More Science...And Much More Money

By Dick Thompson

Dr. Robert Califf, arguably one of the most important people at Duke Med, is on a flight to Washington, where he is scheduled to lead an international strategy session on how heart-failure drugs should be studied. As director of the Duke Clinical Research Institute, he is charged with doing whatever he can to take the guesswork out of medical care, and he has a specific statistic he wants to change. "Only 15% of the decisions a doctor makes every day are based on evidence," he recites.

Califf knows doctors cannot base every decision on the evidence since there is never enough. But he believes medical scientists can do a lot more to codify what works best. "We're in an era where we can no longer afford to guess whether things are beneficial," says Califf. And Duke officials believe his DCRI, which coordinates a worldwide network of clinical investigators, will make Duke a leader in evidence-based medicine, driving down costs at the medical center without harming health while bringing in millions of dollars in funding from pharmaceutical firms.

To help doctors make more informed decisions, Califf has created what may be the biggest clinical-research machine of its kind in the world. He has gathered a staff of 750 physicians, statisticians and computer jocks in a $44.8 million high-tech high-rise on the edge of the medical center. DCRI is currently coordinating 12 international studies, involving more than 1,500 clinical investigators in 35 countries. With net revenues this year projected to top $55 million (up from $30 million in '96), DCRI has the potential of becoming the largest single profit center at Duke.

DCRI has been designed to find vital but frequently obscure medical information. Califf's favorite illustration involves an antiarrhythmia drug that had passed clinical trials, was approved by the FDA and was being given to thousands of patients before it was discovered that the drug was killing some patients. "You'd think that doctors would notice people falling over dead," says Califf. "But these things happen over years." These problems not only happen over time; they also often happen in patients who had other medical conditions that might have killed them. And they happen amid a large pool of people who are doing well on the drug.

Califf thought that such "hidden" information would be easier to find if studies were done on enormous groups of patients.

In 1985 Genentech backed the idea. At the time, European researchers had reported that the biotech company's clot-busting drug, TPA, worked no better, yet cost far more, than the standard clot buster. If TPA was to survive, it had to quantify its benefits to insurers. With a fortune on the line, Genentech turned to Califf. Within two years, Califf and the Cleveland Clinic organized a network that enrolled 41,000 patients. Conclusion: compared with the standard drug, TPA saved more than 2,000 lives a year.

This "large, simple trial" has become standard for DCRI. And DCRI continues to do trials to determine the health benefit of products already on the market.

Science also wins in these studies, says Califf. By funding the trials, pharmaceutical companies inject clinical-research centers with new revenue. And Califf ensures that data collected from the study belong to the researchers, so that the results are published no matter what the outcome.

The studies also give the clinical investigators a mountain of information to mine. About 150 research papers flowed from the Genentech study alone. And scientists are able to piggyback studies onto DCRI jobs that would otherwise be difficult to fund. For example, for the Genentech study, scientists were able to investigate the difference in heart patients treated in the U.S. and Canada. Result: Canadian patients felt their quality of life following a heart attack was not so good as it was for similar patients in the U.S.

Support for such evidence-based medicine is mixed at Duke. Some physicians argue that the approach cannot measure such ambiguous outcomes as quality of life. Other critics are worried that such "cookbook" medicine will further erode a doctor's freedom. And with increasing funds coming from drug companies--such as Ciba-Geigy, Hoffmann-La Roche and Glaxo--many people at Duke are concerned about industry's growing influence over research.

All good arguments. Still, it seems to be time for someone to find out what works best in medicine.

--By Dick Thompson