Cancer control in Latin America and the Caribbean: recent advances and opportunities to move forward.

The increasing burden of cancer represents a substantial problem for Latin America and the Caribbean. Two Lancet Oncology Commissions in 2013 and 2015 highlighted potential interventions that could advance cancer care in the region by overcoming existing challenges. Areas requiring improvement included insufficient investment in cancer control, non-universal health coverage, fragmented health systems, inequitable concentration of cancer services, inadequate registries, delays in diagnosis or treatment initiation, and insufficient palliative services. Progress has been made in key areas but remains uneven across the region. An unforeseen challenge, the COVID-19 pandemic, strained all resources, and its negative effect on cancer control is expected to continue for years. In this Series paper, we summarise progress in several aspects of cancer control since 2015, and identify persistent barriers requiring commitment of additional resources to reduce the cancer burden in Latin America and the Caribbean.

Brazilian health-care policy for targeted oncology therapies and companion diagnostic testing.

A growing understanding of the molecular pathology of tumours combined with a surge of new drugs and associated diagnostic technologies (ie, precision medicine) has translated into substantial improvements in survival for patients with cancer. However, to achieve the promise that precision medicine has to offer will require overcoming hurdles within a national health-care system in which it is to be implemented. Brazil is one such nation, an emerging middle-income country with a very complex health-care system. To address the challenges associated with implementing precision medicine into a country such as Brazil, a group of experts convened (Nov 16-18, 2015, Miami) to discuss challenges related to precision medicine within an oncology setting. Complex regulatory hurdles, a shortage of human and technical resources, and the complexities of a two-tiered health-care delivery system were all identified as the main shortcomings to effectively implementing this new field of medicine. A path forward was proposed that relies on active collaboration between clinicians, private organisations, and government. It seems entirely possible that, despite many intrinsic economic and political problems, Brazil can readily emerge as a model for other countries in Latin America for the potential benefits of precision medicine and companion diagnostics.

Planning cancer control in Latin America and the Caribbean.

Non-communicable diseases, including cancer, are overtaking infectious disease as the leading health-care threat in middle-income and low-income countries. Latin American and Caribbean countries are struggling to respond to increasing morbidity and death from advanced disease. Health ministries and health-care systems in these countries face many challenges caring for patients with advanced cancer: inadequate funding; inequitable distribution of resources and services; inadequate numbers, training, and distribution of health-care personnel and equipment; lack of adequate care for many populations based on socioeconomic, geographic, ethnic, and other factors; and current systems geared toward the needs of wealthy, urban minorities at a cost to the entire population. This burgeoning cancer problem threatens to cause widespread suffering and economic peril to the countries of Latin America. Prompt and deliberate actions must be taken to avoid this scenario. Increasing efforts towards prevention of cancer and avoidance of advanced, stage IV disease will reduce suffering and mortality and will make overall cancer care more affordable. We hope the findings of our Commission and our recommendations will inspire Latin American stakeholders to redouble their efforts to address this increasing cancer burden and to prevent it from worsening and threatening their societies.

The burden of systemic therapy administration route in treating HER2-positive breast cancer (for patients, healthcare professionals, and healthcare system): a systematic literature review.

Introduction: Breast cancer (BC) is one of the leading causes of cancer and is the first cause of death from malignant tumors among women worldwide. New cancer therapies receive regulatory approval yearly and to avoid health disparities in society, the health systems are challenged to adapt their infrastructure, methodologies, and reimbursement policies to allow broad access to these treatments. In addition, listening to patients' voices about their therapy preferences is essential. We aim to investigate the administration route preferences [subcutaneous (SC) or intravenous (IV)] among patients diagnosed with HER2 positive BC and healthcare professionals (HCPs) and to investigate healthcare resources utilization (quality and quantity) for each route of administration (SC or IV) for treating those patients. Methods: We conducted a systematic literature review focused on clinical trials and observational and economic studies, using PubMed (MEDLINE), Cochrane Library, Virtual Health Library (VHL), Scientific Electronic Library Online (SciELO), and Latin American and Caribbean Health Sciences Literature (LILACS) databases based on the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement. Results: The literature review included 25 studies in the analysis. Studies have reported that patients and HCPs prefer the SC route of administration to IV because it saves time in terms of chair time, administration, and preparation and is less painful. In addition, SC administration might be a more cost-saving option when analyzing direct and indirect costs. Discussion: As BC stands as a significant global health concern and the leading cause of cancer-related deaths in women worldwide, understanding and incorporating patient and HCPs preferences in the choice of administration route become paramount. The observed preference for SC administration not only aligns with the imperative of adapting health systems to facilitate broad access to new cancer therapies but also underscores the importance of considering patient experiences and economic implications in shaping treatment strategies. These insights are crucial for healthcare policymakers, clinicians, and stakeholders in optimizing healthcare resources and enhancing the overall quality of BC care.

