Skegg D C
Department of Preventive and Social Medicine, University of Otago, Dunedin, New Zealand.
Stat Med. 2001 Dec 15;20(23):3557-69. doi: 10.1002/sim.1077.
Toxicological studies and clinical trials cannot be expected to predict all important adverse effects of medicines and contraceptives. Post-marketing surveillance is essentially an epidemiological task that involves detecting associations between drugs and events. The first alerts about drug safety problems have often come from case reports, but epidemiological studies are needed to confirm adverse (or beneficial) effects and to provide quantitative information. This article illustrates methodological principles by considering three examples from the field of contraceptive safety: oral contraceptives and breast cancer, intrauterine contraception and pelvic inflammatory disease, and newer oral contraceptives and venous thromboembolism. Key issues that emerge include bias and confounding, the place of subgroup analyses, random error, and the use of computerized databases. In research on contraceptive and drug safety, conclusions usually need to be based on careful assessment of multiple observational studies.
毒理学研究和临床试验无法预测药物及避孕药具的所有重要不良反应。上市后监测本质上是一项流行病学任务，涉及检测药物与事件之间的关联。有关药物安全问题的最初警示往往来自病例报告，但需要开展流行病学研究来确认不良反应（或有益作用）并提供定量信息。本文通过考量避孕安全领域的三个实例阐述方法学原则：口服避孕药与乳腺癌、宫内避孕与盆腔炎，以及新型口服避孕药与静脉血栓栓塞。出现的关键问题包括偏倚和混杂、亚组分析的作用、随机误差以及计算机化数据库的使用。在避孕与药物安全研究中，结论通常需基于对多项观察性研究的审慎评估。
