Hujoel P P, DeRouen T A
Department of Dental Public Health Sciences, University of Washington, Seattle 981951, USA.
J Clin Periodontol. 1995 May;22(5):397-407. doi: 10.1111/j.1600-051x.1995.tb00167.x.
Endpoints are conditions or events that are associated with individual study subjects and that are used to assess treatment efficacy. 2 types of endpoints can be distinguished: "true" endpoints (reflect unequivocal evidence of tangible benefit to the patient) and "surrogate" endpoints (usually a measure of disease process). The purpose of this study was to survey four aspects of endpoint usage in randomized controlled trials (RCT's) on the treatment of periodontitis: (1) the typical number of endpoints per RCT, (2) the proportion of RCTs using the same endpoint, (3) the proportion of RCTs using true endpoints, and (4) whether treatment choice influenced endpoint choice. 92 publications (1988-1992) reporting on 82 RCT's were identified. The typical number of endpoints per RCT was 6 (range: 1-28). The 3 most frequently used endpoints were mean probing depth (78% of the trials), mean probing attachment level (66%), and the plaque index (37%). In total, 153 distinct surrogate endpoints were defined. Most of these were used infrequently; over 80% of the 153 endpoints were used in fewer than 5 of the 82 trials. No trials used tooth loss as a true endpoint. In the design of an RCT, treatment choice influenced surrogate endpoint choice. Surrogate endpoints based on re-entry surgery were exclusively used for regenerative procedures and microbiological surrogate endpoints were mostly used for RCT's on anti-microbials. The conclusion is that the typical RCT used multiple surrogate endpoints, some of which were used infrequently by other trials. Such endpoint usage characteristics are suitable for exploratory RCTs (designed to identify active treatments or to elucidate treatment mechanisms). The question is raised as to whether periodontal research has reached the point of needing properly designed definitive studies, whose purpose it would be to provide unequivocal evidence of tangible benefits to the patient by the various treatments. If a need for definitive randomized controlled trials is perceived, then the use of (multiple) surrogate endpoints as primary outcomes should be questioned. Surrogate endpoint usage has led to both false positive and false negative conclusions in other chronic disease studies. Endpoint selection and validation in RCTs may be an important element in resolving controversies about periodontal treatments.
终点指标是与个体研究对象相关联且用于评估治疗效果的状况或事件。可区分出两种类型的终点指标：“真实”终点指标（反映对患者有切实益处的确凿证据）和“替代”终点指标（通常是疾病进程的一种度量）。本研究的目的是调查牙周炎治疗随机对照试验（RCT）中终点指标使用的四个方面：（1）每个RCT的典型终点指标数量，（2）使用相同终点指标的RCT的比例，（3）使用真实终点指标的RCT的比例，以及（4）治疗选择是否影响终点指标选择。确定了92篇报告82项RCT的出版物（1988 - 1992年）。每个RCT的典型终点指标数量为6个（范围：1 - 28个）。3个最常用的终点指标是平均探诊深度（78%的试验）、平均探诊附着水平（66%）和菌斑指数（37%）。总共定义了153个不同的替代终点指标。其中大多数使用频率较低；在这153个终点指标中，超过80%在82项试验中的使用次数少于5次。没有试验将牙齿脱落用作真实终点指标。在RCT的设计中，治疗选择影响替代终点指标的选择。基于再次手术的替代终点指标仅用于再生治疗程序，而微生物学替代终点指标大多用于抗菌治疗的RCT。结论是，典型的RCT使用多个替代终点指标，其中一些在其他试验中的使用频率较低。这种终点指标使用特征适用于探索性RCT（旨在识别有效治疗方法或阐明治疗机制）。有人提出疑问，牙周病研究是否已达到需要进行设计合理的确定性研究的阶段，其目的是通过各种治疗为患者提供切实益处的确凿证据。如果认为需要进行确定性随机对照试验，那么将（多个）替代终点指标用作主要结局指标的做法就值得质疑。在其他慢性病研究中，替代终点指标的使用已经导致了假阳性和假阴性结论。RCT中的终点指标选择和验证可能是解决牙周病治疗争议的一个重要因素。
