More than a decade ago, Pfizer officials crowed about the response to study data for its Celebrex painkiller in a way that may come back to haunt the drugmaker. “They swallowed our story, hook, line and sinker,” senior research director Samuel Zwillich wrote in an e-mail to a colleague. However, the results showed only the first six months of a year-long study and Celebrex was really no better at protecting the stomach from gastrointestinal problems than other drugs.
The e-mail, which was sent in 2000, was among thousands of pages of internal documents and depositions unsealed recently by a federal judge in a long-standing securities fraud lawsuit against Pfizer, The New York Times reports. The overall revelations are not new, but some documents do illustrate the approach too pitch the medicine that was taken by Pfizer and its colleagues at Pharmacia, which sold Celebrex and was purchased by the bigger drugmaker.
In one example: in February 2000, Pharmacia employees came up with a game plan on how they might present the findings once they were available. “Worse case: we have to attack the trial design if we do not see the results we want,” a memo read. “...If other endpoints do not deliver, we will also need to strategize on how we provide the data.” Another document proposed explaining poor results as “statistical glitches” (you can read the e-mails here; see pages 1, 5 and 9).
Meanwhile, some employees were quietly questioning whether the study had any value. In September 2000, Emilio Arbe, a Pharmacia associate medical director, wrote that "I wouldn't feel too comfortable presenting a fudged version of the facts" and described the decision to use the limited results as “data massage.” And in May 2001, Mona Wahba, who worked on Celebrex, sent an e-mail to colleagues in which she wrote that a new analysis was “cherry-picking” six-month results.
How are physicians responding to the disclosure? The Times asked M. Michael Wolfe, a gastroenterologist who had cautiously praised the study in a medical journal at the outset, for his thoughts. This is what he had to say after reviewing the unsealed documents: “I always try to give investigators the benefit of the doubt," he tells the paper, "but these communications make it quite challenging for me.”
The move by Pfizer and Pharmacia to withhold data became known in 2001, after the FDA released the complete study results, the paper notes. As a result, several pension funds filed their lawsuit in 2004, charging Pfizer and Pharmacia had misled investors and were responsible for a drop in Pharmacia stock after the full results were revealed (here is the lawsuit).
“The few documents handpicked by lawyers suing Pfizer and being reported... are not a fair representation of this body of evidence," Pfizer maintains. And the drugmaker has argued that presenting the limited data was legitimate because so many people taking a comparison drug, diclofenac, and dropped out of the study, which caused later results to be biased. Separately, a Pfizer spokesman tells the paper that Wahba sent the e-mail only after the full study became known, although in a deposition, Wahba maintained she did not recall what she meant.
Meanwhile, controversy over Celebrex continues to this day. A study that began six years to evaluate heart risks is still not complete and will not end until May 2014, when Celebrex patent protection ends and sales can be expected to nosedive (see page 13 here). Steve Nissen, the Cleveland Clinic cardiologist who is overseeing the trial, tells the paper that Pfizer has spent hundreds of millions of dollars and enrolled about 20,000 patients, but that recruitment has lagged, in part, because European Union countries have barred patients with heart risks.
He dismissed criticism that Pfizer is delaying the trial, which is known as Precision, over concerns about the outcome. “The last thing in the world I want to do is to be sitting here twiddling my thumbs with a public health concern,” he says. Separately, he wrote last week in an editorial in the European Heart Journal that, "when completed, the Precision trial will hopefully replace heated debate with sunlight" (read here). Meanwhile, Celebrex is ringing the register. Last year, the painkiller generated more than $2.5 billion in sales, a 6 percent increase over the previous year (see page 12 here).
45 Comments
"Interesting" that Pfizer now saying the investigators are "cherry picking"....
Susan Okie broke the original story ten years ago in the Wash Post. Except for people like those of us here, it went mostly unnoticed. Of course, there were great quotes from Wolfe in the aftermath about being "duped," and also from FDA's Bob Temple that "the hype [in major journals] has more impact than our labeling does." (FDA never approved the claim that Cel. had GI benefits, but looked on while Pfizer/Pharmacia got the most out of the "refabricated" study.
Not sure I understand Ram's point re: Merck. In their marketing dept, wasn't the "cardio card" more or less the same kind of dupery?
Many people have lost interest in the value of the NYTimes as well.
Yawn.
