Curbs on testing stall lifesaving technologies

THE BALTIMORE SUN

It's a conflict that pits a precious human right against the need for new lifesaving technologies.

Two years ago, federal regulators cracked down on the widespread practice of using unconscious patients in tests of experimental treatments after they were wheeled into emergency rooms.

Now, some emergency specialists say that crackdown has made it difficult or impossible to recruit human subjects for resuscitation research. It has slowed or blocked development of at least a dozen new therapies, they say, that could help victims of stroke, drug overdose and brain injury.

Last week, CardioLogic Systems Inc., a Baltimore company, suspended its 8-month-old trials of a mechanical vest designed to revive cardiac arrest victims, saying it couldn't complete the study under current Food and Drug Administration rules. Company officials contend that their device, developed by researchers at Johns Hopkins University's School of Medicine, could save 45,000 lives a year.

The issue is informed consent -- the principle of using humans in medical experiments only if they understand the dangers of participating and give permission.

That principle serves as the foundation of modern medical ethics. Informed consent grew out of the Nuremberg war crimes trials, which focused in part on the Nazis' use of humans as

guinea pigs in hideous experiments.

Ethicists say patient rights must remain paramount in medical research. "The answer isn't just throw out informed consent and forget about it," said Arthur Caplan, a bioethicist at the University of Pennsylvania.

Medical scientists, meanwhile, say they can't prove that promising new therapies are safe and effective without testing them. People lying unconscious in a hospital emergency room obviously are in no shape to give consent, informed or otherwise. Family members or legal representatives can approve participation in a study, but aren't always easily reached.

Before 1993, the in-house boards that govern research at academic hospitals -- called institutional review boards -- often waived informed consent for emergency research on promising therapies.

But then the issue of informed consent emerged in stories about Cold War radiation experiments on unwitting human subjects. The FDA and the National Institutes of Health warned review boards to curb their waivers of informed consent.

Dr. Michelle Biros, the leader of a coalition of trauma care researchers, said stricter enforcement of the consent rule has hindered at least a dozen promising research projects. They include:

* A study using an asthma drug to restart the hearts of patients who didn't respond to standard treatment.

* Research into the use of calcium to control very rapid heartbeat, or superventricular tachycardia.

* Tests of whether higher-than-normal doses of epinephrine could save more children who suffer cardiac arrest.

* Trials using a more concentrated salt solution to restore body fluids to severely injured patients.

"There are patients with devastating pathologies who aren't going to have the opportunity to benefit from potential therapies," said Dr. Biros, research director for the emergency department at the Hennepin County Medical Center in Minneapolis. "Those patients are the most critically ill and up until now, have been the least successfully treated."

Federal regulators say they are trying to come up with a compromise that balances patient rights against the need to test new treatments. But the agencies are moving cautiously, mindful of past research abuses.

"We're seeking an exquisite balance between respect for an individual subject's autonomy and the need to do good for all future patients who might benefit," said Gary B. Ellis, director of the federal Office for Protection from Research Risks.

Sharon Snider, an FDA spokeswoman, said the agency is "very much aware of the problem with the informed consent regulation." While the agency's priority is "to protect patient rights," she said, "I think everyone agrees that there are some instances where patients can't give informed consent. At the moment there is no way around the regulation."

When CardioLogic, the Baltimore company, began clinical trials of its mechanical vest for cardiopulmonary resuscitation eight months ago, the FDA required it to obtain informed consent from thousands of heart patients in advance. Then, investigators were supposed to wait until some of those patients went into cardiac arrest.

After eight months of work at five hospitals, researchers manged to enroll just 16 patients in trials, said Jeffrey D. Koepsell, president of the company. Four hundred patients would be needed to complete a scientifically meaningful study.

At the rate the trials were proceeding, Mr. Koepsell said, they would take eight to 10 years and cost $25 million, far more than his small company could afford.

Among those with an equity interest in the Joh Avenue company are Johns Hopkins, the Hopkins researchers who invented the machine and the city of Baltimore, which invested $200,000 in the firm through its Enterprise Development Fund, a unit of the quasi-public Baltimore Development Corp.

Without a waiver of the consent rule in the next 30 to 60 days, CardioLogic may shift its trials overseas, Mr. Koepsell said. But that could jeopardize the vest's chances for FDA approval in this country: The agency often views data from foreign studies skeptically.

Each year, some 300,000 Americans suffer cardiac arrest, where the heart essentially stops beating. Only 15 percent of victims treated with CPR survive. CardioLogic estimates that the vest could double the current survival rate.

The device could also make a lot of money. Mr. Koepsell estimated that there is, potentially, a $1.8 billion market for the vest.

"This research has the potential to save more lives than any drug on the market today," he said.

Jean Ann McLaughlin, 44, of North Harwich, Mass., was the victim of an accident and thinks there is sometimes justification for waiving the consent rule.

She survived a head-on collision 10 years ago but suffered a head injury that left her hospitalized for six months. It caused swelling of the brain, which damaged her eyesight.

Despite surgery, she said, "to this day, I have double vision." To her, research into new trauma drugs is vital.

"If doctors have had positive experience with a drug, and they don't have anybody to give any kind of consent, then they should go ahead and use it," she said.

Dr. Caplan, the bioethicist, counsels caution.

He said regulators should require scientists to ask the relatives or friends of patients for their consent. Or researchers should develop a universal research subject consent card, like an organ donor card, that people could carry.

"Or you put in tough standards that say not every knucklehead can do this, that they have to be pretty good researchers with good track records," he said. "You put up a higher bar to jump over for people who claim that informed consent is impossible."

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