CDER Postmarketing Studies that Used Real-World Evidence
FDA Use of Real-World Evidence in Regulatory Decision Making
510(k) - 510(k) premarket notification
ACE - Angiotensin-converting enzyme
AEMS – Adverse Event Monitoring System
ARB - Angiotensin receptor blocker
BLA - Biologics License Application
CBER - Center for Biologics Evaluation and Research
CDER - Center for Drug Evaluation and Research
CDRH - Center for Devices and Radiological Health
CMS - Center for Medicare and Medicaid Services
DSC - Drug Safety Communication
EHR- Electronic health records
EMR - Electronic medical records
ESA - Erythropoietin stimulating agent
GBCA - Gadolinium-based contrast agent
GLP-1 RA - Glucagon-like peptide-1 receptor agonists
HCTZ - Hydrochlorothiazide
HDE - Humanitarian device exemption
IAA - Inter-Agency Agreement
IDE - Investigational Device Exemption
MACE - Major adverse cardiac event
NDA - New Drug Application
OSE - Office of Surveillance and Epidemiology
OUS - Outside the U.S.
PLLR - Pregnancy and Lactation Labeling Rule
PMA - Premarket approval application
PPI - Proton pump inhibitor
REMS - Risk Evaluation and Mitigation Strategy
RWD - Real-World Data
RWE - Real-World Evidence
SEE – Substantial Evidence of Effectiveness
U.S. - United States
VHA - Veterans Health Administration
VTE - Venous thromboembolism
| Product Name & Number | Sponsor/Applicant | Data Source(s) | Data Source Description(s) | Study Design(s) | PMR/PMC Set/Number and Description | Summary of RWE use and/or Regulatory Action | Type / Date of Regulatory Action(s) and/or Other Action(s) | Related Document(s) or Communication(s) |
|---|---|---|---|---|---|---|---|---|
| Elelyso (Taliglucerase Alfa) BLA 22458 | Pfizer Inc. | Registry | Taliglucerase Alfa Surveillance (TALIAS) | Cohort | PMR 1895-6: To evaluate the effect of ELELYSO (taliglucerase alfa) for injection on pregnancy and fetal outcomes, and to collect detailed clinical status information on newborns and infants whose mothers are treated with ELELYSO (taliglucerase alfa) for injection during lactation. | Labeling updated in the Pregnancy (8.1) and Lactation (8.2) sub-sections | Labeling updates: 12/22/2025 | Labeling |
| Vimizim (Elosulfase Alfa) BLA 125460 | Biomarin Pharmaceutical Inc. | Registry | Morquio A Registry Study (MARS) | Cohort | PMR 2337-1: Evaluate the long-term safety of Vimizim in adult and pediatric patients enrolled in the Morquio A Registry for a period of ten years, including but not limited to the occurrence of serious hypersensitivity reactions, anaphylaxis, and changes in antibody status (i.e., detection and titers of binding and neutralizing antibodies, and detection of IgE antibodies). Pregnancy exposure data, including maternal, neonatal and infant outcomes, will also be collected and analyzed. Include incidence rate calculations as part of long-term safety evaluation assessments to monitor and characterize risk of exposure to Vimizim. In addition, assessment of clinical outcomes (e.g., anthropometric measures, progression of skeletal deformities, frequency and time to orthopedic surgeries) will be performed. | Labeling updated in the Pregnancy (8.1) sub-section | Labeling updates: 10/30/2025 | Labeling |
| Otezla (Apremilast) NDA 205437 | Amgen Inc. | Registry | Apremilast Pregnancy Exposure Registry | Cohort | PMR 2135-1: A prospective, observational, controlled, pregnancy exposure registry study to monitor pregnancies exposed to apremilast with the primary objective to evaluate whether there is any increase in the risk of birth defects. | Labeling updated in the Pregnancy sub-section (8.1) | Labeling updates: 12/23/2025 | Labeling |
| Belbuca (buprenorphine hydrochloride) NDA 207932, Xtampza ER (oxycodone) NDA 208090, Nucynta ER (tapentadol) NDA 200533, MS Contin (morphine sulfate) NDA 19516, OxyContin (oxycodone hydrochloride) NDA 22272, Hysingla ER (hydrocodone bitartrate) NDA 206627, Butrans (buprenorphine) NDA 21306 | Biodelivery Sciences International Inc, Collegium Pharmaceutical Inc, Purdue Pharma LP | Multiple | Electronic medical records; Medical and pharmacy claims; Patient questionnaire and interview | Cohort | PMR 3033-1: A prospective, observational study designed to quantify the serious risks of misuse, abuse, and addiction associated with long-term use of opioid analgesics for management of chronic pain among patients prescribed ER/LA opioid analgesics. This study must address at a minimum the following specific objectives: a. Estimate the incidence of misuse, abuse, and addiction associated