Page R C, DeRouen T A
Department of Periodontics, University of Washington, Seattle.
J Periodontal Res. 1992 Jul;27(4 Pt 2):395-404; discussion 412-6. doi: 10.1111/j.1600-0765.1992.tb01704.x.
Guidelines for clinical trials demonstrating equivalence or superiority for treatments for periodontitis are badly needed because of the great variety of drugs, agents, and devices now being developed. This paper focuses on three design issues. These are primary outcome variables and their measurement, disease-active vs disease-inactive sites and patients, and study duration. Determinants for selection of outcome variables include the biologic events to be observed, changes that are specific for periodontitis, and methods chosen to detect those changes. The primary outcome variables specific for periodontitis and appropriate for use in clinical trials are periodontal attachment level and alveolar bone status. Improved methods for measurement of both with excellent accuracy and reproducibility are now becoming available. Studies performed on untreated patients over the past decade demonstrate clearly that disease-active and disease-inactive pockets exist, at any given point in time most are inactive, disease progression is episodic and in most patients infrequent, and a rather small portion of the population--possibly around 5%--are unusually susceptible to rapid disease progression. These observations need to be taken into account in enrolling subjects into periodontitis clinical trials. Conducting a prestudy to identify actively diseased sites and susceptible subjects, or screening to enrich the proportion of active sites, is recommended. Determination of study duration is a very complex issue. It is related to the length of time required for maximal change and stabilization to occur in the biological events to be observed, the outcome variable(s) used to detect change, and the nature of the therapeutic interventions to be studied. No single duration is applicable to all periodontitis clinical trials. Large gaps in our knowledge about the design of periodontitis trials still exist, and additional research is needed.
由于目前正在研发的药物、药剂和器械种类繁多，因此迫切需要有关证明牙周炎治疗等效性或优越性的临床试验指南。本文重点关注三个设计问题。这些问题是主要结局变量及其测量、疾病活动期与非活动期的部位和患者，以及研究持续时间。结局变量选择的决定因素包括要观察的生物学事件、牙周炎特有的变化以及用于检测这些变化的方法。牙周炎特有的且适用于临床试验的主要结局变量是牙周附着水平和牙槽骨状况。现在已有测量这两者的改进方法，其准确性和可重复性都非常出色。过去十年对未经治疗患者进行的研究清楚地表明，疾病活动期和非活动期的牙周袋是存在的，在任何给定时间，大多数牙周袋是不活动的，疾病进展是间歇性的，并且在大多数患者中很少见，而且相当一小部分人群（可能约5%）异常容易出现快速疾病进展。在招募牙周炎临床试验受试者时需要考虑这些观察结果。建议进行预研究以识别活跃的患病部位和易感受试者，或者进行筛查以增加活跃部位的比例。确定研究持续时间是一个非常复杂的问题。它与观察到的生物学事件发生最大变化并稳定所需的时间长度、用于检测变化的结局变量以及要研究的治疗干预的性质有关。没有一个单一的持续时间适用于所有牙周炎临床试验。我们在牙周炎试验设计方面的知识仍然存在很大差距，需要进行更多研究。
