April 28 (Bloomberg) -- Artificial blood raised death risks by 30 percent and almost tripled the odds of heart attacks in 16 clinical trials analyzed by researchers who say U.S. regulators should have stopped the studies eight years ago.

Five trials involving substitute blood products are ongoing, and a new one is about to begin, the researchers reported. The Food and Drug Administration is holding a workshop in Bethesda, Maryland, tomorrow to discuss safety of the products.

The researchers, in a report in the Journal of the American Medical Association, said the FDA in 2000 received data on individual studies showing increased risks that should have triggered suspension of testing until a large-scale analysis. Now the agency should end all trials and Congress should review rules forcing the FDA to keep information on new products confidential for competitive reasons, the researchers said.

``If you have secret science, things like this can happen,'' said Charles Natanson, a septic shock researcher at the National Institutes of Health, said in a telephone interview. ``Once you've randomized patients, your results can't be a trade secret. It's a measure of protection to the American public.''

The blood substitutes studied in the analysis were made by Baxter International Inc., Biopure Corp., Hemosol BioPharma Inc., Northfield Laboratories Inc., and Sangart Inc.

Biopure rose 2 cents to 53 cents at 1:42 p.m. in Nasdaq Stock Market composite trading. Baxter rose 65 cents to $62.64 in New York Stock Exchange composite trading. Northfield fell 7 cents to 99 cents in Nasdaq composite trading. Sangart and Hemosol are closely held.

Still Not Public

Some finished studies still aren't public. Five trials are ongoing internationally, in places including the U.K., and at least one more is planned, the researchers said.

``One straightforward solution to these problems would be for Congress to reverse the FDA's policy of treating as confidential all corporate materials submitted during the product development process, including the investigational drug application,'' the researchers wrote.

Jay Epstein, director of the office of blood research and review at the FDA, said analyzing several studies together as one, a process called meta-analysis, has its limitations. The agency also has unpublished information not available to the study's authors that shows potential benefits of artificial blood, he said.

Flawed?

``There are vast differences among these products that make any pooling of data flawed,'' said Tiana Gorham, spokeswoman for Biopure, in an e-mailed statement.

Baxter, of Deerfield, Illinois, discontinued work on such products more than five years ago, said Deborah Spak, a company spokeswoman, in a telephone interview. Sangart, of San Diego, had no comment. David Bell, vice president of development at Hemosol, didn't return a call for comment.

``Meta-analysis is not designed to provide answers about specific products or to examine fully the risk/benefit ratio of any particular product,'' said Steven Gould, chief executive officer of Northfield Labs, in an e-mailed statement.

``The most important thing is to recognize there's an important medical need,'' the FDA's Epstein said. ``Both in the past and recently, the FDA has placed studies on clinical hold when there were safety concerns that outweighed clinical benefit.''

Lifesaving Artificial Blood

Developing a blood substitute that requires no refrigeration, has a long shelf-life, and doesn't cause infection could prevent deaths from blood loss, the researchers wrote in their article.

Lawmakers and consumer groups have criticized the FDA's oversight of research after reports of elevated heart risks prompted the withdrawal of Merck & Co.'s painkiller Vioxx in 2004 and stronger warnings on GlaxoSmithKline Plc's diabetes pill Avandia last year. The Government Accountability Office said last month it will investigate whether the agency approves drugs without enough evidence of safety and effectiveness.

The blood-product study comes before tomorrow's FDA workshop on the safety of manufactured hemoglobin-based oxygen carriers. Biopure will make a presentation at the meeting, according to an e-mailed statement. Northfield Labs will also be presenting, according to an e-mailed statement.

Biopure knew there was higher risk of heart attack midway through a clinical trial in orthopedic surgery patients, said William Hoffman, chief of the cardiac surgery intensive care unit at Massachusetts General Hospital in Boston and the former medical director of Biopure.

Decreased Blood Flow

Human tests of all substitute blood products should be suspended, said Hoffman, who wasn't an author of the latest study. They ``have differences, but the differences don't matter with heart attack,'' he said. ``The risk is similar.''

The blood products may cause harm because manufactured hemoglobin isn't part of a red blood cell, and can scavenge nitric oxide, resulting in decreased blood flow and the formation of clots, the authors theorized in the study.

Hoffman said he quit Biopure in 2000 after the company insisted going ahead with clinical trials against his advice.

Gorham, in an e-mailed statement, said Biopure disagrees with Hoffman's account of his departure. She didn't elaborate. Hoffman returned to Biopure, of Cambridge, Massachusetts, as a paid consultant in 2005 to help the company move forward in clinical trials, Gorham said.

`Inexcusable'

Hoffman said he returned to advise the company after it was under new management, and before data from another company's trials also showed a higher risk of heart attack.

None of the trial results were published immediately after the studies were completed and the FDA reviewed each separately, said Sidney Wolfe, a coauthor of the article and the director of the health research group of Public Citizen Inc., a Washington- based advocacy organization.

``When we talk about things that make it more likely people will be harmed or killed, and you keep it a trade secret, it's inexcusable,'' Wolfe said.

To contact the reporter on this story: Elizabeth Lopatto in New York at elopatto@bloomberg.net.

Last Updated: April 28, 2008 14:16 EDT