Clinical perspectives on the use of composite endpoints
Clinical perspectives on the use of composite endpoints
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DOI：
10.1016/s0197-2456(97)00005-6
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发表时间：
1997-12-01
期刊：
影响因子：
--
通讯作者：
Cannon, CP
中科院分区：
文献类型：
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作者：
Cannon, CP
虽然死亡率是评估新方案的最重要的终点，但坚持将其用作临床试验的唯一终点可能需要对数千名患者进行研究。因此，复合终点越来越多地被用于增加总体事件发生率，从而减少试验所需的患者数量。对于作为复合终点的一部分，非致命性终点应该具有临床意义，即与不良的后续预后相关。在急性心肌梗死(MI)中，急性心肌梗死(MI)的病理生理机制中的几个中间终点与不良的长期结局相关：复发的MI、新发的充血性心力衰竭或心源性休克、左心功能不全、大面积梗死，以及未能实现梗塞相关动脉的早期通畅。此外，在急性心肌梗死中，改善这些非致命性终点的新疗法也提高了死亡率，从而验证了这一方法。一旦建立了这种联系，这种非致命的终点就可以有效地用于评估新的治疗方法。然而，请注意，如果没有建立这种联系(即当非致命性终点减少时死亡率降低)，就像用抗心律失常治疗抑制室性早搏那样，非致命性终点不能被有效地使用。因此，适当设计和验证的复合终点可以提供一种有效的手段，在比仅使用死亡率的试验中测试新的治疗方法。它们的使用应该允许测试更多的新方案，从而在改善患者临床结果方面取得更快的进展。(C)Elsevier Science Inc.1997。
Although mortality is the most important endpoint in evaluating new regimens, insistence on its use as the only endpoint in clinical trials can require that thousands of patients be studied. Accordingly, composite endpoints have been increasingly used to increase the overall event rate and thereby reduce the number of patients needed for the trial.For use as part of composite endpoint, nonfatal endpoints should be clinically meaningful, i.e., related to an adverse subsequent prognosis. In acute myocardial infarction (MI), several intermediate endpoints in the well-described pathophysiology of acute MI have been correlated with an adverse long-term outcome: recurrent MI, new onset congestive heart failure or cardiogenic shock, left ventricular dysfunction, large infarct size, and failure to achieve early patency of the infarct-related artery. Furthermore, in acute MI, new therapies that improve these nonfatal endpoints also improve mortality, thereby validating this approach. Once this link is established, such nonfatal endpoints can be validly used in evaluating new therapies. Note, however, if this link has not been made (that mortality is reduced when there is a reduction in the nonfatal endpoint), as in the case of suppression of ventricular premature complexes with antiarrhythmic therapy, the nonfatal endpoint cannot be used validly.Thus, appropriately designed and validated composite endpoints can provide a valid means of testing new treatments in a smaller trial than one using mortality alone. Their use should allow testing of a greater number of new regimens, thereby allowing more rapid progress toward improving the clinical outcome of patients. (C) Elsevier Science Inc. 1997.