Potential life years not saved due to lack of access to anti-EGFR tyrosine kinase inhibitors for lung cancer treatment in the Brazilian public healthcare system: Budget impact and strategies to improve access. A pharmacoeconomic study

ABSTRACT BACKGROUND: Lung cancer is the fourth most common cancer in Brazil. In the 2000s, better understanding of molecular pathways led to development of epidermal growth factor receptor (EGFR)-targeted treatments that have improved outcomes. However, these treatments are unavailable in most Brazilian public healthcare services (Sistema Único de Saúde, SUS). OBJECTIVE: To assess the potential number of years of life not saved, the budget impact of the treatment and strategies to improve access. DESIGN AND SETTING: Pharmacoeconomic study assessing the potential societal and economic impact of adopting EGFR-targeted therapy within SUS. METHODS: We estimated the number of cases eligible for treatment, using epidemiological data from the National Cancer Institute. We used data from a single meta-analysis and from the Lung Cancer Mutation Consortium (LCMC) study as the basis for assessing differences in patients' survival between use of targeted therapy and use of chemotherapy. The costs of targeted treatment were based on the national reference and were compared with the amount reimbursed for chemotherapy through SUS. RESULTS: There was no life-year gain with EGFR-targeted therapy in the single meta-analysis (hazard ratio, HR, 1.01). The LCMC showed that 1,556 potential life-years were not saved annually. We estimated that the annual budget impact was 125 million Brazilian reais (BRL) with erlotinib, 48 million BRL with gefitinib and 52 million BRL with afatinib. Their incremental costs over chemotherapy per life-year saved were 80,329 BRL, 31,011 BRL and 33,225 BRL, respectively. A drug acquisition discount may decrease the budget impact by 30% (with a 20% discount). A fixed cost of 1,000 BRL may decrease the budget impact by 95%. CONCLUSION: Reducing drug acquisition costs may improve access to EGFR-targeted therapy for lung cancer.

Incidencia, mortalidad y costos de la atención por cáncer de pulmón en el Instituto Mexicano del Seguro Social / Incidence, mortality and associated costs of lung cancer in the Mexican Institute of Social Security

Resumen: Objetivo: Analizar la tendencia temporal de la incidencia y la mortalidad del cáncer de pulmón, así como los costos asociados con su atención médica. Material y métodos: Se estimó el número de casos incidentes a partir de los egresos hospitalarios de 276 hospitales del Instituto Mexicano del Seguro Social (IMSS) entre 2006 y 2016. Se calcularon tasas de mortalidad crudas y ajustadas. Los costos del tratamiento ambulatorio y hospitalario se calcularon con base en los costos médico-técnicos de referencia o costos estándar de 2015. Resultados: Tanto la incidencia como la mortalidad muestran tendencia descendente. El costo de la atención médica de los 2 539 pacientes de 2017 fue de 42 millones de dólares americanos, con costo promedio por paciente de 16 527 dólares americanos. El gasto promedio anual de pensiones por invalidez es de 97.2 millones de pesos. Conclusiones: Es probable que la reducción del riesgo de enfermar y morir por cáncer de pulmón en derechohabientes del IMSS se deba a las medidas de control del humo de tabaco. Todavía es necesario establecer estrategias para diagnosticar y tratar a los pacientes en estadios tempranos.

Abstract: Objective: To describe temporal trends in lung cancer incidence, mortality and associated health care costs in the Mexican Institute of Social Security. Materials and methods: Incident cases were estimated from hospital discharges in 276 IMSS hospitals between 2006 and 2016. Crude and adjusted mortality rates were calculated. The costs of outpatient and inpatient treatment were calculated based on the medical-technical costs of reference o standard cost. Results: Both incidence and mortality had a decreased time trend. The cost of medical care for the 2 539 patients in 2017 was 42 million US dollars, with an average cost per patient of 16 537 US dollars. The cost per annum of disability pensions is 97.2 million pesos. Conclusions: It is likely that the reduction of the risk of getting sick and dying from lung cancer in IMSS affiliates is due to the control measures of tobacco smoke. It is still necessary to establish strategies to diagnose and treat patients in early stages.

