The US Food and Drug Administration Sentinel System: a national resource for a learning health system

Brown, Jeffrey S.; Mendelsohn, Aaron B.; Nam, Young Hee; Maro, Judith C.; Cocoros, Noelle M; Rodriguez-Watson, Carla; Lockhart, Catherine M; Platt, Richard; Ball, Robert; Pan, Gerald J. Dal; Toh, Sengwee

doi:10.1093/jamia/ocac153

Cited by 18 publications

(10 citation statements)

References 65 publications

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“…ARIA analyses include a wide variety of medical products and have included drug utilization studies, signal identification studies, and targeted signal evaluation studies of particular exposure‐outcome pairings. Additionally, ARIA has impacts beyond the FDA including through adoption of some of its key components by international organizations such as the Canadian Network of Observational Drug Effect Studies (CNODES) and industry sponsors 44 …”

Section: Discussionmentioning

confidence: 99%

“…Additionally, ARIA has impacts beyond the FDA including through adoption of some of its key components by international organizations such as the Canadian Network of Observational Drug Effect Studies (CNODES) and industry sponsors. 44 Between 2016 and 2021, the FDA determined that ARIA was insufficient to evaluate 197 safety concerns; this determination is required if the FDA is to issue a postmarket requirement. Many of the underlying reasons for the insufficiency determinations have been remedied.…”

Section: Articlementioning

confidence: 99%

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Six Years of the US Food and Drug Administration's Postmarket Active Risk Identification and Analysis System in the Sentinel Initiative: Implications for Real World Evidence Generation

Maro

Nguyen

Kolonoski

et al. 2023

Clin Pharma and Therapeutics

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Congress mandated the creation of a postmarket Active Risk Identification and Analysis (ARIA) system containing data on 100 million individuals for monitoring risks associated with drug and biologic products using data from disparate sources to complement the US Food and Drug Administration's (FDA's) existing postmarket capabilities. We report on the first 6 years of ARIA utilization in the Sentinel System (2016–2021). The FDA has used the ARIA system to evaluate 133 safety concerns; 54 of these evaluations have closed with regulatory determinations, whereas the rest remain in progress. If the ARIA system and the FDA's Adverse Event Reporting System are deemed insufficient to address a safety concern, then the FDA may issue a postmarket requirement to a product's manufacturer. One hundred ninety‐seven ARIA insufficiency determinations have been made. The most common situation for which ARIA was found to be insufficient is the evaluation of adverse pregnancy and fetal outcomes following in utero drug exposure, followed by neoplasms and death. ARIA was most likely to be sufficient for thromboembolic events, which have high positive predictive value in claims data alone and do not require supplemental clinical data. The lessons learned from this experience illustrate the continued challenges using administrative claims data, especially to define novel clinical outcomes. This analysis can help to identify where more granular clinical data are needed to fill gaps to improve the use of real‐world data for drug safety analyses and provide insights into what is needed to efficiently generate high‐quality real‐world evidence for efficacy.

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Section: Discussionmentioning

confidence: 99%

Section: Articlementioning

confidence: 99%

Six Years of the US Food and Drug Administration's Postmarket Active Risk Identification and Analysis System in the Sentinel Initiative: Implications for Real World Evidence Generation

Maro

Nguyen

Kolonoski

et al. 2023

Clin Pharma and Therapeutics

Self Cite

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“…We used administrative claims data from five Data Partners contributing to the FDA's Sentinel Distributed Database, 5,6 representing privately and publicly insured U.S. individuals. We identified treatment episodes from individuals aged 15-64 years with evidence of a diagnosis of ADHD or narcolepsy (Table S1) and prevalent use (utilization analyses) or ≥60-day continuous supply (switching analyses) of any immediate-release MAS during January 1, 2013, through December 31, 2019.…”

Section: Methodsmentioning

confidence: 99%

Switching patterns of immediate‐release forms of generic mixed amphetamine salts products among privately and publicly insured individuals aged 15–64 years in the United States, 2013–2019

