FDA officials conspired with Merck to defame Truth Teller–NEJM credibility ?

In this case, Merck and FDA officials colluded to deceive the public about the safety of widely prescribed drugs–in this case, Vioxx. Furthermore,  prestigious medical journals publish reports about drug trials whose lethal effects are concealed—in this case, The New England Journal of Medicine.

The drug’s hazards are shown to have been carefully hidden from the public and from prescribing doctors through a coordinated effort by Merck and FDA officials.  Bloomberg News reports that Merck has set aside $970 million to defend the Vioxx lawsuits and nothing to cover liability. The company has vowed to fight every case.

FDA officials have not only failed to protect the public from lethal or defective drugs, vaccines, and medical devices—documents show that FDA officials have conspired with industry to trash the reputation of scientists who blow the whistle.

Bloomberg News reports (below) that a transcript of the sealed videotaped testimony by Dr. David Graham, in a Vioxx litigation case (May 9), accused senior FDA officials of working hand in glove'' with Merck to tarnish his reputation. <br />I experienced threats, intimidation and actually what, in my view, appears to have been a very organized and orchestrated campaign to smear and discredit me.”  

Documents (mostly e-mail correspondence) also show that the very FDA reviewers who had recommended approval of Vioxx for marketing—and who clearly bear some responsibility for failing to detect the safety hazards—had the gall to accuse Dr. Graham of engaging in “simply bad science” when he blew the whistle on the mounting human casualties.

And documents show that top FDA officials colluded with Merck in an effort to prevent Dr. Graham from presenting his data analysis (1) before a professional meeting in France (2004); (2) to his peers in the prestigious scientific British journal, The Lancet; (3) to the Senate Finance Committee; and (4) in judicial proceedings.

Instead of protecting the public health, top FDA officials attempted to protect Merck’s reputation and financial interests by doing their utmost to conceal the truth from the public.  In the Lancet article, Dr. Graham estimated that Vioxx caused 88,000 to 140,000 cases of serious coronary heart disease.

The truth about Vioxx-related deaths and heart attacks hurts the company’s defense strategy which hinges on the claim that the FDA saw no safety problems.  To help Merck make maintain that false claim, former FDA Commissioner Dr. Lester Crawford—who is currently under federal investigation for failing to divest of stocks in companies overseen by the FDA—went so far as to offer Dr. Graham a promotion nine days before his Senate testimony (November 21, 2004).

The commissioner is offering me this really high-level job with a lot of responsibility, and then one week later, he's calling me all sorts of names in an FDA public statement that's issued on the eve of my Senate testimony'' &nbsp;<br /><br />Unless and until a courageous professional with moral integrity who values human lives (and the safety of patients) more than career advancement, until an individual rings the alarms and blows the whistle, hundreds of thousands of lives are sacrificed on the altar of corporate profits.<br /><br />Bloomberg News reports that Dr. Anne Trontell, one of the senior FDA officials who had&nbsp; attempted to prevent Dr. Graham from presenting his analysis of the Vioxx data, said his testimony showed heoverstepped the bounds” of what he could say about Vioxx.

Her opinion was contradicted by Merck’s admission that its statistical analysis does not, in fact, support the company’s claim that the cardiac risk only affects patients who continuously take Vioxx for 18 months or more.

The New York Times (below) quotes drug safety analyst, Dr. Alistair Wood of Vanderbilt University, who said: "There never was any evidence for the 18-month story."

Similarly, Dr. Steven E. Nissen, the interim chairman of cardiovascular medicine at the Cleveland Clinic, said the mistake the company disclosed yesterday was yet another example of Merck’s mishandling data to make Vioxx seem safer.
 "They’re acknowledging that they misrepresented the Approve data, when they reported that there was a statistically significant difference between the first and the second 18 months. There is no biologically plausible reason to expect an 18-month delay. I never thought it made any sense."

However, Merck’s, now admittedly, false claim was published in a report in The New England Journal of Medicine (March 17, 2005).  What does that say about the credibility of reports published by the NEJM?

