Evidence map›Paper›PMID 25053577›Full record

ArticleJournal of the American Medical Informatics Association : JAMIA2015

Validating drug repurposing signals using electronic health records: a case study of metformin associated with reduced cancer mortality.

Hua Xu, Melinda C Aldrich, Qingxia Chen, Hongfang Liu, Neeraja B Peterson, Qi Dai, Mia Levy, Anushi Shah, Xue Han, Xiaoyang Ruan and 7 more

Registry-linked trialOpen access · bronzeAbstract readComparative Study
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of the American Medical Informatics Association : JAMIA, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03477162 (Metformin Pharmacology in Human Cancers), which is not on this map. Cited by 117 papers, 16 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
117citing papers in PubMed, 16 pooled it
10.5field-weighted citation impact, top 1% 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.

NCT03477162 early_phase1terminatednot on this mapstarted 2018, after this paper: background citation

Metformin Pharmacology in Human Cancers

TypeinterventionalSponsorDartmouth-Hitchcock Medical CenterRan2018 to 2021Enrolled18ConditionsThoracic NeoplasmArmsMetformin
3 · Its place in the literature

Who cites it

117 citing papers in PubMed, 16 syntheses or guidelines pooled it, 229 citations in OpenAlex.

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  14. Effects of metformin on survival outcomes of lung cancer patients with type 2 diabetes mellitus: a meta-analysis.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2016
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57 more citing papers are in PubMed but not listed here.

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

17 authors at 4 institutions in 1 country.

Hua XuThe University of Texas School of Biomedical Informatics at Houston, Houston, Texas, USA.
Melinda C AldrichDepartment of Thoracic Surgery, Vanderbilt University School of Medicine, Nashville, Tennessee, USA Division of Epidemiology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
Qingxia ChenDepartment of Biostatistics, Vanderbilt University School of Medicine, Nashville, Tennessee, USA Department of Biomedical Informatics, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
Hongfang LiuDivision of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, Minnesota, USA.
Neeraja B PetersonDepartment of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
Qi DaiDivision of Epidemiology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
Mia LevyDepartment of Biomedical Informatics, Vanderbilt University School of Medicine, Nashville, Tennessee, USA Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
Anushi ShahDepartment of Biomedical Informatics, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
Xue HanDepartment of Biostatistics, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
Xiaoyang RuanDivision of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, Minnesota, USA.
Min JiangThe University of Texas School of Biomedical Informatics at Houston, Houston, Texas, USA.
Ying LiDepartment of Biomedical Informatics, Columbia University, New York, New York, USA.
Jamii St JulienDepartment of Thoracic Surgery, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
Jeremy WarnerDepartment of Biomedical Informatics, Vanderbilt University School of Medicine, Nashville, Tennessee, USA Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
Carol FriedmanDepartment of Biomedical Informatics, Columbia University, New York, New York, USA.
Dan M RodenDepartment of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, USA Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
Joshua C DennyDepartment of Biomedical Informatics, Vanderbilt University School of Medicine, Nashville, Tennessee, USA Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
Vanderbilt University · USColumbia University · USMayo Clinic · USUniversity of Houston · US

Funding

VANDERBILT UNIVERSITY CTSA FOR PEDIATRIC RESEARCHUL1RR024975 · NCRR · VANDERBILT UNIVERSITY · PI BERNARD, GORDON RAPHAEL · 2007 to 2011
$45.7M
TARGETING NOTCH 3 IN LUNG CANCERP50CA090949 · NCI · VANDERBILT UNIVERSITY · PI SANDLER, ALAN · 2001 to 2011
$24.1M
Pharmacogenomics of Arrhythmia TherapyU19HL065962 · NHLBI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI RODEN, DAN M · 2010 to 2014
$17.4M
Natural language processing for clinical and translational researchR01GM102282 · NIGMS · MAYO CLINIC ROCHESTER · PI LIU, HONGFANG, PAKHOMOV, SERGUEI VS · 2013 to 2016
$2.5M
An in-silico method for epidemiological studies using Electronic Medical RecordsR01CA141307 · NCI · VANDERBILT UNIVERSITY · PI XU, HUA · 2009 to 2012
$1.0M
Unraveling Genetic Determinants of Lung Cancer Risk in African AmericansK07CA172294 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI ALDRICH, MELINDA · 2013 to 2017
$801k
A New Approach to Correct Verification Bias Using Auxiliary InformationR21HL097334 · NHLBI · VANDERBILT UNIVERSITY · PI CHEN, QINGXIA · 2011 to 2012
$428k
NCI NIH HHS K07 CA172294NCI NIH HHS K07CA172294NCI NIH HHS P50 CA090949NCI NIH HHS R01CA141307NCRR NIH HHS 1UL1RR024975NHLBI NIH HHS R21HL097334NHLBI NIH HHS U19 HL065962NIGMS NIH HHS R01 GM102282
6 · The paper itself

Abstract

objectivesDrug repurposing, which finds new indications for existing drugs, has received great attention recently. The goal of our work is to assess the feasibility of using electronic health records (EHRs) and automated informatics methods to efficiently validate a recent drug repurposing association of metformin with reduced cancer mortality.

methodsBy linking two large EHRs from Vanderbilt University Medical Center and Mayo Clinic to their tumor registries, we constructed a cohort including 32,415 adults with a cancer diagnosis at Vanderbilt and 79,258 cancer patients at Mayo from 1995 to 2010. Using automated informatics methods, we further identified type 2 diabetes patients within the cancer cohort and determined their drug exposure information, as well as other covariates such as smoking status. We then estimated HRs for all-cause mortality and their associated 95% CIs using stratified Cox proportional hazard models. HRs were estimated according to metformin exposure, adjusted for age at diagnosis, sex, race, body mass index, tobacco use, insulin use, cancer type, and non-cancer Charlson comorbidity index.

resultsAmong all Vanderbilt cancer patients, metformin was associated with a 22% decrease in overall mortality compared to other oral hypoglycemic medications (HR 0.78; 95% CI 0.69 to 0.88) and with a 39% decrease compared to type 2 diabetes patients on insulin only (HR 0.61; 95% CI 0.50 to 0.73). Diabetic patients on metformin also had a 23% improved survival compared with non-diabetic patients (HR 0.77; 95% CI 0.71 to 0.85). These associations were replicated using the Mayo Clinic EHR data. Many site-specific cancers including breast, colorectal, lung, and prostate demonstrated reduced mortality with metformin use in at least one EHR.

conclusionsEHR data suggested that the use of metformin was associated with decreased mortality after a cancer diagnosis compared with diabetic and non-diabetic cancer patients not on metformin, indicating its potential as a chemotherapeutic regimen. This study serves as a model for robust and inexpensive validation studies for drug repurposing signals using EHR data.

Indexed as

Drug RepositioningElectronic Health RecordsAdministration, OralAdultDiabetes Mellitus, Type 2HumansHypoglycemic AgentsInformation Storage and RetrievalMetforminNatural Language ProcessingNeoplasmsRegistriesSurvival AnalysisHypoglycemic AgentsMetformindrug repurposingelectronic health recordsmetforminnatural language processing

Identifiers

PMID25053577
PMCPMC4433365
OpenAlexW2105050951

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Texttitle and abstract
LicenceCC BY-NC
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Registered trials

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.