Empowering quality data - the Gordian knot of bringing real innovation into healthcare system.

OBJECTIVES: The introduction of Personalised Medicine (PM) into healthcare systems could benefit from a clearer understanding of the distinct national and regional frameworks around the world. Recent engagement by international regulators on maximising the use of real-world evidence (RWE) has highlighted the scope for improving the exploitation of the treasure-trove of health data that is currently largely neglected in many countries. The European Alliance for Personalised Medicine (EAPM) led an international study aimed at identifying the current status of conditions. METHODS: A literature review examined how far such frameworks exist, with a view to identifying conducive factors - and crucial gaps. This extensive review of key factors across 22 countries and 5 regions revealed a wide variety of attitudes, approaches, provisions and conditions, and permitted the construction of a comprehensive overview of the current status of PM. Based on seven key pillars identified from the literature review and expert panels, the data was quantified, and on the basis of further analysis, an index was developed to allow comparison country by country and region by region. RESULTS: The results show that United States of America is leading according to overall outcome whereas Kenya scored the least in the overall outcome. CONCLUSIONS: Still, common approaches exist that could help accelerate take-up of opportunities even in the less prosperous parts of the world.

Framework for Adoption of Next-Generation Sequencing (NGS) Globally in the Oncology Area.

Radical new possibilities of improved treatment of cancer are on offer from an advanced medical technology already demonstrating its significance: next-generation sequencing (NGS). This refined testing provides unprecedentedly precise diagnoses and permits the use of focused and highly personalized treatments. However, across regions globally, many cancer patients will continue to be denied the benefits of NGS as long as some of the yawning gaps in its implementation remain unattended. The challenges at the regional and national levels are linked because putting the solutions into effect is highly dependent on cooperation between regional- and national-level cooperation, which could be hindered by shortfalls in interpretation or understanding. The aim of the paper was to define and explore the necessary conditions for NGS and make recommendations for effective implementation based on extensive exchanges with policy makers and stakeholders. As a result, the European Alliance for Personalised Medicine (EAPM) developed a maturity framework structured around demand-side and supply-side issues to enable interested stakeholders in different countries to self-evaluate according to a common matrix. A questionnaire was designed to identify the current status of NGS implementation, and it was submitted to different experts in different institutions globally. This revealed significant variability in the different aspects of NGS uptake. Within different regions globally, to ensure those conditions are right, this can be improved by linking efforts made at the national level, where patients have needs and where care is delivered, and at the global level, where major policy initiatives in the health field are underway or in preparation, many of which offer direct or indirect pathways for building those conditions. In addition, in a period when consensus is still incomplete and catching up is needed at a political level to ensure rational allocation of resources-even within individual countries-to enable the best ways to make the necessary provisions for NGS, a key recommendation is to examine where closer links between national and regional actions could complement, support, and mutually reinforce efforts to improve the situation for patients.

Delivering precision oncology to patients with cancer.

With the increasing use of genomic profiling for diagnosis and therapy guidance in many tumor types, precision oncology is rapidly reshaping cancer care. However, the current trajectory of drug development in oncology results in a paradox: if patients cannot access advanced diagnostics, we may be developing drugs that will reach few patients. In this Perspective, we outline the major challenges to the implementation of precision oncology and discuss critical steps toward resolving these, including facilitation of equal access to genomics tests, ensuring that clinical studies provide robust evidence for new drugs and technologies, enabling physicians to interpret genomics data, and empowering patients toward shared decision-making. A multi-stakeholder approach to evidence generation, value assessment, and healthcare delivery is necessary to translate advances in precision oncology into benefits for patients with cancer globally.

