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The watchdog group Public Citizen is alleging that ethics violations were made during the CHAMPION PHOENIX trial, in which researchers compared cangrelor and clopidogrel as thromboprophylaxis for patients undergoing coronary stent procedures.
Public Citizen said the trial “needlessly threatened” the lives of subjects assigned to the control group, and trial participants may not have been informed about the potential risks of enrollment.
Public Citizen sent a letter to the Office of Research Oversight (ORO) at the US Department of Veterans Affairs (VA) asserting that the CHAMPION PHOENIX trial unnecessarily increased the risk of death, heart attack, and other adverse cardiac events for subjects placed in the control group.
The trial was conducted at 153 institutions around the world, including 3 VA facilities: the Dallas VA Medical Center, the Jesse Brown VA Medical Center in Chicago, and the VA Boston Healthcare System. The study involved more than 11,000 subjects, 84 of whom were patients at the 3 VA medical centers.
The primary goal of the trial was to determine whether cangrelor is more effective than clopidogrel at preventing death, heart attacks, and other serious cardiac complications in patients undergoing coronary artery stent procedures.
Public Citizen said the increased risk to subjects in the control group resulted from failure to ensure they were treated with clopidogrel prior to their coronary stent procedures.
An analysis by a senior medical reviewer at the US Food and Drug Administration revealed that failure to administer the necessary antiplatelet treatment occurred in 89% of subjects enrolled at the 3 VA facilities, compared with 30% of subjects enrolled at non-VA facilities.
“The seriously flawed trial protocol paved the way for inappropriate and shocking delays in antiplatelet therapy for subjects enrolled in the control group at all trial institutions,” said Michael Carome, MD, director of Public Citizen’s Health Research Group.
“Inexplicably, the rate of such delays was extraordinarily high at the VA trial sites, making participation in the trial even more hazardous for subjects randomized to the control group at those sites compared with other sites.”
Public Citizen’s complaint contends that the trial’s research protocol was unethical because it failed to require that control group subjects receive lifesaving antiplatelet medications as soon as possible prior to undergoing coronary artery stent procedures.
Prior research conducted by the same research team, expert clinical practice guidelines, and other data available to the researchers established that withholding clopidogrel until after the coronary stent procedures constitutes substandard care.
Indeed, one of the two lead researchers for the trial stated publicly before the trial’s initiation, “If you ask the experts, they will all tell you to give antiplatelet therapy upfront before the PCI [coronary stent] procedure.”
Public Citizen is calling on the ORO to investigate why the institutional review boards responsible for reviewing human research at the 3 VA medical facilities approved the trial given a design that was unethical and failed to minimize the risks to the control group subjects.
The complaint also urges the ORO to investigate whether proper consent of the subjects was obtained in light of the risks, as required by the VA’s human subjects protection rules.
Public Citizen said another issue that requires further inquiry—but falls outside the scope of the ORO’s jurisdiction—is whether inappropriate delays in antiplatelet therapy were more widespread at VA healthcare facilities for patients who did not participate in the trial.
In a separate letter, Public Citizen urged the VA’s Office of Inspector General to launch an investigation to find out.
