Design and rationale for the WARFA trial: a randomized controlled cross-over trial testing the therapeutic equivalence of branded and generic warfarin in atrial fibrillation patients in Brazil.

BACKGROUND: Warfarin is a commonly used anticoagulant. Whether a given dose of the different formulations of Brazilian warfarin will result in the same effect on the international normalized ratio (INR) is uncertain. The aim of the WARFA trial is to determine whether the branded and two generic warfarins available in Brazil differ in their effect on the INR. METHODS: WARFA is a cross-over RCT comparing three warfarins. The formulations tested are the branded Marevan® (Uniao Quimica/Farmoquimica) and two generic warfarin (manufactured respectively by Uniao Quimica Farmaceutica Nacional and Laboratorio Teuto Brasileiro). All of them were manufactured in Brazil, are available in all settings of the Brazilian healthcare system and were purchased from retail drugstores. Eligible participants had atrial fibrillation or flutter, had been using warfarin for at least 2 months with a therapeutic range of 2.0-3.0 and had low variability in INR results during the 1st period of the trial. Our primary outcome, for which we have an equality hypothesis, is the difference between warfarins in the mean absolute difference between two INR results, obtained after three and 4 weeks with each drug. Our secondary outcomes, that will be tested for inequality (except for the mean INR, which will be tested for equality), include the difference in the warfarin dose, and time in therapeutic range. Clinical events and adherence were also recorded and will be reported. DISCUSSION: To our knowledge, WARFA will be the first comparison of the more readily applicable INR results between branded and generic warfarins in Brazil. WARFA is important because warfarins are commonly switched between in the course of a chronic treatment in Brazil. Final results of WARFA are expected in May 2017. TRIAL REGISTRATION: ClinicalTrials.gov NCT02017197 . Registered 11 December 2013.

Statins and Fibrates for Diabetic Retinopathy: Protocol for a Systematic Review.

BACKGROUND: Diabetic retinopathy (DR) is a common microvascular complication of diabetes mellitus, and more than 75% of patients who have had diabetes for more than 20 years will have some degree of DR. This disease is highly destructive to self-esteem and puts a high burden on public health and pension systems due to the effects that it has on people of working age. The current mainstay of treatment is laser photocoagulation, which causes impairment of vision and discomfort to patients. Thus, finding a systemic drug that could act on all microcirculation and prevent direct manipulation of the eyes would be highly desirable. OBJECTIVE: To assess the efficacy and safety of the drugs in the statin and/or fibrate groups for the prevention and treatment of DR. METHODS: In this systematic review, we will select randomized controlled trials of fibrates or statins used for the treatment or prevention of DR. Our search strategy will include free text terms and controlled vocabulary (eg, MeSH, Emtree) for, "diabetic retinopathy", "statins", "fibrates", "hypolipidemic agents", and for drugs from both groups. Databases that will be used include Medical Literature Analysis and Retrieval System/PubMed, Embase, Cochrane Central Register of Controlled Trials, Latin American and Caribbean Center on Health Sciences Information, Clinicaltrials.gov, World Health Organization International Clinical Trials Registry Platform, and OpenGrey, and we will not have language or date limits. Two review authors will independently select eligible studies and assess the risk of bias using the Cochrane Collaboration's tool. We will report structured summaries of the included studies and, if possible, conduct meta-analyses. RESULTS: This is a protocol for a systematic review, therefore results are not available. We registered a short version of this protocol before progressing in the review and we are currently in the process of selecting the studies for inclusion. CONCLUSIONS: Intensive glucose control and lowering blood pressure and lipids are mechanisms that protect macrocirculation in diabetic patients. Both macrovascular and microvascular events in diabetic patients appear to have a common pathway, starting with endothelial injury. Thus, prevention and treatment of microvascular events may benefit from the same interventions. In the review for which we have written this protocol, we will assess whether the use of lipid-lowering oral drugs of the statin and/or fibrate groups may prevent and/or retard progression of DR, with the added benefit of preserving visual acuity. TRIAL REGISTRATION: PROSPERO CRD42016029746.

Statins and Fibrates for Diabetic Retinopathy: Protocol for a Systematic Review

BACKGROUND:Diabetic retinopathy (DR) is a common microvascular complication of diabetes mellitus, and more than 75% of patients who have had diabetes for more than 20 years will have some degree of DR. This disease is highly destructive to self-esteem and puts a high burden on public health and pension systems due to the effects that it has on people of working age. The current mainstay of treatment is laser photocoagulation, which causes impairment of vision and discomfort to patients. Thus, finding a systemic drug that could act on all microcirculation and prevent direct manipulation of the eyes would be highly desirable.OBJECTIVE:To assess the efficacy and safety of the drugs in the statin and/or fibrate groups for the prevention and treatment of DR.METHODS:In this systematic review, we will select randomized controlled trials of fibrates or statins used for the treatment or prevention of DR. Our search strategy will include free text terms and controlled vocabulary (eg, MeSH, Emtree) for, "diabetic retinopathy", "statins", "fibrates", "hypolipidemic agents", and for drugs from both groups. Databases that will be used include Medical Literature Analysis and Retrieval System/PubMed, Embase, Cochrane Central Register of Controlled Trials, Latin American and Caribbean Center on Health Sciences Information, Clinicaltrials.gov, World Health Organization International Clinical Trials Registry Platform, and OpenGrey, and we will not have language or date limits. Two review authors will independently select eligible studies and assess the risk of bias using the Cochrane Collaboration's tool. We will report structured summaries of the included studies and, if possible, conduct meta-analyses.