with long-term use of opioid analgesics for chronic pain. Examine the effect of product/formulation, dose and duration of opioid use, prescriber specialty, indication, and other clinical factors (e.g., concomitant psychotropic medications, personal or family history of substance abuse, history of psychiatric illness) on the risk of misuse, abuse, and addiction. b. Evaluate and quantify other risk factors for misuse, abuse, and addiction associated with long-term use of opioid analgesics for chronic pain, including but not limited to the following: demographic factors, psychosocial/behavioral factors, medical factors, and genetic factors. Identify confounders and effect modifiers of individual risk factor/outcome relationships. | Labeling updated to include safety information related to long-term use of opioids based on findings from observational studies in the following sections: 1 Indications and Usage; 2 Dosage and Administration; 5 Warnings and Precautions; 6 Adverse Reactions | DSC: 7/31/2025, Labeling updates: 12/22/2025 | Labeling: |
| Belbuca (buprenorphine hydrochloride) NDA 207932, Xtampza ER (oxycodone) NDA 208090, Nucynta ER (tapentadol) NDA 200533, MS Contin (morphine sulfate) NDA 19516, OxyContin (oxycodone hydrochloride) NDA 22272, Hysingla ER (hydrocodone bitartrate) NDA 206627, Butrans (buprenorphine) NDA 21306 | Biodelivery Sciences International Inc, Collegium Pharmaceutical Inc, Purdue Pharma LP | Multiple | Electronic medical records; Medical and pharmacy claims; National Death Index (NDI) | Cohort | PMR 3033- 2: An observational study designed to measure the incidence and predictors of opioid overdose and death (OOD), as well as opioid abuse/addiction, using patient health records, insurance claims, and death records. This study must address at a minimum the following specific objectives: a. Estimate the incidence of abuse/addiction, overdose, and death associated with long-term use of opioid analgesics for chronic pain. Stratify overdose by intentionality wherever possible. Examine the effect of product/formulation, dose and duration of opioid use, prescriber specialty, indication, and other clinical factors (e.g., concomitant psychotropic medications, personal or family history of substance abuse, history of psychiatric illness) on the risk of abuse/addiction, overdose, and death. b. Evaluate and quantify other risk factors for abuse/addiction, overdose, and death associated with long-term use of opioid analgesics for chronic pain, including but not limited to the following: demographic factors, psychosocial/behavioral factors, medical factors, and genetic factors. Identify confounders and effect modifiers of individual risk factor/outcome relationships. Stratify overdose by intentionality wherever possible. | Labeling updated to include safety information related to long-term use of opioids based on findings from observational studies in the following sections: 1 Indications and Usage; 2 Dosage and Administration; 5 Warnings and Precautions; 6 Adverse Reactions | DSC: 7/31/2025, Labeling updates: 12/22/2025 | Labeling: |
| Oral anticoagulants: Eliquis (Apixaban), Pradaxa (Dabigatran), Xarelto (Rivaroxaban) Multiple NDAs | Multiple | Administrative Healthcare Claims | Sentinel System | Cohort | N/A | Following reports of cutaneous small-vessel vasculitis (CSVV) in patients treated with non-vitamin K oral anticoagulants (NOAC) from premarket trials and the FDA Adverse Event Monitoring System (AEMS), the FDA conducted a study in Sentinel to assess CSVV risk. The study compared CSVV incidence among new users of NOACs versus warfarin in patients with atrial fibrillation. No statistically significant differential CSVV risk was observed between new users of NOACs and warfarin, and FDA determined that no regulatory action was required. | N/A | |
| Angiotensin receptor blockers Multiple NDAs | Multiple | Administrative Healthcare Claims | Sentinel System | Descriptive | N/A | Following recalls of valsartan products containing potentially carcinogenic nitrosamine impurities, N-nitrosodimethylamine (NDMA) and N-nitrosodiethylamine (NDEA), beginning in July 2018, the FDA conducted studies using the Sentinel System and data from the UK, Canada, and Denmark to estimate the number of patients exposed to recalled products and examine angiotensin II receptor blocker usage and switching patterns before and after the recalls. These findings indicated that exposure to nitrosamine impurities in valsartan products in the U.S. was limited, and determined further studies on cancer risk were not necessary. | N/A | |
