Lotus Clinical Research, Huntington Hospital, Department of Anesthesia, Pasadena, CA, USA Department of Diagnostic Sciences, Rutgers School of Dental Medicine, Newark, NJ, USA.
Pain. 2014 Mar;155(3):441-456. doi: 10.1016/j.pain.2013.09.002. Epub 2013 Sep 6.
When a clinical trial of an analgesic produces a negative finding, it is important to consider the influence (if any) of experimental error on the validity of that result. Although efforts to identify and minimize experimental error in chronic pain investigations have begun in earnest, less work has been performed on the optimization of acute pain methodology. Of the acute surgical pain methodology articles that have been published over the last decade, almost all focus on either the dental or bunion model. Analgesics are typically evaluated in a variety of surgical models that eventually include hospital-based models (eg, joint replacement and soft tissue surgery). Every surgical procedure has unique clinical characteristics that must be considered to optimize study design and conduct. Much of the methodological knowledge garnered from bunion and dental studies is applicable to other surgical models, but some extrapolations are hazardous. The purposes of this review were (1) to qualitatively describe the clinical and experimental characteristics of the 4 classic surgical models: dental extraction, bunionectomy, joint replacement, and soft tissue surgery; and (2) to quantitatively compare the models by analyzing 3 factors: effect size, enrollment rate, and demographics. We found that the dental extraction and bunionectomy models had higher assay sensitivity than the joint replacement and soft tissue surgery models. It is probable that this finding is secondary to the superior experimental conditions under which the dental and bunion models are executed (utilization of few centers that have the ability to reduce surgical, anesthetic, and postoperative confounders).
当一项镇痛药临床试验得出阴性结果时，重要的是要考虑实验误差对该结果有效性的影响（如有）。尽管在慢性疼痛研究中已经开始认真努力识别和最小化实验误差，但在优化急性疼痛方法学方面的工作却较少。在过去十年中发表的急性外科疼痛方法学文章中，几乎所有文章都集中在牙科或拇囊炎模型上。镇痛药通常在各种外科模型中进行评估，最终包括基于医院的模型（例如，关节置换和软组织手术）。每个外科手术都有独特的临床特征，必须加以考虑，以优化研究设计和实施。从拇囊炎和牙科研究中获得的许多方法学知识适用于其他外科模型，但有些推断是危险的。本综述的目的是（1）定性描述 4 种经典外科模型的临床和实验特征：拔牙、拇囊炎切除术、关节置换和软组织手术；（2）通过分析 3 个因素：效应大小、入组率和人口统计学，对模型进行定量比较。我们发现，拔牙和拇囊炎切除术模型的检测灵敏度高于关节置换和软组织手术模型。这一发现很可能是由于牙科和拇囊炎模型执行的实验条件优越所致（利用少数有能力减少手术、麻醉和术后混杂因素的中心）。