BRAF Testing in Melanoma and Colorectal Cancer in Latin America: Challenges and Opportunities.

The incidence of colorectal cancer in Argentina and Brazil has reached levels comparable to those in higher-income countries. Similarly, the incidence of melanoma in Latin America has increased during the past decades. BRAFmutation is seen frequently in melanomas and colorectal cancer. Discovering the expression of this specific biomarker in both cancers has unleashed the potential for targeted molecular therapies.In patients with BRAF-mutated melanoma, adopting a combined targeted treatment approach has shown a dramatic increase in overall survival. However, several barriers impede the development of early BRAF testing in Latin America, jeopardizing the potential for personalized therapies and care. To address this, the Americas Health Foundation convened a virtual meeting of Latin American oncologists to address the barriers to BRAF testing in melanoma and colorectal cancer. During a three-day conference, expert oncologists used literature reviews and personal experience to detail the barriers to early BRAF testing in their region. They proposed actionable steps to overcome the barriers identified, which included deficiencies in knowledge, treatment options, equitable distribution, timely results, and local data on BRAF mutations. Oncologists proposed several actions to overcome barriers, including raising public and healthcare awareness about the importance of BRAF testing, expanding treatment options in clinics across the region, developing centers in underserved areas, and increasing affordable treatment options for patients who test positive for BRAF mutations.

Correction: BRAF Testing in Melanoma and Colorectal Cancer in Latin America: Challenges and Opportunities.

[This corrects the article DOI: 10.7759/cureus.31972.].

Fighting Cancer around the World: A Framework for Action.

Tackling cancer is a major challenge right on the global level. Europe is only the tip of an iceberg of cancer around the world. Prosperous developed countries share the same problems besetting Europe-and the countries and regions with fewer resources and less propitious conditions are in many cases struggling often heroically against a growing tide of disease. This paper offers a view on these geographically wider, but essentially similar, challenges, and on the prospects for and barriers to better results in this ceaseless battle. A series of panels have been organized by the European Alliance for Personalised Medicine (EAPM) to identify different aspects of cancer care around the globe. There is significant diversity in key issues such as NGS, RWE, molecular diagnostics, and reimbursement in different regions. In all, it leads to disparities in access and diagnostics, patients' engagement, and efforts for a better understanding of cancer.

Cost-effectiveness of ribociclib plus letrozole versus palbociclib plus letrozole or letrozole as monotherapy in first-line treatment of postmenopausal women with HR+/HER2- locally advanced or metastatic breast cancer: a Brazilian private payer perspective.

BACKGROUND: The global burden of breast cancer (BC) is high, especially in advanced stages. CDK 4/6 inhibitors represent a paradigm shift in the treatment of advanced BC HR+/HER2-, given the clinically and statistically significant gain in overall survival associated with this new class of medications. Nevertheless, as an innovation, the incorporation of these drugs impacts healthcare budgets, requiring cost-effectiveness analyses for decision-making. The aim of this study was to evaluate the cost-effectiveness of ribociclib plus letrozole compared with palbociclib plus letrozole or letrozole as monotherapy for first-line treatment of postmenopausal women with HR+/HER2- locally advanced or metastatic BC (aBC) from a Brazilian private healthcare system perspective. METHODS: A model including progression-free survival (PFS), progressed disease, and death health states was used to simulate lifetime costs and outcomes. PFS and overall survival were derived from the MONALEESA-2 trial (lifetime horizon). Healthcare costs included drug acquisition and monitoring, subsequent therapies, adverse events, and end-of-life costs. Effectiveness was measured in quality-adjusted life-years (QALYs). Deterministic and probabilistic sensitivity analyses were performed. RESULTS: The total cost of treatment with ribociclib plus letrozole was USD 72,091.82 versus USD 92,749.64 for palbociclib plus letrozole. Total QALYs were 3.30 and 3.16, respectively. Base-case analysis showed ribociclib as dominant over palbociclib in first-line treatment of women with HR+/HER2- aBC, associated with cost savings and QALY gains. The total cost of treatment with ribociclib plus letrozole was USD 83,058.73 versus USD 29,215.10 for letrozole. Total QALYs were 3.84 and 2.61, respectively. Compared with letrozole, ribociclib plus letrozole was associated with an incremental cost of USD 53,843.64 and an incremental QALY gain of 1.23, with incremental cost-effectiveness ratio of USD 43,826.91 per QALY gained. CONCLUSIONS: As demonstrated by the cost-effectiveness dominance over palbociclib, ribociclib results in savings when used as first-line treatment in postmenopausal women with HR+/HER2- aBC, warranting incorporation in the private healthcare system.

