Huitfeldt B
Rev Infect Dis. 1986 Jul-Aug;8 Suppl 3:S350-7. doi: 10.1093/clinids/8.supplement_3.s350.
Controlled clinical trials are important tools for evaluating antibiotics in acute infections. External and internal validity, definition of efficacy criteria, and size of the patient sample constitute special statistical problems in such studies. Critical issues regarding external validity pertain to the selection of patients and to the concept of consecutive patients. The internal validity of a study is influenced by the withdrawal of patients from the evaluation after randomization and the comparability of treatment groups with regard to prognostic factors. The definition of efficacy criteria on the basis of bacteriologic outcomes across control visits is not straightforward. Particularly, the evaluation of efficacy at the last follow-up visit must take into account the accumulated information rather than the cross-sectional information. The most common situation in comparative trials of antibiotics is that rather small differences in efficacy can be anticipated. Sometimes, the question at issue is the demonstration of antibiotic equivalence. For valid conclusions to be made in such situations, large samples must be used. A basic problem affecting many studies of antibiotics is that this criterion is not fulfilled.
对照临床试验是评估急性感染中抗生素的重要工具。外部效度和内部效度、疗效标准的定义以及患者样本量在这类研究中构成了特殊的统计学问题。关于外部效度的关键问题涉及患者的选择以及连续患者的概念。一项研究的内部效度会受到随机化后退出评估的患者以及治疗组在预后因素方面的可比性的影响。基于对照访视时的细菌学结果来定义疗效标准并非易事。特别是，在最后一次随访时对疗效的评估必须考虑累积信息而非横断面信息。抗生素比较试验中最常见的情况是，预计疗效差异相当小。有时，争议的问题是证明抗生素等效性。要在这种情况下得出有效的结论，必须使用大样本。影响许多抗生素研究的一个基本问题是，这一标准未得到满足。