Estimated costs of advanced lung cancer care in a public reference hospital / Estimativa dos custos da assistência do câncer de pulmão avançado em hospital público de referência

ABSTRACT OBJECTIVE To estimate the direct medical costs of advanced non-small cell lung cancer care. METHODS We assessed a cohort of 277 patients treated in the Brazilian National Cancer Institute in 2011. The costs were estimated from the perspective of the hospital as a service provider of reference for the Brazilian Unified Health System. The materials and procedures used were identified and quantified, per patient, and we assigned to them monetary values, consolidated in phases of the assistance defined. The analyses had a descriptive character with costs in Real (R$). RESULTS Overall, the cohort represented a cost of R$2,473,559.91, being 71.5% related to outpatient care and 28.5% to hospitalizations. In the outpatient care, costs with radiotherapy (34%) and chemotherapy (22%) predominated. The results pointed to lower costs in the initial phase of treatment (7.2%) and very high costs in the maintenance phase (61.6%). Finally, we identified statistically significant differences of average cost by age groups, education levels, physical performance, and histological type. CONCLUSIONS This study provides a current, useful, and relevant picture of the costs of patients with non-small cell lung cancer treated in a public hospital of reference and it provides information on the magnitude of the problem of cancer in the context of public health. The results confirm the importance of radiation treatment and hospitalizations as the main components of the cost of treatment. Despite some losses of follow-up, we assess that, for approximately 80% of the patients included in the study, the estimates presented herein are satisfactory for the care of the disease, from the perspective of a service provider of reference of the Brazilian Unified Health System, as it provides elements for the management of the service, as well as for studies that result in more rational forms of resource allocation.

RESUMO OBJETIVO Estimar os custos médicos diretos da assistência ao câncer de pulmão não pequenas células avançado. MÉTODOS Foi avaliada uma coorte de 277 pacientes matriculados no Instituto Nacional do Câncer em 2011. Os custos foram estimados sob a perspectiva do hospital como prestador de serviços de referência para o SUS. Insumos e procedimentos utilizados foram identificados e quantificados, por paciente, sendo a eles atribuídos valores monetários, consolidados por fases da assistência definidas. As análises tiveram caráter descritivo com custos em reais (R$). RESULTADOS Em termos globais, a coorte representou um custo de R$2.473.559,91, sendo 71,5% relacionados à atenção ambulatorial e 28,5% as internações. Na atenção ambulatorial, predominaram os custos com radioterapia (34%) e quimioterapia (22%). Os resultados apontaram para custos menores na fase inicial de tratamento (7,2%) e custos muito elevados na fase de manutenção (61,6%). Por fim, identificaram-se diferenças estatisticamente significativas das médias dos custos por faixas etárias, níveis de escolaridade, desempenho físico e tipo histológico. CONCLUSÕES Este estudo fornece um retrato atual, útil e relevante sobre os custos de pacientes com câncer de pulmão não pequenas células assistidos em um hospital público de referência e provê elementos sobre a magnitude do problema do câncer no âmbito da saúde pública. Os resultados ratificam a importância do tratamento radioterápico e das internações como principais componentes de custo do tratamento. Apesar de algumas perdas de seguimento avalia-se que, para cerca de 80% dos pacientes incluídos no estudo, as estimativas aqui apresentadas sejam satisfatoriamente fidedignas ao cuidado da doença, sob a perspectiva de um prestador de referência do SUS, fornecendo elementos para a gestão do serviço, bem como para estudos que redundem em formas mais racionais de alocação de recursos.

