The U.S. Food and Drug Administration recently awarded the University of Arkansas for Medical Sciences a $1.26 million, three-year contract to study new approaches to testing drug safety. Alison Harrill, Ph.D., Assistant Professor in the Department of Environmental and Occupational Health at the UAMS Fay W. Boozman College of Public Health, is lead investigator of the project, entitled “The Diversity Outbred: a Tool to Improve Preclinical Safety Testing and Pharmacogenomics Analysis.”
Currently, it costs more than $1 billion to develop, test and get a new drug on the market. Fewer drugs are being approved in recent years, in part because of safety concerns. Of those approved, some still carry rare safety risks because different people respond differently to the same drug.
The primary goal of Harrill’s study is help predict adverse reactions to a drug before it is on the market and to do so more quickly, so that people needing medications can get them sooner and those with a genetic predisposition to an adverse reaction will not be put at risk.
Typical drug safety testing uses animal models that have a very limited degree of diversity. In Harrill’s study, a stock of laboratory mice will be used that have been specially bred to reflect human population diversity. Using genomic tools and bioinformatics, the genetic makeup of each mouse will be known. A second goal of the project is to use that genetic information to identify biomarkers, or risk factors, for drug toxicity. That knowledge will contribute to the growing field of personalized medicine for humans with specific genetic mutations.
“This model represents a significant departure from classical drug safety assessment, which is performed in animals with limited genetic diversity that may miss relevant safety risks that occur in uniquely sensitive people,” Dr. Harrill said.
Harrill will use a diverse mouse population, the Diversity Outbred, which was developed by The Jackson Laboratory. Gary Churchill, Ph.D., professor at The Jackson Laboratory, has been a key collaborator with Harrill on this research.