Web-Based Data Tool Designed to Enhance Drug Safety

Team at the Division of Biomedical Informatics at Cincinnati Children's HospitalAlthough the FDA's database offers an extensive array of reports and related data on the clinical use of drugs and adverse effects, study authors said that current methods for information retrieval and analysis are difficult –running the risk of losing statistical power and the ability to detect important differential effects.

AERSMine is designed for easy use and supports analysis of millions of clinical records containing details on drug exposures, disease indications, and clinical outcomes. Researchers said the tool is expected to strengthen access to and analysis of drug safety and effectiveness data. It also has the potential to discover improved uses of individual drugs or drug combinations and develop novel treatments for diseases.

"One of the capabilities that makes AERSMine different from any other clinical data mining system is its ability to use knowledge frameworks – ontologies –to form the groupings of patients, medications, and outcomes and gain what we believe is an unprecedented power to explore and identify both unexpectedly negative and positive drug effects. Doing this has the potential to uncover new uses for drugs and drug regimen combinations," said Bruce Aronow, PhD, senior study author and co-director of the Computational Medicine Center at Cincinnati Children's.

Using the database

The researchers evaluated the effectiveness and utility of the data mining tool by running a series of analyses involving both known side effects as well as more complex scenarios focused on improved use of three important classes of drugs and clinical disorders: 1) lithium – used to treat manic depression/bipolar disorder; 2) anti-tumor necrosis factor (anti-TNF) drugs – used to treat inflammatory conditions such as rheumatoid arthritis; 3) NSAIDs – non-steroidal anti-inflammatory drugs used for pain management.

Their analysis of lithium, for example, showed that 22,575 patients had used lithium with a total of 4,180 adverse drug events. AERSMine-dissected data shows that 327 adverse events significantly correlated with patients that use lithium, including aggression, anger, suicidal tendencies, tremors, irritability, etc., have a significantly reduced rate of occurrence in patients taking angiotensin receptor blocks (ARBs, usually taken to control hypertension). The intriguing possibility suggested by AERSMine analysis then is that ARBs could result in a reduction of these sometimes lethal outcomes of bipolar patients taking lithium.

When the authors studied the use of NSAIDs for arthritis, chronic pain, etc., they were able to see differential rates of adverse clinical events depending on if people used propionic acid derivatives (like ibuprofen) or so-called cox-2 inhibitors known as coxibs, and patient groups for whom the risks of NSAID adverse events are much lower than others (for example patients with chronic arthritis).  

"Next generation functions of AERSMine, and part of what we believe provides its underlying power is based on the functions of networks of genes that link the co-occurring clinical phenotypes and drug mechanisms of action to the functions of biological systems," said Anil Jegga, DVM, MRes, study co-author and a computational biologist in the Division of Biomedical Informatics.  "This allows the molecular basis for drug-related adverse events to be detected, leveraged, and used to identify opportunities for repositioning drugs for new clinical uses."

AERSMine is accessible at: https://research.cchmc.org/aers/

Funding support for the study came in part from: the National Institutes of Health (National Center for Advancing Translational Sciences) UL1 TR000077 and from Cincinnati Children's.

About Cincinnati Children's

Cincinnati Children's, a non-profit, pediatric, academic medical center established in 1883, is internationally recognized for improving child health and transforming delivery of care through fully integrated, globally recognized research, education and innovation.  It is one of the top three recipients of pediatric research grants from the National Institutes of Health, ranked third in the nation among all Honor Roll hospitals in U.S. News and World Report's Best Children's Hospitals, and a research and teaching affiliate of the University of Cincinnati's College of Medicine.  Its patient population includes the eight-county primary service area covering parts of Ohio, Kentucky and Indiana.  A destination for children with complex medical conditions, it also served patients from all 50 states and nearly 70 countries during the past year.   Additional information can be found at www.cincinnatichildrens.org. Connect on the Cincinnati Children's blog, via Facebook and on Twitter.

SOURCE Cincinnati Children's Hospital Medical Center

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