Budget impact from the incorporation of positron emission tomography - computed tomography for staging lung cancers / Impacto orçamentário da incorporação da tomografia de emissão de pósitrons - tomografia computadorizada para estadiamento de câncer pulmonar

OBJECTIVE To estimate the budget impact from the incorporation of positron emission tomography (PET) in mediastinal and distant staging of non-small cell lung cancer.METHODS The estimates were calculated by the epidemiological method for years 2014 to 2018. Nation-wide data were used about the incidence; data on distribution of the disease´s prevalence and on the technologies' accuracy were from the literature; data regarding involved costs were taken from a micro-costing study and from Brazilian Unified Health System (SUS) database. Two strategies for using PET were analyzed: the offer to all newly-diagnosed patients, and the restricted offer to the ones who had negative results in previous computed tomography (CT) exams. Univariate and extreme scenarios sensitivity analyses were conducted to evaluate the influence from sources of uncertainties in the parameters used.RESULTS The incorporation of PET-CT in SUS would imply the need for additional resources of 158.1 BRL (98.2 USD) million for the restricted offer and 202.7 BRL (125.9 USD) million for the inclusive offer in five years, with a difference of 44.6 BRL (27.7 USD) million between the two offer strategies within that period. In absolute terms, the total budget impact from its incorporation in SUS, in five years, would be 555 BRL (345 USD) and 600 BRL (372.8 USD) million, respectively. The costs from the PET-CT procedure were the most influential parameter in the results. In the most optimistic scenario, the additional budget impact would be reduced to 86.9 BRL (54 USD) and 103.8 BRL (64.5 USD) million, considering PET-CT for negative CT and PET-CT for all, respectively.CONCLUSIONS The incorporation of PET in the clinical staging of non-small cell lung cancer seems to be financially feasible considering the high budget of the Brazilian Ministry of Health. The potential reduction in the number of unnecessary surgeries may cause the available resources to be more efficiently allocated.

OBJETIVO Estimar o impacto orçamentário da incorporação da tomografia por emissão de pósitrons (PET) no estadiamento mediastinal e à distância do câncer pulmonar de células não pequenas.MÉTODOS As estimativas foram calculadas pelo método epidemiológico para os anos de 2014 a 2018. Utilizaram-se dados nacionais de incidência; de distribuição de doença e acurácia das tecnologias procedentes da literatura, e de custos, de estudo de microcustos e das bases de dados do Sistema Único de Saúde. Analisaram-se duas estratégias de uso da PET: oferta a todos os pacientes recém-diagnosticados, e restrita àqueles que apresentassem resultados negativos de tomografia computadorizada (TC) prévia. Foram realizadas análises de sensibilidade univariadas e por cenários extremos para avaliar influência de fontes de incertezas nos parâmetros utilizados.RESULTADOS A incorporação da PET-TC ao Sistema Único de Saúde implicaria na necessidade de recursos adicionais de R$158,1 (US$98,2) milhões para oferta restrita a R$202,7 (US$125,9) milhões para oferta abrangente em cinco anos, com diferença entre as duas estratégias de oferta de R$44,6 (US$27,7) milhões no período. Em termos absolutos, o impacto orçamentário total da incorporação no Sistema Único de Saúde, em cinco anos, seria de R$555 (US$345) e R$600 (US$372,8) milhões, respectivamente. Custos do procedimento PET-TC foram o parâmetro de maior influência nos resultados. No cenário por extremos mais otimista, os impactos orçamentários incrementais reduzir-se-iam para R$86,9 (US$54) e R$103,8 (US$64,5) milhões, considerando PET-TC para TC negativa e PET-TC para todos, respectivamente.CONCLUSÕES A incorporação da PET no estadiamento clínico do câncer pulmonar de células não-pequenas parece ser financeiramente factível frente à magnitude do orçamento do Ministério da Saúde. A potencial redução no número de cirurgias desnecessárias pode produzir maior eficiência na alocação dos recursos disponíveis.