| Glucagon-like peptide-1 receptor agonists (GLP-1 RA) Multiple NDAs | Multiple | Administrative Healthcare Claims | Sentinel System | Cohort | N/A | FDA conducted a retrospective cohort study using administrative healthcare claims data from the Sentinel System to compare the risk of intentional self-harm between new users of glucagon-like peptide-1 (GLP-1 RAs) and sodium-glucose cotransporter 2 inhibitors (SGLT2i) in patients with type 2 diabetes mellitus and did not find an increased risk of intentional self-harm in GLP-1 RA users compared to SGLT2i users. The study results were consistent with other evidence, including a comprehensive meta-analysis of clinical trials across GLP-1 RA drug development programs, and contributed to the regulatory action. FDA issued a Drug Safety Communication to communicate that the findings of its evaluation indicated no increased risk of suicidal ideation and behavior associated with the use of GLP-1 RA medications and requested removal of the warning for suicidal behavior and ideation from the labeling of Saxenda (liraglutide), Wegovy (semaglutide), and Zepbound (tirzepatide) on January 13, 2026. | DSC: 1/13/2026 | |
| Sodium-Glucose Co-Transporter 2 Inhibitors Multiple NDAs | Multiple | Administrative Healthcare Claims | Sentinel System | Descriptive | N/A | In 2018 and 2024, the FDA conducted studies using the Sentinel System to describe the risk of diabetic ketoacidosis (DKA) among patients with type 1 diabetes mellitus (T1DM) who received SGLT2 inhibitors over time and across stages of chronic kidney disease (CKD). These descriptive analyses found that crude incidence rates of DKA in patients with T1DM who initiated SGLT2 inhibitors did not appear to have declined from 2013 to 2024 and that there is an increase in incidence rate of DKA with advancing CKD stage in patients with T1DM, regardless of SGLT2 inhibitor use. The findings were presented at the January 17, 2019, and October 31, 2024 Endocrinologic and Metabolic Drugs Advisory Committee (EMDAC) meetings where the benefits and risks of Zynquista (sotagliflozin) were discussed. | AC Meeting: 1/17/2019 and 10/31/2024 | |
| Keppra (Levetiracetam) NDA 21035, NDA 21505, NDA 21872, and NDA 22285 | UCB Inc. | Administrative Healthcare Claims | Sentinel System | Descriptive | N/A | To evaluate a potential safety signal for anaphylaxis and angioedema with the use of Keppra (levetiracetam) identified during routine post-market safety surveillance of the FDA Adverse Event Monitoring System (AEMS), FDA conducted an analysis in the Sentinel System as part of an integrated safety review. The Sentinel analysis found that the incidence rate of angioedema in new users of levetiracetam was similar to the rates for other antiepileptic drugs that were already labeled for this risk. Based on the totality of evidence from the case series and the Sentinel analysis, the FDA approved a safety-related labeling change for Keppra (levetiracetam) on April 24, 2017, to add the risk of anaphylaxis and angioedema to several sections of the labeling, including the Warnings and Precautions section. | Labeling updates: 4/24/2017 | |
| Proton pump inhibitors Multiple NDAs | Multiple | Administrative Healthcare Claims | Sentinel System | Cohort | N/A | To assess safety signals from published reports, FDA conducted a Sentinel System study to determine whether use of proton pump inhibitors (PPIs) increases the risk of COVID-19 hospitalization and severe COVID-19 outcomes. This cohort study found no significant increase in the risk of COVID-19 hospitalization or severe COVID-19 outcomes with PPI use compared to famotidine use, which was consistent with results from an FDA-led case-control study conducted using Medicare data, strengthening FDA's conclusion that there is no association between PPI use and the risk of COVID-19 hospitalization. Based on these findings, FDA determined that no regulatory action was required. | N/A | Sentinel website |
| Stelara (ustekinumab) BLA 761044 | Janssen Biotech | Administrative Healthcare Claims | Sentinel System | Cohort | N/A | In response to safety concerns raised during the BLA review for Stelara (ustekinumab), the FDA conducted this Sentinel System study to assess the risk of serious infection in patients with Crohn's disease (CD) during use of ustekinumab (Stelara). The study identified no increased risk for serious infection with ustekinumab use versus a comparator biologic, and FDA determined that the safety information in ustekinumab labeling related to the risk of serious infection in patients with CD was adequate. | N/A | Sentinel website |
