Hampton J R
University Hospital, Nottingham, United Kingdom.
Eur Heart J. 1997 Dec;18 Suppl F:F22-7. doi: 10.1093/eurheartj/18.suppl_f.22.
Very large clinical trials have become the norm in the evaluation of thrombolytic agents, and these 'megatrials' are administratively complex and expensive. It remains to be seen whether new thrombolytics will lead to further large reductions in fatality from an acute myocardial infarction, but new agents may well have advantages in areas such as safety and ease of administration, in addition to other clinical benefits (i.e. fewer cases of cardiac shock, heart failure and atrial fibrillation). The problem is how to introduce such new agents without a megatrial for each one. Endpoints other than fatality have some advantages and, in thrombolysis, angiographic studies are a necessary step in the development of new agents. However, such studies may not always correlate precisely with the results of mortality endpoint studies. Measurements of the resolution of ST segment elevation in myocardial infarction seem to provide a very useful method of assessing thrombolysis, but although such a technique can be applied to large numbers of patients, it cannot totally replace mortality endpoint trials. The 'equivalence' of two treatments is a clinical, not a statistical, concept, although statistical principles that allow equivalence to be investigated with medium-sized trials should be applied. Demonstrating equivalence in outcome between the new thrombolytic reteplase and streptokinase was the aim of the INJECT study.
大型临床试验已成为评估溶栓药物的常态，而这些“大型试验”在管理上复杂且成本高昂。新型溶栓药物是否会进一步大幅降低急性心肌梗死的死亡率仍有待观察，但除了其他临床益处（如减少心源性休克、心力衰竭和心房颤动的病例）外，新型药物在安全性和给药便利性等方面可能具有优势。问题在于如何在不针对每种新药进行大型试验的情况下引入这些新药。除死亡率外的其他终点有一些优势，在溶栓治疗中，血管造影研究是新药研发的必要步骤。然而，此类研究可能并不总是与死亡率终点研究的结果精确相关。测量心肌梗死中ST段抬高的消退情况似乎提供了一种评估溶栓效果的非常有用的方法，尽管这种技术可应用于大量患者，但它不能完全取代死亡率终点试验。两种治疗方法的“等效性”是一个临床概念，而非统计学概念，不过应运用能通过中型试验研究等效性的统计学原理。证明新型溶栓药物瑞替普酶与链激酶在疗效上的等效性是INJECT研究的目的。