Estimativa dos custos diretos da assistência oncológica do câncer de pulmão não pequenas células avançado em um hospital público de referência / Estimate of the direct costs of cancer care of lung cancer advanced non-small cell in a public referral hospital

Este estudo teve como objetivo geral estimar os custos diretos da assistência oncológica do câncer de pulmão não pequenas células avançado (estádio IIIB/IV) metastático para uma coorte de 277 pacientes matriculados no INCA no ano de 2011 e acompanhados por até 18 meses. Os custos foram estimados sob a perspectiva do Instituto Nacional do câncer (INCA), como prestador de serviços de referência para o SUS. Foram considerados somente os custos médicos diretos, sendo identificados e quantificados, por paciente, os insumos utilizados na produção de serviços/ procedimentos, aos quais foram atribuídos valores monetários. Tais serviços/procedimentos foram alocados por fases da assistência oncológica estabelecidas para este estudo: (1) fase inicial –procedimentos relativos ao diagnóstico; (2) fase de manutenção: procedimentos relativos ao tratamento proposto; e (3) fase terminal: período de três meses que antecede o óbito. As análises realizadas tiveram caráter descritivo, focalizando as distribuições de variáveis sóciodemográficas, clínicas, relativas ao uso de tecnologias de diagnóstico e tratamento e, centralmente, relativas aos custos (expressos em reais) do cuidado à doença na população do estudo. Metade da coorte foi a óbito em pouco mais de seis meses. Houve perda de seguimento de alguns pacientes incluídos no estudo, enquanto outros ainda se mantiveram vivos após o período de observação estabelecido, mas,ainda assim, avalia-se que, para cerca de 80% dos pacientes, as estimativas aqui apresentadas sejam satisfatoriamente fidedignas ao cuidado da doença, sob a perspectiva de um prestador de referência do SUS. Em termos globais a coorte correspondeu a um custo de R$ 2.473.559,91, dos quais 71,5 por cento relacionados à atenção ambulatorial e 28,5 por cento à atenção hospitalar (internações). Na atenção ambulatorial,predominaram os custos com radioterapia (34 por cento) e quimioterapia (22 por cento)...

This study aimed to estimate the direct costs of oncology care of lung cancer advancednon-small cell (stage IIIB / IV) metastatic to a cohort of 277 patients enrolled in INCAin 2011 and followed for up to 18 months. Costs were estimated from the perspective ofthe National Cancer Institute (INCA), and reference services provider to the NHS. We considered only the direct medical costs, identified and quantified, per patient, the rawmaterials used in the production of services / procedures, to which monetary values were assigned. These services / procedures were allocated in stages of cancer careestablished for this study: (1) early stage - procedures for diagnosis; (2) maintenance phase: procedures for the proposed treatment; and (3) the terminal phase: three monthsprior to death. The analyses were descriptive, focusing on the distribution of sociodemographic variables, clinical, on the use of diagnostic and treatment technologies and, and centrally, on costs care (expressed in Reais) of disease in the studied population. Half cohort died in just over six months. There was loss of some patients included in the study, while still others remained alive after the established observation period, but still, it is evaluated that for about 80 pecent of patients, the estimates presentedhere are satisfactorily reliable to care of the disease, from the perspective of a SUS reference provider. Overall cohort corresponded to a cost of R$ 2,473,559.91, of which71.5 percent related to ambulatory care and 28.5 percent for hospital care (hospitalization). At the outpatient care, radiotherapy costs were predominant (34 percent) and chemotherapy (22 percent). In addition, the results showed the incidence of lower costs in the initial phase of treatment (7.2 percent), more focused on exams, very high costs in the maintenance phase (61.6 percent), and also high costs in the terminal phase (31.2 percent)...

Epidemiologic Characteristics of Compensated Occupational Lung Cancers among Korean Workers

An understanding of the characteristics of occupational lung cancer is important to establish policies that prevent carcinogen exposure and to compensate workers exposed to lung carcinogens. This study analyzed the characteristics of occupational lung cancers in workers who were compensated under the Industrial Accident Compensation Insurance Law between 1994 and 2011. A total of 179 occupational lung cancers were compensated. The main carcinogenic exposure was asbestos, followed by crystalline silica and hexavalent chromium. The mean exposure duration and latency were 19.8 and 23.2 yr. The most common industry was manufacturing, followed by construction and transportation. The most common occupation was maintenance and repair, followed by foundry work, welding, painting, and spinning or weaving. Although asbestos was predominant carcinogen, the proportion of these cases was relatively low compared to other developed countries. Proper surveillance system is needed to monitor occupational lung cancer and improve prevention measures.

