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Nissen's entire approach is a case study of how to use statistical tools to manufacture biased results. In “Why Most Scientific Research Findings Are False†John Ioaniddis, a professor nstitute for Clinical Research and Health Policy Studies, Department of Medicine, Tufts-New England Medical Centera notes that a study relying on meta-analytic finding from inconclusive studies where pooling is used to “correct†the low power of single studies, is probably false and biased.
Research findings from underpowered, early-phase clinical trials would be true about one in four times, or even less frequently if bias is present. Epidemiological studies of an exploratory nature perform even worse, especially when underpowered, but even well-powered epidemiological studies may have only a one in five chance being true. Nissen’s research which combines small clinical trials to conduct a epidemiological study of an exploratory nature that deliberately excludes patients without heart attacks, that does not independent confirm if one took place and does not have access to patient level data, to find a risk he believes is there may or may not be true but it is certainly biased and likely to be false.
Indeed, stating that there is a increase of 40 percent risk in heart attacks relative in Avandia users compared to others raises two other troubling questions. First, it is generally true that, as Ioannidis claims that independent of molecular or genetic confirmation of a cause and effect, “too large and too highly significant effects may actually be more likely to be signs of large bias in most fields of modern research.â€
They should lead investigators to careful critical thinking about what might have gone wrong with their data, analyses, and results.
For instance, in the 1980s a Swedish epidemiological study found that people with hip and knee replacements had a 30 percent greater increase of kidney cance than those who had no surgery. That study did not cause the authors to run to Congress and the media with results at a politically sensitive time. Instead, it suggested further epidemiological analysis and observational analysis which lead to the conclusion that the ‘relationship’ between orthopedic implants and kidney cancer was “noise†as opposed toa signal of something going wrong.
The proper response to the Avandia exercise would be to conduct further research and to put the general risk of heart events in context, Nissen, the authors of the editorials supporting his claim and the NEJM have not done either. Instead Nissen ran to the media and Congress with a highly speculative report. The NEJM gave the article prominence and failed to run a cautionary editorial.
Research findings from underpowered, early-phase clinical trials would be true about one in four times, or even less frequently if bias is present. Epidemiological studies of an exploratory nature perform even worse, especially when underpowered, but even well-powered epidemiological studies may have only a one in five chance being true. Nissen’s research which combines small clinical trials to conduct a epidemiological study of an exploratory nature that deliberately excludes patients without heart attacks, that does not independent confirm if one took place and does not have access to patient level data, to find a risk he believes is there may or may not be true but it is certainly biased and likely to be false.
Indeed, stating that there is a increase of 40 percent risk in heart attacks relative in Avandia users compared to others raises two other troubling questions. First, it is generally true that, as Ioannidis claims that independent of molecular or genetic confirmation of a cause and effect, “too large and too highly significant effects may actually be more likely to be signs of large bias in most fields of modern research.â€
They should lead investigators to careful critical thinking about what might have gone wrong with their data, analyses, and results.
For instance, in the 1980s a Swedish epidemiological study found that people with hip and knee replacements had a 30 percent greater increase of kidney cance than those who had no surgery. That study did not cause the authors to run to Congress and the media with results at a politically sensitive time. Instead, it suggested further epidemiological analysis and observational analysis which lead to the conclusion that the ‘relationship’ between orthopedic implants and kidney cancer was “noise†as opposed toa signal of something going wrong.
The proper response to the Avandia exercise would be to conduct further research and to put the general risk of heart events in context, Nissen, the authors of the editorials supporting his claim and the NEJM have not done either. Instead Nissen ran to the media and Congress with a highly speculative report. The NEJM gave the article prominence and failed to run a cautionary editorial.
"I provided a preliminary analysis to congressional staff" prior to giving it the FDA and NEJM..
Dr. Nissen regards this as moral and ethical.
Dr. Nissen regards this as moral and ethical.
Today's hearing was supposed to be Steve Nissen and Henry Waxman's grand unveiling of a new master plan for FDA reform. Instead it was an embarassing examination of how Nissen's effort to explain away why he went to Congress (rather than the FDA) with a preliminary analysis of Avandia.
