Risk of bias assessment of clinical trials referenced in the technical notes on direct-acting oral anticoagulants available on e-NatJus / Avaliação do risco de viés dos ensaios clínicos referenciados nas notas técnicas sobre os anticoagulantes orais diretos disponíveis no e-NatJus

Objective: Assess and classify the risks of bias in the clinical trials (CTs) that make up the technical notes (TNs) referring to direct-acting oral anticoagulants (DOAC) requests. Methods: The TNs related to the DOAC requests of apixaban, dabigatran, edoxaban, and rivaroxaban were selected on the e-NatJus website and, after excluding duplicate references, an analysis of the CT used for their writing was carried out. The CT risk of bias (low, high, or uncertain bias) was assessed using the Cochrane Risk of Bias tool, and the results were added to Review Manager 5.4. Results: 181 TNs were selected, 236 articles were analyzed and after applying the inclusion criteria, 28 CTs were analyzed in full. None of the CTs were free of bias. Most CTs, 71% (20/28), had a low risk of bias regarding attrition bias and reporting bias. In contrast, 61% (17/28) of the studies did not control for selection, performance, and detection bias, as they present uncertainties and a high risk of bias. In addition, it was observed that 21% (6/28) of the CTs had a high risk of bias for conflict of interest. Conclusion: The biases present in the CT cited as a reference for the TN referring to the DOAC request are significant and compromise their quality (AU).

Objetivo: Avaliar e classificar os riscos de vieses dos ensaios clínicos (EC) que compõem as NTs referentes à solicitação dos DOAC. Métodos: As NTs relacionadas à solicitação dos DOAC apixabana, dabigatrana, edoxabana e rivaroxabana foram selecionadas no website e-NatJus e, após exclusão das referências duplicadas, foi realizada uma análise dos EC utilizados para a redação das mesmas. O risco de viés dos EC (baixo, alto ou viés incerto) foi avaliado utilizando a ferramenta Cochrane Risk of Bias e os resultados foram adicionados no Review Manager 5.4. Resultados: Foram selecionadas 181 NTs, analisados 236 artigos e após aplicação dos critérios de inclusão, resultou em 28 EC analisados na íntegra. Nenhum dos EC ficou isento de viés. A maioria dos EC, 71% (20/28), apresentou baixo risco de viés em relação ao viés de atrito e viés de relato. Por outro lado, 61% (17/28) dos estudos não controlaram o viés de seleção, performance e detecção, uma vez que apresentam incertezas e alto risco de viés. Além disso, foi observado que 21% (6/28) dos EC apresentaram alto risco de viés para conflito de interesses. Conclusão: Os vieses presentes nos EC citados como referência das NT referentes a solicitação dos DOAC são significativos e comprometem a sua qualidade (AU).

Análise da qualidade das evidências científicas sobre a eficácia e segurança nas bulas de anticoagulantes orais diretos comercializados no Brasil / Analysis of the quality of scientific evidence on efficacy and safety in the package leaflets of direct oral anticoagulants marketed in Brazil

Objetivo: Identificar e analisar a qualidade das evidências científicas sobre a eficácia e segurança dos anticoagulantes orais direto (DOAC) disponíveis nos ensaios clínicos referenciados nas bulas dos medicamentos comercializados no Brasil. Método: Trata-se de um descritivo documental dividido em duas etapas, sendo elas: (i) identificação e análise da disponibilidade das referências bibliográficas contidas nas bulas dos DOAC e (ii) análise da qualidade dos estudos contidos nas bulas através da ferramenta da Cochrane Risk of Bias RevMan versão 5.4. Foram analisados setes domínios de importâncias para ensino clínico, sendo que cada domínio foi classificado como alto, incerto ou baixo risco de viés, segundo a avaliação dos colaboradores. Resultados: Foram analisadas 10 bulas destinadas aos profissionais da saúde. Sendo que destas, foram avaliados 25 ensaios clínicos. A análise da qualidade das evidências científicas, referenciadas nas bulas para profissionais dos DOAC, mostrou que os estudos citados apresentaram consistência metodológica. Entretanto, na maioria dos estudos, os domínios foram classificados como viés incerto, ou seja, não foi possível identificar como esses pontos foram abordados nos estudos. Conclusão: Portanto, o presente estudo evidenciou que a qualidade dos ensaios clínicos referenciados nas bulas dos DOAC apresentou incertezas metodológicas em seus ensaios. Sugere-se a necessidade de normativas que estabeleçam atualizações do conteúdo informativo presente nas bulas profissionais e estabeleçam descrição dos métodos de forma clara e coesa (AU).

