Division of Epidemiology, Office of Surveillance and Epidemiology, Center for Drug Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave, Silver Spring, MD, 20993, USA.
Division of Pediatric and Maternal Health, Office of New Drugs, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA.
Drug Saf. 2018 Jan;41(1):87-94. doi: 10.1007/s40264-017-0591-5.
Pregnancy registries and spontaneous reports are essential pharmacovigilance tools to evaluate drug safety during pregnancy.
The aim of this study was to evaluate postmarket capture of exposed pregnancies.
Pregnancy registries for drugs and biologics were identified in a systematic review. Through a standardized questionnaire, manufacturers provided information on (1) pregnancy registry enrollment and retention, and (2) worldwide receipt of spontaneous reports for exposed pregnancies. A validated algorithm for live-birth pregnancies allowed calculation of exposure rates per 100,000 live births using claims data.
Among 34 products with a pregnancy registry, median (interquartile range) registry enrollment was 36 pregnancies (5-258) and median spontaneous report capture was 450 pregnancies (89-1192). Products used in >20/100,000 live births had a median registry enrollment of 490 pregnancies and median capture of 1061 spontaneously reported exposed pregnancies. Lower median registry enrollment and spontaneous report capture was observed for products used in 0.5-20/100,000 live births (36 from registries, 541 spontaneous reports) and <0.5/100,000 live births (3 from registries, 41 spontaneous reports). Among 24 registries enrolling ≥10 pregnancies, median capture of pregnancy outcomes (e.g. live birth, spontaneous abortion) was 83.9%. For 19 registries enrolling ≥10 infants, the median proportion of infants achieving protocol-specified follow-up was 89.9% for up to 4 weeks post-birth, 75.0% for 1-5 months, and 57.1% for ≥6 months.
Relatively higher product utilization among pregnant women predicted greater pregnancy registry enrollment. For products rarely used during pregnancy, registry enrollment was low and differences in registry enrollment compared with worldwide spontaneous report receipt were most pronounced. Products with very low utilization levels during pregnancy may require a combination of worldwide pharmacovigilance, pregnancy registries, and additional study methods to achieve adequate surveillance.
妊娠登记和自发报告是评估妊娠期间药物安全性的重要药物警戒工具。
本研究旨在评估上市后对暴露妊娠的监测情况。
通过系统评价确定了药物和生物制品的妊娠登记处。制造商通过标准化问卷提供了以下信息：（1）妊娠登记处的入组和保留情况；（2）全球收到的暴露妊娠自发报告情况。使用索赔数据，通过验证有效的算法对活产妊娠进行计算，可得出每 10 万活产妊娠的暴露率。
在有妊娠登记处的 34 种产品中，登记处入组的中位数（四分位距）为 36 例（5-258 例），自发报告的中位数捕获量为 450 例（89-1192 例）。在 20/100,000 活产以上使用的产品的登记中位数为 490 例，自发报告的暴露妊娠中位数为 1061 例。在 0.5-20/100,000 活产和<0.5/100,000 活产中使用的产品，其登记中位数和自发报告捕获量较低（登记中位数分别为 36 例和 541 例，自发报告中位数分别为 41 例和 1192 例）。在纳入≥10 例妊娠的 24 个登记处中，妊娠结局（如活产、自然流产）的捕获中位数为 83.9%。在纳入≥10 例婴儿的 19 个登记处中，出生后 4 周内达到方案规定随访的婴儿中位数比例为 89.9%，1-5 个月为 75.0%，6 个月以上为 57.1%。
孕妇中相对较高的产品使用率预测了妊娠登记处的更高入组率。对于妊娠期间很少使用的产品，登记处的入组率较低，与全球自发报告的接收率相比，登记处的入组率差异最为明显。妊娠期间使用率极低的产品可能需要结合全球药物警戒、妊娠登记处和其他研究方法来实现充分的监测。