Perez‐Vilar,

Kempner,

Dutcher

et al. 2023

Pharmacoepidemiology and Drug

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PurposeImmediate‐release forms of generic mixed amphetamine salts (MAS) have been the subject of passive surveillance reports signaling lack of effectiveness. We examined switching patterns that might suggest whether long‐term users of specific MAS are more likely to switch away or switch back after use of the MAS of interest in the FDA's Sentinel Distributed Database.MethodsWe required at least 60‐day continuous supply of selected MAS grouped by Abbreviated New Drug Application (ANDA) to describe patterns of switching away from and to generics approved under the ANDAs of interest among individuals ages 15–64 years with attention deficit hyperactivity disorder or narcolepsy during 2013–2019.ResultsWe observed the greatest number of treatment episodes for ANDA 040422 (n = 525 771), followed by ANDA 202424 (n = 181 693), ANDA 040439 (n = 62 363), ANDA 040440 (n = 21 143), and ANDA 040480 (n = 8792). Of those with switches away from their original ANDA, episodes initiated on generic products under ANDA 040422 (48.6%) and ANDA 202424 (43.0%) were most likely to switch back, while those initiated on generic product under ANDA 040480 were least likely (24.1%). Of those episodes with switches to a generic under an ANDA of interest, about one‐third (range 27.1% to 37.0%) switched back to the same product. These switches back had a median time to switch of about 30 days.ConclusionsThese descriptive analyses, although subject to limitations, did not suggest increased switching away or switching back after use of the generics of interest. Continued post‐marketing surveillance is warranted.

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“…Provisional cases were retrospectively identified in two U.S. electronic administrative claims databases from CVS Health: the Aetna Enterprise Data Warehouse (AEDW), which contained the most recent healthcare utilization as reflected by administrative health insurance claims, and the Aetna Sentinel Common Data Model (SCDM), which contained longitudinal follow up since 2008 and updated on a quarterly basis, 8 together referred to as “the database” thereafter. The linked database contained information on any type of healthcare utilization, physician diagnoses, dispensed prescriptions, inpatient and outpatient diagnoses, treatments and procedures, and medical provider contact information.…”

Section: Methodsmentioning

confidence: 99%

Validation of an ICD‐10 case‐finding algorithm for endometrial cancer in US insurance claims

Djibo,

Margulis,

McMahill‐Walraven

et al. 2023

Pharmacoepidemiology and Drug

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PurposeTo evaluate the positive predictive value (PPV) of an endometrial cancer case finding algorithm using International Classification of Disease 10th revision Clinical Modification (ICD‐10‐CM) diagnosis codes from US insurance claims for implementation in a planned post‐marketing safety study. Two algorithm variants were evaluated.MethodsProvisional incident endometrial cancer cases were identified from 2016 through 2020 among women aged ≥50 years. One algorithm variant used diagnosis codes for malignant neoplasms of uterine sites (C54.x), excluding C54.2 (malignant neoplasm of myometrium); the other used only C54.1 (malignant neoplasm of endometrium). A random sample of medical records of recent incident provisional cases (2018–2020) was requested for adjudication. Confirmed cases showed biopsy evidence of endometrial cancer, documentation of cancer staging, or hysterectomy following diagnosis. We estimated the PPV of the variants with 95% confidence intervals (CI) excluding cases that had insufficient information.ResultsOf 294 provisional cases adjudicated, 85% were from outpatient settings (n = 249). Mean age at diagnosis was 69.3 years. Among the 294 adjudicated cases (identified with the broader algorithm variant), the same 223 were confirmed endometrial cancer cases by both algorithm variants. The PPV (95% CI) for the broader algorithm variant was 84.2% (79.2% and 88.3%), and for the variant using only C54.1 was 85.8% (80.9% and 89.8%).ConclusionWe developed and validated an algorithm using ICD‐10‐CM diagnosis codes to identify endometrial cancer cases in health insurance claims with a sufficiently high PPV to use in a planned post‐marketing safety study.

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The US Food and Drug Administration Sentinel System: a national resource for a learning health system

Cited by 18 publications

References 65 publications

Six Years of the US Food and Drug Administration's Postmarket Active Risk Identification and Analysis System in the Sentinel Initiative: Implications for Real World Evidence Generation

Six Years of the US Food and Drug Administration's Postmarket Active Risk Identification and Analysis System in the Sentinel Initiative: Implications for Real World Evidence Generation

Switching patterns of immediate‐release forms of generic mixed amphetamine salts products among privately and publicly insured individuals aged 15–64 years in the United States, 2013–2019

Validation of an ICD‐10 case‐finding algorithm for endometrial cancer in US insurance claims

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