Modeling Human Drug Trials — Without the Human

[The Straight Story]

Modeling Human Drug Trials — Without the Human

I. In 1997, the UK Department of Health launched a study to determine whether a popular cardiovascular drug, atorvastatin, could reduce the number of heart attacks and strokes in diabetic patients. The trial, known as the Collaborative Atorvastatin Diabetes Study (Cards), took seven years to complete. Money had to be raised, doctors had to be recruited, and then 2,838 patients had to be monitored weekly. Half of the diabetics were given the drug. The other half received a placebo.

In early 2004, a few months before the results of the trial were released, the American Diabetes Association asked a physician and mathematician named David Eddy to run his own Cards trial. He would do it, though, without human test subjects, instead using a computer model he had designed called Archimedes. The program was a kind of SimHealth: a vast compendium of medical knowledge drawn from epidemiological data, clinical trials, and physician interviews, which Eddy had laboriously translated into differential equations over the past decade. Those equations, Eddy hoped, would successfully reproduce the complex workings of human biology — down to the individual chambers of a simulated person’s virtual heart.

Because the results of the real Cards trial were still secret, Eddy knew only the broadest facts about its participants, such as their average age and blood pressure. So Eddy and his team created a simulated population with the same overall parameters. Each person “developed” medical problems as they aged, all dictated by the model’s equations and the individual risk profiles. These doubles behaved just like people: Some, for example, forgot to take their pills every once in a while.

It took Eddy and his team roughly two months to construct the virtual trial, but once they hit Return, the program completed the study in just one hour. When he got the results, Eddy sent them to the ADA. He also mailed a copy to the Cards investigators. Months later, when the official results were made public, it became clear that Eddy had come remarkably close to predicting exactly how everything would turn out. Of the four principal findings of the study, Archimedes had predicted two exactly right, a third within the margin of error, and the fourth just below that. Rather than seven years, Eddy’s experiment had taken just a couple of months. And the whole project had cost just a few hundred thousand dollars, which Eddy estimates to be a 200th of the cost of the real trial. The results seemed to vindicate his vision for the future of medicine: faster, cheaper, broader clinical trials — all happening inside a machine.

http://www.wired.com/magazine/2009/11/ff_archimedes