Doing It Again, After Promising Not To--Pfizer's Amazing Record

Once again I can kick back and let the nice folks over at Health Care Renewal do all the heavy lifting:
http://hcrenewal.blogspot.com/2012/12/pfizers-13th-legal-settlement-will-it.html

I want to highlight several things reported in that post that pick up on themes previously discussed here.

Dr. Roy Poses tracked down a couple of recent Federal settlements involving Pfizer. These settlements did not get much media attention--in one case Dr. Poses could not even find any details about what the company supposedly did wrong--and the amounts of the settlements are chickenfeed compared to earlier numbers, less than $100M each. So I won't even go to the trouble to do my usual scorecard of latest Pharma fraud judgments.

What does matter, and as Dr. Poses noted, was not mentioned at all in the very limited media coverage, was Pfizer's overall track record of paying settlements due to alleged or admitted illegal behavior. As he has reconstructed it, and he admits he might have missed a few things, it looks like this since the turn of the century:

• 2002: Pfizer and affiliates Warner-Lambert and Parke-Davis, $49M, failure to pay proper federal and state rebates for Lipitor
• 2004: Pfizer and affiliate Warner-Lambert, $430M, off-label promotion of Neurontin
• 2007: Pfizer and affiliate Pharmacia & Upjohn, $35M, illegal kickbacks to promote Genotropin
• 2009: Pfizer, $2.3B, illegal marketing of Bextra
• 2010: Jury finds Pfizer guilty of violation of anti-racketeering statute for marketing of Neurontin, assesses $142M damages
• 2010: Another case, no details provided
• 2011: Pfizer affiliate Pharmacia, settlement with New York for overcharging
• 2011: Pfizer and affiiliate Quigley settle class action suit for $265M over asbestos exposure
• 2011: Pfizer, $14.5M, illegal marketing of Detrol
• 2012: Pfizer, $60M, allegations of subsidiaries bribing foreign government officials
• 2012: Pfizer and subsidiary Wyeth, $55M, illegal marketing of Protonix
• 2012: Pfizer, $43M paid to 33 states, illegal marketing of Zyvox and Lyrica

As Dr. Poses (and previous posts here) have noted, several of these settlements involed promises by Pfizer that it had learned its lesson and would not do those sorts of things again. They obviously did learn their lesson, which is that you can do these sorts of things again, pay your fine, and keep merrily toting up all the profits.

Dr. Poses then appropriately juxtaposes these recent small-potatoes judgments against Pfizer with two larger events. The one you may have heard of is the scandal involving the monster British bank HSBC, found to have laundered money for Mexican drug cartels, and to have helped numerous bad guys around the world dodge international sanctions. As the New York Times opined in an editorial:
http://www.nytimes.com/2012/12/12/opinion/hsbc-too-big-to-indict.html?_r=0
--the Feds's failuire to indict any top executives of this bank shows that "the government has bought into the notion that too big to fail is too big to jail."

The other event that you probably never heard about was the 15th International Anti-Corruption Conference, sponsored by Transparency International, in Brasilia, which led to the Brasilia Declaration decrying the failure of governments to properly punish corrupt officials. Without such punishment, said the group, don't expect any reduction in corrupt practices:
http://15iacc.org/about/declarations/the-brasilia-declaration/

As I have previously blogged:
http://brodyhooked.blogspot.com/2011/05/where-in-world-do-you-find-corruption.html
--it's naive to imagine that corruption is something that happens in poor nations on the other side of the globe, when we have splendid examples of corporate corruption cropping up all over the US and Europe. So the rules for what needs to be done to thwart corruption should be applied here first and foremost.

From Kalman Applbaum: How Pharma Does Business

Thanks to my esteemed colleague Daniel Goldberg for alerting to to this post--
http://somatosphere.net/2012/01/the-banality-of-corporate-corruption-janssen%e2%80%99s-reimbursement-department-takes-the-stand-risperdal-on-trial-cont%e2%80%99d.html
--by our old friend anthropologist Kalman Applbaum, for example as summarized here:
http://brodyhooked.blogspot.com/2010/06/how-does-drug-industry-exert-power.html

Dr. Applbaum, showing us once again that academic research is far from glamorous, is apparently camped out in a courtroom watching the unfolding of the whistle-blower case regarding the antipsychotic drug Risperdol, Janssen/J&J, and the various state Medicaid agencies, primarily Texas and Pennsylvania, that the drug firms attempted to influence (or more bluntly, to bribe) to assure that their own drugs were promoted to physicians by getting written into the official treatment guidelines. To get a full sense of the case see the earlier posts in this series by Dr. Applbaum.

