May 05, 2008
The Hazards of Secret Science
The development of a blood substitute -- a liquid that has a long shelf life, does not need refrigeration and does not cause infection -- would provide a potentially lifesaving option for surgical and trauma patients with shock from loss of blood. Such a product would be especially in rural areas and military settings.
Most blood substitutes developed to date have been hemoglobin-based products (hemoglobin is the oxygen-carrying protein in red blood cells). Past studies of these blood substitutes suggested that they may be more dangerous than real blood, although the differences have not always been statistically significant.
Charles Natanson and colleagues at the National Institutes of Health teamed up with health advocates from Public Citizen to conduct a meta-analysis of existing trial data on blood substitutes, which was published on-line in JAMA on April 28. By combining the results of 16 trials, they found a 30 percent increased risk of death and an almost threefold increase in risk of heart attack in patients who received blood substitutes, as compared with patients receiving usual care.
The authors call for existing and future blood substitutes to be tested in animals before further clinical trials in humans are allowed to proceed. They point out that if the FDA had conducted a meta-analysis of blood substitute trials by 2000, the increased risks would have become known, and further harm to patients could have been prevented.
Because much of this data was nonpublic, it was impossible for scientists outside the FDA to fully assess the risks. "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," the authors wrote.
The authors call for Congress to enact three major changes to the availability of information on clinical trials:
* Reverse the FDA's policy of treating as confidential all corporate materials submitted to it during the product development process, including the investigational new drug application.
* Amend Exemption 4 to the Freedom of Information Act to allow the public interest to be considered when the material sought is considered confidential commercial information.
* Require the results of all clinical trials to be publicly reported, including trials of drugs that have not been approved by the FDA.
-- PM
Great run-down, PM -- now. . . .
A question, here: In the studies with which I am familiar, blood substitutes were only tested on/offered to trauma arrivals at emergency-rooms, and only truly-critically-injured patients -- read: each very near death, to begin with -- when, and where NO human blood, blood product, or plasma was available to them, at that moment (in rural hospitals, mostly). . . .
So, should the above -- if true -- matter at all to the report's conclusion that "[with] meta-analysis of blood substitute trials by 2000, the increased risks would have become known, and further harm to patients could have been prevented. . . ."?
In the trials with which I am familiar, all of the patients would likely have died, had they not received the bloog substitute. NOW, it is absolutely TRUE that those same patients died at increased rates, than similarly situated patients given *real blood* products.
That is true.
And that, alone, is likely a good reason to be very careful with all blood substitute products -- I think it plain that we do not *really* understand fully how they work (or don't).
But I am not sure that the data, as I understand what I've seen with my own eyes, supports the inference that "more harm could have been prevented".
These folks literally had no other viable option -- bleed to death, or give a try to an experimental blood substitute. For what it is worth, just MHO.
Great post here, on the broader outlines of this story!
-- condor
Posted by: condor at May 5, 2008 01:30 PMCondor,
The studies included in the Natanson meta-analysis included some studies of trauma patients, but also patients undergoing various types of surgery (Table 2). The control groups in the studies received alternatives to blood substitutes, including allogeneic blood, LR solution, normal saline, packed red blood cells, 6% Hetastarch, 10% Pentastarch, standard solutions, and ringer acetate (Table 2). The increased risk of heart attack and death were as compared to those alternatives. The estimated number needed to harm was 62 patients treated with a blood substitute for each treatment-related death and 50 patients treated for each treatment-related heart attack. None of the studies compared the use of blood substitutes to no fluid at all, and a clinical trial designed in that way would be unethical, IMO.
However, I would be interested in reading the studies you are referring to. Have they been published? One can of course imagine emergency situations where no alternative to a blood substitute was available, but that would not be part of a clinical trial. It is hard for me to understand how or why that would happen in real life, at least in this country, given that no hemoglobin-based blood substitute has been approved by the FDA.
PM
Posted by: PM at May 5, 2008 08:59 PMPM -- I have written you, privately here, about this.
I think we have misunderstood one another, and I am almost certain that this state of affairs is entirely my fault.
I completely agree with the larger point -- more study is needed -- and these experimental products should not be used in humans, unless there is literally no other option.
I simply meant to wonder about the conclusion that "additional harm could have been avoided". It seems enough to say that "oxygen transport in live human beings is far more complicated than anyone can possibly imagine. . . ." -- and so, additional study is warranted. Scientific study, where researchers share their learnings with one-another.
No, I am no fan of the kind of "secret science" you describe.
I hope this helps.
Posted by: condor at May 6, 2008 11:18 AM