Integrative oncology: Addressing the global challenges of cancer prevention and treatment.

The increase in cancer incidence and mortality is challenging current cancer care delivery globally, disproportionally affecting low- and middle-income countries (LMICs) when it comes to receiving evidence-based cancer prevention, treatment, and palliative and survivorship care. Patients in LMICs often rely on traditional, complementary, and integrative medicine (TCIM) that is more familiar, less costly, and widely available. However, spheres of influence and tensions between conventional medicine and TCIM can further disrupt efforts in evidence-based cancer care. Integrative oncology provides a framework to research and integrate safe, effective TCIM alongside conventional cancer treatment and can help bridge health care gaps in delivering evidence-informed, patient-centered care. This growing field uses lifestyle modifications, mind and body therapies (eg, acupuncture, massage, meditation, and yoga), and natural products to improve symptom management and quality of life among patients with cancer. On the basis of this review of the global challenges of cancer control and the current status of integrative oncology, the authors recommend: 1) educating and integrating TCIM providers into the cancer control workforce to promote risk reduction and culturally salient healthy life styles; 2) developing and testing TCIM interventions to address cancer symptoms or treatment-related adverse effects (eg, pain, insomnia, fatigue); and 3) disseminating and implementing evidence-based TCIM interventions as part of comprehensive palliative and survivorship care so patients from all cultures can live with or beyond cancer with respect, dignity, and vitality. With conventional medicine and TCIM united under a cohesive framework, integrative oncology may provide citizens of the world with access to safe, effective, evidence-informed, and culturally sensitive cancer care.

Health technology assessment in Brazil - an international perspective. / O processo de incorporação de tecnologias em saúde no Brasil em uma perspectiva internacional.

Given the financial impact of the adoption of new health technologies in health systems, choosing what technology should be introduced and when poses a major challenge for health managers. The health technology assessment (HTA) process should therefore be underpinned by transparent and objective criteria. The objective of this study was to analyze HTA processes in Brazil, overseen by the National Commission for the Incorporation of Health Technology (CONITEC), and to compare these processes with those in countries considered to be at the forefront of this field: Australia, Canada, and the United Kingdom. The following categories were used for the comparative analysis: program structure, definition and selection of topics, evidence review, use of HTA in decision making, program products and dissemination, and transparency. The findings show that there are more similarities than differences between these countries' processes and the CONITEC processes. The main differences identified were: composition of committees, entitlement to appeal, program evaluation, and timeframes for the implementation of recommendations/decisions. Despite making major strides in recent years, Brazil should continue to promote continuous improvement of its HTA process.

Dado o impacto financeiro da incorporação de novas tecnologias em saúde, é um desafio para os gestores escolher qual delas deve ser incorporada e quando isto deve ocorrer. Assim, é necessário contar com um processo de avaliação e de incorporação de tecnologias baseado em critérios transparentes e objetivos. Neste trabalho objetivou-se analisar o processo nacional da Comissão Nacional de Incorporação de Tecnologias em Saúde do Ministério da Saúde (Conitec) e compará-lo com o de agências de países de referência: Austrália, Canadá e Reino Unido. Utilizaram-se as seguintes categorias para a comparação: estrutura, indicação e seleção de temas, condução da revisão de evidências, uso de Avaliação Tecnológica em Saúde (ATS) na tomada de decisão, produtos do programa de ATS, divulgação e transparência. O processo da Conitec legalmente previsto apresentou mais similaridades do que distinções em comparação com os das agências estudadas. As principais diferenças foram em relação a: composição dos comitês, apresentação de recursos, avaliação do programa, seleção e prazos para oferta da tecnologia incorporada. Apesar dos avanços, a incorporação de tecnologias em saúde no Brasil deve buscar a melhoria contínua.

O processo de incorporação de tecnologias em saúde no Brasil em uma perspectiva internacional / Health technology assessment in Brazil - an international perspective

Resumo Dado o impacto financeiro da incorporação de novas tecnologias em saúde, é um desafio para os gestores escolher qual delas deve ser incorporada e quando isto deve ocorrer. Assim, é necessário contar com um processo de avaliação e de incorporação de tecnologias baseado em critérios transparentes e objetivos. Neste trabalho objetivou-se analisar o processo nacional da Comissão Nacional de Incorporação de Tecnologias em Saúde do Ministério da Saúde (Conitec) e compará-lo com o de agências de países de referência: Austrália, Canadá e Reino Unido. Utilizaram-se as seguintes categorias para a comparação: estrutura, indicação e seleção de temas, condução da revisão de evidências, uso de Avaliação Tecnológica em Saúde (ATS) na tomada de decisão, produtos do programa de ATS, divulgação e transparência. O processo da Conitec legalmente previsto apresentou mais similaridades do que distinções em comparação com os das agências estudadas. As principais diferenças foram em relação a: composição dos comitês, apresentação de recursos, avaliação do programa, seleção e prazos para oferta da tecnologia incorporada. Apesar dos avanços, a incorporação de tecnologias em saúde no Brasil deve buscar a melhoria contínua.