| Clozaril (clozapine) NDA 019758, Versacloz (clozapine) NDA 203479 | Heritage Life | Multiple | Sentinel System using Administrative Healthcare Insurance Claims and Medical Records | Descriptive | N/A | To inform a comprehensive reevaluation of the clozapine Risk Evaluation and Mitigation Strategy (REMS), FDA conducted analyses in the Sentinel System to understand clozapine users' adherence to absolute neutrophil count (ANC) monitoring requirements, estimate the prevalence of clozapine-associated neutropenia, and understand the clinical context of suspected neutropenia events. These findings were presented, along with other evidence, at the November 19, 2024 Joint Meeting of the Drug Safety and Risk Management Advisory Committee and Psychopharmacologic Drugs Advisory Committee and contributed to the FDA's decision to remove the clozapine REMS. | AC Meeting: 11/19/2024, DSC: 8/27/2025 | |
| Sinuva (Mometasone Furoate Sinus Implant) NDA 209310 | Intersect ENT Inc. | Administrative Healthcare Claims | Sentinel System | Descriptive | N/A | In response to safety concerns raised during the NDA review for Sinuva, FDA conducted a postmarket study to assess the risk of cataracts, diminished visual acuity, glaucoma, nasal septal perforation, and ocular hypertension in the Sentinel System. Given the absence of evidence indicating increased risk and the declining use of Sinuva, the FDA concluded that no regulatory action was necessary. | N/A | Sentinel website |
| CLOZARIL (clozapine) NDA 019758, Versacloz (clozapine) NDA 203479 | Heritage Life Sciences (Barbados) c/o Heritage Life Sciences Therapeutics (USA) | Medical Records | Veterans Health Administration (VHA) medical and pharmacy records | Descriptive | N/A | In FDA's review of the effectiveness of the clozapine REMS, FDA conducted several analyses of clozapine registry patients, describing adherence to absolute neutrophil count monitoring, as specified by the clozapine REMS, and estimating the cumulative risk of severe neutropenia. | DSC: 8/27/2025 | DSC |
| Toprol-XL and Lopressor (Metoprolol), Inderal LA (propranolol), [beta blockers] Multiple NDAs | Multiple sponsors | Administrative Healthcare Claims | Sentinel System | Cohort | N/A | The results from a retrospective cohort study in Sentinel indicated an association between beta blocker use and hypoglycemia in pediatric populations. FDA approved safety labeling changes to describe the risk for hypoglycemia in pediatrics or individuals unable to communicate signs of hypoglycemia. | Labeling updates: 7/25/2025 | Sentinel webpage |
| Entyvio (vedolizumab) BLA 761359 | Takeda Pharmaceuticals | Administrative Healthcare Claims | Sentinel System | Descriptive | N/A | The results from a descriptive Sentinel study did not indicate an increased risk for Interstitial lung disease (ILD) in patients treated with vedolizumab or natalizumab for inflammatory bowel disease. However, there were other data from case reports from the medical literature and FDA AEMS. | Labeling updates: 4/18/2024 | Sentinel webpage |
| Prolia (Denosumab) BLA 125320 | Amgen | Administrative Healthcare Claims | Medicare claims data | Cohort | N/A | In FDA's review of denosumab, an FDA retrospective cohort study in Medicare found an increased risk of severe hypocalcemia in patients with advanced chronic kidney disease taking this medication. This resulted in a DSC and addition of a Boxed Warning. | DSC: 1/19/2024 | DSC |
| Anticoagulant, oral Multiple NDAs | Multiple sponsors | Administrative Healthcare Claims | Sentinel System | Cohort | N/A | FDA conducted a retrospective cohort study in the Sentinel System to examine severe uterine bleeding events requiring medical intervention in women treated with oral anticoagulants. The study found a risk of clinically significant uterine bleeding, potentially requiring gynecological surgical interventions. | Labeling updates: 1/28/2021 | Sentinel webpage |
| Methotrexate, oral Multiple NDAs | Multiple sponsors | Medical Records | Sentinel System | Cohort | N/A | An FDA medical chart review analysis conducted in a Sentinel Data Partner, found the incidence of low-dose oral methotrexate wrong frequency dosing errors to be 0.4%. This resulted in adding the risk of improper dosing to Section 5 (Warnings and Precautions). | Labeling updates: 12/17/2021 | Sentinel webpage |