New Challenges in Oncology for the Brazilian Private Health Sector: Specialists' Concerns After the ISPOR International Congress in Boston, Massachusetts, 2017.

The congress of the International Society for Pharmacoeconomics and Outcomes Research is one of the main worldwide forums for the dissemination of research and knowledge on healthcare economics. Brazil is the largest country in Latin America, with a per-capita gross domestic product of $15 200 in 2017 and healthcare expenditure of the order of $1 318 per inhabitant. Brazilian specialists participated actively in the society's latest congress, which took place in Boston, Massachusetts, from May 20 to 24, 2017. They met to discuss the main topics dealt with at the congress and their applicability to Brazilian realities. The topics chosen were precision medicine, new challenges for economic modeling within oncology and immuno-oncology, data to aid in managerial decision making (ie, data from real-world studies), and, lastly, strategies for accessing high-cost medications in Brazil. This opinion article sought to report the main conclusions and consensus reached by this group of specialists on the occasion of this discussion.

The Value of Biomarkers in Optimizing the Use of Immuno-oncologic Therapy.

The development of therapies that restore or activate the host immune response - the socalled "immuno-oncologic" therapy - has improved the survival of some cancer patients harboring specific tumor types. These drugs, however, are very expensive which has greatly limited their use and consequently reduced the number of patients who could likely benefit. Not to mention, the proportion of patients who display a clinical benefit from therapy is limited. Thus, from a clinical and health economics perspective, there is a pressing need to identify and treat those patients for whom a given immuno- oncologic therapy is most likely to be beneficial. At this end, the identification, validation and use of biomarkers emerge as an important therapeutic tool. Here, we briefly review the state of immunologic biomarker development and utilization and make suggestions for interested clinicians, health policy makers and other stakeholders to prepare for the broader use of biomarkers associated with immuno-oncologic therapy in routine practice. The biomarker field is clearly in its earliest stages and there is no doubt that continued research will identify new biomarkers with valuable clinical indications. Of course, the clinical utility of a biomarker must consider patient preferences and perspectives. In addition, health economic analyses are crucial to better define the value of immunotherapy based on precision medicine strategies and promote value-based pricing.

Cost-minimisation analysis of erlotinib in the second-line treatment of non-small-cell lung cancer: a Brazilian perspective.

OBJECTIVE: A cost-minimisation and budget impact analysis of erlotinib versus docetaxel or pemetrexed as second-line treatment for advanced non-small-cell lung cancer (NSCLC). METHODS: Costs and budgetary impacts were estimated from the perspective of a Brazilian private healthcare payer, based on results of the BR.21 study of erlotinib and pivotal trials of docetaxel and pemetrexed. A 126-day timeframe was evaluated, based on the progression-free survival determined for erlotinib in BR.21. A Delphi panel identified local practices and associated costs in Brazil. Other costs accounted for included medical payments, pre- and post-chemotherapy medication and drug administration costs. Multivariate sensitivity analyses were performed, but given the short time frame used, discounting was not applied. RESULTS: Total costs were R$26,825 for erlotinib, R$42,284 for docetaxel and R$79,841 for pemetrexed. Cost savings with erlotinib were attributable to lower acquisition costs (R$26,795 vs. R$40,217 for docetaxel and R$78,911 for pemetrexed) and lower costs for the management of side effects. Sensitivity analyses confirmed the robustness of the results. The budget impact analysis showed savings with erlotinib in the first year, ranging from R$3 million to R$28 million. CONCLUSION: Erlotinib is cost-saving over established chemotherapy in the second-line treatment of advanced NSCLC under the Brazilian private healthcare system.

