Cervical cancer screening in low- and middle-income countries: A systematic review of economic evaluation studies

Abstract Economic assessments are relevant to support the decision to incorporate more cost-effective strategies to reduce Cervical Cancer (CC) mortality. This systematic review analyzes the economic evaluation studies of CC prevention strategies (HPV DNA-based tests and conventional cytology) in low- and middle-income countries. Medline, EMBASE, CRD, and LILACS were searched for economic evaluation studies that reported cost and effectiveness measures of HPV DNA-based tests for CC screening and conventional cytology in women, without age, language, or publication date restrictions. Selection and data extraction were carried out independently. For comparability of results, cost-effectiveness measures were converted to international dollars (2019). Report quality was assessed using the CHEERS checklist. The Dominance Matrix Ranking (DRM) was used to analyze and interpret the results. The review included 15 studies from 12 countries, with cost-effectiveness analyzes from the health system's perspective and a 3% discount rate. The strategies varied in age and frequency of screening. Most studies used the Markov analytical model, and the cost-benefit threshold was based on the per capita GDP of each country. The sensitivity analysis performed in most studies was deterministic. The completeness of the report was considered sufficient in most of the items evaluated by CHEERS. The Dominance Interpretation (DRM) varied; in 6 studies, the HPV test was dominant, 5 studies showed a weak dominance evaluating greater effectiveness of the HPV test at a higher cost, yet in 2 studies conventional cytology was dominant. Although the context-dependent nature of economic evaluations, this review points out the challenge of methodological standardization in the analytical models.

Novas ferramentas para o diagnóstico de infecção latente por Mycobacterium tuberculosis / New tools for the diagnostics of latent Mycobacterium tuberculosis infection

Esta tese objetivou identificar estratégias de triagem para infecção latente por Mycobacterium tuberculosis (Mtb) ­ ILTB em profissionais de saúde que viabilizem o uso mais eficiente dos recursos disponíveis. No Brasil, recomenda-se que os profissionais de saúde, um dos grupos de risco para a ILTB, realizem triagem periódica para detecção da infecção e aqueles que apresentarem conversão aos testes de diagnóstico, indica-se o tratamento preventivo da tuberculose (TB) ­ TPT uma vez que pessoas com conversão recente apresentam elevada chance de progressão para a doença. Desenvolvemos, no primeiro artigo, um modelo preditivo para identificar profissionais de saúde com maior probabilidade de resultado negativo para dois testes de diagnóstico da ILTB a partir de uma análise secundária de dados publicados anteriormente de 708 profissionais de saúde da atenção primária, de cinco capitais brasileiras, submetidos à prova tuberculínica (PT) e ao Quantiferon®-TB Gold in-tube (QFT-IT®). Construímos um modelo preditivo utilizando árvore de classificação e regressão (CART, classification and regression tree). A avaliação do desempenho foi realizada por meio da análise receiver operating characteristics (ROC) e area under the curve (AUC). Utilizou-se o mesmo banco de dados para validação cruzada do modelo. Entre os 708 profissionais de saúde, 247 (34,9%) apresentaram resultado negativo para os testes. A CART identificou que os médicos e agentes comunitários de saúde apresentaram chances duas vezes maior de testes negativos (probabilidade = 0,60) do que os enfermeiros e técnicos/auxiliares de enfermagem (probabilidade = 0,28) naqueles com menos de 5,5 anos de atuação na atenção primária. Na validação cruzada, a acurácia do modelo preditivo foi de 68% [intervalo de confiança de 95% (IC95%) 65 ­ 71) ], AUC de 62% (IC95% 58 ­ 66), especificidade de 78% (IC95% 74 ­ 81) e sensibilidade de 44% (IC95% 38 ­ 50). Apesar do baixo poder preditivo do modelo, a CART permitiu identificar subgrupos com maior probabilidade de terem ambos os testes negativos. No segundo artigo, analisou-se a razão de custo-efetividade de dois testes de sensibilidade cutânea baseados em antígenos específicos do Mtb -Diaskintest® e C-TST® - e a do QFT-Plus® para o diagnóstico da ILTB comparadas com a estratégia diagnóstica atual (PT) entre profissionais de saúde. Desenvolveu-se um modelo analítico de decisão, representado por coorte hipotética de 100.000 profissionais de saúde, de ambos os sexos, com resultado negativo para a PT no ano anterior, horizonte temporal de cinco anos, na perspectiva do Sistema Único de Saúde. Avaliaram-se três regimes de tratamento para a ILTB: três meses de doses semanais de rifapentina (900 mg) e isoniazida (900 mg) (3HP), seis e nove meses de doses diárias de isoniazida (300 mg) (6H e 9H, respectivamente). Aplicou-se taxa de desconto de 5% na efetividade, medida em casos de TB ativa evitados, e nos custos das estratégias de triagem e de tratamento avaliados, estimados em dólares americanos (US$) com taxa média anual de 2021 de acordo com o Banco Central (US$ 1 = 5,39 reais). Foram realizadas análises de sensibilidade determinística univariada e probabilística. Os testes Diaskintest®, C-TST® e QFT-Plus® apresentam maior especificidade (0,98, 0,98 e 0,97, respectivamente). Os custos com QFT-Plus® foram maiores devido aos equipamentos, mão de obra e ao custo do kit. O Diaskintest® foi o teste mais econômico (US$ 7.042, US$ 5.781 e US$ 18.892 por caso de TB ativa evitado para os regimes de tratamento com 3HP, 6H e 9H, respectivamente), inclusive nas análises de sensibilidade. No cenário nacional, o Diaskintest® foi o teste de melhor custo-efetividade para avaliação anual dos profissionais de saúde.