This particular post may not mean much if you've not been following the case closely, so I cut to the chase by appending his final comments. Dr. Applbaum refers here both to his extensive experience in interviewing pharmaceutical executives, and also the recently settled case regarding another antipsychotic, Seroquel:

While the scale of the organization of deceit revealed in the Seroquel documents astonishes, what should strike us the most in the depiction of the implemented marketing plans is how routine they appear to be. The spectacle of the court trial is in this sense a distraction, since it focuses our attention on violation, on breach. But while the actions under investigation may be legal contraventions, they are not managerial ones. On the contrary, the marketing practices conform to business and organizational norms that are positively embraced as sound managerial principles.

Because of this, the most florid violations lie on a simple continuum with all pharmaceutical marketing practices. The prosecuted cases are distinguished, if at all, by degree and not kind with other examples. If for no other reason than that competitive pressures drive companies to behave in similar ways, one can guarantee that the marketing strategies and tactics for drugs of a single class will resemble each other. When Vioxx blew, industry watchers knew that the other Cox-2 inhibitors (Celebrex and Bextra) were potentially not far behind. When Zyprexa [Lilly’s SGA] was called to account, informed observers knew that the other manufacturers of atypical antipsychotics (of which Seroquel is one) were guilty of similar crimes, which would become visible if the opportunity arose for opening up their marketing records.

Dr. Applbaum heads this post "The Banality of Corporate Corruption" which probably says it all.

GSK To Set Record with $3B Settlement, and More on Avandia

I usually use a standard form to report the latest drug firm settling with the Feds for wrongdoing, without admitting any wrongdoing, as in:
http://brodyhooked.blogspot.com/2011/09/same-song-i-lost-count-of-which-verse.html

The most recent report, however, won't fit my standard form for a couple of reasons. First, GlaxoSmithKline has apparently not yet actually settled, there are just rumors of a settlement. Second, they are settling three different actions on three different drugs, according to the reports. But in any event, if the rumors are correct then GSK will set a new record by settling for $3B, almost twice as much as the previous high, as Dr. Roy Poses reports over at Health Care Renewal:
http://hcrenewal.blogspot.com/2011/11/to-sir-andrew-with-settlement.html

The issues that got GSK into this much trouble are: alleged improper marketing of 9 of its best-selling drugs, including Avandia, Wellbutrin, and Advair; cheating under the Medicaid rebate program; and alleged improper promotion of Avandia for diabetes.

The settlement is tentative and reportedly would be concluded in 2012, so one might wonder why it is being announced now. The speculation Dr. Poses passes along is that GSK's UK CEO, Andrew Witty, is being pushed for a knighthood, and so the company wished to clear the decks and not have embarrassing news coming out later when it could interfere with Mr. Witty becoming Sir Andrew.

Along the way Dr. Poses cites a nice review by Deborah Cohen in the British Medical Journal (BSJ) on the ins and outs of the entire Avandia debacle:
http://www.bmj.com/content/341/bmj.c4848

Ms. Cohen's piece reviews the skimpy evidence presented to both the FDA and the European drug review agency that Avandia was safe and effective, even at the time it was first approved and before later evidence emerged on the extent of the heart disease risk that it posed. The reasons why it made it through approval on such a slim basis? Clearly smart drug company promotion and lobbying played a role. But at least a part of the problem was the diabetes-endocrinology community. The glitazone drugs represent a new pharmacological approach to diabetes treatment, unlike any existing class of drugs. They promise not to replace what insulin does, but rather to treat the insulin resistance of other body tissues that is a big part of type II diabetes. The first glitazone, troglitazone (Rezulin) had to be withdrawn when patients started dying of liver failure--though its maker, Warner-Lambert, lobbied like heck within the FDA to keep its drug on the market, as I recounted at length in HOOKED. So having another glitazone as an alternative was a big priority for endocrinologists. Apparently it was such a big priority that these smart specialists forgot to ask if there was any evidence that Avandia actually improved the long-term outlook of people with diabetes, instead of just making their numbers look better right now, and especially whether it actually prevented the heart and vessel disease which is the primary serious complication of Type II diabetes.

And here we return to another theme I harp on--why many within the FDA say they must ignore conflicts of interest because if they excluded all "experts" with COI from their scientific advisory committees, there would be none left to serve. My reply to this has often been that it depends on who you call an "expert," and why more of my own colleagues in primary care fields are not asked to serve on an FDA committee. I think here you have a case in point. Who is more likely to get all misty-eyed over the fact that Avandia works by a novel pharmacological pathway? An endocrinologist. Who is more likely to be skeptical and demand proof that it really helps patients? A primary care physician. I rest my case.

ADDENDUM 11/21/11: I erred above in saying that the GSK settlement was nearly twice the previous high settlement. I had thought that the most recent Pfizer settlement was in the middle $1B range, but according to the Bloomberg News coverage of another recent settlement, Abbott Labs (see post just above), Pfizer settled its charges over the marketing of the painkiller Bextra for $2.3B in 2009.