The impact of patients with generalized anxiety disorder in the Brazilian Private Healthcare System: a claim database study with expert's perspective / O impacto de pacientes com transtorno de ansiedade generalizada no Sistema Único de Saúde: um estudo de base de sinistros com a perspectiva de especialistas

This study describes the healthcare resource use and costs associated with anxiety assessing claim database outcomes and expert opinion from the perspective of the Brazilian Private Healthcare System. A retrospective analysis of the Orizon database was conducted, containing claims data of anxiety patients reported in Private Healthcare Systems (2015-2017) according to the ICD-10 code (F40 or F41 and their subtypes). Further, a 3-hour online meeting brought together five anxiety and Health Insurance Companies experts to discuss their perspectives. The total cost of the 18,069 patients identified in the database was BRL 490 million: related to medical appointments (2%), exams (16%), emergency room (5%), and others (77%). The mean number of appointments was 5.1 in a 4-year period, performed by 61% of the patients. Approximately 2,595 visits were made to psychiatrists by 923 patients, and 95% underwent at least one examination (100.6 examinations per patient, on average). The identification of anxiety patients and their corresponding burden is challenging to estimate. The higher impact is related to the frequency of healthcare use before the diagnosis than the treatment itself. These outcomes may help plan and implement adequate healthcare programs for patients with anxiety.

Este estudo descreve o uso de recursos de saúde e os custos relacionados à ansiedade associando resultados de uma base de dados administrativa e opinião de especialistas na perspectiva do Sistema Privado de Saúde Brasileiro. Foi realizada uma análise retrospectiva da base de dados da Orizon de pacientes com ansiedade em atendimento hospitalizar ou ambulatorial no Sistema Privado de Saúde (2015 - 2017) com o código CID-10 (F40 ou F41 e os seus subtipos), adicionalmente promovemos uma reunião online de 3 horas com cinco especialistas em ansiedade e em seguros de saúde para discutir as suas perspectivas. O custo total dos 18.069 pacientes identificados no banco de dados foi de R$ 490 milhões, relacionados a consultas médicas (2%), exames (16%), pronto-socorro (5%) e outros (77%). A média de consultas foi de 5,1 em um período de 4 anos, realizadas por 61% dos pacientes. Aproximadamente 2.595 visitas foram feitas a psiquiatras por 923 pacientes, e 95% realizaram pelo menos um exame (média de 100,6 exames por paciente. É desafiador identificar e estimar o impacto da doença no Sistema Privado de Saúde Brasileiro. O impacto maior está relacionado à frequência de uso de serviços de saúde antes do diagnóstico, em comparação com o próprio tratamento. Esses resultados podem ajudar a planejar e implementar programas de saúde adequados para pacientes com ansiedade.

The impact of depression in the Brazilian private healthcare system: patient journey and economic burden study associating claim database and expert's opinion approach / O impacto da depressão no sistema de saúde privado brasileiro: estudo da jornada do paciente e da carga econômica associando banco de dados de sinistros e abordagem de opinião de especialistas

Objective: The study aimed to describe the profile and economic burden of patients with depression from the perspective of the Brazilian Private Healthcare System (PHS). Methods: A two-step methodological quantitative-qualitative research design was performed: retrospective descriptive analysis of the Orizon database of patients with at least one claim of depression (F33, F38, or F39) in PHS (2013-2019) and experienced physicians perspective from an expert meeting. Results: 1,802 patients fulfilling the eligibility criteria counted BRL 74,978 million across the 4-year period. Over this period, nearly 60% of patients had a medical appointment (6.6 appointments per patient, on average), 61% had a psychologist, 9.8% had a psychiatrist appointment, and an average of 115.2 exams and 8.7 emergency visits per patient were performed. According to the experts, the economic impact of depression is more significant when considering the indirect costs related to productivity loss and impairment in occupational and interpersonal functioning. Conclusion: Identifying and diagnosing patients with depression and their real burden is challenging; even with significant costs identified in the claim database analyses in the Brazilian PHS, the real impact must be higher if indirect costs are considered. The depressive disorder should be prioritized in the Brazilian PHS to establish more adequate health policies.

