Minneapolis cardiologist says red tape thwarts research to improve cardiac arrest treatments

Quickly restoring blood flow after a heart attack limits the amount of heart tissue that dies from lack of oxygen.

But abruptly restarting blood flow may also cause damage by spreading molecules that form in the absence of blood flow. Doctors now believe that limiting the so-called "reperfusion injury" from restarting coronary blood flow is one of the best opportunities in heart attack care to preserve tissue that can keep the heart beating for years to come.

So why is it so hard to do clinical testing on ways to prevent reperfusion injury?

The key stumbling block, a prominent Minneapolis cardiologist argues, is getting patients to sign an "informed consent" form to take part in research while they are also in the hospital having a heart attack — a condition that worsens by the minute without treatment.

Regulators want to protect patients from research experiments that they don't understand.

But in an editorial in the peer-reviewed journal Circulation Research, Dr. Jay Traverse says the Food and Drug Administration and the private companies that manage research are using so much red tape that it stands in the way of research on lifesaving treatments in emergency medicine.

"How does a patient with ongoing chest pain and potential hemodynamic instability or arrhythmias read, let alone comprehend, a 15-page consent form and HIPAA documentation? Research suggests they do not!" Traverse's opinion article says. (HIPAA is the Health Insurance Portability and Accountability Act, which established national standards for medical record privacy.)

Traverse is director of research at the Minneapolis Heart Institute Foundation and an associate professor of heart medicine at the University of Minnesota. His article in Circulation Research recounted a real-world example of difficulties faced by a federally funded clinical trial of a treatment to prevent reperfusion injury at Allina Health's Abbott Northwestern Hospital in Minneapolis.

The study was approved by Allina's institutional review board (IRB) and started enrolling patients in 2011. The IRB allowed patients to agree verbally beforehand to the treatment — in which a doctor inflates a small balloon inside the coronary artery several times during reperfusion — and then give full informed consent within 24 hours.

The experiment was considered low-risk, and indeed none of the 90 patients enrolled in the clinical trial by 2014 had a single complication or adverse event, the article says.

Unfortunately, Traverse says, Allina Health began using outside IRB agencies to renew clinical trials in 2014.

The group that took over decided that FDA rules didn't permit verbal consent, and that an expensive and laborious "emergency waiver" process had to be conducted, including phone surveys, public talks, and ads about the trial that allowed people to prospectively opt out.

The extra requirements ate up $15,000 in expenses and put federal funding of the trial on hold for a year, delaying research into treatment options for a condition — cardiac arrests outside a hospital — that kills 347,000 Americans a year. The survival rate for out-of-hospital cardiac arrest is about 10 percent.

"A minuscule 1 percent improvement in survival would save 3,000 lives," Traverse's article notes. "Unfortunately, research in cardiac arrests that could improve survival has been decreasing because of the high regulatory burden."

Several groups declined to comment on Traverse's article, including the U.S. Food and Drug Administration and the federal Office of Human Research Protections, which both publish rules on clinical trials under the U.S. Department of Health and Human Services (HHS).

Federal offices have published informed consent guidelines in recent years, but the FDA's website describes a normal trial consent this way:

"Giving a subject adequate information concerning the study, providing adequate opportunity for the subject to consider all options, responding to the subject's questions, ensuring that the subject has comprehended this information, obtaining the subject's voluntary agreement to participate and, continuing to provide information as the subject or situation requires."

In 2013, the FDA published a 64-page nonbinding guidance document covering exceptions to informed consent rules for emergency research when neither the patient nor a legally designated representative can provide adequate consent to the research. Those rules came after the HHS saw an urgent need to waive informed consent rules for emergency research:

"HHS is authorizing this waiver in response to growing concerns that current regulations, absent this waiver, are making high-quality research in emergency circumstances difficult or impossible to carry out at a time when the need for such research is increasingly recognized," HHS officials wrote.

That sentence was published in the Federal Register in October 1996.

Joe Carlson • 612-673-4779