Now of the more zealous critics of the FDA are now left hanging out to dry by Nissen's own measured statements about not recommending that any doctor stop prescribing or not prescribe Avandia on the basis of his study. Of course to say that totally contradicts his claim that Avandia was "worse than 9/11" is an understatment. Too bad the head of GSK research didn't have the chance to take him head on. CMPI will try to offer him that opportunity as well as the researchers of the RECORD study.
That did not stop Bruce Psaty from waving the bloody shirt of safety at the hearings, though he was reduced to irrelevancy by the end.
One by one the safety extremists are marginalizing themselves. Dr. Nissen was alternately defensive, evasive and hesitant.
Now of the more zealous critics of the FDA are now left hanging out to dry by Nissen's own measured statements about not recommending that any doctor stop prescribing or not prescribe Avandia on the basis of his study. Of course to say that totally contradicts his claim that Avandia was "worse than 9/11" is an understatment. Too bad the head of GSK research didn't have the chance to take him head on. CMPI will try to offer him that opportunity as well as the researchers of the RECORD study.
That did not stop Bruce Psaty from waving the bloody shirt of safety at the hearings, though he was reduced to irrelevancy by the end.
One by one the safety extremists are marginalizing themselves. Dr. Nissen was alternately defensive, evasive and hesitant.
One of these things is not like the other ...
Analysis of Avandia Finds
No Increased Risk of Death
-- Wall Streeet Journal
Glaxo: Diabetes pill does not raise heart risk
-- USA Today
Avandia No Riskier Than Other Diabetes Drugs Says Interim Study
-- Medical News Today
Diabetes Drug Still Has Heart Risks, Doctors Warn
-- New York Times
Analysis of Avandia Finds
No Increased Risk of Death
-- Wall Streeet Journal
Glaxo: Diabetes pill does not raise heart risk
-- USA Today
Avandia No Riskier Than Other Diabetes Drugs Says Interim Study
-- Medical News Today
Diabetes Drug Still Has Heart Risks, Doctors Warn
-- New York Times
Here's the Washington Times editorial page on the subject of Waxman and Nissen (along with Furberg and Psaty) as a defacto FDA:
"Dr. Nissen thus used his prominence and ties to Mr. Waxman and the media in order to engage in what one pundit has called drug safety vigilantism. So, while the media and Mr. Waxman have put Avandia, the FDA and drug companies on trial (once again) the real question is: Do we want Mr. Waxman and those he has anointed to usurp the authority of the FDA and scuttle proposed improvements to the current approach to regulation?
The Waxman-Nissen approach is clear: Come up with possible safety problems with questionable statistical approaches; share them with friendly members of Congress and editorialists who will use the findings to attack the FDA; hold hearings in order to put companies on the defensive and generate more lawsuits. "
Here's a link to the entire editorial:
http://washingtontimes.com/op-ed/20070605-092645-7468r.htm
"Dr. Nissen thus used his prominence and ties to Mr. Waxman and the media in order to engage in what one pundit has called drug safety vigilantism. So, while the media and Mr. Waxman have put Avandia, the FDA and drug companies on trial (once again) the real question is: Do we want Mr. Waxman and those he has anointed to usurp the authority of the FDA and scuttle proposed improvements to the current approach to regulation?
The Waxman-Nissen approach is clear: Come up with possible safety problems with questionable statistical approaches; share them with friendly members of Congress and editorialists who will use the findings to attack the FDA; hold hearings in order to put companies on the defensive and generate more lawsuits. "
Here's a link to the entire editorial:
http://washingtontimes.com/op-ed/20070605-092645-7468r.htm
If sunshine is the best disinfectant -- then let the sunshine in.
Here's our op-ed that appears in today's edition of the Washington Times:
Plaque problem
By Peter J. Pitts and Robert Goldberg
Dr. Steven Nissen, head of cardiovascular medicine at the Cleveland Clinic, by running to Congress and the media about the heart risks of Avandia, has positioned himself as the nation's de facto drug regulatory czar. Today, he will tell Rep. Henry Waxman, California Democrat and the chair of the House Committee on Oversight and Government Reform, that he had no choice but to bypass the Food and Drug Administration, because the agency (in both appearance and reality) is too cozy with industry to move in a timely fashion.
