Departamento de Epidemiologia, Faculdade de Saúde Pública, Universidade de São Paulo - São Paulo (SP), Brasil.
Faculdade de Ciências Farmacêuticas, Universidade de São Paulo - São Paulo (SP), Brasil.
Rev Bras Epidemiol. 2021 Jan 6;23:e200104. doi: 10.1590/1980-549720200104. eCollection 2021.
To describe the methodological characteristics and good research practices of COVID-19 interventional studies developed in Brazil in the first months of the pandemic.
We reviewed the bulletin of the National Research Ethics Committee - Coronavirus Special Edition (Comissão Nacional de Ética em Pesquisa - CONEP-COVID) (May 28, 2020) and the databases of the International Clinical Trials Registry Platform (ICTRP), ClinicalTrials.gov, and Brazilian Clinical Trials Registry (Registro Brasileiro de Ensaios Clínicos - ReBEC) to identify interventional studies registered in Brazil that assessed drug type, biological therapy, or vaccines. We described their methodological characteristics and calculated their power for different effect magnitudes.
A total of 62 studies were included, 55 retrieved from the CONEP website, and 7 from registry databases. The most tested pharmacological interventions in these studies were: chloroquine/hydroxychloroquine, azithromycin, convalescent plasma, tocilizumab, sarilumab, eculizumab, vaccine, corticosteroids, anticoagulants, n-acetylcysteine, nitazoxanide, ivermectin, and lopinavir/ritonavir. Out of 22 protocols published on registry databases until May 2020, 18 (82%) were randomized clinical trials, and 13 (59%) had an appropriate control group. However, 9 (41%) of them were masked, and only 5 (24%) included patients diagnosed with a specific laboratory test (for example, reverse transcription polymerase chain reaction - RT-PCR). Most of these studies had power > 80% only to identify large effect sizes. In the prospective follow-up, 60% of the studies available at CONEP until May 2020 had not been published on any registry platform (ICTRP/ReBEC/ClinicalTrials) by July 21, 2020.
The interventions evaluated during the Brazilian research response reflect those of international initiatives, but with a different distribution and a large number of studies assessing hydroxychloroquine/chloroquine. Limitations in methodological design and sample planning represent challenges that could affect the research outreach.
描述在大流行的最初几个月中，巴西开展的 COVID-19 干预性研究的方法学特征和良好研究实践。
我们查阅了国家伦理研究委员会公告（Comissão Nacional de Ética em Pesquisa - CONEP-COVID）（2020 年 5 月 28 日）和国际临床试验注册平台（ICTRP）、ClinicalTrials.gov 和巴西临床试验注册（Registro Brasileiro de Ensaios Clínicos - ReBEC）数据库，以确定在巴西注册的评估药物类型、生物治疗或疫苗的干预性研究。我们描述了它们的方法学特征，并计算了它们在不同效应大小下的效力。
共纳入 62 项研究，其中 55 项从 CONEP 网站检索，7 项从注册数据库检索。这些研究中测试最多的药理学干预措施包括：氯喹/羟氯喹、阿奇霉素、恢复期血浆、托珠单抗、沙利鲁单抗、依库珠单抗、疫苗、皮质类固醇、抗凝剂、N-乙酰半胱氨酸、硝唑尼特、伊维菌素和洛匹那韦/利托那韦。截至 2020 年 5 月，在注册数据库中公布的 22 项方案中，18 项（82%）为随机临床试验，13 项（59%）有适当的对照组。然而，其中 9 项（41%）为盲法，只有 5 项（24%）纳入了特定实验室检测（例如逆转录聚合酶链反应 - RT-PCR）确诊的患者。这些研究中，大多数仅在识别大效应量时效力>80%。在前瞻性随访中，截至 2020 年 5 月，CONEP 中可用的 60%的研究到 2020 年 7 月 21 日尚未在任何注册平台（ICTRP/ReBEC/ClinicalTrials）上发表。
巴西研究应对期间评估的干预措施反映了国际倡议，但分布不同，大量研究评估羟氯喹/氯喹。方法设计和样本规划方面的局限性是影响研究结果的挑战。
