Study Reveals Doubt on Drug for Cholesterol
A clinical trial of a widely used cholesterol drug has raised questions both about the medicine’s effectiveness and about the behavior of the pharmaceutical companies that conducted the study, cardiologists said Monday.
Merck and Schering-Plough, which make the drug, Zetia, and a pill that contains it, Vytorin, said Monday morning that Zetia had failed to benefit patients in a two-year trial that ended in April 2006.
Merck and Schering repeatedly missed their own deadlines for reporting the results, leading cardiologists around the world to wonder what the study would show. At the same time, millions of patients have continued taking Zetia and Vytorin.
The drug companies blamed the complexity of the data for the delay. Now, barely a month after news articles noted the delay and Congress pressured the companies to disclose the study’s findings, the results are out.
In a press release, Merck and Schering said that not only did Zetia fail to slow the accumulation of fatty plaque in the arteries, it actually seemed to contribute to plaque formation — although by such a small amount that the finding could have been a result of chance.
Dr. Steven E. Nissen, the chairman of cardiology at the Cleveland Clinic, said the results were “shocking.”
Both companies’ shares fell Monday. Sales of the two drugs were $5 billion in 2007, and they are important contributors to Merck’s and Schering’s profits.
The House Energy and Commerce Committee, which is investigating the delay, said in a statement Monday that the negative results added to suspicions that the companies had deliberately sat on their findings from the study, which was known as Enhance. source
Financial Ties Are Cited as Issue in Spine Study
In a study of nearly 240 patients with lower back pain, the doctors said that the Prodisc, an artificial spinal disk, had worked much better than conventional surgery in which patients’ vertebrae were fused.
“As a surgeon, it is gratifying to see patients recover function more quickly than after fusion and return to their normal activities more easily,” Dr. Jack E. Zigler, a well-known spine specialist and one of the study’s lead researchers, said in a 2006 news release announcing the latest results of the Prodisc clinical trial.
As it turns out, Dr. Zigler had more than a medical interest in the outcome. So did doctors at about half of the 17 research centers involved in the study. They stood to profit financially if the Prodisc succeeded, according to confidential information from a patient’s lawsuit settled last year.
The companies behind the disks and the surgeons who were willing to comment say the researchers’ financial interests had no impact on findings of the research, which they say have been published in various peer-reviewed medical journals. The Prodisc, used on thousands of patients, has been shown to benefit many people with back pain, they say. It is unclear, however, whether the disk’s maker fulfilled its legal obligation to inform the Food and Drug Administration of the researchers’ financial interests before it used the study’s results to approve Prodisc in August 2006.
Synthes, the current manufacturer, said it would not comment on whether the F.D.A. had been fully informed of the researchers’ interests. The F.D.A said it was investigating the matter.
In the study results submitted to the F.D.A., moreover, an unusually large number of patients were not included, and some of those patients have said they fared poorly. As a result, some patients and doctors critical of the research say the study may have cast the Prodisc in an overly flattering light.
The way the Prodisc was tested and approved provides a stark example of conflicts of interest among clinical researchers — conflicts that are seldom evident to doctors and patients trying to weigh the value of a new device or drug. Instead of serving as objective gatekeepers who can screen out potentially harmful or ineffective new devices or drugs, some medical experts say, clinical researchers with conflicts may have incentives to overstate the value of a new product for patients.
For better or worse, doctors in this country frequently have financial ties to the companies whose devices or drugs they recommend to patients. But in the case of the Prodisc clinical trial, as with any clinical research, the doctors were supposed to be acting not as advocates for the product but as objective scientists studying whether the disk was safe and effective enough to be widely sold and used in the United States.
One Prodisc study patient who says the surgery left her worse off, Patricia Kennedy, asserts her surgeon “seemed more concerned with the prospects for the Prodisc than for her medical care,” according to the lawsuit settled on undisclosed terms last year. The surgeon, Dr. Richard A. Balderston, who practices in Philadelphia, was one of the researchers with a financial interest in the disk. He referred questions to his lawyer, J. Scott Kramer, who declined to comment. Ms. Kennedy and her lawyer also declined to comment.
Most of the 11 other Prodisc investor-surgeons who were asked to comment also declined. But Dr. Kevin Foley, a Memphis surgeon involved in the study, says he put $20,000 behind the Prodisc because he considered it a promising technology. He said one patient, a schoolteacher, had trouble standing before her Prodisc but was able to go hiking afterward.
But Dr. Foley said some patients do not do as well after surgery and he favored spinal fusion for most.
The F.D.A.’s rules allow clinical investigators to have financial ties with the maker of the device or drug they are studying — on the condition that such relationships are fully disclosed. Lawyers who have worked with the F.D.A. say that when it becomes aware of potential conflict, it tends to subject research to a higher level of scrutiny.
The F.D.A. now says it is checking to see whether there was adequate financial disclosure information about the Prodisc researchers during the clinical trial and at the time that the subsequent application for approval was submitted.
My comment: What's interesting is that all these articles are published in about a month. I keep on hearing about problems with FDA, but somehow, I like to explain them with popular hatred to FDA in the alternative circles. But here we can see very main-stream disturbing information about the lack of control over the researches on medicines and medical appliances , as well as lack of control over the origin of medicines ( the case below). As I'm not american, I won't comment on FDA, I just hope that the americans among you, will ask themselves the right questions. The moral? Prevention above all. If you get to the medical system, your chances are very random.
