'Secret science' puts lives at risk

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 yesterday.

Companies were not required to publish the findings of their trials, leaving research ethics boards that were assessing applications for additional trials - and people being asked to participate in them - in the dark about the fact the products elevated the risks of death and of having a heart attack.

A review of all the available literature on the trials - published online yesterday by the Journal of the American Medical Association - shows that people who received hemoglobin-based blood substitutes in clinical trials were 30 per cent more likely to die and faced a nearly threefold increased risk of heart attack.

The researchers, from the U.S. National Institutes of Health and the Washington-based consumer advocacy group Public Citizen, blame the U.S. Food and Drug Administration for not requiring the companies to publish their negative findings, and for allowing additional trials to be conducted after the risk should have been apparent.

In this 1997 photo, a technician checks a bag of Hemolink. Studies on the product were aborted after risks were identified.

"At some point, somebody should have realized that we've tried it in trauma patients, we've tried it in surgical patients, we've tried it in stroke patients, we've tried many different formulations and we keep finding the same result," said Charles Natanson, lead author of the meta-analysis, a technique in which data from a number of trials are pooled.

"At some point, and we sort of argue in the paper that may have been the year 2000 ... it was time to put a halt" to additional trials, Dr. Natanson said.

Canadian patients were also exposed to the risks in clinical trials of a product called Hemolink, which was made by a now-defunct company called Hemosol Inc. Data from at least one of Hemosol's trials have never been made public.

Dr. Natanson, who is an advocate for patient safety in clinical trials, was paid $10,000 to review the data when Hemosol was trying to decide whether to push on with the research. Having signed a confidentiality agreement, he cannot comment on what he saw or what he recommended. He merely noted: "They went into receivership with PricewaterhouseCoopers."

An editorial accompanying the review points out further studies of these products are under way or planned in a number of countries around the globe.

The authors, from the Ottawa Health Research Institute, argue future work on blood substitute products should not be allowed in humans until it is clear from animal studies that the products are likely to be safer. (Research in animals had suggested the products studied to date were associated with kidney problems and the blood vessel constriction problem that contributed to the heart attacks and deaths.)

Lead author Dean Fergusson, a clinical trials expert, said the withholding of the negative results meant ethics boards and trial participants could not properly assess the risk-benefit ratio of this work.

"How can patients or their decision makers make truly involved consent without all this information? I think that's a huge message," he said.

The lack of disclosure suggests company stock prices were placed at a higher priority than the health of people being asked to go into clinical trials, experts suggest.

"They didn't think beyond the four walls of their corporation, I think, quite frankly," Dr. Fergusson said of the companies.

The review, which pooled findings from 16 clinical trials of five different blood substitutes, was published electronically by the journal in advance of a two-day FDA hearing on blood substitutes to be held in Bethesda, Md., beginning today.

Jay Epstein, director of the FDA's office of blood research and review, said the agency's own analysis of the accumulating experience with the blood substitutes being tested led it to conclude there were safety risks associated with the entire class of drugs.

"It's because of FDA's safety concerns that there currently are no ongoing studies of HBOCs [hemoglobin-based oxygen carriers] in the United States trials and no approved HBOC products," he said in a briefing for journalists.

But he challenged Dr. Natanson's contention that the risk should have been apparent by 2000.

"Basically, even though aware of certain safety signals, our reviewers determined that there were enough differences between products and their intended uses to support a careful weighing of individual clinical trial proposals, only some of which were allowed to proceed," Dr. Epstein said.

Dr. Epstein said the FDA's hands are tied by legislation when it comes to the public release of information the agency receives from private firms.

"There are very distinct limitations to the FDA's ability to share information which is identified as confidential or trade secret," he said.

Health Canada was not available for comment.