Thanks for the comments and for the question. The short answer is not yet. I have been checking and will provide links as soon as possible.
Regards ed
The company I work for has given training on emailing after a Federal settlement. What to say and not to say. Not what is right or integrity, but what to avoid in writing.
The more things change, te more they stay the same.
That said, I'd buy a Merck before a Pfizer any day. (OK, Pharmacia. But it's a kind of habit, yes--Warner-Lambert/Neurontin; Parke-Davis/ Rezulin, etc. If you buy it, you own it. And, as later busts suggest, not much evidence Pfizer was interested in changing the relevant "corporate culture" that leads to such "episodes.")
puerile shenanigans or as Letterman quipped - "...useless behavior and plenty of it..."
none of it funny due to the body counts...
When my students read these "internal documents"--and many of them are pre-med, pre-pharm, etc.--even the most cynical among them are blown away. When they hear directly from folks across the political spectrum and from inside and outside the industry discuss them--trying to be as fair and honestly informing as possible--they continue to be blown away.
And the fact that this does _not_ represent the whole industry or everyone involved in a particular episode (the NYT also cites the emails of those who pushed back) is also not lost on them.
From what I've heard back so far, enough of them really do practice and prescribe or pursue whatever trade differently as a result. Gotta start somewhere.
I don't know that DR ever needed to bribe anyone, given his clout. All he had to do was sit on you until he got what he wanted. Read the story of Nutrasweet.
Finally we decided it was more profitable to become a herbicide company (Monsanto), where we could just klll weeds instead of premature babies. C'est la vie.
If you had the keen and perspicacious mind of the OII you could have minimized your losses like I did.
http://www.nytimes.com/interactive/2012/06/25/health/25celebrex-document.html
I was also curious about a couple of document toward the end of this set which suggested that Celebrex was being co-promoted by Pharmacia and Pfizer, and some of those involved in the discussions are writing from Pfizer email addresses.
Some of these date from 2001. That is before Pfizer formally acquired Pharmacia, yes?
Thus, for those Pfizer folk who (understandably) would wish the company not to have been involved in the ClASS episode as it unfolded, it appears that PFE was.
Right, it's only okay to kill 'em after they're born....20, 40, 50 thousand years of the most brutal cretins winning the war(s) and raping the losing side's women was done as PUNISHMENT. You don't hold the higher moral ground - never did and never will. It's still all about taking out the women threw a pregnancy....not kidding anyone but yourself....
However, my favorite economist was Thorstein Veblen, whose book "Theory of the Leisure Class" is my life manual. I try to practice Veblen's idea of "conspicuous consumption" every day.
Lest anyone here forget -- and to return us to the ACTUAL topic, boys -- this massive, multi-billion-dollar trainwreck occurred in slow-motion, over a period of four years, while legacy Schering-Plough CEO Fred Hassan was at the helm of Pharmacia -- and was being aided directly by Carrie S. Cox (also his No. 2, at legacy Schering-Plough).
". . .[A] study four years ago [then known as Pharmacia] that links its painkiller Celebrex to a ‘statistically significant’ increase in heart problems. The recent disclosure. . . appears to contradict recent statements by the company”. . . .
When all of the CLASS data were considered, most or all of Celebrex’s purported safety advantage disappeared. Six of the seven serious gastrointestinal complications occurring during the second half of the study were in Celebrex users
. . . ."Thus -- as Ed and I have subsequently (and repeatedly) documented -- was born the largest criminal fine in the history of US Pharma. It was a playbook that the Hassan/Cox duo would repeat, while leading legacy Schering-Plough (2004 to 2010) -- with the combo-drug Vytorin®. Thanks again, Fred and Carrie!
Namaste
One or two mentions of the "body count" caused by this industry in 27 comments...
http://www.drugs.com/answers/support-group/zyprexa/
This board is a mixed bag of mostly pharma haters, so if getting your blood boiling does it for you then stick around because the bomb throwers are at lunch right thinking up new ways to crucify my industry that, despite your tragic loss has saved many more than its taken from our midst. That doesn't matter to the posters; they see the Americam Pharmaceutical Industry as nothing more than an extension of the evil, greedy capitalist system that exists solely for for purpose of foisting unimagineable suffering on unsuspecting blokes that we dupe into taking our poisin pils througb devious, false and unethical marketeering.