Tainted Drugs Tied to Maker of Abortion PillBEIJING — A huge state-owned Chinese pharmaceutical company that exports to dozens of countries, including the United States, is at the center of a nationwide drug scandal after nearly 200 Chinese cancer patients were paralyzed or otherwise harmed last summer by contaminated leukemia drugs.
Chinese drug regulators have accused the manufacturer of the tainted drugs of a cover-up and have closed the factory that produced them. In December, China’s Food and Drug Administration said that the Shanghai police had begun a criminal investigation and that two officials, including the head of the plant, had been detained.
The drug maker, Shanghai Hualian, is the sole supplier to the United States of the abortion pill, mifepristone, known as RU-486. It is made at a factory different from the one that produced the tainted cancer drugs, about an hour’s drive away.
The United States Food and Drug Administration declined to answer questions about Shanghai Hualian, because of security concerns stemming from the sometimes violent opposition to abortion. But in a statement, the agency said the RU-486 plant had passed an F.D.A. inspection in May. “F.D.A. is not aware of any evidence to suggest the issue that occurred at the leukemia drug facility is linked in any way with the facility that manufactures the mifepristone,” the statement said.
The director of the Chinese F.D.A.’s drug safety control unit in Shanghai, Zhou Qun, said her agency had inspected the factory that produced mifepristone three times in recent months and found it in compliance. “It is natural to worry,” Ms. Zhou said, “but these two plants are in two different places and have different quality-assurance people.”
The investigation of the contaminated cancer drugs comes as China is trying to restore confidence in its tattered regulatory system. In the last two years, scores of people around the world have died after ingesting contaminated drugs and drug ingredients produced in China. Last year, China executed its top drug safety official for accepting bribes to approve drugs.
Shanghai Hualian is a division of one of China’s largest pharmaceutical companies, the Shanghai Pharmaceutical Group, which owns dozens of factories. Neither Shanghai Hualian nor its parent company would comment on the tainted medicine.
Last week, The New York Times asked the F.D.A. whether the Shanghai Pharmaceutical Group exported to the United States any drugs or pharmaceutical ingredients other than the abortion pill. But after repeated requests, the agency declined to provide that information; it did not cite a reason.
On at least two occasions in 2002, Shanghai Hualian had shipments of drugs stopped at the United States border, F.D.A. records show. One shipment was an unapproved antibiotic and the other a diuretic that had “false or misleading labeling.” Records also show that another unit of Shanghai Pharmaceutical Group has filed papers declaring its intention to sell at least five active pharmaceutical ingredients to manufacturers for sale in the United States.
One major pharmaceutical company, Pfizer, declined to buy drug ingredients from Shanghai Pharmaceutical Group because of quality-related issues, said Christopher Loder, a Pfizer spokesman. In 2006, Pfizer agreed to evaluate Shanghai Pharmaceutical Group’s “capabilities” as an ingredient supplier, but so far the company “has not met the standards required by Pfizer,” Mr. Loder said in a statement.
Problems with the cancer drugs first surfaced last summer after leukemia patients received injections of one cancer drug, methotrexate. Afterward, patients experienced leg pain and, in some cases, paralysis.
The authorities recalled two batches of the drug, but issued only mild warnings because the cause of the problem was unclear. Officials with Shanghai Pharmaceutical Group stood by their products, saying that drug regulators investigating the plant had found no problems. But when another cancer drug made in the same factory — cytarabin hydrochloride — also began causing adverse reactions, investigators suspected contamination.
In September, health and drug officials announced that they had found that the two drugs were contaminated with vincristine sulfate, a third cancer drug, during production. After issuing a nationwide alert, the government announced a wider recall, and Shanghai’s drug agency sealed manufacturing units at the plant.
Family members at the No. 307 hospital have counted 53 victims in Beijing, and say they were told that there were least 193 victims nationwide. It is unclear how many were paralyzed, because the authorities have not released an official figure. Based on interviews with several families in Beijing and Shanghai, it appears that about half of those injected still cannot walk.
A spokeswoman for China’s Food and Drug Administration, Yan Jiangying, said that Shanghai Hualian had been stripped of its license to produce antitumor drugs, but that this action did not affect RU-486.
Hualian is the latest in a string of tainted medicine cases that have undermined confidence in the safety of drugs here. In 2006, at least 18 Chinese died after an intravenous drug used to treat liver disease, Armillarisin A, was laced with diethylene glycol, a toxic chemical used in some antifreeze. Also in 2006, at least 14 Chinese died after taking a Chinese antibiotic, Xinfu, which was not properly sterilized during production. And more than a hundred people died in Panama after taking cold medicine containing a mislabeled and toxic chemical from China.
In each of these cases, the manufacturer failed to follow good manufacturing practices to ensure the final product was safe.
Mr. Zheng at Peking University said that producing multiple drugs in a single workshop was risky, but that some Chinese companies saw it as a way to save money.
My comment:What's scary is that we all get Chinese medicines at some point and obviously, there is no guarantee they are safe. And I don't see how opposition to abortion could prevent a federal agency to control a pill that is already in legal use. Control over medicines is not a popularity contest...