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Drug and Testing Companies Do Legal Dance To Avoid Liability
Posted by Pile
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...the patients had volunteered for the trial after being lured with the offer of £2,000 each to test the drug made by TeGenero, a newly formed German drug firm. Parexel, the American firm that administered the tests, told them there would be no serious side effects.
They were very wrong, and now the companies involved are claiming they're not responsible for destroying the immune system of the test subjects, and are refusing to help treat their new condition. What we learn here is that there are disposable human test subjects being used by drug companies. |
Three months after a trial of a novel drug in a London hospital nearly killed six young and healthy research subjects, that medical catastrophe has provoked reports and recommendations that will change the way drugs are tested for the first time in humans.
But Navneet Modi, 25, and five fellow test subjects suffer a slew of serious medical problems - and they have been unable to get any of the pharmaceutical companies involved in the trial to provide medical expenses or compensation, other than a small one-time payment some months back.
New lab tests and medical reports, provided to the International Herald Tribune, document that the six men are suffering from severely damaged immune systems and that they are likely to suffer immune problems for life. They all have lesser symptoms as well: Modi suffers from poor memory and blackouts that have made it impossible to work, as well as fatigue and diarrhea, he said.
"Everyone's turned their back and I'm angry, really angry," Modi said. The British National Health Service had so far covered his medical costs, he said, but the company that performed the trial would not reimburse the cost of travel to the hospital.
In recent weeks, experts said, new medical tests and investigations into the incident have highlighted loopholes in a drug testing system that in some instances is better designed to bring drugs to market than to protect humans, particularly when it comes to some of the newest medicines.
Regulators in the United States and Europe are taking a go-slow approach as they develop new procedures.
The trial at Northwick Park Hospital "highlighted an urgent need to review the safety of first-in-man trials of novel agents," concluded an interim expert panel report of the British Health Department issued last week. The agency also called for reviews "to examine how risks in medicine development are currently assessed and minimized" by drug makers.
Indeed, although the innovative drug being tested, TGN1412, was a potent immune system stimulant that overrode the body's normal regulatory mechanisms, it was tested according to much the same standards that govern far more ordinary pharmaceuticals.
British regulators approved the TGN1412 trial in just 17 days and the testing company did not have an adequate response plan for adverse reactions, regulators have said.
Since the Northwick Park trial, groups as diverse as the British Department of Health, the U.S. Food and Drug Administration and the Association of the British Pharmaceutical Industry have been reviewing the data and issuing new recommendations for the testing of novel medicines, particularly those aimed at essential biological pathways.
"The lesson learned is that now when we see a molecule like this - one with a novel mechanism - we need a very different approach," said John Jenkins of the Food and Drug Administration. "Now that we've seen this episode, we will be very cautious going forward."
But those epiphanies have done little to help Modi, physically or financially, who spends much of his week in doctors' appointments. TeGenero, the small German biotechnology firm that developed TGN1412 - which it touted as a revolutionary new drug against cancer and arthritis - filed for bankruptcy several weeks ago.
Its insurance coverage was not adequate to cover a calamitous outcome, said Martyn Day of Leigh Day & Company in London, the lawyer for four of the six ill men.
The American-based testing company that conducted the trial, Parexel International, of Waltham, Massachusetts, has said repeatedly that it carried out the trial according to "appropriate policies and procedures."
Parexel, a world leader in contract drug testing, with centers in the United States, Europe and Africa, said it could not provide further information.
The British drug regulators who reviewed the trial performed those duties according to accepted standards and to the best of their ability and so have no liability, lawyers said.
All parties did their jobs according to formal regulatory and legal requirements, narrowly defined.
But, in retrospect, almost all scientists agree that those requirements were inadequate for TGN1412 and that common sense would dictate different testing practices.
Day, the lawyer for four of the men, said that under British law, TeGenero was primarily responsible.
The company, which filed for insolvency on July 4, has maintained that the reactions were unforeseeable. But, Day said, there was plenty of blame to go around.
Day said he would argue that Parexel, which contracts with drug makers to test new medicines, should have made sure that its client had adequate insurance. He also questioned the design and conduct of what it should have seen as a delicate trial, he said.
They gave the six research subjects infusions of new and unknown drugs only 10 minutes apart, so that there was no time to screen for serious side effects.
