PMID- 31141421 OWN - NLM STAT- MEDLINE DCOM- 20200615 LR - 20200615 IS - 2473-4276 (Electronic) IS - 2473-4276 (Linking) VI - 3 DP - 2019 May TI - Discovery of Noncancer Drug Effects on Survival in Electronic Health Records of Patients With Cancer: A New Paradigm for Drug Repurposing. PG - 1-9 LID - 10.1200/CCI.19.00001 [doi] LID - CCI.19.00001 AB - PURPOSE: Drug development is becoming increasingly expensive and time consuming. Drug repurposing is one potential solution to accelerate drug discovery. However, limited research exists on the use of electronic health record (EHR) data for drug repurposing, and most published studies have been conducted in a hypothesis-driven manner that requires a predefined hypothesis about drugs and new indications. Whether EHRs can be used to detect drug repurposing signals is not clear. We want to demonstrate the feasibility of mining large, longitudinal EHRs for drug repurposing by detecting candidate noncancer drugs that can potentially be used for the treatment of cancer. PATIENTS AND METHODS: By linking cancer registry data to EHRs, we identified 43,310 patients with cancer treated at Vanderbilt University Medical Center (VUMC) and 98,366 treated at the Mayo Clinic. We assessed the effect of 146 noncancer drugs on cancer survival using VUMC EHR data and sought to replicate significant associations (false discovery rate < .1) using the identical approach with Mayo Clinic EHR data. To evaluate replicated signals further, we reviewed the biomedical literature and clinical trials on cancers for corroborating evidence. RESULTS: We identified 22 drugs from six drug classes (statins, proton pump inhibitors, angiotensin-converting enzyme inhibitors, beta-blockers, nonsteroidal anti-inflammatory drugs, and alpha-1 blockers) associated with improved overall cancer survival (false discovery rate < .1) from VUMC; nine of the 22 drug associations were replicated at the Mayo Clinic. Literature and cancer clinical trial evaluations also showed very strong evidence to support the repurposing signals from EHRs. CONCLUSION: Mining of EHRs for drug exposure-mediated survival signals is feasible and identifies potential candidates for antineoplastic repurposing. This study sets up a new model of mining EHRs for drug repurposing signals. FAU - Wu, Yonghui AU - Wu Y AD - The University of Texas Health Science Center at Houston, Houston, TX. AD - University of Florida, Gainesville, FL. FAU - Warner, Jeremy L AU - Warner JL AD - Vanderbilt University Medical Center, Nashville, TN. FAU - Wang, Liwei AU - Wang L AD - Mayo Clinic, Rochester, MN. FAU - Jiang, Min AU - Jiang M AD - The University of Texas Health Science Center at Houston, Houston, TX. FAU - Xu, Jun AU - Xu J AD - The University of Texas Health Science Center at Houston, Houston, TX. FAU - Chen, Qingxia AU - Chen Q AD - Vanderbilt University Medical Center, Nashville, TN. FAU - Nian, Hui AU - Nian H AD - Vanderbilt University Medical Center, Nashville, TN. FAU - Dai, Qi AU - Dai Q AD - Vanderbilt University Medical Center, Nashville, TN. AD - Department of Veterans Affairs, Tennessee Valley Healthcare System, Nashville, TN. FAU - Du, Xianglin AU - Du X AD - The University of Texas Health Science Center at Houston, Houston, TX. FAU - Yang, Ping AU - Yang P AD - Mayo Clinic, Rochester, MN. FAU - Denny, Joshua C AU - Denny JC AD - Vanderbilt University Medical Center, Nashville, TN. FAU - Liu, Hongfang AU - Liu H AD - Mayo Clinic, Rochester, MN. FAU - Xu, Hua AU - Xu H AD - The University of Texas Health Science Center at Houston, Houston, TX. LA - eng GR - UL1 TR000445/TR/NCATS NIH HHS/United States GR - R01 GM103859/GM/NIGMS NIH HHS/United States GR - U24 CA194215/CA/NCI NIH HHS/United States GR - R01 LM010685/LM/NLM NIH HHS/United States GR - P30 CA068485/CA/NCI NIH HHS/United States GR - R01 LM010681/LM/NLM NIH HHS/United States PT - Journal Article PT - Meta-Analysis PT - Research Support, N.I.H., Extramural PL - United States TA - JCO Clin Cancer Inform JT - JCO clinical cancer informatics JID - 101708809 SB - IM MH - Clinical Trials as Topic MH - Data Mining MH - Drug Development MH - *Drug Repositioning MH - *Electronic Health Records MH - Humans MH - Neoplasms/drug therapy/*epidemiology/mortality MH - Prognosis MH - Registries MH - Reproducibility of Results MH - Treatment Outcome PMC - PMC6693869 MID - NIHMS1041659 COIS- DISCOVERY OF NONCANCER DRUG EFFECTS ON SURVIVAL IN ELECTRONIC HEALTH RECORDS OF PATIENTS WITH CANCER: A NEW PARADIGM FOR DRUG REPURPOSING: The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO's conflict of interest policy, please refer to www.asco.org/rwc or ascopubs.org/cci/author-center. JEREMY L. WARNER: Stock and Other Ownership Interests: HemOnc.org MIN JIANG: Employment: Pieces Technologies, Eli Lilly Stock and Other Ownership Interests: Eli Lilly QINGXIA CHEN: Employment: HCA Healthcare (I), Cytel (I), J&J Medical Devices (I) Stock and Other Ownership Interests: HCA Healthcare (I), Aimmune Therapeutics Consulting or Advisory Role: Boehringer Ingelheim JOSHUA C. DENNY: Patents, Royalties, Other Intellectual Property: Royalties from research methods licensed by Vanderbilt to Nashville Biosciences, a company wholly owned by Vanderbilt (Inst) HUA XU: Employment: Melax Technologies Stock and Other Ownership Interests: Melax Technologies Consulting or Advisory Role: MORE Health, DCHealth Technologies, Hebta Patents, Royalties, Other Intellectual Property: Receive royalties from software license from The University of Texas Health Science Center No other potential conflicts of interest were reported. EDAT- 2019/05/30 06:00 MHDA- 2020/06/17 06:00 PMCR- 2020/05/29 CRDT- 2019/05/30 06:00 PHST- 2019/05/30 06:00 [entrez] PHST- 2019/05/30 06:00 [pubmed] PHST- 2020/06/17 06:00 [medline] PHST- 2020/05/29 00:00 [pmc-release] AID - 1900001 [pii] AID - 10.1200/CCI.19.00001 [doi] PST - ppublish SO - JCO Clin Cancer Inform. 2019 May;3:1-9. doi: 10.1200/CCI.19.00001.