| Singulair (montelukast) NDA 021409 | Organon | Administrative Healthcare Claims | Sentinel System | Cohort | N/A | Retrospective cohort studies conducted in the Sentinel system informed the re-evaluation of the benefits and risks of montelukast use. Considering the totality of evidence, including the negative Sentinel studies resulted in FDA strengthening existing warnings about serious behavior and mood-related changes with montelukast. | Labeling updates: 3/3/2020 | Sentinel webpage |
| Hydrochlorothiazide (HCTZ)-containing products Multiple NDAs | Multiple sponsors | Administrative Healthcare Claims | Sentinel System | Cohort | N/A | An FDA conducted retrospective cohort study in the Sentinel System assessed the risk of non-melanoma skin cancer for patients treated with HCTZ-containing products. The study identified an association with an increased risk of non-melanoma skin cancer, predominantly for squamous cell carcinoma and in white patients taking large cumulative doses. | Labeling updates: 8/20/2020 | Sentinel webpage |
| Feraheme, infed, injectafer, monoferric, venofer (Parenteral Iron Products) Multiple NDAs | Multiple sponsors | Administrative Healthcare Claims | Sentinel System | Descriptive | N/A | An FDA Sentinel analysis characterized the frequency of IV iron utilization relative to live birth and stillbirth deliveries. The finding contributed to a class-wide labeling update for parenteral iron products to add new safety information to Section 8 (Use in Specific Populations, Pregnancy) of the label. | Labeling updates: 9/11/2020 | Sentinel webpage |
| Comtan, Stalevo (Entacapone) NDA 021485/ 20796 | Orion Corporation | Multiple | VHA claims, medical records, and cancer registry | Cohort | N/A | In FDA's review of entacapone, an FDA conducted retrospective cohort study in the Veterans Affairs database found no clear evidence of an increased risk of prostate cancer in patients treated with entacapone versus add-on dopamine agonist or monoamine oxidase inhibitor. This resulted in a DSC. | DSC: 8/13/2019 | DSC |
| Pradaxa (dabigatran) NDA 022512 | Boehringer Ingelheim Pharmaceuticals, Inc | Administrative Healthcare Claims | Medicare claims data | Cohort | N/A | In FDA's review of dabigatran, an FDA conducted retrospective cohort study among Medicare patients, showed lower risks stroke and death but higher risk for gastrointestinal bleeding with PRADAXA compared to warfarin. FDA still considered Pradaxa to have a favorable benefit/risk profile and made no changes to the labeling. | DSC: 5/13/2014 | DSC |
| Enbrel (etanercept) BLA 103795 | Amgen Inc. | Administrative Healthcare Claims | Sentinel System | Descriptive | N/A | FDA conducted a drug utilization analysis of TNF alpha inhibitors in pregnant women in the Sentinel System. The study found that among pregnant women with a chronic inflammatory condition, there was a preference to use etanercept compared to other TNF alpha inhibitors. | Labeling updates: 7/11/2017 | Sentinel webpage |
| Gadolinium-based contrast agents (GBCA) Multiple NDAs | Multiple sponsors | Administrative Healthcare Claims | Sentinel System | Descriptive | N/A | Analyses on gadolinium retention were done with FDA Sentinel data and other data streams. These analyses, in part, resulted in class-wide updates to Section 5 (Warnings and Precautions) to include the risk of gadolinium retention in tissues, including the brain, for months to years. | Labeling updates: 12/19/2017 | Sentinel webpage |
| Comtan, Stalevo (entacapone) NDA 021485/ 20796 | Orion Corporation | Administrative Healthcare Claims | Medicare claims data | Cohort | N/A | FDA conducted a retrospective cohort study in Medicare to assess cardiovascular risk associated with entacapone use. FDA found no clear evidence of increased cardiovascular risk with entacapone. The study resulted in a publication and DSC. | DSC: 10/26/2015 | DSC |
| Benicar (olmesartan) NDA 021286 | Daiichi Sankyo | Administrative Healthcare Claims | Medicare claims data | Cohort | N/A | In FDA's review of Olmesartan, an FDA conducted retrospective cohort study in Medicare found no clear evidence of increased cardiovascular risks associated with high dose use in diabetic patients. As a result, FDA's recommendations for use of olmesartan in patients with diabetes remained the same. | DSC: 6/24/2014 | DSC |
