Evaluating the safety of medicines, with particular reference to contraception

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. Copyright (C) 2001 John Wiley & Sons, Ltd.