Post-marketing surveillance system for drugs in pregnancy-15 years experience of ENTIS

Teratology Information Services (TIS) provide the public and health professionals with tailor-made information on drug risks in pregnancy. TIS in Europe, Israel and Latin America collaborate in the European Network of Teratology Information Services (ENTIS) in order to optimise interpretation of risk data, risk communication and risk management as well as recommendations for drug treatment in pregnant women. In addition, efforts are undertaken to enhance and harmonise documentation of exposed pregnancies and their outcomes. These prospectively ascertained data are evaluated like controlled, observational cohort studies, where exposed pregnancies are compared to a non-exposed control group for various outcome variables such as (major) malformations, birth measures and the state of the new-born infant, spontaneous abortion. The prospective methodology minimises recall bias of the studied drugs. Evaluating the data collected according to standardised protocols with appropriate statisticals methods substantially improves risk assessment. The comparison of spontaneous abortions between coumarin exposed pregnancies and controls enrolled in the Berlin TIS demonstrates the benefit of the methodology of survival analysis within the framework of the proportional hazard model. The ENTIS multi-centre approach permits studying large exposed cohorts even with seldomly used medicinal products. In terms of post-marketing surveillance there are no alternatives to TIS data. Data collection by TIS uses an already established risk communication system, and has the advantage of low costs and motivated responders. As a TIS is contacted mainly for insufficiently documented drugs or those suspected of acting as developmental toxicants there is even a selection for products needing research.