Virtually all reviews of the trial, including one by ABP1, the British drug industry group, have concluded that such new drugs should be given to one patient at a time, with long intervals in between, so that monitors can screen for serious side effects.
In addition, Day said, the men should have immediately been given high doses of steroids for the disastrous reaction that TGN1412 precipitated. He said that such a reaction was noted as a possibility in the study's official protocol.
As for the British regulators, Day said he was shocked to discover that they had approved the first trial of the new immune regulator after just 17 days, and did not call in specialists to guide them, saying: "It would take three to four months, minimum, to get a paper about this drug published in a peer-reviewed journal."
It took this incident for such issues to come to the fore.
Within hours of being injected with TGN1412, all six men were experiencing a syndrome called cytokine storm, where an outpouring of immune molecules attack organs of the body.
All required weeks of intensive care, suffering failure of kidneys, lungs and circulatory system.
Lab values from their blood have been made public and immunologists have been thunderstruck by the fury of the reaction.
"These numbers are over the top, far greater than those of normal immune responses," said Marc Gavin, who studies immune regulation at the University of Washington in Seattle. "The drug went right to the very heart of immune activation."
In tests on four of the subjects, all are suffering from previously unheard-of severe depletion of a type of immune cell called regulatory T-cells, according to reports from Professor Richard Powell, a consultant immunologist, provided by Day.
The cells serve to modulate the body's reaction to foreign molecules, like those that produce allergies or even infections, and if they are lacking or dysfunctional, it can create serious "over the top" immune reactions against minor allergens or even the body itself.
At the milder end of the spectrum are diseases like lupus and colitis. Powell said that Modi was "highly likely" to develop one of these disorders, at least, based on symptoms and lab tests.
The scion of a wealthy family from Calcutta, Modi had just finished business school in London when he signed up with Parexel to earn a bit of extra money.
He planned to return to India to join his family appliance business or to start his own company this summer.
At 8:30 a.m. on March 13, he was the third human ever to be infused with TGN1412 in a Parexel Research Unit, located at London's Northwick Park Hospital. Within 90 minutes the pain in his head and back was unbearable, Modi said.
Soon, all of the men who had received the drug were moaning, screaming and begging for pain pills. The one doctor and half-dozen nurses from Parexel running the trial urged everyone to remain calm and administered paracetamol.
Later, after Modi had lapsed into semi-consciousness, the team administered steroids, Day said, but at a dose too low.
In any event, the six were not moved from the Parexel Research wing to Northwick Park's intensive care unit for up to 16 hours, despite severe symptoms.
In testimony before the British expert review panel, the intensive care doctors said that while they were aware that the patients seemed to be having an inflammatory reaction, the Parexel team did not inform them of the possibility of a cytokine "storm" until hours after the patients reached the intensive care unit.
It was only then that doctors in the intensive care unit administered high doses of steroids as well as medicines to blunt the subjects' furious immune response. Tests done at the time later revealed measures of immune molecules more than 1,000 times normal levels.
For the past three months, regulators all over the world have been trying to piece together what went wrong, since the drug has not provoked such a response during animal testing.
In retrospect some have concluded that TeGenero's scientists should not have done testing on monkeys, since they may not experience this syndrome and since their own lab tests hinted that it could be a problem, Jenkins of the FDA said.
Others have said that a trial of a related but less potent drug in the United States had provoked an outpouring of immune molecules, hinting at a potential problem.
The United States and Britain have agreements to share such information, but no request was made by the British, FDA officials said.
The FDA is trying to develop better biomarkers for human toxicity that can be used to screen new products for safety before they are introduced into humans.
But Day and his clients want someone to take responsibility for the disaster here and now. TeGenero's insurance policy totaled £2 million, or $3.7 million, not enough to cover the lifetime of care and uncertainty for even one of the patients, Day said. Worse still, it contains a clause that no payment will occur if the subjects sue.
Each subject received £10,000 from TeGenero before the company went bankrupt, Modi said.
Parexel continues to run research units at Northwick Park and has taken all mentions of the trial off its Web site. The night Modi was transferred to the intensive care unit, Parexel, "turned their back and drew up the drawbridge," Modi said. |
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| Posted by Subnormal on 2006-08-03 02:32:58 | looks like bush just found his new bio-weapon
only half kidding. |
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