Developing and refining methods to assess medical product utilization, safety, and effectiveness during pregnancy is a focus of FDA’s Sentinel System. The Sentinel Common Data Model (SCDM) includes a Mother-Infant Linkage (MIL) table that enables routine evaluation of the effects of medical product exposures during pregnancy on infant outcomes. Descriptions of efforts led by the Center for Drug Evaluation and Research are shown below. Please visit the links to learn more about each area of activity.
In this report, we describe the utilization of various medical products during pregnancies ending in live-birth delivery in the Sentinel Distributed Database (SDD). Medical products of interest (MOIs) include those with pregnancy‐related postmarketing requirements (PMRs) and/or postmarketing commitments (PMCs), those involved in pregnancy registries, or those investigated in studies listed in ClinicalTrials.gov that fulfilled the following search criteria elements with respect to their use during pregnancy: 1) Pregnant, Pregnancy, Observational, 2) Limited to studies associated with a drug or biologic.
We distributed this request to five Sentinel Data Partners on January 12, 2023. The study period includes data from January 1, 2008 to June 30, 2022.
A companion analysis describes utilization of various medical products during pregnancies ending in live-birth delivery where the mother is linked to a singleton infant in the Sentinel Common Data Model (SCDM) Mother‐Infant Linkage (MIL) table.
In this report, we examined bevacizumab and other cancer medication use during pregnancy in the Sentinel Distributed Database (SDD). The study period includes data from January 1, 2001 to September 30, 2015. We distributed this request to 14 Sentinel Data Partners on July 21, 2016.
This analysis describes clinical characteristics of pregnancies with live birth deliveries among patients who were exposed to fingolimod, dimethyl fumarate, beta interferons, or received no treatment for multiple sclerosis (MS) in the first trimester of pregnancy. In this analysis, we describe the occurrence of cardiac malformations, urinary malformations, other (non-cardiac, non-urinary) malformations, or and any congenital malformations. These outcomes were evaluated based on evidence available in the mothers’ records in the Sentinel Distributed Database (SDD). We did not utilize the Mother-Infant Linkage (MIL) table in this analysis. We distributed this request to 12 Sentinel Data Partners on January 9, 2023. The study period includes data from January 1, 2011 to August 1, 2022.
The analytic package associated with this analysis can be found externally in Sentinel's Git Repository located here. The Git Repository serves as Sentinel's version control tracking system for analytic packages and technical documentation.
A companion analysis describes the clinical characteristics of pregnancies with linked live birth deliveries among patients with evidence of MS who were exposed to fingolimod, dimethyl fumarate, beta interferons, or received no MS treatment in the first trimester of pregnancy. That analysis also describes the occurrence of cardiac malformations, urinary malformations, other (non-cardiac, non-urinary) malformations, and any congenital malformations evaluated based on evidence available in the mothers’ or linked infants’ records in the SDD, from the Sentinel Common Data Model MIL Table.
This analysis describes the clinical characteristics of pregnancies with linked live birth deliveries among patients with evidence of multiple sclerosis (MS) who were exposed to fingolimod, dimethyl fumarate, beta interferons, or received no MS treatment in the first trimester of pregnancy. This analysis also describes the occurrence of cardiac malformations, urinary malformations, other (non-cardiac, non-urinary) malformations, and any congenital malformations. These outcomes were evaluated based on evidence available in the mothers’ or linked infants’ records in the Sentinel Distributed Database (SDD), from the Sentinel Common Data Model Mother-Infant Linkage (MIL) Table. We distributed this request to five Sentinel Data Partners on January 24, 2023. The study period includes data from January 1, 2011 to June 30, 2022.
The analytic package associated with this analysis can be found externally in Sentinel's Git Repository located here. The Git Repository serves as Sentinel's version control tracking system for analytic packages and technical documentation.
A companion analysis describes clinical characteristics of pregnancies with live birth deliveries among patients with evidence of MS who were exposed to fingolimod, dimethyl fumarate, beta interferons, or received no MS treatment in the first trimester of pregnancy. In that analysis, we describe the occurrence of cardiac malformations, urinary malformations, other (non-cardiac, non-urinary) malformations, and any congenital malformations. These outcomes were evaluated based on evidence available in the mothers’ records in the SDD. We did not utilize the MIL table in that analysis.