Abstract Given the financial impact of the adoption of new health technologies in health systems, choosing what technology should be introduced and when poses a major challenge for health managers. The health technology assessment (HTA) process should therefore be underpinned by transparent and objective criteria. The objective of this study was to analyze HTA processes in Brazil, overseen by the National Commission for the Incorporation of Health Technology (CONITEC), and to compare these processes with those in countries considered to be at the forefront of this field: Australia, Canada, and the United Kingdom. The following categories were used for the comparative analysis: program structure, definition and selection of topics, evidence review, use of HTA in decision making, program products and dissemination, and transparency. The findings show that there are more similarities than differences between these countries' processes and the CONITEC processes. The main differences identified were: composition of committees, entitlement to appeal, program evaluation, and timeframes for the implementation of recommendations/decisions. Despite making major strides in recent years, Brazil should continue to promote continuous improvement of its HTA process.

Cisplatin, Fluorouracil in Bolus Injection, and Leucovorin in First-Line Therapy for Advanced Gastric Cancer as an Alternative to Protocols With Infusional Fluorouracil.

PURPOSE: Gastric cancer (GC) is the fourth most common cancer and the second leading cause of cancer death worldwide. Platinum agents and fluoropyrimidines are the main compounds used in the first-line setting for advanced GC. Given the activity of fluorouracil (FU) bolus, the PFL protocol, a chemotherapy regimen combining cisplatin, FU bolus, and leucovorin, was incorporated at the Brazilian National Cancer Institute, because this schedule does not require hospitalization or infusion pumps. This study aims to evaluate the outcomes of PFL in the first-line setting for patients with advanced GC. MATERIALS AND METHODS: This was a retrospective cohort study evaluating patients with advanced GC treated in the first-line setting with cisplatin 80 mg/m2 on day 1 and FU bolus 400 mg/m2 plus leucovorin 20 mg/m2 on days 1, 8, 15, and 22 every 4 weeks, from January 2008 to December 2014. RESULTS: A total of 109 patients were enrolled. The median number of cycles received per patient was four (one to 11). Complete responses were achieved in 6.4% and partial responses in 14.7%. Median progression-free survival was 6.3 months (95% CI, 5.08 to 7.58 months) and median overall survival was 8.3 months (95% CI, 6.79 to 9.87 months). Thirty-four (31.2%) patients were alive in 1 year. Grade 3 and 4 adverse events were experienced by 26.6% and 3.7% of patients, respectively, with dose reduction necessary in 9.1%. CONCLUSION: PFL is active in advanced GC and could be an alternative for FU continuous infusion protocols in institutions with limited resources and/or low budget, which is the reality in many nations all over the world.

A randomised phase II study of chemoradiotherapy with or without nimotuzumab in locally advanced oesophageal cancer: NICE trial.

PURPOSE: Chemoradiotherapy is the standard treatment for patients with inoperable locally advanced oesophageal cancer. We sought to assess the safety and efficacy of chemoradiation combined with nimotuzumab, a humanised antibody directed against epidermal growth factor receptor (EGFR). PATIENTS AND METHODS: Untreated patients with inoperable locally advanced oesophageal cancer and no distant metastases were randomised to chemoradiotherapy (cisplatin and fluorouracil combined with external beam radiation) alone or in combination with nimotuzumab. The primary end-point was the endoscopic complete response (eCR) rate, and secondary end-points comprised quality of life (QoL) and safety. The combined eCR and pathologic complete response (cEPCR) and overall survival (OS) were also evaluated. RESULTS: We enrolled 107 patients with a mean age of 59 years, and 93% had squamous cell carcinoma. Toxicity was manageable in both arms with no important differences in adverse events (AEs). We performed post-treatment endoscopies in 67 patients, including 60 who had a biopsy. In the intent-to-treat population, the eCR rates with and without nimotuzumab were 47.2% and 33.3% (P = 0.17), respectively, and the cEPCR rates were 62.3% and 37.0% (P = 0.02), respectively. With a median follow-up of 14.7 months, the hazard ratio (HR) for OS was 0.68 (95% confidence interval (CI): 0.44-1.07; P = 0.09) with a median OS of 15.9 months for the nimotuzumab arm and 11.5 months for the control arm. Regarding QoL, a significant difference was observed for the physical subscale score (P = 0.03) with lower values for the control arm. CONCLUSION: Combined chemoradiotherapy plus nimotuzumab is safe for patients with locally advanced oesophageal cancer, it appears to increase the cEPCR rate, and without compromising QoL. CLINICAL TRIALS: Identification number: EF024-201; Trial registry: NCT01249352.

