Heart failure clinical trials don't test the average patient, SFVAMC study says

BOSTON - Most heart failure clinical trials do a poor job of representing the average patient in their study groups, according to a new study from San Francisco Veterans Affairs Medical Center researchers. Fewer than 20 percent of average heart failure patients would qualify for most clinical trials. The researchers said drugs should be tested more extensively, to show how well they work in average patients.

Most doctors think of the clinical trial as the "gold standard" of medicine, and drugs that are proven in trials often are incorporated into the standard treatment guidelines followed by most doctors.

Unfortunately, most heart failure clinical trials test their drug only on a narrowly selected group of patients, said Maria Ansari, MD, director of the Transitional Care Unit at SFVAMC and UCSF assistant professor of medicine.

"They select a group of patients with a very clearly defined set of criteria for heart failure. Many patients, such as those who see primary care physicians and those who have never been hospitalized, are often underrepresented, and yet these patients are the main targets for the treatment recommendations that follow from clinical trials," she said.

Because the clinical trial subjects are different from the average patient, the drugs may not be as effective, or as safe, as in the clinical trial, the researchers said.

In their study, presented here Wednesday, March 21, at the annual meeting of the American College of Cardiology, Ansari and her colleagues compared heart failure patients in clinical trials to heart failure patients treated at a Northern California HMO (Kaiser), and at SFVAMC. They analyzed the medical charts for these patients, and compared this data to the patients studied in five of the most important heart failure clinical trials conducted since 1991.

Fewer than 20 percent of the 778 heart failure patients they surveyed would have been eligible for four of the five trials, the researchers found. Even the fifth trial, which was more inclusive, would have admitted fewer than half of the patients.

In most cases the patients would have been excluded because they did not meet the clinical trial's specific requirements. For instance, roughly half of the excluded patients were left out because they did not have one of the hallmarks of heart failure, a poorly functioning heart muscle, Ansari said. Other characteristics that excluded patients were a low heart rate, major diseases besides heart failure, or advanced age.

In general, clinical trial patient groups were younger, included fewer women, had poorer heart function, and were less likely to have other diseases compared with the "average" populations, the researchers found.

However, Ansari acknowledges that in order to see clearly the effects of a new drug in a clinical trial, it is necessary to select patients that have a uniform diagnosis of heart disease and few other conditions that might confuse the results.

Instead of bringing more patients into a drug's first clinical trial, Ansari recommends performing secondary clinical tests after the drug has been proven.

"We're not saying they shouldn't carefully select patients for the initial clinical trial," Ansari said. "But these drugs need to be tested in a general practice environment to ensure than the results hold true for the general population of patients, and to give these doctors a better idea of what to expect when they give the drug to their patients," she said.

Drug companies could improve their initial clinical trials by including more women and ethnic minorities, Ansari said. This would help to give a better picture of a drug's effectiveness and side effects in these populations, she said.

Co-authors on this study included Barry Massie, MD, SFVAMC chief of cardiology and UCSF professor of medicine; Ali Tutar, MD, SFVAMC/UCSF postdoctoral fellow; John Teerlink, MD, UCSF assistant professor of cardiology and SFVAMC cardiologist; David Bello, MD, cardiology fellow at Northwestern University; and Mark Alexander, PhD, Kaiser Permanente division of research.

The study was supported by grants from the California affiliate of the American Heart Association, and the Department of Veterans Affairs.

The San Francisco Veterans Affairs Medical Center has been a primary affiliate of University of California, San Francisco since 1974. The UCSF School of Medicine and the SFVAMC collaborate to provide medical student and housestaff education and training programs at SFVAMC. SFVAMC maintains full responsibility for patient care and facility management of the medical center. Physicians at SFVAMC are employed by the Department of Veterans Affairs and also hold UCSF faculty appointments.