TORONTO - U.S. and Canadian regulatory rules allowed companies to conduct "secret science" that jeopardized the lives and health of hundreds of people who took part in clinical trials for a human blood substitute, even though earlier tests had shown the existing products were dangerous, researchers reported Monday.
A review of data from 16 clinical trials showed people who got blood substitutes were 30 per cent more likely to die than those who did not. And the risk of heart attack in patients who received the products was nearly three times higher, according to the study.
The authors and others suggested rules should be changed to require companies to publish study data promptly, especially negative findings that might red flag future such studies by other groups. And if they won't do so, critics say, regulatory agencies like the U.S. Food and Drug Administration or Health Canada should.
"If the research isn't published or otherwise made public, someone knows that the proposed therapy may be harmful, but that somebody won't tell anybody else," said Dr. Joel Lexchin, a York University researcher who closely monitors regulation of the pharmaceutical industry.
"So you have research ethics boards approving studies where the therapy may be dangerous. You have patients enrolling. You have the doctors who are running the trials undertaking them. . . . You've got all these people participating in something which is inherently unethical."
Health Canada was not immediately available for comment. But an FDA official noted the agency's hands are tied by legislation.
"There are very distinct limitations to the FDA's ability to share information which is identified as confidential or trade secret," Dr. Jay Epstein, director of the office of blood research and review, said in a briefing for journalists.
"And that sort of information would not be made public under current laws and regulations."
The study was published Monday by the Journal of the American Medical Association in advance of a two-day FDA hearing on blood substitutes that will be held in Bethesda, Md., beginning Tuesday.
A safe substitute for human blood would be enormously useful, especially in theatres of war and in remote settings.
Researchers in the U.S. military and a number of biotech companies have been working for years to devise such products, aiming for something that would have a long shelf-life, wouldn't require refrigeration, would eliminate the risk of transmission of HIV or other blood-borne infections and could be given to anyone, regardless of their blood type.
But the products devised so far - called hemoglobin-based oxygen carriers or HBOCs - have been a disappointment. Despite numerous trials in a variety of different patient populations, they have failed to show benefit and, this new study reveals, have shown significant risk. Only one country, South Africa, has approved a blood substitute product.
The researchers, from the U.S. National Institutes of Health and the Washington-based consumer advocacy group Public Citizen, pooled data from 13 published studies, and three more for which results were either disclosed in a press release or in an FDA review. They made several attempts to get additional data from companies that had conducted studies but the requests were either ignored or rebuffed.
