Predicting Adverse Drug Events Using Pharmacological Network Models

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Science Translational Medicine  21 Dec 2011:
Vol. 3, Issue 114, pp. 114ra127
DOI: 10.1126/scitranslmed.3002774

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The Power of Prediction

We’ve all done it: googled a combination of medical terms to describe how we feel after taking a new medication. The result is a seemingly infinite list of Web sites telling us that the nausea is normal, or that the headaches warrant another visit to the doctor. Oftentimes, important adverse effects of drugs are discovered and added to the drug label only years after a drug goes on the market. But what if scientists could know about certain adverse drug effects before they are clinically discovered? Cami and colleagues develop a mathematical approach to predicting such adverse events associated with the drugs we take, in hopes of reducing drug-related morbidity—and mortality.

After its release to the market, any given drug undergoes rigorous evaluation to determine associated ADEs (adverse drug effects). This post hoc analysis is usually unable to detect rare or delayed-onset ADEs until enough clinical evidence accumulates–a process that may take years. The method devised by Cami and coauthors does not need to wait for such evidence to accumulate. Instead, it can inform drug safety practitioners early on of likely ADEs that will be detected down the line.

The authors first collected a “snapshot” of 809 drugs and their 852 related adverse events that had been documented in 2005. These drug-safety associations were combined with taxonomic and biological data to construct a network that is reminiscent of a web. Cami et al. then used this drug-ADE network to train a logistic regression predictive model—basically creating a formula that would indicate the likelihood of unknown side effects of any drug in the network. The predictive capabilities of the model were prospectively validated using drug-ADE associations newly reported between 2006 and 2010. Such prospective evaluation preserves the chronological order of drug adverse event reporting, making it a realistic method for predicting future ADEs. With their network, the authors were able to predict with high specificity seven of eight drug ADEs identified by pharmacological experts as having emerged after 2005, including the relationship between the anti-diabetes drug rosiglitazone (Avandia) and heart attack.

The benefit for patients? With this powerful model in place, certain unknown adverse drug effects may be discovered earlier, helping to prevent drug-related morbidity and mortality through appropriate consumer label warnings.

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