But Dr. Nissen, who has often said, "Even the appearance of bias can damage trust as actual impropriety," has his own credibility gap to deal with. As Dr. Nissen admitted to The Wall Street Journal, he was in touch with Mr. Waxman -- but not with the FDA -- well before his study was even published in the New England Journal of Medicine. FDA Commissioner Andy von Eschenbach received a letter about Avandia from Mr. Waxman and Dr. Nissen. That means Dr. Nissen was strategizing with Mr. Waxman well before rushing to save the public from cardiovascular Armageddon. Or at least that is how it appears. But "even the appearance of bias can damage trust as actual impropriety," so says the self-appointed and media-anointed Patron Saint of Drug Safety.
Indeed, avoiding the appearance of bias is why Dr. Nissen tells anyone with a pulse that he donates all "drug industry consulting fees offered to me to a philanthropic charity run by the American College of Cardiology ACC." Saint Steven the Pure.
Except the "charity" was the Steven E. Nissen Healthy Heart Fund, and it subsidized such philanthropic activities as gym memberships for the staff of the American College of Cardiology. In 2005 the $1 million in the Healthy Heart Fund was folded into the ACC Foundation. In 2006 the ACC elected a new president: Dr. Steve Nissen.
"Even the appearance of bias can damage trust as actual impropriety." Dr. Nissen regularly claims that the pharmaceutical industry hypes the value of new medicines while soft-pedaling or not publishing safety problems. Yet he has hawked early clinical results of several drugs such as ones he had been paid to study, including some that ended up causing heart attacks and kidney failure.
And then there's the question of scientific consistency. In his hotly debated New England Journal of Medicine Avandia article, he questioned the FDA's "use of blood glucose measurements as a surrogate endpoint in regulatory approval." Yet, the cornerstone of Dr. Nissen's approach to drug evaluation -- the intravascular ultrasound (IVUS) study of plaque in the wall of heart arteries -- is itself a surrogate endpoint for regulatory approval of cardiovascular and diabetes medications.
Is hypocrisy too strong a word? Or maybe the word is self-promotion. In 2004 Dr. Nissen was involved in the evaluation of AGI-1067, a drug designed to reduce the level of fatty plaque deposits (atherosclerosis) in a person's arteries. The company that developed the compound, Atherogenics, predicted the drug would positively influence many different types of serious heart problems. But the original results were unclear.
Enter Dr. Nissen, who did an IVUS re-analysis of the Atherogenics trials. Suddenly, AGI-1067 was a breakthrough. As Dr. Nissen told Forbes Magazine, "There is no other interpretation." Actually there was. A 2007 study of AGI-1067 showed that it not only failed to reduce plaque but actually increased bad cholesterol levels, decreased good cholesterol and increased the overall number of heart failures. When the negative results of the study were published, Dr. Nissen's name was not among the authors. Nice touch for a guy who beats up on drug companies for hiding safety problems.
Coincidentally, in the wake of Dr. Nissen's hit piece on the FDA and Avandia, AGI-1067 was reintroduced. And, coincidentally, Atherogenics wants to see if it treats glycemia, the same condition treated by... Avandia. Another coincidence: glycemia may contribute to arterial plaque -- a substance measured by (yes, you guessed it) Dr. Nissen's IVUS.
Dr. Nissen also worked on a drug called ETC-216, made by the company Esperion. ETC-216 was a synthetic version of good cholesterol. Dr. Nissen did an IVUS study on 47 people and claimed ETC-216 reversed plaque by 4 percent in 5 weeks. He gave several interviews in the press calling it "liquid Drano for the coronary arteries." (He's always had a good ear for media soundbites. On Nightline he called Avandia "worse than 9/11.") Though Dr. Nissen's presentation about ETC-216 figured in Esperion being acquired for $1.3 billion, there has been no additional study of the drug. Coincidentally, Esperion's former CEO, Roger Newton, is a friend of Dr. Nissen's and Delos Cosgrove, CEO of the Cleveland Clinic, is a limited partner of Canaan Partners, a firm that had a stake in Esperion.
For someone who is concerned about the appearance of impropriety, Dr. Nissen's conduct is characterized by a series of uncomfortable coincidences. Most involve putting his career ahead of the safety of patients. Members of Congress -- especially those that exalt him as the unimpeachable savior of the public health -- should use today's hearing to ask Dr. Nissen tough questions about his methods and motives.
