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 where the mother is linked to a singleton infant in the Sentinel Common Data Model (SCDM) Mother‐Infant Linkage (MIL) table. 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 four Sentinel Data Partners on March 24, 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 but does not utilize the Mother‐Infant Linkage (MIL) table.
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.
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 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.
This presentation provides an overview of TreeScan signal identification methods and discusses how such methods can be used for surveillance of potential adverse infant events following maternal medication exposure during pregnancy. Methods and results from a simulation analysis to assess the performance of TreeScan under known conditions are reviewed, as well as a case study which aimed to demonstrate the use of TreeScan in real-world data, in a cohort of pregnant women linked to their live-born infants.
It was presented at the Canadian Network for Observational Drug Effect Studies (CNODES) Virtual Seminar, held on March 9, 2022.
In this report we describe exposure to multiple sclerosis (MS) drugs before, during and after pregnancies resulting in a live-born delivery among women in the Sentinel Distributed Database (SDD). We also describe MS drug use among matched women during episodes without evidence of a live-birth delivery.
The study period includes data from January 1, 2001 to December 31, 2020. We distributed this request to six Sentinel Data Partners on June 25, 2021.