IMPLICATIONS OF GLOBAL PRICING POLICIES ON ACCESS TO INNOVATIVE DRUGS: THE CASE OF TRASTUZUMAB IN SEVEN LATIN AMERICAN COUNTRIES.

OBJECTIVES: Differential pricing, based on countries' purchasing power, is recommended by the World Health Organization to secure affordable medicines. However, in developing countries innovative drugs often have similar or even higher prices than in high-income countries. We evaluated the potential implications of trastuzumab global pricing policies in terms of cost-effectiveness (CE), coverage, and accessibility for patients with breast cancer in Latin America (LA). METHODS: A Markov model was designed to estimate life-years (LYs), quality-adjusted life-years (QALYs), and costs from a healthcare perspective. To better fit local cancer prognosis, a base case scenario using transition probabilities from clinical trials was complemented with two alternative scenarios with transition probabilities adjusted to reflect breast cancer epidemiology in each country. RESULTS: Incremental discounted benefits ranged from 0.87 to 1.00 LY and 0.51 to 0.60 QALY and incremental CE ratios from USD 42,104 to USD 110,283 per QALY (2012 U.S. dollars), equivalent to 3.6 gross domestic product per capita (GDPPC) per QALY in Uruguay and to 35.5 GDPPC in Bolivia. Probabilistic sensitivity analysis showed 0 percent probability that trastuzumab is CE if the willingness-to-pay threshold is one GDPPC per QALY, and remained so at three GDPPC threshold except for Chile and Uruguay (4.3 percent and 26.6 percent, respectively). Trastuzumab price would need to decrease between 69.6 percent to 94.9 percent to became CE in LA. CONCLUSIONS: Although CE in other settings, trastuzumab was not CE in LA. The use of health technology assessment to prioritize resource allocation and support price negotiations is critical to making innovative drugs available and affordable in developing countries.

Implications of global pricing policies of pharmaceuticals for access the innovative drugs: the case of trastuzumab in seven Latin American countries

Background: Differential pricing (DP) on the basis of countries' purchasing power has been recommended by the WHO to secure more affordably priced medicines. However, in developing counties (DC) many innovative drugs have similar or even higher prices than in high-income countries (HIC). We conducted a cost-effectiveness (CE) analysis to estimate the impact of this pricing policy on the CE of trastuzumab in Latin-America (LA). Methods: Model structure and a common methodology for identifying costs and resource use were agreed with country teams. A Markov model was designed to evaluate life years (LY), quality adjusted life years (QALYs) and costs \r\nfrom a health care sector perspective. A systematic search on effectiveness, local epidemiology and costs studies was undertaken to populate the model. A base case scenario using transition probabilities from trastuzumab clinical trials, and two alternative scenarios with transition probabilities adjusted to reflect breast cancer epidemiology in each country, were built to better fit local cancer prognosis. Findings: Incremental discounted benefits and costs of the trastuzumab strategy ranged from 0·87 to 1·00 LY, 0·51 to 0·60 QALY and $24,683 to $60,835 (2012 US dollars). Incremental CE ratios ranged from $42,104 to $110,283 per QALY, equivalent to 3·6 gross domestic products per capita (GDPc) per QALY in Uruguay to up to 35·5 GDPc per QALY in Bolivia. The probabilistic sensitivity analysis showed a 0% probability that trastuzumab is CE if the willingness-to-pay (WTP) threshold is one GDPpc per QALY, and remains 0% at a WTP threshold of three GDPc except in Chile and Uruguay (probability 4·3% and 26·6% respectively). Conclusion: Despite its proven CE in other settings, trastuzumab was not CE in LA at its current price. Better cooperation between the public and private sectors is still needed to make innovative drugs available and affordable in DC.

Validation of the Portuguese version of functional assessment of cancer therapy-fatigue (FACT-F) in Brazilian cancer patients.

GOALS OF WORK: The purpose of this study was to validate the Portuguese version of the Functional Assessment of Cancer Therapy-Fatigue (FACT-F) in order to establish its assessment properties, including validity and reliability in a sample of Brazilian cancer patients. MATERIALS AND METHODS: Two hundred seventy patients with different types of cancer were included for this study; the mean age was 50.5 years. The reliability was assessed by internal consistency and reproducibility. Construct validity was assessed through convergent validity and discriminant validity. Convergent validity was examined by comparing the FACT-F to the SF-36. Discriminant validity of the FACT-F evaluated the ability of the scale to differentiate defined groups, discriminating patients according to Eastern Cooperative Oncology Group Performance Status and different stages of disease. MAIN RESULTS: FACT-F had high internal consistency (Cronbach alpha coefficient was 0.78 for physical well-being, 0.68 for social/family well-being, 0.75 for emotional well-being, 0.74 for functional well-being, 0.91 for fatigue, and 0.92 for total FACT-F). The range of test-retest intraclass correlation was from 0.72 to 0.91 (p < 0.0001). The Pearson product correlation revealed good correlations between the total FACT-F and subscales of the SF-36 in most dimensions, ranging from r = 0.51 to r = 0.76, except for SF-36 physical (r = 0.31). The positive correlations between the SF-36 vitality scale and FACT-F total (r = 0.76) and the fatigue subscale (r = 0.77) support the convergent validity. CONCLUSIONS: The Portuguese version of FACT-F is a reliable and valid instrument to assess quality of life and fatigue, representing a valid tool to screen cancer-related fatigue in Brazilian cancer patients.