Here's our op-ed that appears in today's edition of the Washington Times:
Plaque problem
By Peter J. Pitts and Robert Goldberg
Dr. Steven Nissen, head of cardiovascular medicine at the Cleveland Clinic, by running to Congress and the media about the heart risks of Avandia, has positioned himself as the nation's de facto drug regulatory czar. Today, he will tell Rep. Henry Waxman, California Democrat and the chair of the House Committee on Oversight and Government Reform, that he had no choice but to bypass the Food and Drug Administration, because the agency (in both appearance and reality) is too cozy with industry to move in a timely fashion.
But Dr. Nissen, who has often said, "Even the appearance of bias can damage trust as actual impropriety," has his own credibility gap to deal with. As Dr. Nissen admitted to The Wall Street Journal, he was in touch with Mr. Waxman -- but not with the FDA -- well before his study was even published in the New England Journal of Medicine. FDA Commissioner Andy von Eschenbach received a letter about Avandia from Mr. Waxman and Dr. Nissen. That means Dr. Nissen was strategizing with Mr. Waxman well before rushing to save the public from cardiovascular Armageddon. Or at least that is how it appears. But "even the appearance of bias can damage trust as actual impropriety," so says the self-appointed and media-anointed Patron Saint of Drug Safety.
Indeed, avoiding the appearance of bias is why Dr. Nissen tells anyone with a pulse that he donates all "drug industry consulting fees offered to me to a philanthropic charity run by the American College of Cardiology ACC." Saint Steven the Pure.
Except the "charity" was the Steven E. Nissen Healthy Heart Fund, and it subsidized such philanthropic activities as gym memberships for the staff of the American College of Cardiology. In 2005 the $1 million in the Healthy Heart Fund was folded into the ACC Foundation. In 2006 the ACC elected a new president: Dr. Steve Nissen.
"Even the appearance of bias can damage trust as actual impropriety." Dr. Nissen regularly claims that the pharmaceutical industry hypes the value of new medicines while soft-pedaling or not publishing safety problems. Yet he has hawked early clinical results of several drugs such as ones he had been paid to study, including some that ended up causing heart attacks and kidney failure.
And then there's the question of scientific consistency. In his hotly debated New England Journal of Medicine Avandia article, he questioned the FDA's "use of blood glucose measurements as a surrogate endpoint in regulatory approval." Yet, the cornerstone of Dr. Nissen's approach to drug evaluation -- the intravascular ultrasound (IVUS) study of plaque in the wall of heart arteries -- is itself a surrogate endpoint for regulatory approval of cardiovascular and diabetes medications.
Is hypocrisy too strong a word? Or maybe the word is self-promotion. In 2004 Dr. Nissen was involved in the evaluation of AGI-1067, a drug designed to reduce the level of fatty plaque deposits (atherosclerosis) in a person's arteries. The company that developed the compound, Atherogenics, predicted the drug would positively influence many different types of serious heart problems. But the original results were unclear.
Enter Dr. Nissen, who did an IVUS re-analysis of the Atherogenics trials. Suddenly, AGI-1067 was a breakthrough. As Dr. Nissen told Forbes Magazine, "There is no other interpretation." Actually there was. A 2007 study of AGI-1067 showed that it not only failed to reduce plaque but actually increased bad cholesterol levels, decreased good cholesterol and increased the overall number of heart failures. When the negative results of the study were published, Dr. Nissen's name was not among the authors. Nice touch for a guy who beats up on drug companies for hiding safety problems.
Coincidentally, in the wake of Dr. Nissen's hit piece on the FDA and Avandia, AGI-1067 was reintroduced. And, coincidentally, Atherogenics wants to see if it treats glycemia, the same condition treated by... Avandia. Another coincidence: glycemia may contribute to arterial plaque -- a substance measured by (yes, you guessed it) Dr. Nissen's IVUS.
Dr. Nissen also worked on a drug called ETC-216, made by the company Esperion. ETC-216 was a synthetic version of good cholesterol. Dr. Nissen did an IVUS study on 47 people and claimed ETC-216 reversed plaque by 4 percent in 5 weeks. He gave several interviews in the press calling it "liquid Drano for the coronary arteries." (He's always had a good ear for media soundbites. On Nightline he called Avandia "worse than 9/11.") Though Dr. Nissen's presentation about ETC-216 figured in Esperion being acquired for $1.3 billion, there has been no additional study of the drug. Coincidentally, Esperion's former CEO, Roger Newton, is a friend of Dr. Nissen's and Delos Cosgrove, CEO of the Cleveland Clinic, is a limited partner of Canaan Partners, a firm that had a stake in Esperion.