This thesis aimed to identify screening strategies for tuberculosis infection (TBI) in healthcare workers (HCW) that enable the most efficient use of available resources. Investigation of TBI in HCWs is recommended in Brazil as part of the worker's pre-employment and periodic (annual) health visits. HCWs with a first tuberculin skin test (TST) induration < 10 mm are invited to repeat the test in one to three weeks to assess the booster effect (induration size increment of 10 mm). Those with a persistent TST < 10 mm will undergo a one-step TST every 12 months. TPT is recommended when conversion (10 mm increment over latest induration size) occurs. We developed, in the first manuscript, a predictive model to identify HCWs best targeted for TBI screening. We carried out a secondary analysis of previously published results of 708 HCWs working in primary care services in five Brazilian State capitals who underwent two TBI tests: tuberculin skin test and Quantiferon®-TB Gold in-tube. We used a classification and regression tree (CART) model to predict HCWs with negative results for both tests. The performance of the model was evaluated using the receiver operating characteristics (ROC) curve and the area under the curve (AUC), cross-validated using the same dataset. Among the 708 HCWs, 247 (34.9%) had negative results for both tests. CART allowed us to identify that physicians or a community health agents were twice more likely to be uninfected (probability = 0.60) than registered or aid nurse (probability = 0.28) when working less than 5.5 years in the primary care setting. In cross validation, the predictive accuracy was 68% [95% confidence interval (95%CI): 65 ­ 71], AUC was 62% (95%CI 58 ­ 66), specificity was 78% (95%CI 74 ­ 81), and sensitivity was 44% (95%CI 38 ­ 50). Despite the low predictive power of this model, CART allowed to identify subgroups with higher probability of having both tests negative. In the second manuscript, we analyzed the cost-effectiveness of two TB antigen-based skin tests (TBST) using the recombinant ESAT-6 and CFP-10 immunogens (Diaskintest® and C-TST®) and of QFT-Plus® for TBI diagnosis compared with the current standard of care, TST, among HCWs in Brazil. A state-transition Markov model was created, simulating a cohort of 100,000 HCWs (five annual cycles) for TBI treatment scenarios with 3 months of weekly doses of rifapentine (900 mg) and isoniazid (900 mg) (3HP). We adopted the Brazilian public health system perspective. Effects [tuberculosis disease (TBD) averted) and costs for screening and treating TBI were discounted at 5%. Incremental cost-effectiveness per TBD averted was calculated. Hypothetical cohort of 100,000 HCWs of both sexes with a negative result of TST in the previous year. Diaskintest®, C-TST® and QFT-Plus® tests have higher specificity (0.98, 0.98 and 0.97, respectively). Costs with QFT-Plus® were higher due to equipment, human labor and cost of the kit by test. Diaskintest® was the most cost-effective test (US$ 7,042, US$ 5,781, and US$18,892 per case of TBD averted for the 3HP, 6H, and 9H treatment regimens, respectively), including sensitivity analyses. In the Brazilian scenario, Diaskintest® is the most cost-effective test for sequential testing of HCWs.

