A group of Boston doctors is proposing to join a study that would provide emergency treatment for brain-injured patients without obtaining the trauma victims’ consent, arguing that they often arrive at the hospital unconscious or without family members who can speak on their behalf.
Federal law and the generally accepted ethics of medical research require that patients or their surrogates be told about any risks of participating in a study and have the chance to refuse enrollment. But the law allows for an exemption in certain cases involving emergency care.
This would be the first study using the exemption at a Boston hospital since the Food and Drug Administration created the rules allowing it in 1996, said Dr. James Feldman, an investigator and the chairman of a Boston University Medical Campus panel that reviews research.
Research without consent is controversial, and some ethicists argue that it is almost never appropriate. “People don’t expect to be researched on when they go to an emergency department, and they don’t consent to research just by being in an accident,” said George Annas, a BU bioethicist who is not involved in the brain trauma proposal.
The study team, from Boston Medical Center and Massachusetts General Hospital, is hoping to join a national trial looking at whether giving the hormone progesterone to patients in the hours immediately after a traumatic brain injury could prevent further neurologic damage.
Swelling, fluid build-up, or metabolic changes in the hours after someone experiences a head trauma make up what is referred to as a “secondary cascade” of brain injury, as cells continue to die. Slowing that process has been a challenge.
“We have a devastating disease that causes tremendous lifelong disability for people around the country and around the world, with no proven treatment,” said Dr. Joshua Goldstein, an investigator and director of the Center for Neurologic Emergencies at Mass. General. “We’re hoping that the time has come to find a treatment.”
Researchers began considering progesterone after Dr. Donald Stein of Emory University decades ago noticed that female rats performed significantly better after a brain injury than male rats.
In 2006, Stein and others published a small study of 100 people that found that administering progesterone to people with traumatic brain injury was safe and may lower the mortality rate after one month. Progesterone is a hormone involved in women’s menstrual cycle.
Stein’s 2006 study was conducted with consent of patients or their family. Lead author Dr. David Wright, director of emergency neurosciences at Emory University School of Medicine, said it took at least 4½ hours from the point of injury to obtain consent. But scientists believe that the “secondary cascade” of brain damage can begin immediately after trauma.
“We knew if we were going to get [the progesterone] in early, we would have to get the exception,” he said.
With 40 hospitals participating, the trial led by Wright has enrolled more than 760 people, he said. Adding patients from the Boston hospitals would help the study reach its 1,140-person target before the funding ends in 2014.
It’s not clear exactly how progesterone might work, but the early evidence of its neuroprotective effects is promising, said Dr. Vassilis Koliatsos, who studies neural injury at Johns Hopkins University School of Medicine and is not involved in this study. In a field that “has been plagued by negative studies” disproving treatment options, he said it is worth pursuing.
Koliatsos, Goldstein, and others have great hope for the therapy, but Annas, the BU bioethicist, argues that the potential is not enough to outweigh the rights of patients to approve or reject participation in research. “You need something that’s as powerful as consent,” he said.
Instead of seeking consent from individual patients, researchers are trying to build community support for the study. Annas said, however, that is difficult because there is no clear constituency of people likely to be treated at the hospital for a traumatic brain injury because the injury is so often sudden and random.
The Boston researchers have issued surveys, hosted a table at Boston University’s wellness fair, convened focus groups, and made presentations to various community groups. Other study sites have tried billboards.
Research oversight boards for Boston Medical Center and Mass. General have approved the study protocol but are waiting for researchers to present the results of their efforts to build support for the study.
Nationally, studies of research without consent remain rare. In the decade after the rules were put in place, just 56 applications to conduct research without consent were submitted to the FDA.
Some local hospitals have turned down such trials. Boston Medical Center rejected a proposal several years ago to test an artificial blood in trauma patients without their consent. Reviewers balked because patients would have continued receiving the blood substitute even after they arrived at the hospital, where a blood transfusion was available.
Annas, who was vocal in his criticism of that trial, said that he was encouraged by some steps researchers were taking in this one. For example, in the first hour after a patient’s injury, the researchers must search for family members who could give their consent before administering the drug.
But Annas questioned why a progesterone study could not be done only on those patients for whom researchers could obtain consent. Researchers said they wanted to be able to include the full range of head injury in this trial.
When Sam Robinson of Sharon Hill, Pa., was transported to the hospital in March 2011, after a motorcycle accident, first responders could not identify him. He was not wearing a helmet and had a serious head injury. He was not able to communicate, and his wallet and cellphone were left in his bike.
His family did not find him until the next day at the Hospital of the University of Pennsylvania, where he had been enrolled in the study as a John Doe. Dannita Robinson felt that her husband was “locked in” to the trial at that point, she said. She was given the option to pull him out, but she said she worried: What if the drug was helping?
Now 42, Sam Robinson is doing well physically and mentally and is back to work as a bus driver, his wife said. The family does not know if he received the progesterone or a placebo.
The study has a database where people can put themselves on a do-not-enroll list, in case they are hospitalized with a brain injury. If they gain approval to join the study, researchers said the Boston sites probably would enroll one to two people each month over the next two years.
Because these trials are not common, it is unclear what enrolling patients without their consent could mean for researchers’ legal liability.
The patients who would be enrolled in this trial are gravely injured, so researchers argue it is a reasonable risk to try a treatment for which there is some early evidence of success. However, even in studies performed with consent, researchers can remain liable for egregious errors.