Principles from clinical trials relevant to clinical practice: Part I
Principles from clinical trials relevant to clinical practice: Part I
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DOI：
10.1161/01.cir.0000023260.78078.bb
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发表时间：
2002-08-20
期刊：
影响因子：
37.8
通讯作者：
DeMets, DL
中科院分区：
文献类型：
--
作者：
Califf, RM;DeMets, DL
临床试验结果表明，在具有给定诊断的群体中有效的大多数疗法在该群体的大多数成员中也有效。抗血小板试验者协作组4-6、最近的血管紧张素转换酶（ACE）抑制剂协作组7-9和纤溶治疗试验者协作组10最引人注目的发现之一是亚组中治疗效果的一致性（图2）。在试验中的整个亚组中，治疗效果逆转的情况很少见;对大多数确诊患者有益的治疗方法很少对确诊患者的亚组造成损害。尽管存在明显的例外情况，例如接受纤溶治疗的无ST段抬高型MI患者，8但在系统综述中，这一发现非常常见。在使用β受体阻滞剂治疗心力衰竭的试验中也发现了类似的一致性。11-13这一发现的临床结果是，当一种疗法被证明对患有临床病症的患者有益时，该疗法可以在临床实践中系统地应用于人群。临床医生的责任是证明不治疗的合理性，而不是证明用诊断来治疗每个病人的合理性。这种方法允许实践和卫生系统制定临床实践标准和绩效衡量标准，可以引入医院和诊所，以确保可靠地使用有效的实践。当一组与另一组相比对治疗的反应存在显著差异，但两组的治疗效果（获益或损害）方向相同时，就会发生定量相互作用。定量的相互作用是常见的，病情较重的患者几乎总是比病情较轻的患者从治疗中获益更大。病情较重的患者从治疗中获得更多益处的这一发现与从业者在自己的患者中通常观察到的情况不一致，即病情较轻的患者治疗效果更好。当然，这种来自“临床经验”的直观教训是不正确的，因为它没有考虑到这样一个事实，即病情较轻的患者在不接受治疗的情况下也会表现得更好，这一原则对治疗方法的选择具有重要意义。重要的是选择那些与没有治疗的情况相比，治疗的结果是最有利的患者，而不是选择那些接受给定治疗的患者具有最佳结果。多项研究表明，选择血管造影术14和血运重建术14 -16的患者往往倾向于获益较少的低风险患者，而不是获益最大的高风险患者。同样，老年人不太可能接受二级预防治疗，尽管一致的研究结果表明，
clinical trial results indicates that most therapies that are effective in a population with a given diagnosis are effective in most members of that population. One of the most striking findings of the Antiplatelet Trialists’ Collaboration, 4–6 the recent Angiotensin-Converting Enzyme (ACE) Inhibitor Collaboration, 7–9 and the Fibrinolytic Therapy Trialists’ Collaborative Group, 10 is the consistency of treatment effects in subgroups (Figure 2). Across the spectrum of subgroups within a trial, reversal of a treatment effect is rare; a treatment that is beneficial for most patients with a diagnosis is rarely detrimental in a subgroup of patients with that diagnosis. Although notable exceptions exist, such as patients without ST-segment elevation MI who are given fibrinolytic therapy, 8 this finding is remarkably common across systematic overviews. A similar consistency is found across trials in heart failure that use ß-blockers. 11–13 The clinical consequence of this finding is that when a therapy is shown to be beneficial for patients with a clinical condition, the therapy can be applied systematically to the population in clinical practice. The burden is on the clinician to justify failing to treat rather than having to justify treating each patient with the diagnosis. This approach allows practices and health systems to develop clinical practice standards and performance measures that can be introduced into hospitals and clinics to ensure reliable use of effective practices. A quantitative interaction occurs when there is a significant difference in response to treatment in one group compared with another, but the direction of the treatment effect (benefit or harm) is the same in both groups. Quantitative interactions are common, and the sicker patients almost always have a greater benefit from treatment than do the less sick patients. This finding that sicker patients derive more benefit from treatment is at odds with what practitioners commonly observe in their own patients, which is that less sick patients have better outcomes with treatments. This intuitive lesson from “clinical experience” is incorrect, of course, because it cannot take into account the fact that less sick patients also do better without treatment.This principle has important implications for treatment selection. Rather than selecting patients who have the best outcomes with a given therapy, the important construct is to select patients in whom the outcome with therapy is most favorable compared with what would have happened without the therapy. Multiple studies have shown that selection of patients for angiography14 and revascularization14–16 tends to err toward low-risk patients who get less benefit rather than high-risk patients who get the greatest benefit. Similarly, the elderly are less likely to be treated with secondary prevention therapies, despite consistent findings that show greater ben-