Part of Study Testing Experimental Treatments for Trauma Victims Is Shut Down

By Rob Stein
Washington Post Staff Writer
Friday, March 27, 2009

A key part of a controversial project that has been testing experimental treatments on trauma victims has been shut down after the researchers discovered that one new therapy offered no benefit and that patients receiving it appeared to die more quickly.

The research has been subject to intense ethical debates because the patients, who were often unconscious or disoriented because of their injuries, could not give consent to participate.

More analysis will be needed to examine why there were more deaths initially among the patients receiving the experimental treatment, a concentrated form of a salt solution that was being tested in seriously injured patients who were in shock from severe blood loss, federal officials said yesterday.

But they stressed that there was no overall longer-term increase in deaths among the patients receiving that therapy and that the study was halted primarily because it failed to meet a higher standard required for experimenting on patients without their consent: providing a clear benefit over standard care.

"There was high hope based on all the evidence at the time we designed the study that this would be beneficial," said George Sopko of the National Heart, Lung and Blood Institute, which sponsored the research. "But we found that there was no chance it was going to be better, so it would have been unethical to continue."

Critics, however, said the results illustrated why such research is unethical and called for the government to shut down two other large studies that are part of the same project.

"They shouldn't be doing these kinds of studies," said George J. Annas, a Boston University bioethicist. "You shouldn't be doing research on people without their consent. People have a right not to have the government invade their body."

The study was one of three being conducted as part of a $50 million, five-year, federally funded project, the most ambitious set of studies ever mounted under a federal exemption that allows researchers to conduct some kinds of medical experiments without first getting patients' informed consent.

The project was designed to study more than 20,000 patients in 10 sites in the United States and Canada in the hopes of improving treatment after car accidents, shootings, cardiac arrest and other emergencies. Because such patients are usually unconscious at a time when every minute counts, it is often difficult if not impossible to get consent from them or their families.

"In these situations, where someone has collapsed or is about to die, you are not going to have a chance to ask for consent, because minutes matter," Sopko said.

Although the project was endorsed by many trauma experts and some bioethicists, others have questioned it, noting that attempts to test treatments such as blood substitutes under the same exemption may have put patients at risk.

The study that was halted was designed to involve about 3,700 patients who were in shock as a result of severe bleeding. Typically, emergency medical workers infuse such patients with a normal-strength saline solution in the ambulance until they can get to the hospital to receive blood transfusions. Some research, however, has suggested that the highly concentrated saline might be superior, either by itself or combined with another substance known as dextran.

The study was suspended on Aug. 25, after 846 patients had been enrolled, when an independent panel monitoring the project found that after an average of 28 days, there was no difference in the death rates between those receiving concentrated saline and those receiving normal saline, which was the study's predetermined measure of success. Moreover, more patients receiving concentrated saline died on their way to the hospital or in the emergency room, officials said.

Sopko did not release additional details, saying more analysis is needed. But he said the lack of excess deaths after 28 days indicated that the treatment, while not superior, had not harmed patients.

"The key is you want to see whether the patient leaves the hospital or is alive after 28 days," he said.

Annas, however, said the findings suggest the therapy may have harmed study participants.

"So they're saying it doesn't matter when you die -- it doesn't matter if you die today or in 28 days, that the last 28 days of life are not important?" Annas said. "That's ridiculous. It may turn out they killed people with this experiment -- people who didn't even know they were in it and died before they were even told they were in an experiment."

Further analysis of data from about 545 patients in the shock study in February prompted organizers to permanently end that trial, Sopko said. Despite the disappointing findings, Sopko said the study was worth conducting.

"This is essentially what clinical trials are for: to provide you with solid evidence for how to practice the best medicine," Sopko said. "That's the danger of small studies that seem to produce spectacular results. If you don't get them confirmed by big trials, you might get false hope."

In August, officials also suspended a second study designed to test the same approach on about 2,100 patients with head injuries. But an analysis of preliminary data from about 800 patients in that study found no reason to halt that trial, and the study resumed in November after emergency medical workers at the participating centers received additional training to make sure they did not include shock patients in the study, Sopko said. The third study, which is comparing different ways of resuscitating patients who have suffered sudden cardiac arrest, is also continuing in more than 16,000 subjects.

© 2009 The Washington Post Company