For someone who is concerned about the appearance of impropriety, Dr. Nissen's conduct is characterized by a series of uncomfortable coincidences. Most involve putting his career ahead of the safety of patients. Members of Congress -- especially those that exalt him as the unimpeachable savior of the public health -- should use today's hearing to ask Dr. Nissen tough questions about his methods and motives.
Though you wouldn't know if by the defiant tone of the editorials...
Link
Nissen did a meta-analysis looking at the increased risk of myocardial infarction and death from cardiovascular causes from Avandia and found a 41 percent greater risk and his analysis excluded anyone with a high risk of or a prior MI. The RECORD team released interim results showing that there was little difference in the risk of MI or death of all people on the drug with or without a history of MI... "As compared with the control group, the rosiglitazone group had no evidence of an increased risk of death, either from any cause (hazard ratio, 0.93; 95% CI, 0.67 to 1.27) or from cardiovascular causes (hazard ratio, 0.80, 95% CI, 0.52 to 1.24). The primary end point included all first hospitalizations or deaths from cardiovascular causes and as such included myocardial infarction and congestive heart failure. "
NEJM changes the goal post and definition of safety by demanding that Avandia show that it is cardioprotective...to wit; David Nathan's unctuous editorial comment: "Considering the low power of the study and the trend for more adverse cardiovascular outcomes in the rosiglitazone-treated group, it is highly unlikely that the study will ever establish a cardiovascular benefit for rosiglitazone." Thanks David and maybe it will be a source of renewable energy too.
Nathan goes on to write: "It is reasonable to ask whether physicians should feel comfortable using a drug that might have an 8% excess risk of severe cardiovascular disease or death from cardiovascular causes. " And as we all know, there are subpopulations that will carry about 80 percent of that risk.
In patients that have a 50 percent greater chance of having a stroke, heart attack or heart failure if they stop taking the medcine? No one is doubting that there are other tools out there for controlling diabetes but the last time I checked the incidence of the disease was increasing as was the prevalence. More people are dying from the disease and if a PPAR can reduce that a 50 percent increase in absolute risk of stroke with a drug that carries a 2 percent or less risk of MI and other treatments are not working....
Link
Nissen did a meta-analysis looking at the increased risk of myocardial infarction and death from cardiovascular causes from Avandia and found a 41 percent greater risk and his analysis excluded anyone with a high risk of or a prior MI. The RECORD team released interim results showing that there was little difference in the risk of MI or death of all people on the drug with or without a history of MI... "As compared with the control group, the rosiglitazone group had no evidence of an increased risk of death, either from any cause (hazard ratio, 0.93; 95% CI, 0.67 to 1.27) or from cardiovascular causes (hazard ratio, 0.80, 95% CI, 0.52 to 1.24). The primary end point included all first hospitalizations or deaths from cardiovascular causes and as such included myocardial infarction and congestive heart failure. "
NEJM changes the goal post and definition of safety by demanding that Avandia show that it is cardioprotective...to wit; David Nathan's unctuous editorial comment: "Considering the low power of the study and the trend for more adverse cardiovascular outcomes in the rosiglitazone-treated group, it is highly unlikely that the study will ever establish a cardiovascular benefit for rosiglitazone." Thanks David and maybe it will be a source of renewable energy too.
Nathan goes on to write: "It is reasonable to ask whether physicians should feel comfortable using a drug that might have an 8% excess risk of severe cardiovascular disease or death from cardiovascular causes. " And as we all know, there are subpopulations that will carry about 80 percent of that risk.
In patients that have a 50 percent greater chance of having a stroke, heart attack or heart failure if they stop taking the medcine? No one is doubting that there are other tools out there for controlling diabetes but the last time I checked the incidence of the disease was increasing as was the prevalence. More people are dying from the disease and if a PPAR can reduce that a 50 percent increase in absolute risk of stroke with a drug that carries a 2 percent or less risk of MI and other treatments are not working....
because it will seal the fate for thousands of others who will die hoping for a chance at life. The House bill makes safety superior to drug approvals and makes the pseudo analysis of Steve Nissen -- which gives the meta-reality of danger -- pre-eminence in the drug approval process. Given this additional hurdle more drugs that show a targeted benefit will be pulled because all fear mongers will have to do is lump all the questionable safety risks into one sample to create a signal of danger.
