Several countries maintain universal health coverage, which implies responsibility to organize de... more Several countries maintain universal health coverage, which implies responsibility to organize delivery formats of healthcare services and products for citizens. In Brazil, the health system has a principle of universal access for more than 30 years, but many deficiencies remain and the country observes a day practice for those seeking judicial decisions to determine provision of healthcare.
medRxiv (Cold Spring Harbor Laboratory), Nov 28, 2022
Author contributions: IZL was responsible for the conceptualization, methodology, validation, vis... more Author contributions: IZL was responsible for the conceptualization, methodology, validation, visualization, and writing (original draft preparation). RVF was responsible for data conceptualization, formal analysis, methodology, validation, and writing (review and editing). CCH and AJLA were responsible for the conceptualization, supervision, and writing (review and editing). CLBS was responsible for project administration, supervision, and writing (review and editing). MVS, FF, and EBC were responsible for validation and writing (review and editing). GSJ supervised the research and revised the manuscript. .
Integrase Inhibitors are a promising new class of antiretroviral. However, studies of these drug... more Integrase Inhibitors are a promising new class of antiretroviral. However, studies of these drugs in tuberculosis (TB) and, HIV/aids coinfection are scarce. Therefore, the aim of this review was evaluate the efficacy, effectiveness, and safety of integrase inhibitors in the treatment of HIV/AIDS in patients coinfected with tuberculosis (TB). The searches were performed in the MEDLINE, EMBASE, LILACS, COCHRANE, Web of Science, Scopus, and CINAHL databases using the terms “HIV”, “AIDS”, “tuberculosis”, “raltegravir potassium”, “dolutegravir”, “elvitegravir”, “bictegravir”, “integrase inhibitor”, and their respective synonyms. Reports from three randomised clinical trials and a historical cohort were included. Patients coinfected with TB and HIV/AIDS showed a good response to TB treatment (cure or treatment completed), which was above 85% in all arms of the evaluated studies. As a primary outcome, the HIV viral load suppression rates at week 48 were greater than 60% in all arms. The t...
Revista Brasileira de Farmácia Hospitalar e Serviços de Saúde, Mar 25, 2022
Greece has a public universal health system, the National Health System (ESY)-with mandatory insu... more Greece has a public universal health system, the National Health System (ESY)-with mandatory insurance coverage (IKA) for all working people (either employees or self-employed). On top of that, people can voluntarily have private insurance. EOPYY (National Organisation for Healthcare Provision) is the only responsible party for purchasing health services funded by public resources based on the National Social Security Fund (EFKA) contributions and state budget. There is only a limited number of drugs being exclusively provided by the public health care system, for free (EOPYY pharmacies) like the high-cost medications. Other than these, patients can buy any drug they want. National Organization for Medicines (EOF) is the regulatory authority and also responsible for pharmacovigilance of medicines, medical products, of beauty and veterinary drugs. In 2011, the pricing and reimbursement processes were separated, with pricing taking place after marketing authorization; subsequently, analysis for reimbursement by the social health insurance is allowed with inclusion in a positive list. New pharmaceutical products follow an external reference pricing system, in which the maximum ex-factory price for medicines under patent is defined by the mean of the three lowest prices for the same drug in European Union (EU) countries, this same rule being applied to biological and biosimilar medicines. Generic drugs are priced either by the mean of the three lowest prices charged in the EU or by a 50% price reduction in relation to the period in which the medication was under patent; thus, the maximum prices of the generic drugs are set at 65% of the price of the respective reference product. In 2018, the Health Technology Assessment (HTA) was introduced in the country to evaluate medications and to issue recommendations to the Ministry of Health on the inclusion or removal of products from the Positive List. As the HTA process is still being reformed in Greece, it is believed that, in the coming years, the country will have the opportunity to improve the implementation, having the linking of the HTA results with the clinical guidelines as one of the major challenges.
