Study Finds New Blood Substitutes Increase Risk of Death, Heart Attacks; Authors Question FDA’s Approval Process, Records Access

April 28, 2008

Study Finds New Blood Substitutes Increase Risk of Death, Heart Attacks; Authors Question FDA’s Approval Process, Records Access

Findings Are Detailed in the Journal of the American Medical Association

WASHINGTON, D.C. – While the idea of a blood substitute that doesn’t need refrigeration or cross-matching and has a long shelf life would be an exciting scientific advance, a new study being released Monday online by the Journal of the American Medical Association (JAMA) found that these products significantly increase the risk of heart attacks and death.

The authors from the National Institutes of Health and Public Citizen also raise serious questions about the role of the Food and Drug Administration (FDA) in continuing to allow human trials of these products, despite evidence from past clinical trials that found patients given these hemoglobin-based blood substitutes face a 30 percent greater risk of death and a 171 percent increased risk of heart attack than those treated conventionally.

The authors will present their findings April 29-30 at an FDA public workshop on the “Safety of Hemoglobin-based Oxygen Carriers.” The workshop will be held at the Natcher Conference Center, Bldg. 45, National Institutes of Health, 8800 Rockville Pike, Bethesda, Md.

Currently, such blood substitutes are not approved for use in the U.S., although at least one product is approved for use outside the U.S. and new clinical trials are being conducted worldwide.

In the JAMA article analysis, the authors identified 16 different trials of five different blood substitutes. The studies were combined by the authors using a statistical technique called meta-analysis.

Of those trials, 13 were published in medical literature, sometimes years after they were completed, while others were never published at all. In some cases, the only information available came from company news releases.

One serious problem the authors encountered is that the FDA does not make much of the research into these blood substitutes available for review even though companies are required by law to report such data to the agency.

“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 increased risks unnecessarily,” the authors wrote.

Studies available to the FDA, but not always to the scientific community at-large, would have made it clear by 2000 that these hemoglobin-based blood substitutes posed a significant risk to patients. By that point there was already a 27 percent greater risk of death and a 177 percent greater risk of heart attacks based on trials of four products.

“Had the agency placed a moratorium on trials at that point, product-related deaths and [heart attacks] in subsequent trials most likely would have been prevented,” the authors wrote.

The authors recommend that the FDA require new and existing blood substitutes to be tested in animals before any further human trials are allowed. They also called on Congress to make it easier for independent researchers to review information and studies submitted to the FDA during the product development process, either through changing FDA policy or amending the Freedom of Information Act.

The authors of the article, titled “Cell-Free Hemoglobin-Based Blood Substitutes and Risk of Myocardial Infarction and Death,” are Peter Lurie, M.D. and Sidney Wolfe, M.D., from the Health Research Group at Public Citizen, and Charles Natanson, M.D., Steve Kern, B.S., and the late Steven Banks, Ph.D, from the National Institutes of Health.

READ the study.