Objective: Identify and analyze the quality of scientific evidence on the efficacy and safety of direct oral anticoagulants (DOAC) available in clinical trials referenced in the package leaflets of drugs marketed in Brazil. Method: This is a descriptive documentary study divided into two stages: (i) identification and analysis of the availability of the bibliographic references contained in the package leaflets of DOACs and (ii) analysis of the quality of the studies contained in the package leaflets through the Cochrane Risk of Bias RevMan tool version 5.4. Seven domains of importance for clinical teaching were analyzed, and each domain was classified as high, uncertain or low risk of bias, according to the assessment of the collaborators. Results: Ten package leaflets intended for health professionals were analyzed. Of these, 25 clinical trials were evaluated. The analysis of the quality of the scientific evidence referenced in the package leaflets for health professionals showed that the cited studies presented methodological consistency. However, in most studies, the domains were classified as uncertain bias, i.e., it was not possible to identify how these points were addressed in the studies. Conclusion: Therefore, the present study evidenced that the quality of clinical trials referenced in the package leaflets of DOACs presented methodological uncertainties in their trials. It is suggested the need for regulations that establish updates of the information content present in the professional package inserts and establish a description of the methods in a clear and cohesive way (AU).

Notas técnicas para judicialização de anticoagulantes orais diretos: uma avaliação do perfil / Technical notes for judicialization of direct oral anticoagulants: a profile assessment

Fundamentos: A judicialização da saúde no Brasil gera aumento anual significativo das demandas por recursos financei-ros. Em 2016, com intuito de promover uma comunicação entre o sistema jurídico e o sistema de saúde, implementaram o sistema e-NatJus (Núcleos de Apoio Técnico do Poder Judiciário). A função do e-NatJus é fornecer apoio técnico aos juízes nas questões relativas à saúde por meio da elaboração de Notas Técnicas (NT). Objetivo: Analisar o perfil e a qualidade das NT de solicitação de anticoagulantes orais diretos (DOACs) disponíveis no portal eletrônico do e-NatJus para consultas por juízes. Métodos: Trata-se de um estudo documental descritivo, em que foram avaliadas as características sociodemo-gráficas, do diagnóstico e tratamento dos pacientes, bem como informações sobre as evidências da eficácia e segurança da tecnologia e conclusão de todas as NT referentes à solicitação de DOACs obtidas na plataforma e-NatJus desde sua im-plantação em 2018 até junho de 2020. Resultados: Foram incluídas no estudo 181 NT: rivaroxabana (67,0%), apixabana (16,0%), dabigatrana (12,0%) e edoxabana (5,0%). A média de idade dos indivíduos foi de 65,7 (±15,1) anos, sendo, (50,3%) do sexo feminino. São Sebastião do Paraíso foi o município que mais solicitou apoio nas NT (5,0%), e o estado com mais solicitações foi Santa Catarina (34,8%). Em relação ao diagnóstico dos pacientes, os mais prevalentes foram fibrilação atrial (FA)(31,5%) e troembolismo venoso (TEV)(16,4%). Aproximadamente 86 NT estavam com conteúdo semelhante no item evidência científica. Observou-se que (57,5%) tiveram a conclusão não favorável para disponibilizar o medicamento solicitado. Dentre as 77 NT que tiveram a conclusão favorável, (57,1%) não avaliaram as recomendações da Comissão Na-cional de Incorporação de Tecnologias (CONITEC). Conclusão: De forma geral, nosso estudo permitiu conhecer o perfil das NT e os principais motivos de solicitações dos DOACs, com intuito de compreender melhor se são realizadas realmente de forma consciente e responsável. A população que solicitou os DOACs via judicial é uma população idosa e não houve grande diferença entre os sexos. Os diagnósticos mais prevalentes nas NT foram FA e TEV corroborando com a indicação desses medicamentos. Pode-se observar que a maioria das NT que concedeu parecer favorável não evidenciou consulta à CONITEC e não apresentou evidência científica que contemplava de forma concreta sua decisão (AU)

