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

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.

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

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.

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.

Sugar sweetened beverages attributable disease burden and the potential impact of policy interventions: a systematic review of epidemiological and decision models.

BACKGROUND: Around 184,000 deaths per year could be attributable to sugar-sweetened beverages (SSBs) consumption worldwide. Epidemiological and decision models are important tools to estimate disease burden. The purpose of this study was to identify models to assess the burden of diseases attributable to SSBs consumption or the potential impact of health interventions. METHODS: We carried out a systematic review and literature search up to August 2018. Pairs of reviewers independently selected, extracted, and assessed the quality of the included studies through an exhaustive description of each model's features. Discrepancies were solved by consensus. The inclusion criteria were epidemiological or decision models evaluating SSBs health interventions or policies, and descriptive SSBs studies of decision models. Studies published before 2003, cost of illness studies and economic evaluations based on individual patient data were excluded. RESULTS: We identified a total of 2766 references. Out of the 40 included studies, 45% were models specifically developed to address SSBs, 82.5% were conducted in high-income countries and 57.5% considered a health system perspective. The most common model's outcomes were obesity/overweight (82.5%), diabetes (72.5%), cardiovascular disease (60%), mortality (52.5%), direct medical costs (57.35%), and healthy years -DALYs/QALYs- (40%) attributable to SSBs. 67.5% of the studies modelled the effect of SSBs on the outcomes either entirely through BMI or through BMI plus diabetes independently. Models were usually populated with inputs from national surveys -such us obesity prevalence, SSBs consumption-; and vital statistics (67.5%). Only 55% reported results by gender and 40% included children; 30% presented results by income level, and 25% by selected vulnerable groups. Most of the models evaluated at least one policy intervention to reduce SSBs consumption (92.5%), taxes being the most frequent strategy (75%). CONCLUSIONS: There is a wide range of modelling approaches of different complexity and information requirements to evaluate the burden of disease attributable to SSBs. Most of them take into account the impact on obesity, diabetes and cardiovascular disease, mortality, and economic impact. Incorporating these tools to different countries could result in useful information for decision makers and the general population to promote a deeper implementation of policies to reduce SSBs consumption. PROSPERO PROTOCOL NUMBER: CRD42020121025 .

Comparison of EQ-5D Values Sets Among South American Countries.

OBJECTIVE: Social health preference sets are necessary for conducting health economic evaluations. Values from other countries are often used when local sets are not available, which may alter the results. We aimed to evaluate the degree of variability of currently available country-specific value sets of the EuroQol EQ-5D instrument from South American countries (SAC). METHODS: We selected EQ-5D value sets from SAC and 2 reference countries. We obtained crosswalk value sets for the countries that use the EQ-5D-3L instrument. We compared the value sets with the Kruskal-Wallis test and then carried out pairwise comparisons with the Sign test. We also assessed correlations among the countries' value sets using the Spearman test. We calculated the absolute difference across countries for each health state, considering a difference of greater than 0.05 relevant. RESULTS: The range of value sets varied greatly. The Peruvian value set had the widest range (1 to -1.076) and the lowest values (median: 0.055; interquartile range: -0.171 to 0.275). The Ecuadorian set had the highest values (median: 0.587; interquartile range: 0.443-0.704). The Peruvian value set also had the greatest proportion of health states (43.6%) with a negative value, and the Uruguayan set had the smallest proportion (0.9%). Differences among countries were significant in all cases, with the greatest difference between Ecuador and Peru (median difference: 0.495; 95% confidence interval: 0.515-0.528). CONCLUSION: Social health preference sets varied greatly among SAC. Using non-local values could distort resource allocation decisions; hence, we recommend that countries obtain and use local value sets.

Systematic review of microeconomic analysis of pregnancy-associated malaria.

INTRODUCTION: Pregnancy-associated malaria (PAM) is a health problem with serious clinical, epidemiological and economic effects. PURPOSE: To analyze the microeconomic evaluations of PAM reported in the world scientific literature. METHODS: Systematic review with 15 different search strategies in PubMed, ScienceDirect, Scielo, Google Scholar and Malaria in Pregnancy (MiP) Library. A search, selection and extraction protocol was applied, which guaranteed completeness and reproducibility in accordance with preferred reporting items for systematic reviews and meta-analysis guidelines. The methodological quality was evaluated using the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) guide. The analysis were based on frequencies, costs and average and incremental cost-effectiveness ratios in 2018 US dollars adjusted for purchasing power parity. RESULTS: Twenty-two evaluations published between 1990 and 2018 were analyzed, of which 82% addressed cost-effectiveness in Africa. Twelve interventions were studied; of these, intermittent preventive treatment in pregnant women with sulfadoxine-pyrimethamine (IPTp-SP) was the most frequent strategy. The main outcomes were low birth weight, anaemia and DALYs avoided. The best average cost-effectiveness ratio was reported in IPTp-SP with a cost of US$ 2 per DALY avoided, followed by the administration of IPTp-SP in pregnant women with HIV (US$ 14.2). CONCLUSIONS: The studies focus on Africa with a high heterogeneity in the interventions, outcomes, resources and populations studied. All the interventions were highly cost-effective, which demonstrates the importance of including prevention, care and control resources for PAM as a priority in health sector budgets. This is especially true considering the importance of its intervention for social progress and overcoming poverty in endemic areas.

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

Alcohol consumption's attributable disease burden and cost-effectiveness of targeted public health interventions: a systematic review of mathematical models.

BACKGROUND: Around 6% of total deaths are related to alcohol consumption worldwide. Mathematical models are important tools to estimate disease burden and to assess the cost-effectiveness of interventions to address this burden. METHODS: We carried out a systematic review on models, searching main health literature databases up to July 2017. Pairs of reviewers independently selected, extracted data and assessed the quality of the included studies. Discrepancies were resolved by consensus. We selected those models exploring: a) disease burden (main metrics being attributable deaths, disability-adjusted life years, quality-adjusted life years) or b) economic evaluations of health interventions or policies, based on models including the aforementioned outcomes. We grouped models into broad families according to their common central methodological approach. RESULTS: Out of 4295 reports identified, 63 met our inclusion criteria and were categorized in three main model families that were described in detail: 1) State transition -i.e Markov- models, 2) Life Table-based models and 3) Attributable fraction-based models. Most studies pertained to the latter one (n = 29, 48.3%). A few miscellaneous models could not be framed into these families. CONCLUSIONS: Our findings can be useful for future researchers and decision makers planning to undertake alcohol-related disease burden or cost-effectiveness studies. We found several different families of models. Countries interested in adopting relevant public health measures may choose or adapt the one deemed most convenient, based on the availability of existing data at the local level, burden of work, and public health and economic outcomes of interest.

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.