Zannad Faiez, Pfeffer Marc A, Bhatt Deepak L, Bonds Denise E, Borer Jeffrey S, Calvo-Rojas Gonzalo, Fiore Louis, Lund Lars H, Madigan David, Maggioni Aldo Pietro, Meyers Catherine M, Rosenberg Yves, Simon Tabassome, Stough Wendy Gattis, Zalewski Andrew, Zariffa Nevine, Temple Robert
Clinical Investigation Center, Centre Hospitalier Universitaire de Nancy, Nancy, France.
Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Heart. 2017 Aug;103(15):1156-1162. doi: 10.1136/heartjnl-2017-311191. Epub 2017 Apr 28.
Controlled trials provide the most valid determination of the efficacy and safety of an intervention, but large cardiovascular clinical trials have become extremely costly and complex, making it difficult to study many important clinical questions. A critical question, and the main objective of this review, is how trials might be simplified while maintaining randomisation to preserve scientific integrity and unbiased efficacy assessments. Experience with alternative approaches is accumulating, specifically with registry-based randomised controlled trials that make use of data already collected. This approach addresses bias concerns while still capitalising on the benefits and efficiencies of a registry. Several completed or ongoing trials illustrate the feasibility of using registry-based controlled trials to answer important questions relevant to daily clinical practice. Randomised trials within healthcare organisation databases may also represent streamlined solutions for some types of investigations, although data quality (endpoint assessment) is likely to be a greater concern in those settings. These approaches are not without challenges, and issues pertaining to informed consent, blinding, data quality and regulatory standards remain to be fully explored. Collaboration among stakeholders is necessary to achieve standards for data management and analysis, to validate large data sources for use in randomised trials, and to re-evaluate ethical standards to encourage research while also ensuring that patients are protected. The rapidly evolving efforts to streamline cardiovascular clinical trials have the potential to lead to major advances in promoting better care and outcomes for patients with cardiovascular disease.
对照试验能最有效地确定干预措施的疗效和安全性，但大型心血管临床试验已变得极其昂贵和复杂，使得许多重要的临床问题难以开展研究。一个关键问题，也是本综述的主要目标，是如何在保持随机化以维护科学完整性和无偏倚疗效评估的同时简化试验。关于替代方法的经验正在积累，特别是利用已收集数据的基于注册登记的随机对照试验。这种方法解决了对偏倚的担忧，同时仍能利用注册登记的优势和效率。一些已完成或正在进行的试验说明了使用基于注册登记的对照试验来回答与日常临床实践相关的重要问题的可行性。医疗保健组织数据库中的随机试验对于某些类型的调查也可能是简化的解决方案，尽管在这些环境中数据质量（终点评估）可能更受关注。这些方法并非没有挑战，与知情同意、设盲、数据质量和监管标准相关的问题仍有待充分探索。利益相关者之间的合作对于实现数据管理和分析标准、验证用于随机试验的大型数据源以及重新评估伦理标准以鼓励研究同时确保患者得到保护是必要的。为简化心血管临床试验而迅速发展的努力有可能在促进心血管疾病患者获得更好的护理和治疗结果方面取得重大进展。