| Benicar, Benicar hct (Olmesartan), Azor, Tribenzor (medoxomil) Multiple NDAs | Daiichi Sankyo Inc. | Administrative Healthcare Claims | Mini-Sentinel and Medicare | Cohort | N/A | In FDA's review of Olmesartan, an FDA evaluation of the FDA Adverse Event Monitotrin System (AEMS) and the published literature found evidence of an association between olmesartan and sprue-like enteropathy. To evaluate an ARB class association FDA conducted a retrospective cohort study in Mini-Sentinel and Medicare. | Labeling updates: 7/3/2013 | Sentinel webpage |
| Pradaxa (dabigatran) NDA 022512 | Boehringer Ingelheim Pharmaceuticals, Inc | Administrative Healthcare Claims | Mini-Sentinel | Cohort | N/A | In 2012, an FDA conducted retrospective cohort study in Mini-Sentinel that evaluated new information about the risk of serious bleeding associated with use of dabigatran (PRADAXA) and warfarin. The results indicated that bleeding rates associated with new use of Pradaxa did not appear to be higher than bleeding rates associated with new use of warfarin. | DSC: 11/2/2012 | DSC |
| Epogen, Procrit, Aranesp (Erythropoietin stimulating agents (ESA)) BLA 103234 and BLA 103951 | Amgen | Administrative Healthcare Claims | Medicare claims data | Cohort | N/A | In FDA's review of the effects of a labeling change recommending lower doses of ESAs in dialysis patients, an FDA retrospective cohort study in Medicare which assessed the effects of the changes in reimbursement policy in addition to changes in the ESA's drug labeling found that the risk of MACE and mortality was unchanged, and risk of stroke was reduced following the labeling change. | N/A | Publication |
| Avandia (rosiglitazone) NDA 021071 | GlaxoSmithKline | Administrative Healthcare Claims | Medicare claims data | Cohort | N/A | FDA conducted a retrospective cohort study in Medicare that evaluated the risk of heart attacks in patients taking rosiglitazone. The study resulted in labeling changes and an update to the Risk Evaluation and Mitigation Strategy (REMS) to include a restricted access and distribution program. | DSC: 5/18/2011 | DSC |
| Imitrex (sumatriptan), Treximet® (sumatriptan and naproxen sodium) NDA 020626/ 020080/ 020132/ 021926/ | GSK | Registry | Pregnancy registry | Cohort | N/A | The Sumatriptan/Naratriptan/Treximet Pregnancy Registry collected data on fetal malformations and birth defects from in-utero exposure to sumatriptan (January 1996 to September 2012). Section 8 of the label was updated to reflect that data from the prospective pregnancy exposure registry and other epidemiological studies did not show an increased frequency of birth defects. | Labeling updates: 12/14/2017 | Labeling |
| Amerge (naratriptan) NDA 020763 | GSK | Registry | Pregnancy registry | Cohort | N/A | The Sumatriptan/Naratriptan/Treximet Pregnancy Registry collected data on adverse fetal outcomes from in utero exposure to naratriptan. Section 8 of the AMERGE labeling was updated to reflect that no definitive conclusions could be drawn from the registry and epidemiological studies regarding the risk of birth defects. | 11/29/2016: Labeling updates | Labeling |
| Proton pump inhibitors (PPI) Multiple NDAs | Multiple sponsors | Administrative Healthcare Claims | Medicare claims data | Case-control | N/A | In FDA's review of drugs repurposed for treating patients with COVID-19 or drugs being taken by patients with COVID-19, there was concern that PPI use might increase the risk of developing severe COVID-19. An FDA conducted case control study in Medicare found that PPIs were not associated with increased risk uncomplicated or complicated COVID-19 hospitalizations. | N/A | N/A |
| Angiotensin-converting enzyme (ACE) Inhibitors (multiple) and angiotensin receptor blockers (ARB) (multiple) Multiple NDAs | Multiple sponsors | Administrative Healthcare Claims | Medicare claims data | Case-control | N/A | In FDA's review of ACE inhibitors (ACEi) or Angiotensin II Receptor Blockers (ARBs) an FDA conducted case-control study in Medicare evaluated the effect of ACE inhibitors or ARBs on the risk of developing severe COVID-19 and found that use of these drugs was not associated with increased risk of hospitalized COVID-19 or COVID-19-related mortality. | N/A | Publication |
| EPOGEN, PROCRIT, ARANESP (Erythropoietin stimulating agents (ESA)) BLA 103234 and 103951 | Amgen | Administrative Healthcare Claims | Medicare | Cohort | N/A | FDA reviewed the effect of the REMS (Erythropoietin stimulating agents (ESA) use for chemotherapy-induced anemia, during and after the discontinuation of the REMS, and conducted a retrospective cohort study in Medicare that showed that the REMS had minimal impact on ESA use or transfusion rates and that the removal of the REMS did not affect subsequent ESA use or blood transfusions. | N/A | Publication |
