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Avandia News
RE-ANALYSIS OF CONTROVERSIAL META-ANALYSIS
SAYS WRITING OFF ROSIGLITAZONE MAY BE PREMATURE
LOS ANGELES (Aug. 8, 2007) - Rosiglitazone, a drug marketed by GlaxoSmithKline as Avandia® for the treatment of type 2 diabetes, came under fire after an article published online May 21 by the New England Journal of Medicine linked it to significantly increased risk of heart attack and cardiovascular death.
That article was based on a meta-analysis conducted by Dr. Steven Nissen and Kathy Wolski of 42 clinical trials involving 27,847 patients for whom rosiglitazone was prescribed. Now, a re-analysis of the data used in the Nissen and Wolski analysis - using different statistical models - suggests that the earlier methodology may have resulted in inflated risk estimates. The new analysis, conducted by researchers at Cedars-Sinai Medical Center, concludes "that only prospective clinical trials designed for the specific purpose of establishing the cardiovascular benefit or risk of rosiglitazone will resolve the controversy about its safety."
In an Annals of Internal Medicine article, cardiologists George Diamond, M.D., and Sanjay Kaul, M.D., describe additional analyses that provide different perspectives on rosiglitazone's safety issues. "Uncertain Effects of Rosiglitazone on the Risk of Myocardial Infarction and Cardiovascular Death" appeared online Aug. 7. Both physicians testified Monday, July 30, before a Food and Drug Administration advisory committee reviewing the data on rosiglitazone's safety. At the conclusion of hearings, the
panel recommended that Avandia carry new risk warnings but stopped short of calling for the drug to be removed from the market.
"The original meta-analysis employed one statistical model, but there are other approaches that deserve consideration as well. Only when different methods give us the same answers
should we be confident in the results," say Diamond and Kaul.
In their study, Nissen and Wolski pulled together data from wide-ranging clinical trials that were not necessarily designed to track heart attacks and cardiovascular death. In addition,
most of the trials did not report occurrence of any heart attack or cardiovascular death. In this type of "sparse data" situation, the statistical model employed by Nissen and Wolski tends to overestimate risk, and some experts call for applying a "correction factor." When the "corrected" data were recomputed using a different model, risk estimates were found to be lower.
"Although the risks were still elevated, they were no longer statistically significant. There was greater uncertainty about the risk associated with rosiglitazone than was originally
reported, with neither increased nor decreased risk established conclusively," the authors say.
Even with the re-analysis, Diamond and Kaul are concerned about the practicality and reliability of combining data from 42 studies that had a variety of trial designs and protocols.
Therefore, they believe, the controversy over rosiglitazone's risk will only be resolved when clinical trials focusing on all these issues are completed. Diamond is a senior research scientist, emeritus, at Cedars-Sinai. Kaul serves as director of the Cardiology Fellowship Training Program and director of the Vascular Physiology and Thrombosis Research Laboratory at the medical center's Burns and Allen Research Institute.
Citation: Annals of Internal Medicine, online Aug. 7, 2007, “Uncertain Effects of Rosiglitazone on the Risk of Myocardial Infarction and Cardiovascular Death.”
The first in Southern California and one of only 10 hospitals in the state whose nurses have been honored with the prestigious Magnet designation, Cedars-Sinai Medical Center is one of the largest nonprofit academic medical centers in the Western United States. For 19 consecutive years, it has been named Los Angeles’ most preferred hospital for all health needs in an independent survey of area residents. Cedars-Sinai is internationally renowned for its diagnostic and treatment capabilities as well as reakthroughs in biomedical research and superlative medical education. It ranks among the top 10 non-university hospitals in the nation for its research activities and is fully accredited by the Association for the Accreditation of Human Research Protection Programs, Inc. (AAHRPP). Additional information is available at www.cedars-sinai.edu.
Link between infertility, obesity found
August 25 2007 - Sydney - Fat women have fatty eggs in their ovaries that are less likely to develop into healthy embryos, research released in Australia on Saturday shows.
Doctors have long known that overweight women have more difficulty conceiving, but have not known why.
Cadence Minge, a researcher at Adelaide University, found that a protein in cells that surrounded and nourished the egg was the link between obesity and impaired fertility.
In experiments with mice, she found that administering the anti- diabetic drug rosiglitazone activated the protein and helped the egg to mature into a normal healthy embryos.
She warned that rosiglitazone, which is marketed under the proprietary name Avandia, might have harmful side effects and more research was needed to find another way to activate the protein.
She found the eggs of mice that were fed a high-fat diet that made them insulin-resistant and pre-diabetic didn't develop into healthy embryos.
"They were much slower to divide and grow," Minge said. "And the way that the cells developed was also disturbed."
She said losing weight was the most effective way to restore fertility. Even shedding 5-10 kilograms was enough to trigger ovulation in obese women.
"We hope our findings will encourage women to consider carefully the impact of their lifestyle choices on their own future and that of their children," Minge said. - Sapa-dpa
Humana, UM to research drug effects
South Florida Business Journal
August 23, 2007 - The University of Miami Miller School of Medicine and Humana are teaming up to study how to improve prescription drug safety and avoid adverse drug reactions.
The project will use a database of 11 million Humana members to track the possible dangers of drugs after they come to market.
The partners have launched the Pharmacovigilance Initiative, a new program that will track trends in side effects and adverse reactions for a wide range of medications, UM said.
"Right now, the reporting of adverse drug events to the U.S. Food and Drug Administration is strictly voluntary, and the recent drug recalls and stepped-up black box warnings would suggest something more needs to be done to protect patient safety," said Dr. Pascal J. Goldschmidt, senior vice president for medical affairs and dean of the Miller School of Medicine. "This new initiative between the Miller School of Medicine and Humana is the right thing to do for the patient, at the right time."
The initiative will include the analysis of 41,000 diabetics in Humana's membership, including Avandia users. Avandia is the diabetes drug that recently has come under fire because of a reported increase in heart attack risk.
A multi-disciplinary advisory board will be appointed for the initiative. The board will work to determine the scope of the project and communicate research findings to the public.
That communication is expected to begin through public releases and a Web site in early 2008.
Louisville, Ky.-based Humana (NYSE: HUM) is one of the nation's largest health benefits providers, with about 11.3 million medical members.
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