Kirwan Bridget-Anne, Lubsen Jacobus, de Brouwer Sophie, van Dalen Frederik J, Pocock Stuart J, Clayton Tim, Danchin Nicolas, Poole-Wilson Philip A
SOCAR Research, PO Box 2564, CH-1260 Nyon, Switzerland.
Contemp Clin Trials. 2008 Mar;29(2):259-69. doi: 10.1016/j.cct.2007.10.001. Epub 2007 Oct 13.
The ACTION (A Coronary disease Trial Investigating Outcome with Nifedipine GITS) study was an independent, investigator-initiated, multi-national trial comparing nifedipine GITS to placebo in 7665 patients with stable angina pectoris. The trial was sponsored by the manufacturer of the medication concerned. 291 centers in 19 countries participated. Results have been published. We defined quality management (QM) as all activities directed at ensuring data integrity and consistency; and ensuring appropriate trial conduct, including pro-active prevention of deviations from protocol. We describe the QM framework that was adopted for the ACTION trial and the key tools that were used. In the protocol, particular attention was paid to explicit definition of tasks and responsibilities of all participants, and to unequivocal operational definitions of terms such as 'randomized', 'follow-up', etc. that could be applied by investigators, on-site monitors and during data processing at the coordinating centre. A comprehensive clinical trial and study management system based on simultaneous display of scanned documents and data base content had a central role. We describe in detail how compliance with good clinical practice was ensured, how the intention-to-treat principle was implemented, how compliance with study medication and completeness of follow-up was achieved, how double blinding was maintained throughout the study structure, and how patient safety was protected. The protocol ruled out participation in any other study at the same time by ACTION participants. Our experience showed that the reasons for this are not always understood by investigators. Unequivocal operational definitions of the procedural concepts that characterize randomized clinical trials should not only be the basis of QM, but also of reporting results.
ACTION（硝苯地平控释片治疗冠心病转归研究）研究是一项独立的、由研究者发起的多国试验，在7665例稳定型心绞痛患者中比较硝苯地平控释片与安慰剂。该试验由相关药物的制造商赞助。19个国家的291个中心参与其中。结果已发表。我们将质量管理（QM）定义为旨在确保数据完整性和一致性，以及确保试验合理开展（包括积极预防偏离方案情况）的所有活动。我们描述了ACTION试验所采用的质量管理框架以及所使用的关键工具。在试验方案中，特别关注了所有参与者任务和职责的明确界定，以及对“随机分组”“随访”等术语的明确操作定义，这些定义可供研究者、现场监查员以及在协调中心进行数据处理时使用。一个基于同时显示扫描文件和数据库内容的综合临床试验及研究管理系统发挥了核心作用。我们详细描述了如何确保遵循良好临床实践，如何实施意向性分析原则，如何实现对研究药物的依从性和随访的完整性，如何在整个研究结构中维持双盲，以及如何保护患者安全。试验方案排除了ACTION研究参与者同时参与任何其他研究的可能性。我们的经验表明，研究者并非总能理解这样做的原因。明确界定随机临床试验特征性程序概念的操作定义，不仅应作为质量管理的基础，也应作为报告结果的基础。