| LYBREL (ethinyl estradiol; levonorgestrel) NDA 021864 | Pfizer | Administrative Healthcare Claims | Sentinel System | Cohort | N/A | An FDA conducted retrospective cohort study evaluated the risk of venous thromboembolism (VTE) for extended cycle contraceptives to determine whether these posed a greater risk of VTE due to increased hormone exposure, compared to 28-day products. The study provided reassurance that VTE risk was not substantially different. | N/A | Publication |
| Fragmin (Dalteparin Sodium) NDA 20287 | Pfizer Inc. | Medical Records | Medical records | Cohort | PMC 3629-1: To characterize safety of dalteparin treatment in neonates (defined as 0 to 28 days of age; gestational age at least 35 weeks) with venous thromboembolism (VTE), conduct a non-interventional, retrospective medical record review study to describe the safety, dosing, pharmacodynamics, and efficacy using real-world evidence in at least 12 neonates receiving dalteparin. Submit the final report, case report forms, and datasets. | Labeling updated to extend the indication for the "treatment of symptomatic venous thromboembolism (VTE) to reduce the recurrence of VTE in pediatric patients" from 1 month down to birth (gestational age at least 35 weeks). | Labeling updates: 10/15/2024 | Labeling |
| Mircera (Methoxy Polyethylene Glycol-Epoetin Beta) BLA 125164 | Vifor (International) Inc. | Registry | Registry | Cohort | PMR 3385-2: Submit a summary report and registry data that describes the dosing, aggregate level safety data and hemoglobin concentrations in a cohort of pediatric patients with anemia associated with chronic kidney disease treated with US-licensed Mircera. The cohort will include pediatric patients from 3 months to less than 18 years of age, on peritoneal dialysis or hemodialysis, and subcutaneous or intravenous route of administration. The sample size for the cohort will be a minimum of 125 patients. | Labeling updated to extend the indication for the treatment of anemia associated with chronic kidney disease (CKD) in pediatric patients 3 months to 17 years of age on dialysis and not on dialysis. | Labeling updates: 4/30/2024 | Labeling |
| Entyvio (Vedolizumab) BLA 125476 | Takeda Pharmaceuticals U.S.A., Inc. | Registry | Pregnancy registry | Cohort | PMC 2719-7: Conduct a prospective, observational pregnancy exposure registry study in the United States that compares the pregnancy and fetal outcomes of women exposed to Entyvio (vedolizumab) during pregnancy to an unexposed control population or collect Entyvio (vedolizumab) pregnancy exposure data by collaborating with an existing disease-based pregnancy registry. | Labeling updated with pregnancy registry outcomes in the Pregnancy sub-section (8.1). | Labeling updates: 2/23/2024 | Labeling |
| Zithromax (Azithromycin) NDA 50784; NDA 50670; NDA 50693; NDA 50710; NDA 50711; NDA 50730; NDA 50733; NDA 50797 | Pfizer Inc. | Multiple | Electronic medical records linked to a death registry | Cohort | PMR 2130-1: An observational study of the association of azithromycin use with cardiovascular death, compared to amoxicillin or other antibacterial drugs, in one or more study population(s) with sufficient representation of cardiovascular disease and cardiovascular risk factors. The goal is to replicate the analysis conducted in the Ray et al. study published in 2012 in a different population, and to elucidate the risk and potential risk factors for azithromycin-associated cardiovascular death. | Labeling updated to include the risk of cardiovascular death in the following sub-sections: Warnings and Precautions (5.5), Postmarketing Experience (6.2) and Patient Information. | Labeling updates: 11/22/2021 | Labeling |
| Mirena (Levonorgestrel-Releasing Intrauterine System) NDA 21225 | Bayer Healthcare Pharmaceuticals Inc. | Medical Records | Electronic medical records | Cohort | PMR 3129-1: Observational study of incidence and risk factors for uterine perforation among users and particularly when related to breastfeeding and timing of postpartum levonorgestrel intrauterine contraceptive system (IUS) [Mirena] insertion in US women. | Labeling updated to include the risks of perforation and expulsion, and information on timing of insertion to the following sub-sections: Dosage and Administration (2.2), Warnings and Precautions (5.6,5.7), Postmarketing Experience (6.2), and Patient Information. | Labeling updates: 6/8/2021 | Labeling |
