Essentia Health in Duluth, Mayo Clinic named in challenge to clinical trial

A clinical trial planned for heart attack patients at Duluth's Essentia Health and 66 other institutions is unethical and should be suspended, a public interest group argues.

The Myocardial Ischemia and Transfusion Trial "fails to satisfy the basic ethical principles" required of such research, write Drs. Michael A. Carome and Sidney M. Wolfe of the Public Citizen's Health Research Group in a letter to officials at the U.S. Department of Health and Human Services and the Veterans Health Administration.

The letter was released today.

Essentia Health didn't respond directly to the letter, referring questions to Rutgers Robert Wood Johnson Medical School, the lead agency for the trial.

In a statement, principal investigator Dr. Jeffrey L. Carson of Rutgers defended the study, arguing that it "seeks to answer an important question about the optimal amount of blood transfusion that we give to patients with low red blood cell counts who have had a heart attack."

The clinical trial would weigh between an aggressive strategy and a more conservative approach toward raising the counts. The sample consent form from the medical school at Rutgers contains the information that healthy people in North America have red blood cell counts above 12, but that patients often have lower counts following a heart attack.

"Doctors can order blood transfusion to increase the blood count, but it is not known if patients who receive the blood transfusion do better or worse," the form states, adding, "The purpose of this study is to determine at what blood count patients should be given a transfusion."

But in their letter, Carome and Wolfe argue that statement is misleading, because patients aren't informed about previous research showing the more conservative approach had more often been followed by the patient's death or another heart attack within 30 days.

They cited an analysis published earlier this year from 16 previous studies. Across those studies, among 2,770 patients randomly assigned to "liberal" transfusion, 163 died within 30 days; but among 2,745 with more "restrictive" transfusions, 197 died within 30 days, it found.

In a telephone interview, Carome said that at a minimum, patients signing up for the trial should be told of such findings.

"The preponderance of the evidence strongly signals that the restrictive strategies lead to more harms," he said. "That's not definitive, but there is a strong signal for harm."

But in his statement, Carson argued that the previous studies require a more extensive look at the question.

"Previous small trials do not provide adequate data for accurate predictions, which is why the NIH funded this high-quality large trial," Carson said.

He also noted that the independent Data Safety Monitoring Board along with 35 local review boards across the country had approved of the trial.

Carome was dismissive regarding those approvals, saying local review boards often lack the expertise to evaluate a clinical trial, and tend to assume it's "good science" if funded by the National Institutes of Health.

NIH has provided $19 million for the trial over five years, with plans to enroll 3,500 subjects, Carome said.

Under the clinical trial, patients assigned to the "liberal" group would receive a transfusion of red blood cells anytime their count fell below 10. In the "restrictive" group, a transfusion would be permitted if the count fell below 8 and "strongly recommended" if it fell below 7.

In either group, a patient who was "actively bleeding" could be given a transfusion if the doctor believed an emergency transfusion was needed.

"The health and safety of our participants is our top concern," Carson said in his statement.

In addition to Essentia, the Mayo Clinic in Rochester and the University of Minnesota are among the 67 institutions in the U.S. and Canada that agreed to participate in the trial, according to Public Citizen. The group has objected to other clinical trials in the past, Carome said, but often they haven't learned of the trials until they were completed. When it has objected at the beginning of a trial, Public Citizen has never succeeded in getting officials to suspend a trial, he said.

In this case, the Veterans Health Administration could suspend the trial in VA sites, and HHS could suspend it at the other U.S. sites, he said.

Public Citizen sees it is an ongoing battle, Carome said.

"What troubles us is these are not isolated events," he said. "Our system of protecting human subjects is broken."