JAMA: HBBS linked to death, MI risk; FDA called to stop HBBS trials
The use of hemoglobin-based blood substitutes (HBBS) is associated with a significantly increased risk of death and MI, according to a meta-analysis published online April 28 in the Journal of the American Medical Association. The researchers noted that the FDA had ample evidence eight years ago to stop ongoing studies using HBBS, some in cardiac surgery trials, but did not.
HBBSs are infusible oxygen-carrying liquids that have long shelf lives, have no need for refrigeration or cross-matching, and are ideal for treating hemorrhagic shock in remote settings. Some trials of HBBSs during the last decade have reported increased risks without clinical benefit, according to the authors.
As a result of these reports, Charles Natanson, MD, from the critical care medicine department at the National Institutes of Health in Bethesda, Md., and colleagues, undertook the study to assess the safety of HBBSs in surgical, stroke and trauma patients.
The researchers examined 16 trials involving five different products and 3,711 patients in varied patient populations were identified.
Overall, Natanson and colleagues found that there was a statistically significant increase in the risk of death (164 deaths in the HBBS-treated groups and 123 deaths in the control groups) and risk of MI (59 MIs in the HBBS-treated groups and 16 MIs in the control groups) with the HBBSs. Subgroup analysis of the trials indicated the increased risk was not restricted to a particular HBBS or clinical indication, the authors wrote.
The researchers noted that the data reported by sponsors to the FDA are not made public by the agency unless the product is approved or an advisory committee is convened to discuss the product.
The authors said their cumulative mortality analysis “indicates that prompt meta-analyses of the HBBS trials by the FDA most likely would have demonstrated significant risks by 2000. Had the agency placed a moratorium on trials at that point, product-related deaths and MIs in subsequent trials most likely would have been prevented.” However, for the past eight years, such data were not made available to scientists.
The researchers said that there are five ongoing trials of HBBSs, and at least one is being planned.
The authors warned that the “risks of these HBBS products should be weighed against any benefits the products may have demonstrated.”
“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,” Natanson and colleagues concluded.
HBBSs are infusible oxygen-carrying liquids that have long shelf lives, have no need for refrigeration or cross-matching, and are ideal for treating hemorrhagic shock in remote settings. Some trials of HBBSs during the last decade have reported increased risks without clinical benefit, according to the authors.
As a result of these reports, Charles Natanson, MD, from the critical care medicine department at the National Institutes of Health in Bethesda, Md., and colleagues, undertook the study to assess the safety of HBBSs in surgical, stroke and trauma patients.
The researchers examined 16 trials involving five different products and 3,711 patients in varied patient populations were identified.
Overall, Natanson and colleagues found that there was a statistically significant increase in the risk of death (164 deaths in the HBBS-treated groups and 123 deaths in the control groups) and risk of MI (59 MIs in the HBBS-treated groups and 16 MIs in the control groups) with the HBBSs. Subgroup analysis of the trials indicated the increased risk was not restricted to a particular HBBS or clinical indication, the authors wrote.
The researchers noted that the data reported by sponsors to the FDA are not made public by the agency unless the product is approved or an advisory committee is convened to discuss the product.
The authors said their cumulative mortality analysis “indicates that prompt meta-analyses of the HBBS trials by the FDA most likely would have demonstrated significant risks by 2000. Had the agency placed a moratorium on trials at that point, product-related deaths and MIs in subsequent trials most likely would have been prevented.” However, for the past eight years, such data were not made available to scientists.
The researchers said that there are five ongoing trials of HBBSs, and at least one is being planned.
The authors warned that the “risks of these HBBS products should be weighed against any benefits the products may have demonstrated.”
“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,” Natanson and colleagues concluded.