| OxyContin (Oxycodone Hydrochloride) NDA 22272 | Purdue Pharma L.P. | Multiple | Claims data and electronic medical records | Cohort | PMR 2923-2: Conduct a nationally representative drug utilization study of sufficient detail to characterize use of OxyContin in children aged 17 years and younger. The data from this study will provide a denominator for the risks assessed in PMR #2923-1 and any future safety studies and clinical trials used to assess those risks. The following analyses should be conducted with the data collected: 1) Total number of prescriptions dispensed across all settings of care a. stratify by age group (0-1, 2-5, 6-10, 11-17), indication, setting of care, and prescriber specialty, and geographic location b. provide characteristics of dose dispensed (mean, median, range) 2) Total number of unique patients receiving dispensed prescriptions across all settings of care a. stratify by age group (0-1, 2-5, 6-10, 11-17), indication, setting of care, and prescriber specialty i. provide unique incident users every quarter-year b. patient demographics of users of the product c. clinical characteristics of users of the product (including what percentage of patients are opioid tolerant at the time they get the OxyContin prescription) 3) Duration of therapy (include definitions of allowable gaps in drug therapy in calculating duration of therapy) a. total and stratified by indication b. exploration of possible 'intermittent' use c. percentage of patients switching from immediate-release opioids to OxyContin d. percentage of patients switching from other extended-release opioids to OxyContin dose adjustments over time. | New PMR established. PMR 2923-3: Conduct a retrospective cohort study in pediatric patients aged 17 years and younger to examine the association between opioid nontolerance at initiation of OxyContin therapy and serious risks such as respiratory depression as well as non-fatal and fatal overdose. | New PMR established: 4/8/2021 | NA |
| Truvada (Emtricitabine and Tenofovir Disoproxil Fumarate) NDA 21752 | Gilead Sciences Inc. | Registry | Antiretroviral Pregnancy Registry | Cohort | PMR 1906-1: Through collaboration with the Antiretroviral Pregnancy Registry, conduct a prospective observational study to collect and analyze data on maternal and fetal outcomes in 200 women who become pregnant while taking Truvada® for a pre-exposure prophylaxis (PrEP) indication and choose to continue Truvada during their pregnancies and in 200 women who become pregnant while taking Truvada for PrEP and choose to discontinue it. Collect and analyze data from at least a similarly sized comparator group of pregnant HIV-infected women taking antivirals other than emtricitabine/tenofovir disoproxil fumarate. Data collected on pregnancy outcomes should include but not be limited to: timing of initiation and duration of Truvada or other antiretrovirals, HIV seroconversions in mothers and infants, spontaneous and elective abortions, spontaneous and scheduled pre-term deliveries, stillbirths, infant weight (normal or low) and infant outcomes, including the presence or absence of congenital malformations. | Labeling updated with pregnancy registry outcomes in the Pregnancy sub-section (8.1). | Labeling updates: 5/15/2018 | Labeling |
| Jadenu (Deferasirox) NDA 206910 | Novartis Pharmaceuticals Corp. | Registry | Registry | Cohort | PMR 2888-1: Establish a registry for children aged 2 to < 6 years to enroll approximately 200 patients receiving deferasirox and follow them for 5 years. Collect data at least monthly for renal function and blood pressure and yearly for growth and development and analyze the data for adverse renal reactions and delayed growth and development | Labeling updated; Conversion to traditional approval for the treatment of chronic iron overload due to blood transfusion in patients 2 year of age and older. | Labeling updates: 5/11/2018 | Labeling |
| Jadenu Sprinkle (Deferasirox) NDA 207968 | Novartis Pharmaceuticals Corp. | Registry | Registry | Cohort | PMR 3342-1: Establish a registry for children aged 2 to < 6 years to enroll approximately 200 patients receiving deferasirox and follow them for 5 years. Collect data at least monthly for renal function and blood pressure and yearly for growth and development and analyze the data for adverse renal reactions and delayed growth and development. | Labeling updated; Conversion to traditional approval for the treatment of chronic iron overload due to blood transfusion in patients 2 year of age and older. | Labeling updates: 5/11/2018 | Labeling |