Provenge protesters interested in getting access to the new drug should direct their phone calls to the following individuals who now constitute the new drug regulatory regime in America
Congress Henry Waxman (202) 225-3976
Dr. Steve Nissen (216) 445-6852
Senator Charles Grassley 202.224.3744
Gardiner Harris, The New York Times 212-556-1234
Provenge protesters interested in getting access to the new drug should direct their phone calls to the following individuals who now constitute the new drug regulatory regime in America
Congress Henry Waxman (202) 225-3976
Dr. Steve Nissen (216) 445-6852
Senator Charles Grassley 202.224.3744
Gardiner Harris, The New York Times 212-556-1234
While it's very nice to have Dr.Goldberg recognized as one of health care's most influential bloggers (see Boston Globe article in previous blog) -- it's downright frightening to see one of our nation's most aggressive tort lawyers supporting Dr. Steve Nissen as the next Commssioner of the FDA.
As the Globe article states,
"To W. Mark Lanier , an attorney nationally known for representing patients in cases against drug companies, such positions would make Nissen a fine candidate for FDA commissioner."
Thus the King of Torts dubs Steven Nissen, Doctor of Torts.
As the Globe article states,
"To W. Mark Lanier , an attorney nationally known for representing patients in cases against drug companies, such positions would make Nissen a fine candidate for FDA commissioner."
Thus the King of Torts dubs Steven Nissen, Doctor of Torts.
Diedtra Henderson interviews Steve Nissen who responds -- sort of-- to my blog calling him "small and craven" as he shifts positions and engages in self promotion in a campaign to become defacto FDA commissioner....
Just remember these words from St. Steven the Pure because they will come back to haunt him and those who have annointed him the savior of drug safety in the weeks ahead:
“Even the appearance of bias can damage trust as actual impropriety"
Watchdog draws growls in return
Cardiologist-FDA adviser says his goal is drug safety; critics say he's bucking to run agency
By Diedtra Henderson, Globe Staff | June 5, 2007
WASHINGTON -- Vioxx . Ritalin. Drug-eluting stents .
Those popular drugs and medical devices are on a growing list of therapies used by millions of people that have shown up on the radar of Dr. Steven E. Nissen , a prominent heart specialist.
Leveraging his power as a federal adviser, tapping the reach of medical publications, and whispering in the ears of key members of Congress, the Cleveland Clinic cardiologist has questioned the heart safety of each product. In doing so, he's chipped away at the credibility of the Food and Drug Administration as the nation's top drug safety watchdog.
Avandia , the world's best-selling oral diabetes treatment, is the latest drug targeted by Nissen. In a New England Journal of Medicine article last month, he said it increases the risk of heart attack. Avandia's manufacturer, GlaxoSmithKline , called Nissen's analysis flawed. But Nissen is scheduled to testify tomorrow at a congressional hearing on Avandia , again commanding the media spotlight.
Nissen, son of a physician and husband of a journalist , calls himself the "point on the end of the spear" during drug safety debates, raising awareness on matters he says the FDA has overlooked. Time magazine last month included the 58-year-old among 100 people "whose power, talent, or moral example is transforming the world."
Others say his motivation has more to do with wanting to run the FDA. And that worries the drug industry. If a Democrat is elected president next year and Nissen -- or someone like him -- becomes FDA commissioner, they say it could make the FDA more cautious, slowing new product approvals to a crawl and stifling innovation.
Nissen, who joined the Cleveland Clinic in 1992 , now chairs its department of cardiovascular medicine . He is immediate past president of the board of trustees of the American College of Cardiology . He has been published more than 250 times, including books and journals, and has been an early leader in the development of a type of imaging that spots artery damage at its earliest stage and can determine whether anti cholesterol medicines are effective.
But on Capitol Hill and in pharmaceutical company boardrooms, those achievements are trumped by his role as a drug-safety watchdog.
