The Office of Surveillance and Epidemiology in the Center for Drug Evaluation and Research (CDER) leads the Sentinel System. Sentinel was created to meet the mandate described in Section 905 of the Food and Drug Administration Amendments Act 2007 (FDAAA) to create an active postmarket drug safety surveillance system. CDER uses Sentinel to proactively assess the safety of FDA approved drugs under real-world conditions.
The Active Risk Identification and Analysis (ARIA) system is the largest and most developed component of Sentinel. ARIA uses state-of-the-art analysis tools and a distributed database of standardized claims and claims linked with electronic health records (EHR) data to monitor the safety of medications. The data undergo continuous quality checks and refreshes. With ARIA, safety analyses are conducted more efficiently compared to studies with fully customized analytics—often in a matter of months, rather than several years.
How Drug Safety Studies Inform FDA’s Regulatory Process
FDA conducts safety studies in Sentinel for the following purposes, as described in Section 505(o)(3)(B) of FDAAA:
- Assess a known serious risk related to the use of the drug
- Assess signals of serious risk related to the use of the drug
- Identify an unexpected serious risk
Sentinel drug safety studies can contribute to FDA’s regulatory process in a variety of ways. This includes:
- Providing reassuring data to address new concerns about the safety of a medical product
- Contributing evidence to support an FDA Drug Safety Communication or Label Change
- Responding to a citizen's petition
- Informing FDA’s risk management strategy for a drug
- Becoming part of an Advisory Committee deliberation
- Providing evidence that alleviates a drug safety concern
Levels of ARIA Analyses
- Signal Identification: analyses used to detect new and unsuspected potential safety concerns.
- Level 1: analyses used to describe and characterize patterns of medication use or rates of health outcomes of interest. The Sentinel Query Builder application represents a subset of Level 1 functionality. Query Builder analyses are typically run on Merative™ MarketScan® Research Databases but some are also run on Sentinel's distributed database.
- Levels 2 and 3: analyses used to study whether a potential adverse health outcome is related to the use of drug and estimates the size of that risk.
Levels of ARIA Analyses

All Sentinel System Analyses, by Quarter
The graph below captures the total number of analyses conducted by the FDA since 2016 throughout the Sentinel System, including the Sentinel Distributed Database (SDD), IBM Watson Health, IBM Explorys, TriNetX, HCA Healthcare, PCORnet, and Veradigm.

Electronic Health Records (EHR) Data Sources in Sentinel
Sentinel’s ARIA system is complemented by EHR data systems, enabling the selection of a data source that best fits a drug safety question of interest. There are 3 categories of EHR data sources:
- Data Aggregators: Compiles EHR data from multiple, discrete healthcare organizations in a single platform.
- Data Warehouse: Stores extracted, standardized data from transactional systems in a central repository.
- Network: An integrated partnership of standardized EHR data among multiple data partners.
Sentinel's Multi-Modal Response System
All Drug Safety Studies Conducted in Sentinel
All drug safety studies conducted in Sentinel are included below. The table is organized by the drug or population of interest and the health outcome(s) under study. When available, links are provided to the analytic code (package), results, communications and the study’s regulatory outcome.