This specific case involves Merck and its deceptive marketing of Vioxx as safe. It could have been GlaxoSmithKline and its marketing of the antidepressant, Paxil (paroxetine), which New York State Attorney General, Eliot Spitzer called fraud.  GSK has recently acknowledged that its analysis overturns its long-held claim that Paxil is safe: GSK now acknowledged that adults taking Paxil have a 6-fold increased risks of suicide compared to those on placebo. See: http://www.ahrp.org/cms/content/view/166/28/  and http://www.gsk.com/media/paroxetine_adult.htm

Or, it could have been Pfizer’s marketing of the anti-seizure drug, Neurontin—a criminal marketing scam. Pfizer pleaded guilty to criminal fraud (2004).  See: http://www.ahrp.org/infomail/04/05/16.php

Unless and until a courageous professional with moral integrity who values human lives (and the safety of patients) more than career advancement, until an individual rings the alarms and blows the whistle, hundreds of thousands of lives are sacrificed on the altar of corporate profits.

Contact: Vera Hassner Sharav
veracare@ahrp.org
 
http://www.bloomberg.com/apps/news?pid=10000087&sid=aN.4KjPi__7g&refer=top_world_news
FDA Whistleblower Says Agency Smeared Him Over His Vioxx Views
May 31 (Bloomberg) –

A U.S. Food and Drug Administration whistleblower who claimed Merck & Co.’s Vioxx painkiller caused 140,000 heart attacks and strokes testified that co-workers at his agency tried to damage his reputation.

I experienced threats, intimidation and actually what, in my view, appears to have been a very organized and orchestrated campaign to smear and discredit me,'' Dr. David Graham said in a May 9 videotaped testimony taken for Vioxx litigation. FDA officials workedhand in glove” with Merck to tarnish him, Graham said according to a sealed transcript of his remarks obtained by Bloomberg News.

Graham came to prominence in November 2004 when he told a U.S. Senate panel that Vioxx was the single greatest drug safety catastrophe'' in U.S. history and that the FDA wasincapable of protecting America against another Vioxx.” Merck had withdrawn the drug weeks earlier, after a study showed Vioxx doubled the risk of heart attacks after 18 months of use.

Merck, the fourth-largest U.S. drugmaker, faces 12,000 Vioxx lawsuits. Vioxx users and their families already have won $298 million in total damages at three trials, an amount that will be cut to $48 million under state damage limits.

Graham’s testimony may be used by future Vioxx users to challenge Merck’s claim that the FDA’s 1999 approval of the drug shows that it was safe and adequately tested.

Defense Funds
Merck, based in Whitehouse Station, New Jersey, has set aside $970 million to defend the Vioxx lawsuits and nothing to cover liability. The company has vowed to fight every case. Merck has won three other cases at trial.

Dr. Graham's comments do not represent a fair assessment of the science or his own agency,'' said Ted Mayer, a Merck attorney at Hughes Hubbard &amp; Reed in New York.Unlike Dr. Graham, we have the utmost respect for the agency, its dedicated scientists, and its procedures.”

U.S. District Judge Eldon Fallon in New Orleans, who is overseeing 5,200 federal Vioxx suits, ordered Graham’s deposition over FDA objections, saying it was vitally important'' toknow the truth surrounding Vioxx” and the agency’s role.

Graham, an epidemiologist and 22-year FDA veteran, said that agency employees who try to block a drug’s approval or limit its marketability are severely reprimanded, pressured, criticized and threatened.'' <br /><br />Merck attorney Phil Beck sought to undermine Graham's credibility during the deposition. Beck asked about FDA e-mails accusing Graham of usingbad science” in both his Senate testimony and in a 2005 article in the Lancet, a medical journal. In the Lancet article, Graham estimated that Vioxx caused 88,000 to 140,000 cases of serious coronary heart disease.

Vioxx Withdrawal
Beck asked Graham about telling the journal’s editor that the FDA had warned Merck about the article. Beck also asked Graham about saying his analysis was what prompted Merck to pull the drug. Merck says it withdrew Vioxx because of a study showing the increased risk after 18 months.

