Evidence map›Paper›PMID 31933271›Full record

ArticlePharmaceutical medicine2019

Evaluation of the US Food and Drug Administration Sentinel Analysis Tools Using a Comparator with a Different Indication: Comparing the Rates of Gastrointestinal Bleeding in Warfarin and Statin Users.

Ryan M Carnahan, Joshua J Gagne, Christian Hampp, Charles E Leonard, Sengwee Toh, Candace C Fuller, Sean Hennessy, Laura Hou, Noelle M Cocoros, Genna Panucci and 4 more

Abstract readComparative Study
PubMed Publisher
In one paragraph

Article in Pharmaceutical medicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
2.7field-weighted citation impact, top 8% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed, 7 citations in OpenAlex.

  1. Article
  2. Article
  3. Genetic Warfarin-Resistance Resulting in Surgery to Change a Prosthetic Valve.European journal of case reports in internal medicine · 2020
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors at 5 institutions in 1 country.

Ryan M CarnahanDepartment of Epidemiology, College of Public Health, University of Iowa, 145 N. Riverside Dr., S437 CPHB, Iowa City, IA, 52242, USA. Ryan-Carnahan@uiowa.edu.ORCID 0000-0002-7478-4739
Joshua J GagneDivision of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Christian HamppCenter for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, MD, USA.
Charles E LeonardCenter for Pharmacoepidemiology Research and Training, Center for Clinical Epidemiology and Biostatistics, and Department of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
Sengwee TohHarvard Pilgrim Health Care Institute and Harvard Medical School, Boston, MA, USA.
Candace C FullerHarvard Pilgrim Health Care Institute and Harvard Medical School, Boston, MA, USA.
Sean HennessyCenter for Pharmacoepidemiology Research and Training, Center for Clinical Epidemiology and Biostatistics, and Department of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
Laura HouHarvard Pilgrim Health Care Institute and Harvard Medical School, Boston, MA, USA.
Noelle M CocorosHarvard Pilgrim Health Care Institute and Harvard Medical School, Boston, MA, USA.
Genna PanucciHarvard Pilgrim Health Care Institute and Harvard Medical School, Boston, MA, USA.
Tiffany WoodworthHarvard Pilgrim Health Care Institute and Harvard Medical School, Boston, MA, USA.
Austin CosgroveHarvard Pilgrim Health Care Institute and Harvard Medical School, Boston, MA, USA.
Aarthi IyerHarvard Pilgrim Health Care Institute and Harvard Medical School, Boston, MA, USA.
Elizabeth A ChrischillesDepartment of Epidemiology, College of Public Health, University of Iowa, 145 N. Riverside Dr., S437 CPHB, Iowa City, IA, 52242, USA.
Harvard University · USUniversity of Iowa · USUniversity of Pennsylvania · USBrigham and Women's Hospital · USUnited States Food and Drug Administration · US

Funding

FDA HHS HHSF22301008TFDA HHS HHSF223200910006IFDA HHS HHSF223201400030I
6 · The paper itself

Abstract

backgroundThe US Food and Drug Administration's Sentinel System was established to monitor safety of regulated medical products. Sentinel investigators identified known associations between drugs and adverse events to test reusable analytic tools developed for Sentinel. This test case used a comparator with a different indication.

objectiveWe tested the ability of Sentinel's reusable analytic tools to identify the known association between warfarin and gastrointestinal bleeding (GIB). Statins, expected to have no effect on GIB, were the comparator. We further explored the impact of analytic features, including matching ratio and stratifying Cox regression analyses, on matched pairs.

methodsThis evaluation included data from 14 Sentinel Data Partners. New users of warfarin and statins, aged 18 years and older, who had not received other anticoagulants or had recent GIB were matched on propensity score using 1:1 and 1:n variable ratio matching, matching statin users with warfarin users to estimate the average treatment effect in warfarin-treated patients. We compared the risk of GIB using Cox proportional hazards regression, following patients for the duration of their observed continuous treatment or until a GIB. For the 1:1 matched cohort, we conducted analyses with and without stratification on matched pair. The variable ratio matched cohort analysis was stratified on the matched set.

resultsWe identified 141,398 new users of warfarin and 2,275,694 new users of statins. In analyses stratified on matched pair/set, the hazard ratios (HR) for GIB in warfarin users compared with statin users were 2.78 (95% confidence interval [CI] 2.36-3.28) in the 1:1 matched cohort and 3.10 (95% CI 2.76-3.49) in the variable ratio matched cohort. The HR was lower in the analysis of the 1:1 matched cohort not stratified by matched pair (2.22, 95% CI 1.97-2.49), and highest early in treatment. Follow-up for warfarin users tended to be shorter than for statin users.

conclusionsThis study identified the expected GIB risk with warfarin compared with statins using an analytic tool developed for Sentinel. Our findings suggest that comparators with different indications may be useful in surveillance in select circumstances. Finally, in the presence of differential censoring, stratification by matched pair may reduce the potential for bias in Cox regression analyses.

Indexed as

AdolescentAdultAgedAnticoagulantsFemaleGastrointestinal HemorrhageHumansHydroxymethylglutaryl-CoA Reductase InhibitorsMaleMiddle AgedPharmacovigilanceUnited StatesUnited States Food and Drug AdministrationWarfarinYoung AdultAnticoagulantsHydroxymethylglutaryl-CoA Reductase InhibitorsWarfarin

Identifiers

PMID31933271
OpenAlexW2909892980

What OpenQuestion holds

Textmetadata
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.