Sentinel Study Status

Sentinel Study Purpose

FDA Sentinel Drug Studies: from ARIA and other Sentinel Data Sources
Drug/Population | Health Outcome(s) | Impact(s) Posted | Last Updated | Purpose | |
---|---|---|---|---|---|
Gonadotropin-Releasing Hormone (GnRH) Agonists Complete |
utilization characterization |
Regulatory Outcome, Results | 05/25/2023 | Drug Use | No |
Ozempic (semaglutide) Complete |
Analytic Code, Results | 05/04/2023 | Signal Identification | No | |
Zarxio (filgrastim-sndz) Complete |
Analytic Code, Results | 05/04/2023 | Signal Identification | No | |
Epidiolex (prescription cannabidiol) Complete |
utilization |
Regulatory Outcome, Results | 04/27/2023 | Drug Use | No |
Insulin Complete |
coding practices |
Regulatory Outcome, Communication, Results | 04/27/2023 | Drug Use | No |
Brexafemme (ibrexafungerp) Ongoing |
use in pregnancy |
Results | 04/24/2023 | Drug Use | No |
Pediatric patients Complete |
hypertension |
Regulatory Outcome, Communication, Results | 04/13/2023 | Methods and Development | No |
Gilenya (fingolimod) Ongoing |
all congenital malformations , congenital cardiac malformations (primary) , congenital urinary malformations (primary) |
Analytic Code | 03/03/2023 | Drug and Outcome Analysis | No |
Rinvoq (upadacitinib) Ongoing |
acute myocardial infarction , deep vein thrombosis , pulmonary embolism , stroke |
02/24/2023 | Drug and Outcome Analysis | No | |
Ablysinol (dehydrated alcohol) Ongoing |
atrioventricular block , death , heart failure , myocardial infarction , permanent pacemaker placement , septal myectomy , ventricular arrhythmia |
Analytic Code, Communication, Results | 02/09/2023 | Drug and Outcome Analysis | Yes |
Olumiant (baricitinib) Ongoing |
acute myocardial infarction , deep vein thrombosis , pulmonary embolism , stroke |
01/17/2023 | Drug and Outcome Analysis | No | |
Taltz (ixekizumab) Complete |
use in pregnancy |
Regulatory Outcome, Results | 11/14/2022 | Drug Use | No |
Lupron Depot PED (leuprolide acetate) Complete |
any fracture , hip replacement , major fracture (primary) , temporomandibular joint replacement |
Regulatory Outcome, Analytic Code, Communication, Results | 09/16/2022 | Drug and Outcome Analysis | No |
Women with heart failure Complete |
pregnancy |
Regulatory Outcome, Analytic Code, Communication, Results | 08/10/2022 | Drug and Outcome Analysis | No |
Gadolinium-based contrast agents Complete |
seizure |
Regulatory Outcome, Analytic Code, Communication, Results | 07/26/2022 | Drug and Outcome Analysis | No |
Eliquis (apixaban), Pradaxa (dabigatran), and Xarelto (rivaroxaban) Complete |
cutaneous small-vessel vasculitis |
Regulatory Outcome, Analytic Code, Communication, Results | 06/02/2022 | Drug and Outcome Analysis | No |
Makena (hydroxyprogesterone caproate injection) and its generics Complete |
use in pregnancy |
Regulatory Outcome, Communication, Results | 05/31/2022 | Drug Use | No |
Ilumya (tildrakizumab) Ongoing |
lymphoma |
Results | 05/26/2022 | Drug and Outcome Analysis | Yes |
Sinuva (mometasone furoate) Ongoing |
cataracts , diminished visual acuity , glaucoma , nasal septal perforation |
Analytic Code, Communication, Results | 05/26/2022 | Drug and Outcome Analysis | Yes |
Skyrizi (risankizumab) Ongoing |
lymphoma |
Results | 05/26/2022 | Drug and Outcome Analysis | Yes |
Stelara (ustekinumab) Ongoing |
serious infection (Crohn’s disease) , serious infection (ulcerative colitis) |
Results | 05/17/2022 | Drug and Outcome Analysis | Yes |
Aldactone (spironolactone) Complete |
indications for use |
Regulatory Outcome, Communication, Results | 05/16/2022 | Drug Use | No |
Siliq (brodalumab) Ongoing |
hospitalized neutropenia , myocardial infarction and stroke , serious infection |
Results | 04/05/2022 | Drug and Outcome Analysis | Yes |
Prenatal Tests Complete |
stillbirth |
Communication, Results | 02/03/2022 | Methods and Development | No |
Zoloft (sertraline) Complete |
hospitalized depression , intentional self-harm |
Analytic Code, Communication, Results | 01/04/2022 | Methods and Development | No |