Costes informales: definición, obtención y análisis. La importancia de su incorporación en las evaluaciones económicas en salud / Informal costs: definition, obtaining and analysis. The importance of its incorporation in economic evaluations in health

Introducción: Los costes informales derivan de cuidados informales que es la atención prestada a un enfermo o discapacitado por parte de personas que no son profesionales socio sanitarios y que no reciben una remuneración económica. El objetivo del trabajo es explicar los costes informales en salud, su definición, su obtención, análisis y el im­ pacto en su incorporación en las evaluaciones económicas en salud. Materiales y métodos: Se realizó una búsqueda del tema sobre costes informales en la base de datos de Medline­Pubmed y en la búsqueda de la biblioteca de la Universidad Carlos III Madrid vía internet a través de varias bases de datos como EconLit y ABI/IN­ FORM collection. Resultados: Se define los cuidados informales, los métodos para su medición en tiempo, en preferencias reveladas, preferencias establecidos fijados, otros métodos, la importan­ cia de incorporar los costos informales en las evaluaciones económicas en salud. Conclusión: La evaluación económica a nivel de la perspectiva de la sociedad se debe incluir, pero muchas veces se realiza según el pagador por lo difícil que puede ser su medición.

Introduction: Informal costs derive from informal care, which is the care provided to a sick or disabled person by people who are not socio­health professionals and who do not receive financial compensation. The objective of the work is to explain the informal costs in health, its definition, its obtaining, analysis and the impact on its incorporation in the economic health evaluations. Material and methods: A search of the topic on informal costs was carried out in the Medli­ ne­Pubmed database and in the search of the Carlos III Madrid University library via the In­ ternet through several databases such as EconLit and ABI / INFORM collection. Results: Informal care is defined, the methods for its measurement in time, in revealed preferences, established preferences, other methods, the importance of incorporating informal costs in economic health evaluations. Conclusion: The economic evaluation at the level of the society perspective must be in­ cluded, but many times it is carried out according to the payer because of how difficult its measurement can be done

Cost-effectiveness of lung cancer screening worldwide: a systematic review / 中华流行病学杂志

Objective From the economic point of view,this study was to systematically assess the status quo on lung cancer screening in the world and to provide reference for further research and implementation of the programs,in China.Methods PubMed,EMbase,The Cochrane Library,CNKI and Wanfang Data were searched to gather papers on studies related to economic evaluation regarding lung cancer screening worldwide,from the inception of studies to June 30th,2018.Basic characteristics,methods and main results were extracted.Quality of studies was assessed.Cost were converted to Chinese Yuan under the exchange rates from the World Bank.The ratio of incremental cost-effectiveness ratio (ICER) to local GDP per capita were calculated.Results A total of 23 studies (only 1 randomized controlled trial) were included and the overall quality was accepted.22 studies were from the developed countries.Nearly half of the studies (11 studies) took 55 years old as the starting age of the screening program.Smoking history was widely applied for the selection of criteria on target populations (18).Low-dose computed tomography (LDCT) was involved in every study used to evaluate the economic effectiveness.Annual (17) and once-life time (7) screening were more common frequencies.22 studies reported ICERs for LDCT screening,compared to no screening,of which 17 were less than 3 times local GDP per capita,and were considered as cost-effectiveness,according to the WHO's recommendation.15 and 7 studies reported ICERs for annual and once-life time screening,of which 12 and 7 studies were in favor the results of their cost-effectiveness,respectively.Additionally,the cost-effectiveness of once-lifetime screening was likely to be superior to the annual screening.Differences of cost-effectiveness among the subgroups,by starting age or by the smoking history,might exist.Conclusions Based on the studies,evidence from the developed countries demonstrated that LDCT screening programs on lung cancer,implemented among populations selected by age and smoking history,generally appeared more cost-effective.Combined with the local situation of health resource,the findings could provide direction for less developed regions/countries lacking of local evidence.Low frequency of LDCT screening for lung cancer could be adopted when budget was limited.Data on starting ages,smoking history and other important components related to the strategy of screening programs,needs to be precisely evaluated under the situation of local population.

Cost-effectiveness of lung cancer screening worldwide: a systematic review / 中华流行病学杂志

