Study critical of FDA for allowing risky tests of blood substitutes

CHICAGO -- Experimental blood substitutes raised the risk of heart attack and death, yet U.S. regulators allowed human testing to continue despite warning signs, says a scathing new report. The U.S. Food and Drug Administration fell short, the report contends, even as red flags popped up during studies by five biotech companies. Rules barred the agency from releasing company trade secrets, and that kept some information hidden and may have led to unnecessary heart attacks and deaths, wrote the authors, who are government scientists and consumer advocates.

"There shouldn't be secret science," said the lead author of the report, Dr. Charles Natanson, of the National Institutes of Health Clinical Center. Safety data need "to be made public expeditiously so science can build on the mistakes" of previous research, he said.

The report, being published online Monday by the Journal of the American Medical Association, is the latest analysis of the risks of blood substitutes, which have been in testing for more than a decade.

It was written by scientists with the NIH Clinical Center and advocates with the watchdog group Public Citizen. The clinical center in Bethesda, Md., seeks to ensure the safe and ethical conduct of clinical research.

A safe replacement for blood would be a breakthrough for medicine and a big money-maker for companies that produce it. It could save lives on battlefields. Unlike ordinary blood, it could, theoretically, be stored for years without refrigeration. It also would work with any blood type and would not carry infections like hepatitis or the AIDS virus.

By the end of 2000, a dozen studies of blood substitutes had been completed. By then, FDA officials would have known enough about cumulative risks to put a halt on further experiments, the JAMA report contends.

But the FDA looked at each product and each use separately -- in surgery, in trauma, in stroke patients -- rather than pooling the results to get a fuller picture of the risk, Natanson said.

In 2006, after a lawsuit by Public Citizen protesting a closed-door hearing, the FDA halted a test by the Navy, which planned to use a blood substitute on civilian trauma victims. Such tests raised ethical concerns about giving trauma patients an experimental product without their consent.

Dr. Jay Epstein, director of FDA's office of blood research and review, defended the agency's decisions about human testing of the products despite risks. The agency has found enough differences among the individual products and their intended uses to allow some studies to proceed, Epstein said Friday in a conference call with reporters.

Currently, there are no approved blood substitutes or clinical studies of them in the United States. However, American companies are testing them on people in South Africa and seven European countries. South Africa has approved one of the products, Hemopure, made by Biopure Corp., based in Cambridge, Mass., for use in anemic surgery patients.

"It is highly unlikely, I'd say impossible, that any of these countries are aware of the risk," said study co-author Dr. Sidney Wolfe of Public Citizen.

In the new report, researchers analyzed 16 randomized controlled studies of five different blood substitutes. More than 3,700 patients were involved. The studies included elective surgery, trauma and stroke patients.

(April 28, 2008)