That was kind of a wild and crazy charge you made to the editor of Lancet, don't you agree?'' Beck asked Graham, who has worked on 10 drugs that were withdrawn. <br /><br />No, it’s not wild and crazy,” Graham said. If you experienced what I experienced, you would understand.'' <br /><br />The next Vioxx trial begins June 5 in Atlantic City, New Jersey. Elaine Doherty, 68, will try to convince jurors that the drug caused her heart attack. Doherty's attorney, Michael Galpern, wouldn't comment on the deposition. About 6,400 Vioxx lawsuits are awaiting trial in Atlantic City. <br /><br />Graham, associate director of medicine and safety in the FDA's Office of Drug Safety, reached his conclusions about Vioxx after examining its safety with Vanderbilt University researcher Wayne Ray. <br /><br /><strong>The Vigor Study </strong><br />They studied records of 1.4 million patients insured by Kaiser Permanente and looked at a 2000 study, known as Vigor. It found Vioxx caused five times more heart attacks than the painkiller naproxen. They also compared Vioxx with other painkillers, including Pfizer Inc.'s Celebrex. <br /><br />By August 2004, Graham had concluded that Vioxx caused 27,000 heart attacks and strokes and was a risk at doses of more than 25 milligrams. Some FDA colleagues faulted Graham in e- mails, noting that he found only 10 heart attacks among users of high-dose Vioxx. <br /><br />This is misleading at best and deceptive at worst,” Dr. John Jenkins wrote in an e-mail discussed during the videotaped testimony. These types of overstated conclusions are typical of David's writing.'' <br /><br />Another colleague, Sharon Hertz, wrote that Graham's findings weresimply bad science,” according to the testimony. Dr. Anne Trontell said Graham overstepped the bounds'' of what he could say about Vioxx, his testimony showed.&nbsp;&nbsp; Graham declined to comment. <br /><br /><strong>Conference in France </strong><br />Even after the criticism, Graham testified that the FDA still approved his request to present the data at a conference in France. After the meeting, Graham and Ray reclassified high-dose and low-dose Vioxx users, recalculated the number of heart attacks based on rates found in clinical trials and made new assumptions about the drug's 20 million users. The changes led Graham make a higher estimate for the number of heart attacks. <br /><br />The record shows that others in the agency felt that in his article there was evidence of data manipulation, and he makes speculative projections that have no sound basis in science,” Mayer said. It's not surprising that he drew criticism with regard to those matters.'' <br /><br />He presented the new numbers to the Senate Finance Committee on Nov. 18, 2004, and included them in the article submitted to the Lancet, prompting Dr. Steven Galson at Merck to contact the journal's editor, Richard Horton. Merck's intervention delayed publication of the Lancet article, Graham testified. <br /><br /><strong>A Promotion </strong><br />Graham said former FDA Commissioner Lester Crawford had offered him a promotion nine days before his Senate testimony. Graham said he declined and was surprised by the timing. <br />The commissioner is offering me this really high-level job with a lot of responsibility, and then one week later, he’s calling me all sorts of names in an FDA public statement that’s issued on the eve of my Senate testimony,” Graham said.

Notes of a meeting between a Merck scientist and an FDA official before the Senate testimony refer to an opportunity to get message out on Graham,'' according to Graham's testimony. <br /><br />Thomas Kline, who represents Vioxx users, said the FDAwas suggesting to Merck that we provide journalists with a copy of our critique on Graham,” according to the testimony.

Quite shocked'' was how Graham described his reaction to the notes. The evidencedemonstrates more clearly just how widespread the organized campaign to discredit and smear me was, that I’m not crazy and psychotic.”

To contact the reporter on this story:
David Voreacos in Newark, New Jersey
dvoreacos@bloomberg.net.

http://www.nytimes.com/2006/05/31/business/31drug.html?_r=1&oref=slogin  
THE NEW YORK TIMES
May 31, 2006
Merck Admits a Data Error on Vioxx
By ALEX BERENSON

In an admission that could undermine one of its core defenses in Vioxx-related lawsuits, Merck said yesterday that it had erred when it reported in early 2005 that a crucial statistical test showed that Vioxx caused heart problems only after 18 months of continuous use.
That statistical analysis test does not support Merck’s 18-month theory about Vioxx, the company acknowledged yesterday.