@Betsy - there is plenty of money, don't be silly! A big wide fat deep river of money. It's just flowing to embedded political frauds - referred to as "The Wrecking Crew" and big giant vampire squids among other less colorful names. They have a VESTED INTEREST in no new superior products upsetting the flow. Truth.
@oii - you're on my eugenics list...."keep 'em barefoot and pregnant" - Part Deux. 7 men to 1 woman? Why stop there? Make it one queen bee to a hive - oh, wait, the queen does the choosing, never mind...
They also believe in conspicuous consumption. I sing one of their verses every morning in the shower:
"I WANT IT ALL, I WANT IT ALL, I WANT IT ALL, AND I WANT IT NOW!
RIP Freddie Mercury
That said, it is kinda easy. Obviously, the tough questions concern how the industry which does, indeed, save a lot more folks than it kills/injures, can take more seriously and actively (rather than glibly) those whom it does knock off through greed, indifference, obliviousness, self-congratuatiion, booze and toys, dirty tricks, various forms of promotional scuzzery, etc.--all of which you have acknowledged (to your credit).
If all those "unlucky" folks are relegated to some version of "collateral damage," I think you only supply the lumber for your actual and anticipated crucifixion (and think about the narcissism in _that_ metaphor!)
So I would love to hear some serious gospel.
We reviewed about 1000 molecules a year and selected 3-4, at most, to go into man. All still on the market as standard of care. If not because of the unpredictable nature of USA's melting pot genetics, there would be even a better safety profile.
Your dimensional thinking talents would still be talking about the pros and cons of the first molecule :-) It's not a miraculous process to get where you're going if you know where you want to go, ie. slay the flesh-eating bacteria with a therapy. BTW - as some kind of educator, you would find immense enlightenment in the presentation that an FDA old-school scientist used to give at seminars inside pharma companies who invited such sharing of information. It was about the accurate analysis of Phase One human data - how STATS could project out the incidence of side effects seen in the data.
Too bad so many people can imagine where we would be without the oii's and the Hansan and all the ghosts, etc etc etc etc etc
I have been responsible for managing clinical trials for three decades. Tens of thousands of patients have been enrolled in these studies. Some drugs worked, some did not. Some patients improved, some did not, and others died. However, all were treated with attention, compassion, and according to the strictest standards of Good Clinical Practice. I have no regrets in that regard.
Once the drugs are approved we have no control over how they are used by doctors in the marketplace and whether patients are even appropriate candidates. Despite this loss of control we in industry get painted by the guilt-by-association brush whenever one of our products is misused by an incompetent physician. That's part of the deal that I signed up for long ago, which is why I am sometimes self-effacing in the extreme.
When your every move is analyzed, re-analyzed and second guessed by everybody with a stake in the endeavor it's tough not to be cynical.
To use your religious analogy, we in Big Pharma have a Gospel, but unlike everybody who critizes our industry, it is our Cross to Bear and ours alone. I don't mind. If I did I would have quit long ago.
You know the odds. I'm surprised your BD&L folks didn't know them. On the other hand I've worked in companies BD&L was a department in name only, where the R&D was entrusted with the real responsibility of bringing NME's to market. Given your company's track record of failure I'd say that was a bad bet.
So according to you and your ilk, biologists, chemists and engineers failed to deliver on an IMAGINARY metric and, therefore, deserve to be replaced with
(well, what is it today? the wish for a "leader" like Steve Jobs to deliver an app that cures antibiotic resistance tuberculosis)
software programmers in order replace science with gizmo technology that was developed to eliminate the human intelligence needed to perform a task...?
And now, woe is me, the prescribing physicians and other clinicians are incompetent in how they use the new drugs - that's why the uptick in body counts and so cut the post-marketing continuing education arm off (used to be called "sales")...?
And that harping critique (sans data) of yours is the proof, according to you, that only the MARKETING and Business Development corp-politicians are the smartest people on the planet and we're all lucky to have you in big pharma devoted to the greatest good for the greatest number, or at least attempting to save the human species from total genetic decay with miracle drugs?
That you were FOS on so many levels was clear, but I had no idea the depth of your ignorance about how it all happened, FOR REAL, until your comments today.
WOW. The bloodbath won't stop - it's all set for total extraction:
More misery for others = more $$$$ for ME ME ME