ESMO expert consensus statements on the screening and management of financial toxicity in patients with cancer.

BACKGROUND: Financial toxicity, defined as both the objective financial burden and subjective financial distress from a cancer diagnosis and its treatment, is a topic of interest in the assessment of the quality of life of patients with cancer and their families. Current evidence implicates financial toxicity in psychosocial, economic and other harms, leading to suboptimal cancer outcomes along the entire trajectory of diagnosis, treatment, supportive care, survivorship and palliation. This paper presents the results of a virtual consensus, based on the evidence base to date, on the screening and management of financial toxicity in patients with and beyond cancer organized by the European Society for Medical Oncology (ESMO) in 2022. METHODS: A Delphi panel of 19 experts from 11 countries was convened taking into account multidisciplinarity, diversity in health system contexts and research relevance. The international panel of experts was divided into four working groups (WGs) to address questions relating to distinct thematic areas: patients with cancer at risk of financial toxicity; management of financial toxicity during the initial phase of treatment at the hospital/ambulatory settings; financial toxicity during the continuing phase and at end of life; and financial risk protection for survivors of cancer, and in cancer recurrence. After comprehensively reviewing the literature, statements were developed by the WGs and then presented to the entire panel for further discussion and amendment, and voting. RESULTS AND DISCUSSION: A total of 25 evidence-informed consensus statements were developed, which answer 13 questions on financial toxicity. They cover evidence summaries, practice recommendations/guiding statements and policy recommendations relevant across health systems. These consensus statements aim to provide a more comprehensive understanding of financial toxicity and guide clinicians globally in mitigating its impact, emphasizing the importance of further research, best practices and guidelines.

Policy strategies for capacity building and scale up of the workforce for comprehensive cancer care: a systematic review.

BACKGROUND: Patients with cancer in low- and middle-income countries experience worse outcomes as a result of the limited capacity of health systems to deliver comprehensive cancer care. The health workforce is a key component of health systems; however, deep gaps exist in the availability and accessibility of cancer care providers. MATERIALS AND METHODS: We carried out a systematic review of the literature evaluating the strategies for capacity building of the cancer workforce. We studied how the policy strategies addressed the availability, accessibility, acceptability, and quality (AAAQ) of the workforce. We used a strategic planning framework (SWOT: strengths, weaknesses, opportunities, threats) to identify actionable areas of capacity building. We contextualized our findings based on the WHO 2030 Global Strategy on Human Resources for Health, evaluating how they can ultimately be framed in a labour market approach and inform strategies to improve the capacity of the workforce (PROSPERO: CRD42020109377). RESULTS: The systematic review of the literature yielded 9617 records, and we selected 45 eligible papers for data extraction. The workforce interventions identified were delivered mostly in the African and American Regions, and in two-thirds of cases, in high-income countries. Many strategies have been shown to increase the number of competent oncology providers. Optimization of the existing workforce through role delegation and digital health interventions was reported as a short- to mid-term solution to optimize cancer care, through quality-oriented, efficiency-improving, and acceptability-enforcing workforce strategies. The increased workload alone was potentially detrimental. The literature on retaining the workforce and reducing brain drain or attrition in underserved areas was commonly limited. CONCLUSIONS: Workforce capacity building is not only a quantitative problem but can also be addressed through quality-oriented, organizational, and managerial solutions of human resources. The delivery of comprehensive, acceptable, and impact-oriented cancer care requires an available, accessible, and competent workforce for comprehensive cancer care. Efficiency-improving strategies may be instrumental for capacity building in resource-constrained settings.

Biases in study design, implementation, and data analysis that distort the appraisal of clinical benefit and ESMO-Magnitude of Clinical Benefit Scale (ESMO-MCBS) scoring.