Medications for attention deficit hyperactivity disorder Complete |
heart failure or cardiomyopathy |
Regulatory Outcome, Communication, Results | 12/29/2021 | Drug and Outcome Analysis | No |
Gimoti (metoclopramide) Complete |
duration of use |
Regulatory Outcome, Results | 10/12/2021 | Drug Use | No |
Reglan (metoclopramide) Complete |
duration of use |
Regulatory Outcome, Results | 10/05/2021 | Drug Use | No |
Methotrexate, oral Complete |
wrong frequency dosing errors |
Regulatory Outcome, Communication, Results | 09/14/2021 | Methods and Development | No |
Brilinta (ticagrelor) Complete |
concomitant use with Lipitor (atorvastatin) or Crestor (rosuvastatin) |
Regulatory Outcome, Communication, Results | 09/13/2021 | Drug Use | No |
Eliquis (apixaban), Pradaxa (dabigatran), and Xarelto (rivaroxaban) Complete |
severe uterine bleed |
Regulatory Outcome, Analytic Code, Communication, Results | 05/24/2021 | Drug and Outcome Analysis | No |
Entresto (sacubitril/valsartan) Ongoing |
angioedema |
Analytic Code, Communication, Results | 04/21/2021 | Drug and Outcome Analysis | Yes |
Tremfya (guselkumab) Ongoing |
lymphoma |
Results | 03/30/2021 | Drug and Outcome Analysis | Yes |
Provigil (modafinil) and Nuvigil (armodafinil) Ongoing |
congenital cardiac malformations |
Analytic Code, Results | 11/17/2020 | Drug and Outcome Analysis | No |
Uloric (febuxostat) Complete |
duration of use , user characteristics |
Regulatory Outcome, Communication, Results | 11/12/2020 | Drug Use | No |
Eliquis (apixaban), Pradaxa (dabigatran), and Xarelto (rivaroxaban) Ongoing |
gastrointestinal bleeding , intracranial hemorrhage , major extracranial bleeding , thromboembolic stroke |
Analytic Code | 10/30/2020 | Drug and Outcome Analysis | No |
Infed (iron dextran), Venofer (iron sucrose), Feraheme (ferumoxytol), Injectafer (ferric carboxymaltose), Monoferric (ferric derisomaltose) Complete |
exposure in pregnancy |
Regulatory Outcome, Results | 10/13/2020 | Drug Use | No |
Phosphodiesterase type 5 (PDE5) inhibitors Complete |
exposure in pregnancy |
Regulatory Outcome, Communication, Results | 10/05/2020 | Drug Use | No |
Hydrochlorothiazide Complete |
non-melanoma skin cancer |
Regulatory Outcome, Analytic Code, Communication, Results | 09/30/2020 | Drug and Outcome Analysis | No |
Eliquis (apixaban) Complete |
gastrointestinal (GI) bleed , intracranial hemorrhage , stroke |
Analytic Code, Results | 09/28/2020 | Drug and Outcome Analysis | No |
Zantac (ranitidine) Complete |
duration of use |
Regulatory Outcome, Results | 09/15/2020 | Drug Use | No |
Gimoti (metoclopramide nasal spray) Ongoing |
adverse central nervous system reactions , tardive dyskinesia |
07/10/2020 | Drug and Outcome Analysis | Yes | |
Singulair (montelukast) Complete |
Neuropsychiatric adverse events consisting of: inpatient depressive disorder , outpatient depressive disorder , self-harm , suicide |
Regulatory Outcome, Analytic Code, Results | 03/05/2020 | Drug and Outcome Analysis | No |
Anti-obesity medications (benzophetamine, bupropion/naltrexone, diethylpropion, liraglutide, lorcaserin, orlistat, phendimetrazine, phentermine, phentermine/topiramate) Complete |
duration of use , patient characteristics |
Regulatory Outcome, Communication, Results | 11/13/2019 | Drug Use | No |
Opioid analgesics (excluding fentanyl products) Complete |
duration of follow-up , duration of use |
Regulatory Outcome, Results | 11/06/2019 | Drug Use | No |
Zydelig (idelalisib) Complete |
concomitant use |
Regulatory Outcome, Results | 09/19/2019 | Drug Use | No |
Ibsrela (tenapanor) Ongoing |
inflammatory bowel disease (IBD) |
09/16/2019 | Drug and Outcome Analysis | Yes | |
Oxymorphone Complete |
concomitant use with cytochrome P450 (CYP) enzyme inhibitors |
Regulatory Outcome, Communication, Results | 09/04/2019 | Drug Use | No |
Higher dosage strength oral and transmucosal opioid analgesic products Complete |
patient characteristics , utilization patterns |
Regulatory Outcome, Results | 08/07/2019 | Drug Use | No |
Qsymia (phentermine and topiramate extended release) Complete |
patient characteristics |
