J Am Med Inform Assoc - Validating drug repurposing signals using electronic health records: a case study of metformin associated with reduced cancer mortality.

Tópicos

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Resumo

JECTIVES: Drug 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.METHODS: By 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.RESULTS: Among 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.CONCLUSIONS: EHR 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.

Resumo Limpo

jectiv drug repurpos find new indic exist drug receiv great attent recent goal work assess feasibl use electron health record ehr autom informat method effici valid recent drug repurpos associ metformin reduc cancer mortalitymethod link two larg ehr vanderbilt univers medic center mayo clinic tumor registri construct cohort includ adult cancer diagnosi vanderbilt cancer patient mayo use autom informat method identifi type diabet patient within cancer cohort determin drug exposur inform well covari smoke status estim hrs allcaus mortal associ cis use stratifi cox proport hazard model hrs estim accord metformin exposur adjust age diagnosi sex race bodi mass index tobacco use insulin use cancer type noncanc charlson comorbid indexresult among vanderbilt cancer patient metformin associ decreas overal mortal compar oral hypoglycem medic hr ci decreas compar type diabet patient insulin hr ci diabet patient metformin also improv surviv compar nondiabet patient hr ci associ replic use mayo clinic ehr data mani sitespecif cancer includ breast colorect lung prostat demonstr reduc mortal metformin use least one ehrconclus ehr data suggest use metformin associ decreas mortal cancer diagnosi compar diabet nondiabet cancer patient metformin indic potenti chemotherapeut regimen studi serv model robust inexpens valid studi drug repurpos signal use ehr data

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