BACKGROUND: The European Society for Medical Oncology-Magnitude of Clinical Benefit Scale (ESMO-MCBS) is a validated, widely used tool developed to score the clinical benefit from cancer medicines reported in clinical trials. ESMO-MCBS scores assume valid research methodologies and quality trial implementation. Studies incorporating flawed design, implementation, or data analysis may generate outcomes that exaggerate true benefit and are not generalisable. Failure to either indicate or penalise studies with bias undermines the intention and diminishes the integrity of ESMO-MCBS scores. This review aimed to evaluate the adequacy of the ESMO-MCBS to address bias generated by flawed design, implementation, or data analysis and identify shortcomings in need of amendment. METHODS: As part of a refinement of the ESMO-MCBS, we reviewed trial design, implementation, and data analysis issues that could bias the results. For each issue of concern, we reviewed the ESMO-MCBS v1.1 approach against standards derived from Helsinki guidelines for ethical human research and guidelines from the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use, the Food and Drugs Administration, the European Medicines Agency, and European Network for Health Technology Assessment. RESULTS: Six design, two implementation, and two data analysis and interpretation issues were evaluated and in three, the ESMO-MCBS provided adequate protections. Seven shortcomings in the ability of the ESMO-MCBS to identify and address bias were identified. These related to (i) evaluation of the control arm, (ii) crossover issues, (iii) criteria for non-inferiority, (iv) substandard post-progression treatment, (v) post hoc subgroup findings based on biomarkers, (vi) informative censoring, and (vii) publication bias against quality-of-life data. CONCLUSION: Interpretation of the ESMO-MCBS scores requires critical appraisal of trials to understand caveats in trial design, implementation, and data analysis that may have biased results and conclusions. These will be addressed in future iterations of the ESMO-MCBS.

The global landscape of availability, accessibility and affordability of essential diagnostics and therapeutics for the management of HER2-positive breast cancer: The ONCOLLEGE-001 survey.

AIM OF THE STUDY: Barriers in access to essential care are key determinants of disparities in cancer survival. Breast cancer (BC) is the most common cancer and lead cause of mortality among women, 60 % occurring in low- and middle-income countries (LMs). A quarter of BC are characterized by an over-expression of the epidermal growth factor receptor 2 (HER2). Valuable strategies to diagnose and manage patients with HER2-positive BC have been determined and some considered essential health interventions. ONCOLLEGE-001 is a global survey of availability, accessibility, and affordability of essential HER2 diagnostics and therapeutics. METHOD: A self-administered questionnaire was shared electronically to oncologists, identified from oncology networks. Data were analyzed using descriptive statistics, per income areas and geographic regions. RESULTS: We received 191 responses (84 % response rate). The majority of the responders were from LMs (n = 153) and were physician providers. Immunohistochemistry was the most common HER2 diagnostics available (n = 185). A third of the responders from low/lower-middle and a half of upper-middle income countries had HER2 testing only in the private sector. Trastuzumab was not available for 8 %: when available, 15%-21% reported accessibility only as out-of-pocket expenditure; when not reimbursed, only 10 % of the providers could significantly offer this intervention. Availability of trastuzumab biosimilars was reported in more than a half of the responders (n = 107). CONCLUSION: Stark disparities are reported, with high out-of-pocket expenses for HER2 testing and significant financial barriers to access trastuzumab treatments. Policy solutions are urgently warranted for the selection, prioritization, and reimbursement of essential health interventions, to result in improved population health. POLICY SUMMARY STATEMENT: the inclusion of essential services for cancer management should be assured and financed in the benefit packages of healthcare to all. Prioritizing high-value health interventions, including medicines and medical devices, is critical to deliver impactful programs on population health.

QTc prolongation assessment in anticancer drug development: clinical and methodological issues.

Cardiac safety assessments are commonly employed in the clinical development of investigational oncology medications. In anti-cancer drug development there has been increasing consideration for the potential of a compound to cause adverse electrocardiographic changes, especially QT interval prolongation, which can be associated with risk of torsades de pointes and sudden death. Irrespective of overt clinical toxicities, QTc assessment can potentially influence decision making at many levels during the conduct of clinical studies, including eligibility for protocol therapy, dose delivery or discontinuation, and analyses of optimal dose for subsequent development. Given the potential for serious and irreversible morbidity from cardiac adverse events, it is understandable that cardiac safety results can have broad impact on study conduct and patient management. The methodologies for risk management of QTc prolongation for non cardiac drugs have been developed out of experiences primarily from drugs used to treat non life-threatening illnesses in a chronic setting such as antibiotics or antihistamines. Extrapolating these approaches to drugs for treating cancer over an acute period may not be appropriate. Few specific guidelines are available for risk management of cardiac safety in the development and use of oncology drugs. In this manuscript, clinical and methodological issues related to QTc prolongation assessment will be reviewed. Discussions about limitations in phase-I design and oncology drug development will be highlighted. Efforts are needed to refine strategies for risk management, avoiding unintended consequences that negatively affect patient access and clinical development of promising new cancer treatments. A thoughtful risk management plan generated by an organized collaboration between oncologists, cardiologists, and regulatory agencies to support a development programme essential for oncology agents with cardiac safety concerns.