Potential Benefits Outweigh Small Time Delay in Enrolling Patients With Chest Pain in Clinical Trial
NEW ORLEANS, LA -- Enrolling patients with chest pain in a cardiology clinical trial takes time, but not enough to offset the benefits of clinical research, researchers at Duke University Medical Center say.
In the first study that examines such time issues, researchers found it takes an average of 8 minutes longer to enroll a patient in a trial of clot-busting drugs than to treat patients directly (50 minutes compared to 42 minutes).
While that time difference is "statistically significant," it isn't nearly as important as many doctors assume it is, said the study's lead researcher, Duke Clinical Research Institute cardiologist Dr. John Alexander, who prepared his study for presentation Wednesday at the 73rd annual scientific session of the American Heart Association.
"Many doctors have the impression there is a great delay in enrolling patients in trials, and for that reason, they often are hesitant to have their sickest patients participate, believing that every minute to therapy counts," he said.
"This is a mistake. Participation in clinical trials is good for patients and critical for advancing the treatment of heart attacks," Alexander said. "While time is of the essence, especially in the use of thrombolytic therapy, we've found that the delay in enrolling patients in clinical trials is small enough, and the potential benefits large enough, that we believe physicians should change their practice and enroll more of their patients in these trials."
Physicians should, however, work in general to reduce the time it takes to use thrombolytic therapy - whether or not a patient is enrolled in a clinical trial. Guidelines for use of these clot-busting drugs suggest they should be administered to a patient with a suspected heart attack within 30 minutes of arrival at a hospital. "For each hour delay, 1.6 lives are lost per 1,000 patients treated," Alexander said.
The eight additional minutes needed to enroll a patient in a clinical trial is used to determine if the patient qualifies for the trial, to explain the trial to the patient or family member and have a consent form signed, to telephone a study center to "randomize" the patient to a treatment arm, and to retrieve a specified drug kit and administer it. While that seems like a lot to do in a small amount of time, Alexander said researchers have to continue to work to reduce the time even further, such as by making trials less complex. "There is no amount of time when shorter is not better," he said.
Alexander led the "Emergency Department Registry" sub-study, an offshoot of the ASSENT-2 clinical trial that compared two different thrombolytic therapies in patients experiencing a heart attack. He and a team of researchers examined the records of all patients at 63 hospitals in the United States and Canada who had been given clot-busting drugs in the emergency department of these medical centers within a two-month period in 1999. Of these patients, 176 were enrolled in ASSENT-2 and 307 were not. All the patients had chest pain that had lasted less than 12 hours.
The researchers simply examined how long, on average, it took for ASSENT-2 patients to receive their clot-busters (50.5 minutes), compared to the other patients (42 minutes) - a difference of 8.5 minutes. They then "adjusted" those times to reflect differences in the medical condition between patients enrolled in ASSENT-2 and those not enrolled. When the groups were made similar, the difference in time-to-treatment between the two groups was reduced to 38 minutes for patients not enrolled in ASSENT-2 and 43 minutes for ASSENT-2 patients - a difference of only five minutes.
Alexander called this adjusted five-minute delay "modest."
The researchers did not examine differences in the medical outcome of treatment due to the delay in enrolling patients into the trial. "That's not calculable from this study, although I doubt there were significant clinical consequences due to the eight-minute delay," Alexander says. "But we also know, based on other large studies, that the benefit of thrombolytic therapy does decrease as more time passes."