Schaefer Christof, Hannemann Doreen, Meister Reinhard
Pharmakovigilanz- und Beratungszentrum für Embryonaltoxikologie, Berliner Betrieb für Zentrale Gesundheitliche Aufgaben, Spandauer Damm 130, Haus 10, 14050 Berlin, Germany.
Reprod Toxicol. 2005 Sep-Oct;20(3):331-43. doi: 10.1016/j.reprotox.2005.03.012.
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.
致畸学信息服务（TIS）为公众和卫生专业人员提供有关孕期药物风险的定制信息。欧洲、以色列和拉丁美洲的TIS在欧洲致畸学信息服务网络（ENTIS）中开展合作，以优化风险数据的解读、风险沟通和风险管理，以及为孕妇药物治疗提供建议。此外，还努力加强和统一对暴露于药物的妊娠及其结局的记录。这些前瞻性确定的数据将像对照观察队列研究一样进行评估，将暴露于药物的妊娠与未暴露的对照组在各种结局变量上进行比较，如（严重）畸形、出生指标和新生儿状况、自然流产。前瞻性方法可将所研究药物的回忆偏倚降至最低。使用适当的统计方法根据标准化方案对收集的数据进行评估，可显著改善风险评估。在比例风险模型框架内，对香豆素暴露妊娠与柏林TIS登记的对照组之间的自然流产进行比较，证明了生存分析方法的益处。ENTIS的多中心方法允许研究大型暴露队列，即使是使用很少的药品。在上市后监测方面，没有其他数据可以替代TIS数据。TIS的数据收集使用了一个已经建立的风险沟通系统，具有成本低和应答者积极性高的优点。由于TIS主要是针对记录不充分的药物或那些被怀疑具有发育毒性的药物而被联系，因此甚至对需要研究的产品进行了筛选。