The US Food and Drug Administration established the Sentinel System to monitor the safety of medical products. A component of this system includes parameterizable analytic tools to identify mother-infant pairs and evaluate infant outcomes to enable the routine monitoring of the utilization and safety of drugs used in pregnancy. We assessed the feasibility of using the data and tools in the Sentinel System by assessing a known association between topiramate use during pregnancy and oral clefts in the infant. We identified mother-infant pairs using the mother-infant linkage table from six Data Partners contributing to the Sentinel Distributed Database from January 1, 2000, to September 30, 2015. We compared mother-infant pairs with first-trimester exposure to topiramate to mother-infant pairs that were topiramate-unexposed or lamotrigine-exposed and used a validated algorithm to identify oral clefts in the infant. We estimated adjusted risk ratios through propensity score stratification.
Traditional surveillance of adverse infant outcomes following maternal medication exposures relies on pregnancy exposure registries, which are often underpowered. We characterize the statistical power of TreeScan™, a data mining tool, to identify potential signals in the setting of perinatal medication exposures and infant outcomes. We used empirical data to inform background incidence of major congenital malformations and other birth conditions. Statistical power was calculated using two probability models compatible with TreeScan, Bernoulli, and Poisson, while varying the sample size, magnitude of the risk increase, and incidence of a specified outcome. We also simulated larger exposure to referent matching ratios when using the Bernoulli model in the setting of fixed N:1 propensity score matching. Finally, we assessed the impact of outcome misclassification on power.
This presentation identifies and describes pregnancies in claims-based data sources which presents logistical and inferential challenges. FDA’s Sentinel System included data from six sites with linked infant and maternal data, and reusable, parameterizable tools to identify and describe these cohorts. These tools and the methods for identifying pregnancies are publicly available and may be used by anyone following Sentinel’s Common Data Model. In this symposium, Sentinel Operation Center presenters discuss the publicly available analytic tools and recent pharmacoepidemiologic analyses related to pregnancies and outcomes within Sentinel.
It was presented at the Society for Pediatric and Perinatal Epidemiologic Research (SPER) webinar on September 13, 2022.
It is a priority of the US Food and Drug Administration (FDA) to monitor the safety of medications used during pregnancy. Pregnancy exposure registries and cohort studies utilizing electronic health record data are primary sources of information but are limited by small sample sizes and limited outcome assessment. TreeScan™, a statistical data mining tool, can be applied within the FDA Sentinel System to simultaneously identify multiple potential adverse neonatal and infant outcomes after maternal medication exposure. We implemented TreeScan using the Sentinel analytic tools in a cohort of linked live birth deliveries and infants nested in the Merative™ MarketScan® Research Databases. As a case study, we compared first trimester fluoroquinolone use and cephalosporin use. We used the Bernoulli and Poisson TreeScan statistics with compatible propensity score-based study designs for confounding control (matching and stratification) and used multiple propensity score models with various strategies for confounding control to inform best practices. We developed a hierarchical outcome tree including major congenital malformations and outcomes of gestational length and birth weight.
This analysis examines the clinical characteristics in three cohorts including pregnant women with and without heart failure (HF) and non-pregnant women with HF, characterizes use of oral HF-related therapies before, during, and after pregnancy, and examines maternal and fetal outcomes among pregnant patients with and without HF in the Sentinel Distributed Database (SDD). This report follows a previous study, Pregnancy among Women with Heart Failure: A Descriptive Analysis.
The study period included data from January 1, 2010 to March 31, 2021. We distributed this request to four Sentinel Data Partners on December 3, 2021.
The analytic package associated with this analysis can be found externally in Sentinel's Git Repository located here. The Git Repository serves as Sentinel's version control tracking system for analytic packages and technical documentation.
This presentation provides an overview of the Sentinel Distributed Database and its use of real-world data for the surveillance of medications in pregnancy.
It was presented at the FDA Office of Women's Health (OWH) and Johns Hopkins University Center of Excellence in Regulatory Science and Innovation (JH-CERSI) collaborative workshop, held on May 9, 2022.