Catching Up: Pharma Settlements in Criminal Cases

A while back I noted that it was a lot easier to simply do these items as a fill-in-the-blank form. So I started to complete the latest announcement as follows:

Drug Company: Forest Laboratories
Drug: Celexa and Lexapro
Amount of settlement: $313M
The settlement equals what percentage of one year's sales of the drug?: 13.6% (Lexapro only)
Did the company admit wrongdoing? Yes/No: Of course not
Link to detailed news coverage: http://www.nytimes.com/2010/09/16/health/16drug.html?scp=1&sq=natasha%20singer%20forest%20celexa&st=cse

It was only in the process of reading about this settlement, that I came to realize that I had missed the news of a settlement two weeks earlier:

Drug Company: Allergan
Drug: Botox
Amount of settlement: $600M
The settlement equals what percentage of one year's sales of the drug?: 46%
Did the company admit wrongdoing? Yes/No: Of course not
Link to detailed news coverage: http://www.nytimes.com/2010/09/02/business/02allergan.html?hp

Taking the earlier case first, Allergan was accused of pushing Botox for headache, pain, and spasticity associated with cerebral palsy, all unapproved indications according to the FDA. The marketing methods included kickbacks to doctors for off-label uses and helping physicians to get insurers to reimburse for off-label uses by falsely putting in the billing code for an approved indication. (In partial defense of Allergan, British regulators recently accepted company research showing that Botox might be useful in the treatment of chronic migraines, suggesting that the current FDA label for the drug might be too restrictive--though of course legally, the company is supposed to expand its label first and market the drug for those indications second, not the other way around.) The Botox settlement may set a new record, not for the total amount--Pfizer's $2.3B Bextra settlement still holds pride of place--but for the substantial percentage of 1 year's sale of the drug in question. Still, it means that in about 6 months, Allergan will make enough revenue off the drug to pay off the total cost of the settlement.

Now to Forest. They had already pulled off a huge coup by marketing Lexapro, a minor tweak of the Celexa molecule, as a brand-new antidepressant just in time to "evergreen" Celexa as its patent was running out. The major off-label use they were promoting was the use of the drugs for children and adolescents when the FDA had approved adults-only usage. The major methods of marketing alleged by the Feds were huge bribes to docs--examples noted between 1998 and 2005 were tickets to Cardinals and Red Sox games and Broadway shows, a $1000 gift certificate for the gourmet French restaurant Alain Ducasse, and a deep-sea fishing trip off Cape Cod for a doctor and his 3 sons. What is most striking about this list is the suggestion of the effects of the 2002 PhRMA code of conduct. While less stringent than the code that went into effect in January, 2009, the 2002 code was supposed to have done away with such extreme items as sports tickets and leisure junkets (as I wrote about in HOOKED). We don't know the exact dates on the allegations in the Federal suit against Forest, but it would appear at least possible that Forest reps were handing out bribes of a sort that the PhRMA code had supposedly banned, in years after the PhRMA code was supposed to be in effect--perhaps another suggestion on how effective these voluntary codes of conduct within the industry really are.

Final note: Defenders of industry will point out, correctly, that the companies have admitted to none of these charges. The suits against the companies were all based on whistleblower disclosures, which generally lead to the discovery of extensive files of in-house company documents. So we can assume that the Federal allegations are based on the review of those company files.

CNN: Pfizer Too Big to Prosecute; Shadow Company Takes the Hit

A bit of ancient history: As I described in HOOKED, Australian business sociologist John Braithwaite, in the course of doing the research for his 1984 book, Corporate Crime in the Pharmaceutical Industry, was interested to discover that more than one U.S. drug firm had a position in the organizational chart informally called "vice president in charge of going to jail." The lines of authority were arranged so that, if the firm was ever caught doing illegal things, this particular VP would take the hit and thereby protect higher-ups from criminal prosecution; and that VP's compensation package included appropriate recompense for this service. This handy arrangement was later messed up by a U.S. Supreme Court ruling in a case called Park. According to Park, I gather, the court held that if a company did wrong, and somebody had to be blamed, it had to go up to the CEO. So the position of "VP in charge of going to jail" presumably went the way of the dinosaurs and the dodo.

Now fast forward to the present. According to a CNN special report:
http://www.cnn.com/2010/HEALTH/04/02/pfizer.bextra/?hpt=Sbin
--the old VP in charge of going to jail has been replaced with the shell company in charge of being prosecuted for the main firm's misdeeds. This is a much nicer arrangement as there really is no shell company, so no one has to go to jail, or to be paid extra for running the risk.

