FDA Guidance threatens health of volunteers
In April 2005, the FDA released its Draft Guidance for Industry on Exploratory Investigational New Drug Studies. This document states a new class of early clinical trials that would be conducted before full-on drug development. The new class of trial is called "Phase Zero". The logic behind this class is that it will be cost-efficient testing of potential drug compounds on human subjects for pharmaceutical companies and could reduce the number of human subjects required in later trial stages. Phase zero studies do not examine safety and efficacy of a compound. They have been developed to strictly gather data on compound targetting, action and metabolism in the human body.
Straight out of the gate - the FDA is facing a big problem.
In March 2006, a monoclonal antibody (TGN1412) developed by a German company, TeGenero, was part of one of these early trials conducted by an American company, Parexel, at Northwick Park Hospital, London. The result, well publicized now, is that 6 of 8 healthy men involved in a double blind trial of this antibody suffered terrible adverse reactions. Within minutes of injection, the men were writhing and screaming in pain (Bhattacharya and Coghlan, New Scientist. March 23, 2006). All six experienced multiple organ failure and have since developed severe head and neck swelling that has given them an "Elephant Man" appearance - an effect that may be related to the enaction of ordinarily quiesscent regulatory T cells.
It is now apparent that TeGenero was aware that this adverse affect was a possibility. Not only had an article been published in Clinical Immunology ahead of the trial, suggesting human cells may react poorly to the drug - but TeGenero's non-human primate studies indicated that TGN1412 caused severe neck swelling upon injection (Guardian, March 20, 2006). Reportedly, TeGenero and Parexel broke with informed consent. Multiple participants have reported that they were told by company representatives that animal trials had not produced adverse reactions.
The TGN1412 trial is the direct result of a market driven FDA and the illicit conduct of a pharmaceutical company.
The U.S. Food and Drug Adminstration is a market driven department, a point emphasized by the Prescription Drug User Fee Act (PDUFA) of 1992. With that legislation, the FDA instituted user fees which were put directly towards staff hires and various other resources that would speed drug approvals. They also placed themselves at the behest of the companies that pay the fees to have their drugs reviewed. An awkward situation that has led to faster approvals, but is coincident with 10% increase in drug withdrawals. The release of Draft Guidance for Industry on Exploratory Investigational New Drug Studies is a reflection of the FDA's market driven mandate and an exploitation of the potential conflict of interest that PDUFA created.
The TGN1412 trial is being characterized by the pharmaceutical lobby as bathwater (Wadman. March 22, 2006. Nature). This is, however, a trial that would not have occurred without the intitution of phase zero trials. The conduct of the parties involved in the TGN1412 trial greatly violated the rights of clinical trial subjects. This should not be reduced to an unfortunate incident that was could not have been foreseen. This should be all the reason to demand that FDA repeal this guidance in the interests of providing stronger regulatory language that better protects the rights of trial subjects.
Write to your senator. Ask to have this guidance reviewed, revised, repealed. Ask for revisions that provide greater protection to human test subjects in phase zero clinical trials.
Straight out of the gate - the FDA is facing a big problem.
In March 2006, a monoclonal antibody (TGN1412) developed by a German company, TeGenero, was part of one of these early trials conducted by an American company, Parexel, at Northwick Park Hospital, London. The result, well publicized now, is that 6 of 8 healthy men involved in a double blind trial of this antibody suffered terrible adverse reactions. Within minutes of injection, the men were writhing and screaming in pain (Bhattacharya and Coghlan, New Scientist. March 23, 2006). All six experienced multiple organ failure and have since developed severe head and neck swelling that has given them an "Elephant Man" appearance - an effect that may be related to the enaction of ordinarily quiesscent regulatory T cells.
It is now apparent that TeGenero was aware that this adverse affect was a possibility. Not only had an article been published in Clinical Immunology ahead of the trial, suggesting human cells may react poorly to the drug - but TeGenero's non-human primate studies indicated that TGN1412 caused severe neck swelling upon injection (Guardian, March 20, 2006). Reportedly, TeGenero and Parexel broke with informed consent. Multiple participants have reported that they were told by company representatives that animal trials had not produced adverse reactions.
The TGN1412 trial is the direct result of a market driven FDA and the illicit conduct of a pharmaceutical company.
The U.S. Food and Drug Adminstration is a market driven department, a point emphasized by the Prescription Drug User Fee Act (PDUFA) of 1992. With that legislation, the FDA instituted user fees which were put directly towards staff hires and various other resources that would speed drug approvals. They also placed themselves at the behest of the companies that pay the fees to have their drugs reviewed. An awkward situation that has led to faster approvals, but is coincident with 10% increase in drug withdrawals. The release of Draft Guidance for Industry on Exploratory Investigational New Drug Studies is a reflection of the FDA's market driven mandate and an exploitation of the potential conflict of interest that PDUFA created.
The TGN1412 trial is being characterized by the pharmaceutical lobby as bathwater (Wadman. March 22, 2006. Nature). This is, however, a trial that would not have occurred without the intitution of phase zero trials. The conduct of the parties involved in the TGN1412 trial greatly violated the rights of clinical trial subjects. This should not be reduced to an unfortunate incident that was could not have been foreseen. This should be all the reason to demand that FDA repeal this guidance in the interests of providing stronger regulatory language that better protects the rights of trial subjects.
Write to your senator. Ask to have this guidance reviewed, revised, repealed. Ask for revisions that provide greater protection to human test subjects in phase zero clinical trials.
posted by Anthropolochic at 2:29 PM
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