Regulatory Outcome, Results | 08/07/2019 | Drug Use | No |
Non-insulin antidiabetics Complete |
duration of follow-up , duration of use |
Regulatory Outcome, Results | 04/02/2019 | Methods and Development | No |
Onglyza (saxagliptin) and Januvia (sitagliptin) Complete |
acute myocardial infarction (AMI) , heart failure |
Analytic Code, Results | 04/01/2019 | Methods and Development | No |
Sodium-glucose cotransporter-2 (SGLT-2) inhibitors Complete |
diabetic ketoacidosis (DKA) , use in type 1 diabetes mellitus (T1DM) |
Regulatory Outcome, Communication, Results | 04/01/2019 | Drug and Outcome Analysis | No |
Dolutegravir (Tivicay and combination products Juluca, Triumeq) Complete |
exposure in pregnancy |
Regulatory Outcome, Communication, Results | 03/28/2019 | Drug Use | No |
Invokana (canagliflozin) Ongoing |
renal cell carcinoma |
03/04/2019 | Drug and Outcome Analysis | Yes | |
Ranexa (ranolazine) Complete |
seizure |
Regulatory Outcome, Analytic Code, Communication, Results | 01/03/2019 | Drug and Outcome Analysis | No |
Multiple sclerosis (MS) drugs Complete |
exposure before, during, and after pregnancy |
Regulatory Outcome, Communication, Results | 12/06/2018 | Drug Use | No |
Interleukin-1/-6 inhibitors Complete |
interstitial lung disease , pulmonary arterial hypertension |
Regulatory Outcome, Results | 12/03/2018 | Drug and Outcome Analysis | No |
Forteo (teriparatide) Complete |
duration of use |
Regulatory Outcome, Results | 11/30/2018 | Drug Use | No |
Annovera (segesterone acetate and ethinyl estradiol vaginal system) Ongoing |
Early Detection of: arterial thromboembolism (ATE) , venous thromboembolism (VTE) |
Results | 09/24/2018 | Drug and Outcome Analysis | Yes |
Actemra (tocilizumab) Complete |
exposure in pregnancy |
Regulatory Outcome, Results | 08/07/2018 | Drug Use | No |
Multiple Complete |
drug utilization in pregnancy to evaluate enrollment in pregnancy registries compared with spontaneous reports |
Regulatory Outcome, Communication | 07/26/2018 | Mini-Sentinel | |
Continuous or extended cycle oral contraceptives Complete |
venous thromboembolism (VTE) |
Regulatory Outcome, Analytic Code, Communication, Results | 03/05/2018 | Drug and Outcome Analysis | No |
Intravenous iron products Complete |
anaphylaxis |
Regulatory Outcome, Results | 02/12/2018 | Mini-Sentinel | |
Onglyza (saxagliptin) and Januvia (sitagliptin) Complete |
Hospitalized heart failure , acute myocardial infarction (AMI) |
Regulatory Outcome, Communication, Results | 02/02/2018 | Mini-Sentinel | |
Second generation antipsychotic agents Complete |
Achilles tendon rupture (ATR) , Metabolic effects in children (Type 2 diabetes, metabolic syndrome, weight gain) |
Regulatory Outcome, Communication, Results | 02/02/2018 | Mini-Sentinel | |
None Complete |
respiratory syncytial virus-associated illness |
Regulatory Outcome, Results | 01/25/2018 | Other Regulatory | No |
olmesartan medoximil Complete |
Intestinal sprue |
Regulatory Outcome, Results | 01/24/2018 | Mini-Sentinel | |
Pradaxa (dabigatran etexilate) Complete |
gastrointestinal (GI) bleed , intracranial hemorrhage |
Regulatory Outcome, Communication, Results | 01/24/2018 | Mini-Sentinel | |
Xarelto (rivaroxaban) Complete |
gastrointestinal (GI) bleed , intracranial hemorrhage , ischemic stroke |
Regulatory Outcome, Communication, Results | 01/24/2018 | Mini-Sentinel | |
TNF-alpha inhibitors Complete |
use in pregnancy |
Regulatory Outcome, Communication, Results | 12/21/2017 | Drug Use | No |
Gadolinium-based contrast agents Complete |
exposure in pregnancy |
Regulatory Outcome, Communication, Results | 12/19/2017 | Drug Use | No |
Antipsychotic agents (including haloperidol injection) Complete |
stroke |
Regulatory Outcome, Analytic Code, Communication, Results | 12/08/2017 | Drug and Outcome Analysis | No |
Ketoconazole oral tablets Complete |
drug use trends after safety label change and use in labeled indications |
Regulatory Outcome, Results | 12/04/2017 | Drug Use | No |
Keppra (levetiracetam) Complete |
anaphylaxis , angioedema |
Regulatory Outcome, Results | 11/30/2017 | Mini-Sentinel | No |