BackgroundChronic obstructive pulmonary disease (COPD) has an appreciable socioeconomical impact ... more BackgroundChronic obstructive pulmonary disease (COPD) has an appreciable socioeconomical impact in low- and middle-income countries, but most epidemiological data originate from high-income countries. For this reason, it is especially important to understand survival and factors associated with survival in COPD patients in these countries.ObjectiveTo assess survival of COPD patients in Brazil, to identify risk factors associated with overall survival, including treatment options funded by the Brazilian National Health System (SUS).MethodologyWe built a retrospective cohort study of patients dispensed COPD treatment in SUS, from 2003 to 2015 using a National Database created from the record linkage of administrative databases. We further matched patients 1:1 based on sex, age and year of entry to assess the effect of the medicines on patient survival. We used the Kaplan-Meier method to estimate overall survival of patients, and Cox's model of proportional risks to assess risk fa...
Aims: To evaluate the efficacy, effectiveness, and safety of integrase inhibitors in the treatmen... more Aims: To evaluate the efficacy, effectiveness, and safety of integrase inhibitors in the treatment of HIV/AIDS in patients coinfected with tuberculosis (TB). Methods: Clinical trials or observational studies were included. The searches were performed in the MEDLINE, EMBASE, LILACS, COCHRANE, Web of Science, Scopus, and CINAHL databases using the terms “HIV”, “AIDS”, “tuberculosis”, “raltegravir potassium”, “dolutegravir”, “elvitegravir”, “bictegravir”, “integrase inhibitor”, and their respective synonyms. The methodological quality of the studies was independently assessed using the Cochrane risk of bias and Newcastle Ottawa scales. Results: Reports from three randomised clinical trials and a historical cohort were included. Patients coinfected with TB and HIV/AIDS showed a good response to TB treatment, which was above 85% in all arms of the evaluated studies. As a primary outcome, the HIV viral load suppression rates at week 48 were greater than 60% in all arms. The therapies eval...
Expert Review of Pharmacoeconomics & Outcomes Research, 2020
Background: There is a need to evaluate the health equity of atypical antipsychotics users who ob... more Background: There is a need to evaluate the health equity of atypical antipsychotics users who obtain their medicines from the Brazilian National Health System (SUS) through the identification of key factors that influence their health status due to concerns with equity of care. Research design and methods: Cross-sectional study among patients attending state pharmacies in Brazil. Individuals were included if they used atypical antipsychotics, aged ≥18 years, and answered the EQ-5D-3L questionnaire. Sociodemographic, behavioral, and clinical data were collected. The dependent variable was health status. Associations between the independent variables and the dependent variable were analyzed by adjusting a linear regression model. Results: Overall, 388 individuals met the eligibility criteria and were included in the analysis. The final multiple linear regression model demonstrated a statistically significant association between VAS and suicide attempts, private care, current antipsychotics, comorbidities, and perceived family support. Conclusions: The study identified several factors both individual and collective that correlate with the health status of atypical antipsychotic users, and confirmed the importance of providing medicines for treating psychotic disorders. However, other factors are involved including social support. Our results suggest additional activities and policies are necessary including strategies to address the differences in private and public health care.
Introduction: Managed Entry Agreements (MEAs) consist of a set of instruments to reduce the uncer... more Introduction: Managed Entry Agreements (MEAs) consist of a set of instruments to reduce the uncertainty and the budget impact of new high priced medicines; however, there are concerns. There is a need to critically appraise MEAs with their planned introduction in Brazil. Accordingly, the objective is to identify and appraise key attributes and concerns with MEAs among payers and their advisers, with the findings providing critical considerations for Brazil and other high-and middle-income countries. Methods: An integrative review approach was adopted. This involved a review of MEAs across countries. The review question was 'What are the health technology MEAs that have been applied around the world?' This review was supplemented with studies not retrieved in the search known to the senior level co-authors including key South American markets. Afterall, involved senior level decision makers and advisers providing guidance on potential advantages and disadvantages of MEAs and ways forward. Results: 25 studies were included in the review. Most MEAs included medicines (96.8%), focused on financial arrangements (43%), and included mostly antineoplastic medicines. Most countries kept key information confidential including discounts or had not published such data. Few details were found in the literature regarding South America. Our findings and inputs resulted in both advantages including reimbursement and disadvantages including concerns with data collection for outcome-based schemes. Conclusion: We are likely to see a growth in MEAs with the continual launch of new high priced and often complex treatments, coupled with increasing demands on resources. Whilst outcome based MEAs could be an important tool to improve access to new innovative medicines there are critical issues to address. Comparing knowledge, experiences and practices across countries is crucial to guide high-and middle-income countries when designing their future MEAs.