Practical and conceptual issues of clinical trial registration for Brazilian researchers / Aspectos práticos e conceituais do registro de ensaios clínicos para pesquisadores brasileiros

CONTEXT AND OBJECTIVE: Clinical trial registration is a prerequisite for publication in respected scientific journals. Recent Brazilian regulations also require registration of some clinical trials in the Brazilian Clinical Trials Registry (ReBEC) but there is little information available about practical issues involved in the registration process. This article discusses the importance of clinical trial registration and the practical issues involved in this process. DESIGN AND SETTING: Descriptive study conducted by researchers within a postgraduate program at a public university in São Paulo, Brazil. METHODS: Information was obtained from clinical trial registry platforms, article reference lists and websites (last search: September 2014) on the following topics: definition of a clinical trial, history, purpose and importance of registry platforms, the information that should be registered and the registration process. RESULTS: Clinical trial registration aims to avoid publication bias and is required by Brazilian journals indexed in LILACS and SciELO and by journals affiliated to the International Committee of Medical Journal Editors (ICMJE). Recent Brazilian regulations require that all clinical trials (phases I to IV) involving new drugs to be marketed in this country must be registered in ReBEC. The pros and cons of using different clinical trial registration platforms are discussed. CONCLUSIONS: Clinical trial registration is important and various mechanisms to enforce its implementation now exist. Researchers should take into account national regulations and publication requirements when choosing the platform on which they will register their trial.

CONTEXTO E OBJETIVO: O registro dos ensaios clínicos é pré-requisito para publicação em revistas científicas de prestígio. Recentes mecanismos regulatórios brasileiros também exigem o registro de determinados ensaios clínicos na plataforma nacional (Registro Brasileiro de Ensaios Clínicos, ReBEC). Porém há pouca informação disponível sobre questões práticas envolvidas no processo de registro. Este trabalho discute a importância do registro de ensaios clínicos e aspectos práticos envolvidos nesse processo. DESENHO DE ESTUDO E LOCAL: Estudo descritivo realizado por pesquisadores de um programa de pós-graduação em uma universidade pública em São Paulo, Brasil. MÉTODOS: Informações foram obtidas em plataformas de registro de ensaios clínicos, referências dos artigos encontrados e websites (última busca: setembro, 2014) sobre os seguintes temas: definição de ensaio clínico, história, objetivo e importância das plataformas de registro, quais informações devem ser registradas e o processo de registro. RESULTADOS: O registro de ensaios clínicos visa evitar viés de publicação e é exigido por revistas brasileiras disponíveis no LILACS, SciELO e revistas afiliadas ao Comitê Internacional de Editores de Revistas Médicas (ICMJE). Recentes normas brasileiras exigem que todos os ensaios clínicos (fases I a IV) envolvendo novos medicamentos no país sejam registrados no ReBEC. São discutidos os prós e contras da utilização de diferentes bases de registro de ensaios clínicos. CONCLUSÃO: O registro de ensaios clínicos é importante e atualmente existem vários mecanismos que obrigam seu uso. Quando forem escolher em qual plataforma registrar seu ensaio clínico, os pesquisadores devem levar em consideração quais são as normas nacionais e as exigências para publicação.

Practical and conceptual issues of clinical trial registration for Brazilian researchers.

CONTEXT AND OBJECTIVE: Clinical trial registration is a prerequisite for publication in respected scientific journals. Recent Brazilian regulations also require registration of some clinical trials in the Brazilian Clinical Trials Registry (ReBEC) but there is little information available about practical issues involved in the registration process. This article discusses the importance of clinical trial registration and the practical issues involved in this process. DESIGN AND SETTING: Descriptive study conducted by researchers within a postgraduate program at a public university in São Paulo, Brazil. METHODS: Information was obtained from clinical trial registry platforms, article reference lists and websites (last search: September 2014) on the following topics: definition of a clinical trial, history, purpose and importance of registry platforms, the information that should be registered and the registration process. RESULTS: Clinical trial registration aims to avoid publication bias and is required by Brazilian journals indexed in LILACS and SciELO and by journals affiliated to the International Committee of Medical Journal Editors (ICMJE). Recent Brazilian regulations require that all clinical trials (phases I to IV) involving new drugs to be marketed in this country must be registered in ReBEC. The pros and cons of using different clinical trial registration platforms are discussed. CONCLUSIONS: Clinical trial registration is important and various mechanisms to enforce its implementation now exist. Researchers should take into account national regulations and publication requirements when choosing the platform on which they will register their trial.

Ensaio clínico randomizado tipo stepped wedge: características, vantagens, desvantagens e aplicabilidade / Randomized clinical trial type stepped wedge: Features, advantages, disadvantages and applicability

O stepped wedge design é um tipo de ensaio clínico randomizado por cluster que vem sendo usado recentemente como opção para estudos de avaliação de efetividade/eficácia. Por ser relativamente novo e pouco conhecido em nosso meio, apresentamos as principais características desse tipo de estudo e discutimos sua aplicabilidade,vantagens e desvantagens.Tipo de estudo e local: Estudo descritivo na Universidade Federal de São Paulo.Métodos: Foi realizada revisão da literatura no Medline via Pubmed com busca do termo ?stepped wedge?. Os estudos identificados foram selecionados quando descreviam informações relacionadas ao desenho classificadas nas categorias: características, vantagens, desvantagens e aplicabilidade.Resultados: Com base nas informações obtidas nos estudos identificados, apresentamos e discutimos as principais características, aplicabilidade, vantagens e desvantagens do desenho stepped wedge.Conclusão: O desenho stepped wedge é um ensaio clínico melhor direcionado para a avaliação da implementação de intervenções de saúde pública. Também pode ser útil para determinar qual o melhor momento para iniciar uma intervenção ao longo da evolução da doença e qual a duração mais adequada da intervenção. Sua principal vantagem está relacionada a aspectos logísticos e menor tamanho de amostra, e sua principal desvantagem parece estar relacionada ao maior tempo de seguimento...