Years before Vioxx was pulled from the market in 2004, Nissen pointed to its heightened heart attack and stroke risks. In 2005, as the FDA was on the verge of approving Pargluva, a diabetes drug known generically as muraglitazar that works like Avandia , Nissen pointed out cardiovascular problems, effectively killing the drug's development. And he also rallied other federal advisers to prod the FDA to put its harshest warnings on attention- deficit hyperactivity disorder drugs, like Ritalin and Adderall , due to cardiovascular risks.
Such public stands have unleashed a firestorm of criticism. FDA spokesman Douglas Arbesfeld , in an e-mail to reporters days after Nissen's Avandia analysis was published by the New England Journal -- derisively dubbed him "St. Steven ," and wondered whether his feet were made of clay.
Arbesfeld, responding to a Boston Globe question about the e-mail message, said the correspondence -- sent using his FDA e-mail address -- reflected his personal views and not the agency's.
After the Avandia news broke, Robert Goldberg , a conservative pundit and vice president of the Center for Medicine in the Public Interest New York, posted a message on his blog, DrugWonks.com, that said Nissen is campaigning to become FDA commissioner in a way that "makes him look craven and small."
Told of Goldberg's blog entry, Nissen asked, "Who would say such a thing?"
"I'm not running for anything," Nissen added. "I've got a great job here, and I'm not going anywhere."
Goldberg, however, does have more clout than the average blogger. As a senior fellow at New York's Manhattan Institute , he once wrote that a front-runner to become FDA commissioner would so stymie the drug-approval process that the shorthand message to patients would be: "Drop dead." The candidate, Dr. Alastair J.J. Wood, foundered in the face of stiff industry opposition.
In an interview, Goldberg said the cardiovascular risks of such drugs as Vioxx have been highlighted by others, but Nissen is "the most aggressive in promoting himself, whether he is accurately depicting the risks and benefits of products."
Nissen's word carries weight with influential members of Congress intent on FDA reform, including US Representative Henry A. Waxman , a California Democrat, whose assistance Nissen sought when he had difficulty obtaining details about Avandia, and US Senator Charles E. Grassley , an Iowa Republican, who wants to create a separate drug safety center at the FDA.
In a key switch, Nissen now agrees with Grassley on the need for such separation.
Nissen has also earned the praise of US Senator Hillary Rodham Clinton of New York , a Democratic front-runner in the 2008 presidential race.
Like other FDA critics, he says the agency is so reliant on drug industry funding that it is reluctant to swiftly tamp down on drug-safety problems. He seeks to reduce the number of FDA advisers with financial ties to drug and device companies, and wants more and larger clinical trials conducted after drugs are approved for sale. He favors restricting advertising for products that have questionable safety records. And he champions public access to results of the clinical trials that drug makers conduct to gain FDA approval for their products.
To W. Mark Lanier , an attorney nationally known for representing patients in cases against drug companies, such positions would make Nissen a fine candidate for FDA commissioner.
"The current FDA commissioner is, at best, a passivist before a ravenous beast named Big Pharma. At worst, he is their actual lap dog," Lanier said.
Just remember these words from St. Steven the Pure because they will come back to haunt him and those who have annointed him the savior of drug safety in the weeks ahead:
“Even the appearance of bias can damage trust as actual impropriety"
Watchdog draws growls in return
Cardiologist-FDA adviser says his goal is drug safety; critics say he's bucking to run agency
By Diedtra Henderson, Globe Staff | June 5, 2007
WASHINGTON -- Vioxx . Ritalin. Drug-eluting stents .
Those popular drugs and medical devices are on a growing list of therapies used by millions of people that have shown up on the radar of Dr. Steven E. Nissen , a prominent heart specialist.
Leveraging his power as a federal adviser, tapping the reach of medical publications, and whispering in the ears of key members of Congress, the Cleveland Clinic cardiologist has questioned the heart safety of each product. In doing so, he's chipped away at the credibility of the Food and Drug Administration as the nation's top drug safety watchdog.
Avandia , the world's best-selling oral diabetes treatment, is the latest drug targeted by Nissen. In a New England Journal of Medicine article last month, he said it increases the risk of heart attack. Avandia's manufacturer, GlaxoSmithKline , called Nissen's analysis flawed. But Nissen is scheduled to testify tomorrow at a congressional hearing on Avandia , again commanding the media spotlight.
Nissen, son of a physician and husband of a journalist , calls himself the "point on the end of the spear" during drug safety debates, raising awareness on matters he says the FDA has overlooked. Time magazine last month included the 58-year-old among 100 people "whose power, talent, or moral example is transforming the world."
