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The Future of Clinical Trials - Meta-Analysis shows ALL Blood Substitutes Increase Death

In December, 2006, we stated: American medicine is fast descending into lethal medicine thanks to FDA officials who lend the government seal of approval to drugs and experiments that kill. [Link]

A meta-analysis of the data from all clinical trials testing artificial blood products has just been published in the Journal of the American Medical Association. It confirms and quantifies the unsustainable lethal risks of ALL artificial blood products tested in humans. It is freely accessible. [Link] [1]

An accompanying editorial by Dr. Charles Natanson and colleagues from the Critical Care Department of the National Institute of Health and Public Citizen identified 16 clinical trials in which 5 different Hemoglobin-based blood substitutes (HBBS) were tested in 3,711 humans (between 1980-through March 2008). [2]

They are: HemAssist ( Baxter); Hemopure (Biopure); PolyHeme (Northfield Labs); Hemolink (Hemosol BioPharma); Hemospan (Sangart)

The data analysis shows that patients exposed to these blood substitutes (HBBS) have a statistically significant increased risk of death: 164 deaths in patients exposed to HBBS compared to 123 deaths in controls who received saline. The relative risk of death is 1.30. While the relative risk for myocardial infarction was documented at 2.70. There were 59 MI in patients exposed to HBBS compared to 16 in the control group.

One of the most disturbing facts uncovered by this meta-analysis: the risk of mortality associated with blood substitutes was apparent in 1998 from the first HBBS product-HemAssist (manufactured by Baxter): "At least 7 of 9 HemAssist trials were completed in 1998," the authors note. Because of a publication time lag, they were published between 1999-2003.

Drs. Natanson et al report that data on 75% of Hemopure trials, all of which were completed by 2000, have not been published. Their existence was brought to light by a lawsuit filed by Public Citizen in 2006, forcing the FDA to disclose the data to its Advisory Committee in Dec. 2006.

The data from the first trial of Northfield's PolyHeme, were only made public when a critical article in the Wall Street Journal led the company to disclose the data 6 years after the trial was completed. Two additional PolyHeme trials have remained unpublished-both were terminated early for safety reasons.

Inexplicably, the FDA is very much in complicity - having helped manufacturers conceal the findings for years from the medical community and the public-while continuing to approve one after another HBBS trial with similar dire results.

The authors underscore the need "to make known the results of all trials of experimental agents conducted in human beings-from phase 1 to phase 4-should be fully and expeditiously disclosed to the scientific and medical communities. The case study detailed here underscores both the scientific inefficiency and the real risks to patients of the current failure to report data promptly. 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."

An accompanying editorial succinctly defines the circumstances necessary for such trials to be morally permissible, noting that "an adequate and safe blood supply in North America and Europe is available:" ".the pursuit of an artificial blood substitute remains noble if 3 conditions are met: it is safe, effective, and universally available." [2] But "given the observed findings, it is important to consider how the trials were planned and conducted in the face of known and accumulating evidence of harm."

AHRP agrees that ALL the stakeholders involved in these experiments-the investigators, corporate sponsors, FDA officials, and the research ethics boards-be they academic IRBs or CROs-all share responsibility in having been complicit in lending their approval for experiments that violated fundamental medical research standards-both ethical and scientific.

The FDA bears the greatest responsibility for helping conceal the unpublished data, and approving non-consensual testing of PolyHeme in 2004 on unconscious trauma patients. FDA's "waiver of informed consent" violated its own standards. FDA's rule for waived consent is applicable ONLY if there are NO ALTERNATIVES. [Link]

Until this meta-analysis, we had taken the position that artificial blood products might be tested in consenting patients undergoing elective surgery.

But Dr. Dean Fergusson and Dr. Lauralyn McIntyre argue in the editorial that such experimentation is unethical even in such patients because of the overwhelming risks:

"Given the safety of the blood supply, availability of blood products, and technologies to minimize transfusion, it does not seem prudent to study use of HBOCs in elective surgical populations. Finally, although it is difficult to argue that transfusion avoidance supersedes mortality and myocardial infarction as an end point, the onus is on investigators and sponsors to demonstrate that HBOCs are at least as effective in reducing mortality or serious morbidity as the current standards of care."

Blood is the universally acknowledged safe and effective standard of treatment available in urban centers. Yet, the Detroit Free Press reported that African Americans in urban centers were disproportionately subjected to the PolyHeme NON_CONSENSUAL human experiment. In one Illinois town where the product was tested, 83% of the population is black. "If you look at the absolute number of deaths, it kills more patients than saline does." [Link]

  1. Charles Natanson; Steven J. Kern; Peter Lurie; Steven M. Banks; Sidney M. Wolfe Cell-Free Hemoglobin-Based Blood Substitutes and Risk of Myocardial Infarction and Death: A Meta-analysis JAMA, Apr 2008; doi:10.1001/jama.299.19. [Link]
  2. Dean A. Fergusson; Lauralyn McIntyre The Future of Clinical Trials Evaluating Blood Substitutes. Editorial. JAMA, Apr 2008; doi:10.1001/jama.299.19 [Link]