two curative intent trials were included. At approval, 29.1% of non-curative trials were substantial, 45.5% intermediate and 25.5% low benefit. For curative intent trials, one displayed major benefit and one displayed no major benefit. We identified 82 subsequent publications for reassessment. A change in ESMO-MCBS classification was seen in 34.5% of non-curative trials (11 raised and 8 lowered). At 3-year reassessment, 36.4% of non-curative trials were substantial, 34.5% intermediate and 29.1% low benefit. Both curative trials showed no major benefit at reassessment. CONCLUSION: As over a third of trials changed classification, in either direction, reassessing the ESMO-MCBS score of approved cancer drugs may help to inform patients and ensure ongoing relevance of regulatory and reimbursement decisions.

An Arm and a Leg: The Rising Cost of Cancer Drugs and Impact on Access.

Increasing cancer drug prices present global challenges to treatment access and cancer outcomes. Substantial variability exists in drug pricing across countries. In countries without universal health care, patients are responsible for treatment costs. Low- or middle-income countries are heavily impacted, with limited patient access to novel cancer treatments. Financial toxicity is seen across cancer types, countries, and health care systems. Those at highest risk include younger patients, new immigrants, visible minority groups, and those without private health coverage. Currently, cancer drug pricing does not correlate with value or clinical benefit. Value-based pricing of oncology drugs may incentivize development of higher-value medicines and eliminate excess spending on drugs that yield little benefit. Generics and biosimilars in oncology can also improve affordability and patient access, offering dramatic reductions in drug spending while maintaining patient benefit. Oncologists can promote value-based care by following evidence-based clinical guidelines that avoid low-value treatments. Researchers can also engage in value-based research that critically explores optimal cancer drug dosing, schedules, and treatment duration and defines patient populations most likely to benefit (e.g., through biomarker selection). Cancer Groundshot proposes that we improve outcomes for today's patients with cancer, including broader global access for high-value treatments, promotion of affordable cancer control strategies, and reduction of cancer morbidity and mortality through low-cost prevention and screening initiatives. Moving forward, major oncology societies recommend promoting uniform global access to essential cancer medicines and avoiding financial harm for patients as key principles in addressing the affordability of cancer drugs.