McMahon A D, MacDonald T M
Robertson Centre for Biostatistics, University of Glasgow, Glasgow G12 8QQ, Scotland.
Br J Clin Pharmacol. 2000 Nov;50(5):419-25. doi: 10.1046/j.1365-2125.2000.00289.x.
Despite the difficulties involved in designing drug epidemiology studies, these studies are invaluable for investigating the unexpected adverse effects of drugs. The aim of this paper is to discuss various aspects of study design, particularly those issues that are not easily found in either textbooks or review papers. We have also compared and contrasted drug epidemiology with the randomized controlled trial (RCT) wherever possible. Drug epidemiology is especially useful in the many situations where the RCT is not suitable, or even possible. The study base has to be defined before the appropriate cohort of subjects is assembled. If all of the cases are identified, then a referent sample of controls may be assembled by random sampling of the study base. If all of the cases cannot be assembled, a hypothetical secondary base may need to be created. Preferably, only new-users of the drug should be included, and the risk-ratio will be different for acute users and chronic users. Studies will usually only be possible when researching the unintended effects of drugs. It is difficult to study efficacy because of confounding by indication. In occasional circumstances it may be possible to study efficacy (examples are given). Discussion of the dangers of designing with generalisability in mind is provided. Additionally, the similarities in study design between drug epidemiology and the RCT are discussed in detail, as well as the design-characteristics that cannot be shared between the two methods.
尽管设计药物流行病学研究存在诸多困难，但这些研究对于调查药物意外的不良反应而言价值非凡。本文旨在探讨研究设计的各个方面，尤其是那些在教科书或综述文章中不易找到的问题。我们还尽可能地对药物流行病学与随机对照试验（RCT）进行了比较和对比。在许多RCT不适用甚至不可行的情况下，药物流行病学尤为有用。在合适的研究对象队列聚集之前，必须先确定研究基础。如果能识别出所有病例，那么可以通过对研究基础进行随机抽样来聚集对照的参考样本。如果无法聚集所有病例，则可能需要创建一个假设的二级基础。最好只纳入药物的新使用者，急性使用者和慢性使用者的风险比会有所不同。通常只有在研究药物的意外效果时研究才可行。由于指征混杂，很难研究疗效。在某些情况下，有可能研究疗效（给出了示例）。文中还讨论了在设计时考虑普遍性的风险。此外，还详细讨论了药物流行病学与RCT在研究设计上的相似之处，以及两种方法无法共享的设计特征。