Estudio piloto: costos directos atribuibles al tabaquismo en dos hospitales de Santiago / Pilot study: tobacco-attributable direct costs in two hospitais in Santiago, Chile

Background: Tobaceo is the fourth cause of the global burden of disease, accounting for 79.9 million loss of disability-adjusted Ufe years (DALYs) in 2001. In 2002, tobacco-attributable mortality in Chile represented 17 percent of total mortality. Aim: To estimate the direct cost of tobaceo in Ischemic Heart Disease, Chronic Obstructive Pulmonary Disease and Lung Cáncer, explore patients' disposition to answer a health related expenses questionnaire, valídate the instruments used and determine an adequate sample size for an upcoming study. Material and methods: Socio-demographic and health care related variables were investigated among patients attending two publie hospitais for ischemic heart disease, chronic obstructive pulmonary disease and lung cancer, in a cross-sectional study. Costs were estimated using the national publie health insurance price list and market pnces. Tobacco-attributable fraction was then applied to calcúlate the tobacco-attributable cost ofeach disease. Results: The instruments used were validated. The group of lung cáncer patients was smaller due to increased mortality prior to interview. Lung cancer generated the largest total and attríbutable direct costs. The costs in patients with ischemic heart disease were significantly lower Conclusions: There were some difficulties in the application of the questionnaire to register medication use. The sample size needed in a larger study was calculated for each of the three diseases. We recommend that a definitive study addresses tobacco-attributable direct costs related to chronic obstructive pulmonary disease.

The economic burden of smoking-related disease in Thailand: a prevalence-based analysis.

OBJECTIVE: To estimate the direct out-of-pocket medical costs of treating major diseases attributable to smoking in Thailand in 2006. MATERIAL AND METHOD: A prevalence-based, disease-specific, approach was used to estimate the direct medical costs of treating lung cancer, chronic obstructive pulmonary disease (COPD), and coronary heart disease (CHD) attributable to smoking. Epidemiological parameters were obtained from the literature; historical out-of-pocket cost data were used to estimate 2006 expenditure. RESULTS: The number of cases attributable to smoking in 2006 was 5,299 for lung cancer, 624,309 for COPD, and 52,605 for CHD. The out-of-pocket expenditures for treatment were 368.49 million baht for lung cancer, 7,714.88 million baht for COPD, and 1,773.65 million baht for CHD. Total smoking-attributable out-of-pocket medical costs amounted to 9,857.02 million baht, 0.48% of GDP in 2006. CONCLUSION: The prevalence-based, disease-specific, analysis described here shows that the health and economic impact of smoking in Thailand are substantial, and should be reduced by implementing smoking-cessation and related tobacco control policies of the types found effective in reducing the prevalence of smoking in other countries.

Análisis fármaco Económico entre Erlotinib y Pemetrexed en el tratamiento del Cáncer de pulmón en segunda línea / Pharmaeconomics among Erlotinib and Pemetrexed in second line of lung cancer treatment

El Costo Integral del tratamiento es la suma del costo de personal, bienes y servicios en los que se debe incurrir para restablecer la salud del paciente y debe evaluarse a la luz del tiempo que toma lograr el objetivo terapéutico. Este es un elemento vital en la Toma de Decisiones. En este estudio se muestra las ventajas de usar drogas orales como el Erlotinib (Tarceva) frente a drogas intravenosas como el Pemetrexed (Alimta) para el manejo de pacientes con cáncer al pulmón de células no pequeñas (NSCLC) que hayan recibido previamente una o dos líneas de quimioterapia. El estudio muestra que la administración de un tratamiento oral como Erlotinib (Tarceva) permite un ahorro de 14,394 soles por paciente que se atiende en la Seguridad Social - EsSalud. También muestra una mejora en la calidad de vida frente a otros aspectos relacionados con el tratamiento puesto que resalta la percepción de bienestar del paciente ante una terapia oral.