Background Relapsing-remitting multiple sclerosis (RRMM) is a chronic, progressive, inflammatory ... more Background Relapsing-remitting multiple sclerosis (RRMM) is a chronic, progressive, inflammatory and immune-mediated disease that affects the central nervous system and is characterized by episodes of neurological dysfunction followed by a period of remission. The pharmacological strategy aims to delay the progression of the disease and prevent relapse. Interferon beta and glatiramer are commonly used in the Brazilian public health system and are available to patients who meet the guideline criteria. The scenario of multiple treatments available and in development brings the need for discussion and evaluation of the technologies already available before the incorporation of new drugs. This study analyses the effectiveness of first-line treatment of RRMS measured by real-world evidence data, from the Brazilian National Health System (SUS). Methods and findings We conducted a non-concurrent national cohort between 2000 and 2015. The study population consisted of 22,722 patients with RRMS using one of the following first-line drugs of interest: glatiramer or one of three presentations of interferon beta. Kaplan-Meier analysis was used to estimate the time to treatment failure. A univariate and multivariate Cox proportional hazard model was used to evaluate factors associated with treatment failure. In addition, patients were propensity score-matched (1:1) in six groups of comparative first-line treatments to evaluate the effectiveness among them. The analysis indicated a higher risk of treatment failure in female patients (HR = 1.
Objetiva-se avaliar as evidências acerca do perfil de segurança para idosos dos medicamentos util... more Objetiva-se avaliar as evidências acerca do perfil de segurança para idosos dos medicamentos utili-zados no tratamentodo Diabetes Mellitus tipo 2, que são considerados medicamentos potencialmen-te inadequados pelo critério de Beers epela ferramenta STOPP: glibenclamida e clorpropamida. Realizou-se uma revisão integrativa da literatura realizada a partirda base de dados PubMed. Foram utilizados os descritores do banco Medical Subject Headings (MeSH) “chlorpropamide”,“glyburide” e “sulfonylureas” combinados ao descritor “aged”. Foram incluídos artigos que avaliaram o perfil de segurança douso de clorpropamida e/ou glibenclamida por idosos. Sete artigos foram selecionados. Não foi encontrado nenhum estudoque avaliasse a clorpropamida. Dois estudos avaliaram a segu-rança cardiovascular e o risco de morte com glibenclamida,mas não foram apontadas diferenças entre o uso deste medicamento e de outros da classe das sulfonilureias. Os demaistrabalhos eviden-ciaram uma associação entre o uso ...
Introduction: Eculizumab is currently the only treatment available for paroxysmal nocturnal hemog... more Introduction: Eculizumab is currently the only treatment available for paroxysmal nocturnal hemoglobinuria (PNH). It was recently incorporated by Conitec and listed in the specialized component of SUS, making it necessary to develop a Clinical Protocol and Therapeutic Guidelines (PCDT), so that the medicine can be distributed to the population within 180 days. In this context, the challenge arises of rapidly developing a robust, evidence-based and society-validated PCDT for a rare disease with major financial impact on SUS. Conclusion: The HPN PCDT was elaborated and validated with agility, in approximately 60 days, with good acceptance by society.
2020 IEEE 33rd International Symposium on Computer-Based Medical Systems (CBMS), 2020
Healthcare is receiving many improvements from real world evidence. The advances in data manageme... more Healthcare is receiving many improvements from real world evidence. The advances in data management and machine learning models are driving better resources to support decision making. One of the most common techniques to develop recommendations and guidelines to physicians is through systematic reviews. To evaluate the quality of the evidence, among other methods, the researchers uses the Risk of Bias Assessment. Besides, that method is widely used and provides good results it has been done manually by researchers. This work provides the MCRB a multiclassifier tool for the risk of bias assessment using machine learning techniques. The software was tested with four machine learning models: Logistic Regression, SVM, Naive Bayes, and XGBoost. The results show that is quite possible to classify well the seven dimensions of the problem with a macro average AUC Score of 75%
Several countries maintain universal health coverage, which implies responsibility to organize de... more Several countries maintain universal health coverage, which implies responsibility to organize delivery formats of healthcare services and products for citizens. In Brazil, the health system has a principle of universal access for more than 30 years, but many deficiencies remain and the country observes a day practice for those seeking judicial decisions to determine provision of healthcare.