Objective From the economic point of view,this study was to systematically assess the status quo on lung cancer screening in the world and to provide reference for further research and implementation of the programs,in China.Methods PubMed,EMbase,The Cochrane Library,CNKI and Wanfang Data were searched to gather papers on studies related to economic evaluation regarding lung cancer screening worldwide,from the inception of studies to June 30th,2018.Basic characteristics,methods and main results were extracted.Quality of studies was assessed.Cost were converted to Chinese Yuan under the exchange rates from the World Bank.The ratio of incremental cost-effectiveness ratio (ICER) to local GDP per capita were calculated.Results A total of 23 studies (only 1 randomized controlled trial) were included and the overall quality was accepted.22 studies were from the developed countries.Nearly half of the studies (11 studies) took 55 years old as the starting age of the screening program.Smoking history was widely applied for the selection of criteria on target populations (18).Low-dose computed tomography (LDCT) was involved in every study used to evaluate the economic effectiveness.Annual (17) and once-life time (7) screening were more common frequencies.22 studies reported ICERs for LDCT screening,compared to no screening,of which 17 were less than 3 times local GDP per capita,and were considered as cost-effectiveness,according to the WHO's recommendation.15 and 7 studies reported ICERs for annual and once-life time screening,of which 12 and 7 studies were in favor the results of their cost-effectiveness,respectively.Additionally,the cost-effectiveness of once-lifetime screening was likely to be superior to the annual screening.Differences of cost-effectiveness among the subgroups,by starting age or by the smoking history,might exist.Conclusions Based on the studies,evidence from the developed countries demonstrated that LDCT screening programs on lung cancer,implemented among populations selected by age and smoking history,generally appeared more cost-effective.Combined with the local situation of health resource,the findings could provide direction for less developed regions/countries lacking of local evidence.Low frequency of LDCT screening for lung cancer could be adopted when budget was limited.Data on starting ages,smoking history and other important components related to the strategy of screening programs,needs to be precisely evaluated under the situation of local population.

Iniciativas disponibles para el reporte de resultados en investigación biomédica con diferentes tipos de diseño / Initiatives for reporting biomedical research results with different types of designs

La calidad del reporte de los resultados de una investigación no es óptima, razón por la cual, se han desarrollado numerosas iniciativas tendientes a mejorar este aspecto a lo largo de los años. El objetivo de este artículo es mencionar y describir las iniciativas existentes para el reporte de resultados de investigación biomédica en diversos escenarios de investigación clínica y situaciones especiales. Se realizó una búsqueda en las bases de datos THE COCHRANE LIBRARY, MEDLINE, SciELO y Redalyc; y en los buscadores Clinical Evidence, TRIP database, Fisterra, Rafabravo, EQUATOR Network, portal de BIREME y Programa HINARI; para obtener las listas de verificación existentes. Los documentos recuperados fueron agrupados de la siguiente forma: relacionados con escenarios de terapia, diagnóstico, pronóstico, evaluaciones económicas y misceláneas. La búsqueda generó un total de 31 documentos. Doce para escenarios de terapia (CONSORT, QUOROM, MOOSE, STRICTA, TREND, MINCIR-Terapia, RedHot, REHBaR, PRISMA, REFLECT, Ottawa y SPIRIT), 5 para diagnóstico (STARD, QUADAS, QAREL, GRRAS y MINCIR-Diagnóstico), 3 para pronóstico (REMARK, MINCIR-Pronóstico y GRIPS), 4 para evaluaciones económicas (NHS-HTA, CHEERS, ISPOR RCT-CEA y NICE-STA,); y 7 misceláneos (STROBE, COREQ, GRADE, SQUIRE, STREGA, ORION y MINCIR-EOD). Existen diversas iniciativas y declaraciones. Estas deben ser conocidas y utilizadas por escritores, revisores y editores de revistas biomédicas; de forma tal de incrementar la calidad del reporte de resultados de la investigación biomédica.

Quality of results reporting is not perfect, many initiatives tending to improve this aspect of clinical research have been developed in the last decade. The aim of this manuscript is to mention and describe the existent initiatives for reporting biomedical research results in different scenarios and special situations. To obtain check-lists, a search in THE COCHRANE LIBRARY, MEDLINE, SciELO y Redalyc; Clinical Evidence, TRIP database, Fisterra, Rafabravo, EQUATOR Network, BIREME and HINARI Program was developed. Identified documents were grouped in relation with clinical research scenarios (therapy, diagnosis, prognosis and economic evaluations) and miscellaneous. The search allows finding 31 documents. Twelve for therapy (CONSORT, QUOROM, MOOSE,STRICTA, TREND, MINCIR-Therapy, RedHot, REHBaR, PRISMA,REFLECT, Ottawa and SPIRIT), 5 for diagnosis (STARD, QUADAS, QAREL, GRRAS and MINCIR-Diagnosis), 3 for prognosis (REMARK, MINCIR-Prognosis and GRIPS), 4 for economic evaluations (NHS-HTA, CHEERS, ISPOR RCT-CEA and NICE-STA,) and 7 miscellaneous (STROBE, COREQ, GRADE, SQUIRE, STREGA, ORION and MINCIR-EOD). Different initiatives and statements were found. These must be noted and used by writers, reviewers and editors of biomedical journals, in order to improve the quality of reporting results.