FDA Blasted Over Blood Substitute DeathsApr 29, 2008 | Parker Waichman LLP
Blood substitute clinical trials and the blood substitutes themselves are under fire. Apparently, some of the experimental blood substitutes being trested can significantly raise the risk of heart attack and sudden death according to regulators who also said that their use in new experiments should be stopped until safety issues have been cleared up. In an unprecedented pairing, health advocates and federal government researchers teamed up in a joint study. The study of blood substitutes revealed that the Food and Drug Administration's (FDA) confidential oversight of corporate research was putting patients at risk. The groups called for both an end to trials of the blood replacement products and an overhaul of the FDA's requirements to keep corporate secrets.
The study reviewed various trials of five blood substitutes and revealed a 30 percent increased risk of death and a 2.7 times higher risk of heart attack, according to researchers report in the Journal of the American Medical Association. All of the blood substitutes use hemoglobin. Hemoglobin is the molecule that transports oxygen in red blood cells.
The researchers also plan to present their findings at an FDA public workshop on the safety of the products this week. "The case study detailed here underscores both the scientific inefficiency and the real risks to patients of the current failure to report data promptly," wrote Dr. Charles Natanson of the National Institutes of Health and colleagues there and at Public Citizen. "When 'secret science' is allowed, scientists are unable to build on the successes or failures of other researchers testing similar products, and patients can be repeatedly exposed to risks unnecessarily," he added also saying, "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 new drug application."
The FDA stood by it oversight of the experimental blood substitute trials and confirmed it was aware of the safety issues. "There is a major unmet medical need," said Dr. Jay Epstein, director of FDA's office of blood research and review. "Independent of this recent meta-analysis, FDA had already, based on our own analysis, identified concerns about an increasing body of data that has emerged about the safety of (hemoglobin-based blood substitutes)," Epstein said.
For their study, Natanson and colleagues reviewed data from 16 trials involving five products and 3,711 patients. The blood substitutes included Baxter's HemAssist, Biopure's Hemopure, Hemosol BioPharma Inc's Hemolink, Northfield Laboratories' PolyHeme, and Sangart Inc.'s Hemospan. The researchers said if the FDA had conducted similar analysis, it would have been obvious by the year 2000 that these products raised the risk of death adding, "Had the agency placed a moratorium on trials at that point, product-related deaths and MIs (heart attacks) in subsequent trials most likely would have been prevented.”
Epstein disagreed saying that the FDA was aware of "certain signals" and only permitted a select few trials to continue. Epstein did agree with the Natanson team that the products may affect a molecule called nitric oxide and that the products may cause inflammation, with both issues affecting blood pressure and blood flow.