medRxiv (Cold Spring Harbor Laboratory), Nov 28, 2022
Author contributions: IZL was responsible for the conceptualization, methodology, validation, vis... more Author contributions: IZL was responsible for the conceptualization, methodology, validation, visualization, and writing (original draft preparation). RVF was responsible for data conceptualization, formal analysis, methodology, validation, and writing (review and editing). CCH and AJLA were responsible for the conceptualization, supervision, and writing (review and editing). CLBS was responsible for project administration, supervision, and writing (review and editing). MVS, FF, and EBC were responsible for validation and writing (review and editing). GSJ supervised the research and revised the manuscript. .
Integrase Inhibitors are a promising new class of antiretroviral. However, studies of these drug... more Integrase Inhibitors are a promising new class of antiretroviral. However, studies of these drugs in tuberculosis (TB) and, HIV/aids coinfection are scarce. Therefore, the aim of this review was evaluate the efficacy, effectiveness, and safety of integrase inhibitors in the treatment of HIV/AIDS in patients coinfected with tuberculosis (TB). The searches were performed in the MEDLINE, EMBASE, LILACS, COCHRANE, Web of Science, Scopus, and CINAHL databases using the terms “HIV”, “AIDS”, “tuberculosis”, “raltegravir potassium”, “dolutegravir”, “elvitegravir”, “bictegravir”, “integrase inhibitor”, and their respective synonyms. Reports from three randomised clinical trials and a historical cohort were included. Patients coinfected with TB and HIV/AIDS showed a good response to TB treatment (cure or treatment completed), which was above 85% in all arms of the evaluated studies. As a primary outcome, the HIV viral load suppression rates at week 48 were greater than 60% in all arms. The t...
Revista Brasileira de Farmácia Hospitalar e Serviços de Saúde, Mar 25, 2022
Greece has a public universal health system, the National Health System (ESY)-with mandatory insu... more Greece has a public universal health system, the National Health System (ESY)-with mandatory insurance coverage (IKA) for all working people (either employees or self-employed). On top of that, people can voluntarily have private insurance. EOPYY (National Organisation for Healthcare Provision) is the only responsible party for purchasing health services funded by public resources based on the National Social Security Fund (EFKA) contributions and state budget. There is only a limited number of drugs being exclusively provided by the public health care system, for free (EOPYY pharmacies) like the high-cost medications. Other than these, patients can buy any drug they want. National Organization for Medicines (EOF) is the regulatory authority and also responsible for pharmacovigilance of medicines, medical products, of beauty and veterinary drugs. In 2011, the pricing and reimbursement processes were separated, with pricing taking place after marketing authorization; subsequently, analysis for reimbursement by the social health insurance is allowed with inclusion in a positive list. New pharmaceutical products follow an external reference pricing system, in which the maximum ex-factory price for medicines under patent is defined by the mean of the three lowest prices for the same drug in European Union (EU) countries, this same rule being applied to biological and biosimilar medicines. Generic drugs are priced either by the mean of the three lowest prices charged in the EU or by a 50% price reduction in relation to the period in which the medication was under patent; thus, the maximum prices of the generic drugs are set at 65% of the price of the respective reference product. In 2018, the Health Technology Assessment (HTA) was introduced in the country to evaluate medications and to issue recommendations to the Ministry of Health on the inclusion or removal of products from the Positive List. As the HTA process is still being reformed in Greece, it is believed that, in the coming years, the country will have the opportunity to improve the implementation, having the linking of the HTA results with the clinical guidelines as one of the major challenges.
