Published On September 22, 2006
THE BALANCE BETWEEN INDIVIDUAL RIGHTS AND MEDICAL PROGRESS has sparked controversy over two trials under review by the Food and Drug Administration (FDA). Both studies are aimed at gauging the effectiveness of blood substitutes in helping trauma victims.
In ambulances and on battlefields, the use of real blood is virtually impossible because of short shelf life, refrigeration requirements and the need to cross-match types. What’s more, patients tend to be in no condition to provide informed consent. So one study, recently completed, operated under a waiver of consent (which the FDA may allow for research on acute, life-threatening conditions), as will the other if it’s approved by the FDA.
PolyHeme, developed by Northfield Laboratories of Evanston, Ill., was tested in ambulances and emergency rooms at 32 Level 1 trauma centers. In the ambulance tests, PolyHeme offered patients potential benefits because it carries tissue-saving oxygen (otherwise patients would typically receive saline, which only restores blood volume). But the research protocol also called for PolyHeme to be continued up to six units or 12 hours (whichever came first), long after patients reached the ER. This requirement allowed PolyHeme’s effectiveness to be directly compared to donor blood instead of saline.
Although Hemopure, the other substitute, would be tested only in ambulances, controversy over PolyHeme may be fueling resistance to the Hemopure trial, stalled since 2005 because of safety concerns. “PolyHeme has sensitized people to the waiver-of-consent issue,” says Guy Schein, a spokesperson for the U.S. Navy, which is helping fund the Hemopure study with its maker, Biopure Corp. in Cambridge, Mass.
Both PolyHeme and Hemopure have been linked to patient risks, including increased hypertension and other cardiac problems. Both manufacturers, however, contend that benefits outweigh risks.
In places where PolyHeme was tested, hospitals consulted with community members about risks and provided a procedure for opting out. But ethical concerns arose over whether these measures were an adequate substitute for traditional informed consent. In 1998, a nonconsent trial of a blood substitute from Baxter Healthcare was halted after yielding higher mortality rates. Still, Roger J. Lewis, a physician at the Harbor-UCLA Medical Center and chairman of the Data Safety Monitoring Board, an independent oversight body that recommended the halt, doesn’t think nonconsent trials are necessarily unethical: “If you take that position, you’re condemning all future patients to receive the same therapies we use today.”
Others don’t agree. “Is it ethical to substitute a known lifesaving intervention with an unproven one without consent?” asks Leonard Glantz, a lawyer and ethicist at the Boston University School of Public Health. (He served on a review board at the BU Medical Center that declined to participate in the PolyHeme trial.) “The answer is no, across the board.”