But Dr. Peter S. Kim, Merck’s chief scientist, said the company stood by the overall findings it reported in 2005 — including the conclusion that the drug’s heart risks were not apparent if patients took it less than 18 months.

But outside scientists said yesterday that Merck’s admission, when considered along with other clinical trials of the drug and studies tracking real-world Vioxx use, supports critics’ longstanding claims that Vioxx caused heart problems quickly.
"There never was any evidence for the 18-month story," said Dr. Alastair J. J. Wood, a drug safety expert at Vanderbilt University.
The 18-month issue is crucial both for the 20 million Americans who took Vioxx, an arthritis inline=nyt-classifier>  drug and painkiller, and for Merck’s future. Merck faces at least 11,500 lawsuits, covering 23,000 people, from patients who say that Vioxx caused their heart attacks and strokes. Merck cited the 18-month theory when it withdrew Vioxx, a painkiller, from the market in September 2004, based on preliminary findings from a clinical trial called Approve.

In defending the lawsuits, Merck has consistently taken the position that Vioxx can cause heart problems only if it is used continuously for more than 18 months. But in the five Vioxx court cases in which juries have reached decisions so far, Merck has lost three times — twice in cases in which the heart attack victim had taken the drug for fewer than 18 months.
Merck has based the 18-month theory largely on data from the Approve study, in which the company tracked 2,600 patients in a test to see whether Vioxx could prevent colon polyps.

In the Approve study, twice as many patients taking Vioxx suffered heart attacks or strokes as those taking a placebo, or sugar pill. But most of the difference appeared to occur after patients had taken Vioxx for 18 months in a row, Merck has said.

When it reported the Approve results in The New England Journal of Medicine early last year, Merck said that it had performed a statistical test to examine whether Vioxx’s risk changed over time. That test found with almost total certainty that the drug had significantly higher risk than placebo only after the 18-month benchmark — but no extra risk before that time.
Yesterday, Merck said it had made a mistake in reporting that result last year.

In reality, the test that the company said it had used to check the results shows that there is a 7 percent chance that Vioxx has an equally high risk of causing heart attacks both before and after the 18-month benchmark is reached.

That 7 percent figure may seem like a relatively small chance of error, but scientists say it is high enough to mean that Merck has not proved its theory.
Critics had recently raised new questions about the Approve trial’s results, after the company submitted new data to the Food and Drug Administration   as part of a one-year follow-up study of patients in the trial.
Some outside scientists said that the new data indicated that Vioxx’s dangers became evident after only about four months of use. Merck disputed that interpretation and said yesterday that its newly discovered mistake was unrelated to that new data.

Dr. Kim said yesterday that Merck found its mistake only last week and immediately told the F.D.A. and the non-Merck researchers who had taken part in the Approve study, which was published in the March 17, 2005, issue of The New England Journal of Medicine.
"We came forth quickly to let the study authors know about the error, let the regulatory agencies know about the error," Dr. Kim said.

But Dr. Steven E. Nissen, the interim chairman of cardiovascular medicine at the Cleveland Clinic, and a frequent critic of Merck, said the mistake the company disclosed yesterday was yet another example of Merck’s mishandling data to make Vioxx seem safer.

"They’re acknowledging that they misrepresented the Approve data, when they reported that there was a statistically significant difference between the first and the second 18 months," Dr. Nissen said. "There is no biologically plausible reason to expect an 18-month delay. I never thought it made any sense."

Dr. John Baron, a professor at the Dartmouth medical school and one of the authors of the original journal article about Approve, said Merck’s mistake was relatively minor. In general, trying to calculate whether risks change over time is very difficult, Dr. Baron said. "The assessment of this constancy is something of an art. It’s not a ‘cut and dry, it’s there or it’s not’ business," he said.

"The evidence that the Vioxx effect begins immediately or quickly, or however you want to describe it, is far from conclusive. The evidence that it doesn’t begin until 18 months is also not something that has been proven."

The New York Times Company <http://www.nytco.com/>
    
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