BackgroundChronic obstructive pulmonary disease (COPD) has an appreciable socioeconomical impact ... more BackgroundChronic obstructive pulmonary disease (COPD) has an appreciable socioeconomical impact in low- and middle-income countries, but most epidemiological data originate from high-income countries. For this reason, it is especially important to understand survival and factors associated with survival in COPD patients in these countries.ObjectiveTo assess survival of COPD patients in Brazil, to identify risk factors associated with overall survival, including treatment options funded by the Brazilian National Health System (SUS).MethodologyWe built a retrospective cohort study of patients dispensed COPD treatment in SUS, from 2003 to 2015 using a National Database created from the record linkage of administrative databases. We further matched patients 1:1 based on sex, age and year of entry to assess the effect of the medicines on patient survival. We used the Kaplan-Meier method to estimate overall survival of patients, and Cox's model of proportional risks to assess risk fa...
Aims: To evaluate the efficacy, effectiveness, and safety of integrase inhibitors in the treatmen... more Aims: To evaluate the efficacy, effectiveness, and safety of integrase inhibitors in the treatment of HIV/AIDS in patients coinfected with tuberculosis (TB). Methods: Clinical trials or observational studies were included. The searches were performed in the MEDLINE, EMBASE, LILACS, COCHRANE, Web of Science, Scopus, and CINAHL databases using the terms “HIV”, “AIDS”, “tuberculosis”, “raltegravir potassium”, “dolutegravir”, “elvitegravir”, “bictegravir”, “integrase inhibitor”, and their respective synonyms. The methodological quality of the studies was independently assessed using the Cochrane risk of bias and Newcastle Ottawa scales. Results: Reports from three randomised clinical trials and a historical cohort were included. Patients coinfected with TB and HIV/AIDS showed a good response to TB treatment, which was above 85% in all arms of the evaluated studies. As a primary outcome, the HIV viral load suppression rates at week 48 were greater than 60% in all arms. The therapies eval...
Expert Review of Pharmacoeconomics & Outcomes Research, 2020
Background: There is a need to evaluate the health equity of atypical antipsychotics users who ob... more Background: There is a need to evaluate the health equity of atypical antipsychotics users who obtain their medicines from the Brazilian National Health System (SUS) through the identification of key factors that influence their health status due to concerns with equity of care. Research design and methods: Cross-sectional study among patients attending state pharmacies in Brazil. Individuals were included if they used atypical antipsychotics, aged ≥18 years, and answered the EQ-5D-3L questionnaire. Sociodemographic, behavioral, and clinical data were collected. The dependent variable was health status. Associations between the independent variables and the dependent variable were analyzed by adjusting a linear regression model. Results: Overall, 388 individuals met the eligibility criteria and were included in the analysis. The final multiple linear regression model demonstrated a statistically significant association between VAS and suicide attempts, private care, current antipsychotics, comorbidities, and perceived family support. Conclusions: The study identified several factors both individual and collective that correlate with the health status of atypical antipsychotic users, and confirmed the importance of providing medicines for treating psychotic disorders. However, other factors are involved including social support. Our results suggest additional activities and policies are necessary including strategies to address the differences in private and public health care.
Introduction: Managed Entry Agreements (MEAs) consist of a set of instruments to reduce the uncer... more Introduction: Managed Entry Agreements (MEAs) consist of a set of instruments to reduce the uncertainty and the budget impact of new high priced medicines; however, there are concerns. There is a need to critically appraise MEAs with their planned introduction in Brazil. Accordingly, the objective is to identify and appraise key attributes and concerns with MEAs among payers and their advisers, with the findings providing critical considerations for Brazil and other high-and middle-income countries. Methods: An integrative review approach was adopted. This involved a review of MEAs across countries. The review question was 'What are the health technology MEAs that have been applied around the world?' This review was supplemented with studies not retrieved in the search known to the senior level co-authors including key South American markets. Afterall, involved senior level decision makers and advisers providing guidance on potential advantages and disadvantages of MEAs and ways forward. Results: 25 studies were included in the review. Most MEAs included medicines (96.8%), focused on financial arrangements (43%), and included mostly antineoplastic medicines. Most countries kept key information confidential including discounts or had not published such data. Few details were found in the literature regarding South America. Our findings and inputs resulted in both advantages including reimbursement and disadvantages including concerns with data collection for outcome-based schemes. Conclusion: We are likely to see a growth in MEAs with the continual launch of new high priced and often complex treatments, coupled with increasing demands on resources. Whilst outcome based MEAs could be an important tool to improve access to new innovative medicines there are critical issues to address. Comparing knowledge, experiences and practices across countries is crucial to guide high-and middle-income countries when designing their future MEAs.