Objetivo: O estudo teve como objetivo descrever o perfil e a carga econômica de pacientes com depressão na perspectiva do Sistema Único de Saúde (SUS). Métodos: Foi realizado um projeto de pesquisa quantitativo-qualitativo metodológico em duas etapas: análise descritiva retrospectiva do banco de dados Orizon de pacientes com pelo menos uma alegação de depressão (F33, F38 ou F39) no PHS (2013- 2019) e perspectiva de médicos experientes de uma reunião de especialistas. Resultados: 1.802 pacientes que preencheram os critérios de elegibilidade totalizaram R$ 74,978 milhões no período de 4 anos. Nesse período, cerca de 60% dos pacientes tiveram consulta médica (6,6 consultas por paciente, em média), 61% tiveram psicólogo, 9,8% consulta com psiquiatra e foram realizados em média 115,2 exames e 8,7 atendimentos de emergência por paciente . Segundo os especialistas, o impacto econômico da depressão é mais significativo quando considerados os custos indiretos relacionados à perda de produtividade e prejuízo no funcionamento ocupacional e interpessoal. Conclusão: Identificar e diagnosticar pacientes com depressão e sua real carga é desafiador; mesmo com custos significativos identificados nas análises da base de sinistros do SUS brasileiro, o impacto real deve ser maior se considerados os custos indiretos. O transtorno depressivo deve ser priorizado na APS brasileira para o estabelecimento de políticas de saúde mais adequadas.

Chronic pain patients in the Brazilian private healthcare system: a claim database study with the experts' perspective / Pacientes com dor crônica no sistema de saúde suplementar brasileiro: um estudo de banco de dados com a perspectiva dos especialistas

Objective: This study aimed to describe the demands and costs from chronic pain patients over the private Brazilian healthcare system. Methods: This was a retrospective claim database study to assess the resource utilization of pain patients in the private setting. We used a four-year follow-up period to assess inpatient, outpatient, and procedures reported. Further, we promoted a forum of discussion with five pain experts and healthcare managers to address the management of chronic pain and assistance models.Results: We identified 79,689 patients with chronic pain. The orthopedist was the main medical specialist consulted with a total number of 38,879 visits performed. The ophthalmologist, cardiologist, gynecologist, and general practitioner were also frequently consulted (rheumatologist was seldom consulted). Among non-medical specialists, the physical therapist was consulted 87,574 times by 12,342 patients (15% of the entire cohort), Among chronic pain patients, 96% performed at least one exam and 86% of the patients presented at least one ER visit during the follow-up period. In 4 years, we estimate that pain patients costed more than 3 billion reais to the private health care system. According to the experts' opinions, a fragmented healthcare system and the lack of patient centered interdisciplinary approaches contributes to a high ineffective pain management leading to a high use of resources. Conclusion: There is an urgent need to change the chronic pain care model in the Brazilian private setting. Qualification in pain management, a multidisciplinary patient centered care, integrated approaches, pain centers, and patients' education may help changing this scenario.

Objetivo: O objetivo do estudo foi descrever as demandas e custos dos pacientes com dor crônica no sistema privado de saúde brasileiro. Métodos: Neste estudo retrospectivo do banco de dados administrativo, avaliamos a utilização de recursos de pacientes com dor no ambiente privado. Em um período de quatro anos, avaliamos internações, visitas ambulatoriais e procedimentos. Adicionalmente, promovemos um fórum de discussão com cinco especialistas em dor e gerentes de saúde para abordar o manejo da dor e os modelos de assistência. Resultados: Identificamos 79.689 pacientes com dor crônica. O ortopedista foi o principal especialista médico consultado, com 38.879 visitas realizadas. O oftalmologista, o cardiologista, o ginecologista e o clínico geral também foram consultados com frequência (o reumatologista foi raramente consultado). Entre os especialistas não médicos, o fisioterapeuta foi consultado 87.574 vezes por 12.342 pacientes (15% de toda a coorte). Entre os pacientes, 96% realizaram pelo menos um exame e 86% apresentaram pelo menos uma consulta de emergência durante o período. Em 4 anos, estimamos um custo de mais de 3 bilhões de reais para o sistema privado de saúde. De acordo com as opiniões dos especialistas, um sistema de saúde fragmentado e a falta de abordagens centradas no paciente contribuem para um manejo ineficaz da dor, resultando em um alto uso de recursos. Conclusão: Há necessidade de mudar o modelo de manejo da dor crônica no sistema privado brasileiro. Qualificação dos profissionais, atendimento multidisciplinar centrado no paciente, abordagens integradas, centros de dor e educação dos pacientes podem ajudar a mudar esse cenário.