Others say his motivation has more to do with wanting to run the FDA. And that worries the drug industry. If a Democrat is elected president next year and Nissen -- or someone like him -- becomes FDA commissioner, they say it could make the FDA more cautious, slowing new product approvals to a crawl and stifling innovation.
Nissen, who joined the Cleveland Clinic in 1992 , now chairs its department of cardiovascular medicine . He is immediate past president of the board of trustees of the American College of Cardiology . He has been published more than 250 times, including books and journals, and has been an early leader in the development of a type of imaging that spots artery damage at its earliest stage and can determine whether anti cholesterol medicines are effective.
But on Capitol Hill and in pharmaceutical company boardrooms, those achievements are trumped by his role as a drug-safety watchdog.
Years before Vioxx was pulled from the market in 2004, Nissen pointed to its heightened heart attack and stroke risks. In 2005, as the FDA was on the verge of approving Pargluva, a diabetes drug known generically as muraglitazar that works like Avandia , Nissen pointed out cardiovascular problems, effectively killing the drug's development. And he also rallied other federal advisers to prod the FDA to put its harshest warnings on attention- deficit hyperactivity disorder drugs, like Ritalin and Adderall , due to cardiovascular risks.
Such public stands have unleashed a firestorm of criticism. FDA spokesman Douglas Arbesfeld , in an e-mail to reporters days after Nissen's Avandia analysis was published by the New England Journal -- derisively dubbed him "St. Steven ," and wondered whether his feet were made of clay.
Arbesfeld, responding to a Boston Globe question about the e-mail message, said the correspondence -- sent using his FDA e-mail address -- reflected his personal views and not the agency's.
After the Avandia news broke, Robert Goldberg , a conservative pundit and vice president of the Center for Medicine in the Public Interest New York, posted a message on his blog, DrugWonks.com, that said Nissen is campaigning to become FDA commissioner in a way that "makes him look craven and small."
Told of Goldberg's blog entry, Nissen asked, "Who would say such a thing?"
"I'm not running for anything," Nissen added. "I've got a great job here, and I'm not going anywhere."
Goldberg, however, does have more clout than the average blogger. As a senior fellow at New York's Manhattan Institute , he once wrote that a front-runner to become FDA commissioner would so stymie the drug-approval process that the shorthand message to patients would be: "Drop dead." The candidate, Dr. Alastair J.J. Wood, foundered in the face of stiff industry opposition.
In an interview, Goldberg said the cardiovascular risks of such drugs as Vioxx have been highlighted by others, but Nissen is "the most aggressive in promoting himself, whether he is accurately depicting the risks and benefits of products."
Nissen's word carries weight with influential members of Congress intent on FDA reform, including US Representative Henry A. Waxman , a California Democrat, whose assistance Nissen sought when he had difficulty obtaining details about Avandia, and US Senator Charles E. Grassley , an Iowa Republican, who wants to create a separate drug safety center at the FDA.
In a key switch, Nissen now agrees with Grassley on the need for such separation.
Nissen has also earned the praise of US Senator Hillary Rodham Clinton of New York , a Democratic front-runner in the 2008 presidential race.
Like other FDA critics, he says the agency is so reliant on drug industry funding that it is reluctant to swiftly tamp down on drug-safety problems. He seeks to reduce the number of FDA advisers with financial ties to drug and device companies, and wants more and larger clinical trials conducted after drugs are approved for sale. He favors restricting advertising for products that have questionable safety records. And he champions public access to results of the clinical trials that drug makers conduct to gain FDA approval for their products.
To W. Mark Lanier , an attorney nationally known for representing patients in cases against drug companies, such positions would make Nissen a fine candidate for FDA commissioner.
"The current FDA commissioner is, at best, a passivist before a ravenous beast named Big Pharma. At worst, he is their actual lap dog," Lanier said.
Center for Medicine in the Public Interest is a nonprofit, non-partisan organization promoting innovative solutions that advance medical progress, reduce health disparities, extend life and make health care more affordable, preventive and patient-centered. CMPI also provides the public, policymakers and the media a reliable source of independent scientific analysis on issues ranging from personalized medicine, food and drug safety, health care reform and comparative effectiveness.