Background Relapsing-remitting multiple sclerosis (RRMM) is a chronic, progressive, inflammatory ... more Background Relapsing-remitting multiple sclerosis (RRMM) is a chronic, progressive, inflammatory and immune-mediated disease that affects the central nervous system and is characterized by episodes of neurological dysfunction followed by a period of remission. The pharmacological strategy aims to delay the progression of the disease and prevent relapse. Interferon beta and glatiramer are commonly used in the Brazilian public health system and are available to patients who meet the guideline criteria. The scenario of multiple treatments available and in development brings the need for discussion and evaluation of the technologies already available before the incorporation of new drugs. This study analyses the effectiveness of first-line treatment of RRMS measured by real-world evidence data, from the Brazilian National Health System (SUS). Methods and findings We conducted a non-concurrent national cohort between 2000 and 2015. The study population consisted of 22,722 patients with RRMS using one of the following first-line drugs of interest: glatiramer or one of three presentations of interferon beta. Kaplan-Meier analysis was used to estimate the time to treatment failure. A univariate and multivariate Cox proportional hazard model was used to evaluate factors associated with treatment failure. In addition, patients were propensity score-matched (1:1) in six groups of comparative first-line treatments to evaluate the effectiveness among them. The analysis indicated a higher risk of treatment failure in female patients (HR = 1.
Objetiva-se avaliar as evidências acerca do perfil de segurança para idosos dos medicamentos util... more Objetiva-se avaliar as evidências acerca do perfil de segurança para idosos dos medicamentos utili-zados no tratamentodo Diabetes Mellitus tipo 2, que são considerados medicamentos potencialmen-te inadequados pelo critério de Beers epela ferramenta STOPP: glibenclamida e clorpropamida. Realizou-se uma revisão integrativa da literatura realizada a partirda base de dados PubMed. Foram utilizados os descritores do banco Medical Subject Headings (MeSH) “chlorpropamide”,“glyburide” e “sulfonylureas” combinados ao descritor “aged”. Foram incluídos artigos que avaliaram o perfil de segurança douso de clorpropamida e/ou glibenclamida por idosos. Sete artigos foram selecionados. Não foi encontrado nenhum estudoque avaliasse a clorpropamida. Dois estudos avaliaram a segu-rança cardiovascular e o risco de morte com glibenclamida,mas não foram apontadas diferenças entre o uso deste medicamento e de outros da classe das sulfonilureias. Os demaistrabalhos eviden-ciaram uma associação entre o uso ...
Introduction: Eculizumab is currently the only treatment available for paroxysmal nocturnal hemog... more Introduction: Eculizumab is currently the only treatment available for paroxysmal nocturnal hemoglobinuria (PNH). It was recently incorporated by Conitec and listed in the specialized component of SUS, making it necessary to develop a Clinical Protocol and Therapeutic Guidelines (PCDT), so that the medicine can be distributed to the population within 180 days. In this context, the challenge arises of rapidly developing a robust, evidence-based and society-validated PCDT for a rare disease with major financial impact on SUS. Conclusion: The HPN PCDT was elaborated and validated with agility, in approximately 60 days, with good acceptance by society.
2020 IEEE 33rd International Symposium on Computer-Based Medical Systems (CBMS), 2020
Healthcare is receiving many improvements from real world evidence. The advances in data manageme... more Healthcare is receiving many improvements from real world evidence. The advances in data management and machine learning models are driving better resources to support decision making. One of the most common techniques to develop recommendations and guidelines to physicians is through systematic reviews. To evaluate the quality of the evidence, among other methods, the researchers uses the Risk of Bias Assessment. Besides, that method is widely used and provides good results it has been done manually by researchers. This work provides the MCRB a multiclassifier tool for the risk of bias assessment using machine learning techniques. The software was tested with four machine learning models: Logistic Regression, SVM, Naive Bayes, and XGBoost. The results show that is quite possible to classify well the seven dimensions of the problem with a macro average AUC Score of 75%
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