Department of Cardiac Surgery, University of Insubria and Ospedale di Circolo di Varese, Varese, Italy.
Scand Cardiovasc J. 2010 Dec;44(6):321-4. doi: 10.3109/14017431.2010.504859. Epub 2010 Oct 7.
Non-inferiority trials are questionable when death and serious complications are included among outcomes. The term itself "non-inferiority" is misleading, since such a study would not demonstrate that a new treatment is non-inferior to a control treatment, but simply that the inferiority would not reach a pre-specified level, deemed as acceptable by the designers of the trial. Group cross-over, assay-sensitivity and the need of a placebo arm are major issues for the reliability of non-inferiority trials. The SYNTAX trial for severe coronary artery disease was designed on a non-inferiority margin of 6.6%. In this paper we show that the SYNTAX designers were ready to accept up to 30% higher rate of death and major adverse events to claim the non-inferiority of percutaneous coronary intervention versus coronary artery bypass grafting. Eventually the SYNTAX study failed because percutaneous patients sustained an even higher rate of adverse events. We propose major caution in performing non-inferiority randomized trials.
当死亡和严重并发症被包括在结果中时，非劣效性试验是值得怀疑的。“非劣效性”这个术语本身具有误导性，因为这样的研究并不能证明新的治疗方法不比对照治疗方法差，而只是表明其劣势不会达到试验设计者认为可接受的预先设定水平。组交叉、检测敏感性和安慰剂臂的需求是非劣效性试验可靠性的主要问题。严重冠状动脉疾病的 SYNTAX 试验的设计非劣效性边界为 6.6%。在本文中，我们表明 SYNTAX 的设计者准备接受高达 30%更高的死亡率和主要不良事件发生率，以声称经皮冠状动脉介入治疗与冠状动脉旁路移植术的非劣效性。最终，SYNTAX 研究失败了，因为经皮治疗的患者不良事件发生率更高。我们建议在进行非劣效性随机试验时要格外谨慎。
