A Bloody Mess

Emergency research raises the question: Can trials without consent work?

Aug 1, 2006
Glenn McGee

From the moment of trauma, whether for wounded soldiers, victims of motor vehicle accidents, or children hit by bullets, the best solution to blood loss is, obviously, blood. But many ambulances don't carry blood because it is extremely volatile. Paramedics can offer saline solution, sometimes even laced with nonblood "expanders," but saline can't ferry oxygen around the bloodstream to keep cells alive.

Enter Polyheme, an oxygen-carrying blood substitute that could revolutionize emergency medicine. Polyheme is made from a modified hemoglobin molecule, and it carries oxygen. It is more resilient than blood, with a much longer shelf life and better tolerance of the conditions at the scene of a trauma and in transport. It does not need to be matched to a patient's blood type. And as a bonus, unlike an organ transplant or blood transfusion, there is no risk that a communicable disease will be passed in the process.

Oxygen-carrying blood substitutes have been tried for years on consenting research subjects with mixed results, but enough hope has existed that since 1970, no fewer than three companies have fixed their sights on making one. And now Polyheme's sponsor and manufacturer, Northfield Labs, hopes it is just steps away from approval for use on the battlefield or in a trauma helicopter near you. So with what could amount to a significant advance for trauma medicine being on the brink of approval, why are the airwaves, newspapers, academic journals, and magazines riddled with stories about whether research subjects in the trial are human guinea pigs?

The answer is that the community has been caught off guard. In Phase I and Phase II trials of Polyheme, all subjects were required to give informed consent. Eventually, however, Polyheme had to be tried on typical patients who would benefit from artificial blood: victims of trauma. Regulations passed in the mid-1990s called the Final Rule allow such research, provided a list of precautions is followed, including something called "community consultation." The idea is that while enrollees would be too ill to consent, investigators would have informed the community about the trial in advance; anyone who doesn't want to participate can prospectively opt-out by, for example, wearing an armband.

In the current trial, after informing the community about Polyheme, emergency medical technicians randomly administer either saline solution or Polyheme to trauma patients who are in hemorrhagic shock. The control group receives blood, the standard of care. Those randomized to Polyheme receive it for no more than 12 hours; part of that time may be in the hospital when they would otherwise be given blood.

The problem is that most people in the communities where Polyheme trials are going on, from Illinois to North Carolina to New York, don't seem to know about it. Emergency medical research is a bloody mess right now because Polyheme, once unknown to potential subjects, is suddenly on the public radar, but only because of concerns that include undisclosed or inappropriate risks to subjects in the in-hospital phase of the study, worries about whether the sponsor has withheld data from investigators, and now new criticisms from organizations such as the Senate Appropriations Committee and consumer advocacy groups.

Our bioethics institute studied public awareness of the Polyheme trial, and the journal I edit, The American Journal of Bioethics, published a much-cited collection of articles about ethicists' views of the trial. It has become clear, at least to my group, that patients worry about emergency research, and that new methods for informing the community must be devised and tested before proceeding with trials that have such potential to destroy public trust in research. We know some scientific facts: Saline solution doesn't carry oxygen. Polyheme does. Therein lies the potential for a miracle. But Polyheme, and other substances like it, may end up on the Congressional black list because communities that do not trust researchers are not going to let them ride in ambulances.

Glenn McGee is the director of the Alden March Bioethics Institute at Albany Medical College, where he holds the John A. Balint Endowed Chair in Medical Ethics. gmcgee@the-scientist.com