Background: The judicialization of health in Brazil generates an annual increase in demands for financial resources. In 2016, to promote communication between the legal system and the health system, the implementation of e-NatJus system (Technical Support Centers of the Judiciary). The role of e-NatJus is to provide technical support to judges on health-related issues through the preparation of Technical Notes (NT). Objective: Analyze the profile and quality of TNs requesting Direct Oral Anticoagulants (DOACs) available on the e-NatJus electronic portal for consultation by judges. Methods: This is a descriptive documentary study, which evaluated the sociodemographic characteristics, diagnosis, and treatment of patients, as well as information on the evidence of the efficacy and safety of technology and the conclusion of all NT related to the request for DOACs obtained in the e-NatJus platform since its implementation in 2018 to June 24, 2020. Results: The study included 181 NT: rivaroxaban (67,0%), apixaban (16,0%), dabigatran (12,0%), and edoxaban (5,0%). The mean age of the individuals was 65.7 (±15.1) years, being (50,3%) female. São Sebastião do Paraíso was the municipality that most requested support in the NT (5,0%), and the state with the most requests was Santa Catarina (34,8%). Regarding the diagnosis, the most prevalent patients were AF (31,5%) and VTE (16,4%). Approximately 86 NT had similar content in the scientific evidence item. It was observed that (57,5%) had an unfavorable conclusion about making the requested drug available. Among the 77 NT that had a favorable conclusion, (57,1%) did not evaluate the rec-ommendations of the National Commission for the Incorporation of Technologies (CONITEC). Conclusion: In general, our study is effective to know the profile of the NT and the main reasons for consulting DOACs, to better understand the form of knowledge and the DOACs. It can be observed that most NTs granted a favorable opinion, did not evidence CONITEC and did not present scientific evidence that contemplated the concrete form of their decision (AU)

Implementation of a text messaging intervention to patients on warfarin therapy in Brazilian primary care units: a quasi-experimental study.

BACKGROUND: Warfarin remains the most affordable oral anticoagulant in many countries. However, it may have serious side effects, and the success of the therapy depends on the patient's understanding of the medication and their adherence to treatment. The use of short messages services (SMS) is a strategy that can be used to educate patients, but there are no studies evaluating this intervention in patients taking warfarin. Therefore, we aimed to develop, implement, and assess the feasibility of an intervention using SMS to primary care patients taking warfarin in a medium-sized Brazilian city. METHODS: A bank of 79 SMS was drafted and validated by an expert panel. During 6 months, three times a week, patients received messages about anticoagulation with warfarin. At baseline and after 3 months, we assessed their knowledge and adherence with validated instruments. At the end of the follow-up, participants answered a satisfaction questionnaire. Subsequently, a scale-up phase was conducted, with another round of the intervention including 82 participants (29 from the first phase and 53 newly recruited). Seven months after the end of the scale-up, we asked the patients for their insights about the long-term effects of this program. All patients signed informed consent. The study was approved by the Research and Ethics committee of the Universidade Federal de Minas Gerais. RESULTS: In the pilot, 33 (89.2%) patients completed the follow-up. Among the participants who answered the satisfaction questionnaire (n = 29), 86.2% considered that the intervention motivated a healthy lifestyle and improved their understanding of warfarin therapy. All patients were willing to continue receiving the messages. Adherence measured by the Measure of Adherence to Treatment (MAT) test was high in the pre-intervention assessment and remained high (96.7% vs. 93.3%; p = 1.0000). The proportion of patients who achieved > 75% correct answers on the Oral Anticoagulation Knowledge (OAK) test increased from 6.5% to 25.6, p = 0.0703. In the scale-up, 23 patients answered the long-term assessment questionnaire. The main long-term knowledge reported was dietary information. Nine patients received the messages but did not remember their content. CONCLUSION: The intervention was well-accepted and had a positive impact on patient's knowledge about oral anticoagulation therapy. The scale-up assessment reinforced the need to constantly monitor digital interventions.