Avaliações econômicas do uso da vacina contra o Papilomavírus Humano (HPV) em meninas adolescentes: uma revisão sistemática / Economic evaluations of the use of a vaccine against human papillomavirus (HPV) in adolescent girls: a systematic review

O câncer de colo do útero persiste como um importante problema de saúde em todo o mundo, em particular nos países em desenvolvimento. Duas vacinas contra o papilomavirus humano (HPV) encontram-se atualmente disponíveis e aprovadas para uso em meninas adolescentes, antes do início da vida sexual: uma bivalente, contra os sorotipos 16 e 18 e outra quadrivalente, contra os sorotipos 6, 11, 16 e 18. Estes imunobiológicos têm por objetivo induzir uma imunidade contra o papilomavírus e, desta forma, atuar na prevenção primária do câncer do colo de útero. As avaliações econômicas podem ser um elemento que auxiliem nos processos de tomada de decisão sobre a incorporação da vacina em programas de imunização nacionais. Estas avaliações foram o objeto central deste trabalho, que teve como objetivo sintetizar as evidências procedentes de uma revisão sistemática da literatura de estudos de avaliação econômica da utilização da vacina contra o HPV em meninas adolescentes e pré-adolescentes. Foi realizada uma busca na literatura nas bases MEDLINE (via Pubmed), LILACS (via Bireme) e National Health Service Economic Evaluation Database (NHS EED) ate junho de 2010. Dois avaliadores, de forma independente, selecionaram estudos de avaliação econômica completa, que tivessem como foco a imunização para HPV em mulheres com as vacinas comercialmente disponíveis direcionada à população adolescente. Após a busca, 188 títulos foram identificados; destes, 39 estudos preencheram os critérios de elegibilidade e foram incluídos na revisão. Por tratar-se de uma revisão de avaliações econômicas, não foi realizada uma medida de síntese dos valores de relação incremental entre custos e efetividade. Os 39 artigos incluídos envolveram 51 avaliações econômicas em 26 países. Predominaram estudos de custo-utilidade (51%). Do ponto de vista da perspectiva da análise, predominou o dos sistemas de saúde (76,4%)...

Reproducibility of functional assessment of Cancer therapy-fatigue (FACT-F) questionnaire for cancer patients

Objective: The objective of this study was evaluating the reproducibility in Portuguese of Functional Assessment of Cancer Therapy-Fatigue (FACT-F) questionnaire for cancer patients by applying it according to the test-retest method. Material and Methods: Subjects were 85 cancer patients with an average age of 51.0 years, being 56 (65.9%) women and 29 (34.1%) men. FACT-F questionnaire consists of 40 items, divided in five domains, and is applied for evaluating quality of life and fatigue in patients with cancer. We used as a measuring tool intraclass correlation coefficient values obtained from two measures of test-retest and scatter plot proposed by Bland-Altman. Results: In 36.5% of cases the questionnaire was self-administered, and in 63.5% of the cases read by an interviewer and filled after verbal answer. Intraclass correlation coefficient values found for the domains were: physical well-being 0.72; social/family well-being 0.91; emotional well-being 0.90; functional well-being 0.86; fatigue subscale 0.88, and for the FACT-F 0.91. The Bland-Altman plot showed to be adequate, since most points were within the limits of reliability. Conclusions: FACT-F questionnaire in Portuguese has good test-retest reproducibility in patients with different types of cancer, performance status and stages.

Contribuiçäo ao estudo do papel da hemodiálise na transmissäo da hepatite C / Contribution to the study of role of hemodialisis in the transmission of hepatitis C

Foi estudado o papel dos procedimentos hemodialíticos como possível rota de transmissao da infecçao pelo vírus C da hepatite. Analisando a sorologia de 281 pacientes, comparada à de 57 outros, estudados previamente, verificamos soropositividade em percentual superior ao dos relatos na literatura (43,41 por cento), havendo correlaçao positiva entre a soropositividade e o uso de hemotransfusoes prévias. A taxa de soropositividade entre os pacientes que nunca receberam hemotransfusoes (9,02 por cento) parece indício de que o equipamento empregado na hemodiálise possa servir de rota transmissora na infecçao pelo vírus C da hepatite.