Centre for Big Data Research in Health, University of New South Wales, Sydney, New South Wales, Australia.
Faculty of Medicine and Health Science, Macquarie University, Sydney, New South Wales, Australia.
BMJ Open. 2018 Jun 27;8(6):e021064. doi: 10.1136/bmjopen-2017-021064.
The introduction of targeted therapies for cancer has contributed to dramatic improvements in patient survival. Nevertheless, several targeted therapies have been associated with 'off-target' adverse effects, based on varying levels of evidence. To date, this evidence has not been systematically synthesised. We will synthesise published systematic review evidence of cardiovascular toxicity associated with targeted cancer therapies.
We will include systematic reviews of randomised controlled trials and observational studies that report on cardiovascular outcomes for individual agents. We will identify systematic reviews by applying predeveloped, standardised search strategies within Embase, Medline and Cochrane Central. Two independent reviewers will identify reviews published up to 31 December 2016 using predefined eligibility criteria. They will resolve ambiguous cases through consensus, arbitrated by a third reviewer if required. The reviewers will extract and report data according to methodological guidelines for overviews provided by the Cochrane Collaboration, Joanna Briggs Institute and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols. They will assess the quality of included reviews by applying the Assessment of Multiple Systematic Reviews tool. They will judge the quality of evidence in included reviews based on their assessment of bias and incorporation into the interpretation of findings. In synthesising the evidence, we will classify agents based on systematic review evidence of toxicity (sufficient, probable, possible or indeterminate) for specific cardiovascular outcomes (congestive heart failure, myocardial infarction, ischaemic heart disease, left ventricular ejection fraction decline, cerebrovascular disease, pulmonary embolism, thrombosis and hypertension). This will provide clinicians and patients with an accessible synthesis based on robust methodology.
Ethics approval is not required for overviews. We will conduct the study in collaboration with consumer representatives. We will submit results for peer-review publication, and disseminate them through established clinical and consumer networks.
CRD42017080014.
癌症靶向治疗的引入显著提高了患者的生存率。然而，根据不同程度的证据，一些靶向治疗与“脱靶”不良反应相关。迄今为止，这些证据尚未得到系统的综合分析。我们将综合分析已发表的与靶向癌症治疗相关的心血管毒性的系统评价证据。
我们将包括关于个体药物心血管结局的随机对照试验和观察性研究的系统评价。我们将通过在 Embase、Medline 和 Cochrane Central 中应用预先制定的、标准化的搜索策略来识别系统评价。两名独立的审查员将根据预先设定的纳入标准，确定截至 2016 年 12 月 31 日发表的综述。如有必要，将通过第三方审查员进行仲裁来解决有争议的情况。审查员将根据 Cochrane 协作组织、Joanna Briggs 研究所和系统评价和荟萃分析报告的首选报告项目提供的概述方法学指南提取和报告数据。他们将通过应用评估多个系统评价工具来评估纳入综述的质量。他们将根据对偏倚的评估和对结果解释的纳入程度来判断纳入综述的证据质量。在综合证据时，我们将根据特定心血管结局（充血性心力衰竭、心肌梗死、缺血性心脏病、左心室射血分数下降、脑血管疾病、肺栓塞、血栓形成和高血压）的毒性（充分、可能、可能或不确定）对药物进行分类基于系统评价证据。这将为临床医生和患者提供基于可靠方法的易于访问的综合分析。
概述不需要伦理批准。我们将与消费者代表合作开展这项研究。我们将提交同行评审出版物的结果，并通过已建立的临床和消费者网络进行传播。
PROSPERO 注册号：CRD42017080014。
