After a controversial start, the clinical trials on the experimental blood substitute PolyHeme being conducted at Duke University Hospital have hit an ethical snag.
In documents recently acquired and analyzed by the Wall Street Journal, Northfield Laboratories, Inc., stopped an early trial of PolyHeme several years ago on patients undergoing high-risk surgery. Preliminary results showed that nearly one eighth of the patients who received PolyHeme suffered heart attacks.
The lack of openness from the company has spurred some ethicists and physicians to call for a halt to the latest round of clinical trials being conducted on trauma patients.
PolyHeme is a promising blood substitute that, if successful, could be used in situations ranging from serious automobile accidents to battlefield injuries.
Although legal, the study raises ethical concerns because patients who receive the substitute are in severe shock and consequently, are unable to consent to their participation in the study like typical human research subjects.
Now the newly released clinical results have spurred a fresh round of criticisms against Northfield Laboratories.
"The ethics of the research could be called into question if the data that the company refuses to disclose would have had an adverse impact on the original approval of the clinical trial," said Dr. Philip Rosoff, director of clinical ethics at Duke University Hospital.
The clinical trials for PolyHeme were initially approved by the U.S. Food and Drug Administration and have been ongoing at Duke since the summer of 2005.
Since then five patients from Durham have been enrolled in the study, said Dr. Ross McKinney, vice dean of research for the School of Medicine.
DUH is one of 33 centers across the United States that is participating in the study. Nationally, more than 600 patients have been enrolled in the current study.
Northfield Laboratories has defended the new trials, attributing the prior results to the difficulty of the surgery and the way in which doctors administered the substitute.
"We believe that publishing the full data upon closing the study would have shown that PolyHeme could not be isolated as the cause of the observed serious adverse events," Dr. Steven Gould, chair and chief executive officer of Northfield Laboratories, said in a statement. "To suggest the [Acute Normovolemic Hemodilution] data were withheld to further the trauma trial is patently untrue."
University officials have also defended Duke's involvement in the study.
"The Wall Street Journal was simply not accurate," McKinney said, noting that Duke had been informed of the information from the prior study before initiating the trials in Durham.
The results were provided in an investigator brochure that was given to Duke's Institutional Review Board, the group that approves the ethics and legality behind research, and they was also presented by researchers from Johns Hopkins University at two separate meetings. "It's not like it was completely hidden," McKinney said.
In the initial study, PolyHeme was given to patients undergoing aortic aneurism repair, a high-risk surgical procedure.
"Five to 15 percent of people who have aortic aneurism repair will have a heart attack during the surgery," McKinney said. "It's a big-deal surgery. You're slicing open the aorta and patching it back again."
In the current study, PolyHeme is administered to trauma patients suffering from shock and severe blood loss. The current study population is typically considered to be younger and in better health than those that underwent the aortic surgery.
McKinney said PolyHeme is considered advantageous in emergency situations because it provides an alternative to the saline solution that is typically administered.
Real blood is not carried aboard ambulances because of its short shelf life and the need to match blood-types between donors and recipients. In comparison, PolyHeme lasts for about a year and is universally compatible.
Furthermore, PolyHeme, unlike saline, can transport blood and thus has the capacity to minimize multiple organ failure-often a major concern for trauma patients.
The PolyHeme trials were delayed initially at Duke because of a discrepancy between North Carolina and federal laws. Before launching the study, Duke held several meetings in Durham to inform the community about the research.
Those who do not wish to participate can still obtain an "opt-out" bracelet from Duke.
Based on these measures, McKinney said the research is ethical.
"You sometimes need to do an experiment in people in order to figure out how to do things better," he said.
Rosoff said failures to be forthcoming to the public can ultimately bring legitimate research into question.
"A lot of the research enterprise, be it basic science or clinical, is based upon trust and good faith amongst investigators," Rosoff said. "Any assault on that trust and good faith brings into question the veracity of the research enterprise."
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