A number of media sources have been discussing the recent settlement between US Federal prosecutors and Pfizer over the off-label marketing of Bextra. (See my previous post on that topic, http://brodyhooked.blogspot.com/search?q=bextra.) The angle that most of the media have explored is that the actual amount of money paid out by Pfizer in fines and lawsuits, even though it tops $2B, is so far short of the profits the company made from Bextra sales as to be a mere pittance. (CNN calculates that Pfizer has so far paid out the equivalent of three months' worth of profits for a drug that was on the market for several years.) The documented fact that Pfizer was engaged in this illegal off-label marketing of Bextra at the same time as it was pleading guilty to earlier instances of illegal off-label marketing, and promising up, down, and sideways that it had learned its lesson and would never do those terrible things again, shows that for the big companies, these fines are nothing more or less than a cost of doing business and therefore fail to serve as any form of deterrent against future wrongdoing.

CNN chose to shine its spotlight on a somewhat different angle. As I covered in the previous post, the basic Federal problem in prosecuting Pfizer was that it is "too big to jail" in much the same sense that the global banking giants are "too big to fail." The law requires that if Pfizer were to be successfully prosecuted for criminal offenses, it would be immediately banned from doing any business with either Medicare or Medicaid. This would have two consequences. First, a large number of patients who now depend on Pfizer drugs, including some brand name products for which there is no generic substitute, would be unable to get their medicines. Those people and their physicians could be expected to set up an immediate howl that would quickly be heard in the halls of Congress. Second, unable to sell to such huge markets, Pfizer would probably go bust. That would lead to the unemployment of thousands of company employees, most of whom had nothing to do with illegal marketing, in the middle of a severe recession, and the resulting howl would be heard immediately in the halls of Congress.

What to do? The creative Feds have successfully prosecuted a company for Pfizer's misdeeds. That company freely admitted its guilt and as a result is now banned from selling any drugs to Medicare or Medicaid. The company is called Pharmacia & Upjohn Co., Inc. Old-timers might recall that both Upjohn and Pharmacia are former drug firms that were bought out by Pfizer and thereupon ceased to exist as independent firms. Pharmacia & Upjohn Co., Inc. has no assets or employees and manufactures no drugs. It exists only as an on-paper shell company, totally owned by Pfizer. It was actually invented back in 2007 by Pfizer for the same purpose, to take the hit for an earlier prosecution. Since it happened to still be around, on paper, it was the best target to take the hit for this latest offense as well.

As I reviewed in that earlier post, Ann Woolner wrote in Business Week that nothing today prevents the Feds from prosecuting a drug firm and its executives under misdemeanor instead of felony charges. You can throw somebody in jail for certain misdemeanors. If you want to send a message to drug companies that they cannot get away with illegal behavior, while avoiding the serious consequences of a company like Pfizer actually going out of business, the best way to do this (says Woolner) is to charge some of their top executives with misdemeanors and throw them in the slammer for 6 months or whatever the law allows. What we would now have to guard against is these execs setting up shell companies of themselves and telling the Feds to put that shell company into jail instead of them. I guess when you have that kind of bankroll to hire the country's smartest lawyers, anything is possible.

Into the Slammer: Only Answer for Pharma Misdeeds?

Now that our friend, Dr. Roy Poses over at the Health Care Renewal blog, has returned from a trip, I can put my feet up and go back to letting him write this blog for me.

Latest over his way is a post about King Pharmaceuticals having to pay a $42M penalty for a kickback scheme involving the long-acting morphine drug, Kadian:
http://hcrenewal.blogspot.com/2010/03/king-pharmaceuticals-settle-and-one.html

It's been mentioned numerous times that such penalties, that seem so massive to pore ol' folks like us and really are so piddly compared to the profits made by the big drug companies, can be treated by those companies simply as the cost of doing business and form no deterrent whatsoever to future misdeeds of the same sort. As Ann Woolner writes in Business Week, in a column cited by Health Care Renewal:
http://www.businessweek.com/news/2010-03-16/jail-time-for-executives-might-stop-drug-crimes-ann-woolner.html--

The biggest fine ever imposed in U.S. history, $2.3 billion against recidivist Pfizer, represented a mere 14 percent of the revenue stream from selling the drugs at issue over seven years.
So immune to criminal sanctions was the New York-based company that it launched its off-label Bextra campaign at the same time the company was pleading guilty to doing precisely the same thing with other drugs. The anti-inflammatory medication was later yanked from the market because of increased risk of heart attacks and stroke.

This leads Woolner to wonder what would work, which is the main point of the HCR blog post. The FDA could effectively shut down the drug company, which would throw a lot of innnocent people out of work in the middle of the recession and deprive patients of the useful drugs that company makes. A much better alternative, she says, is to note that while felony convictions of individuals--such as responsible company executives--are very difficult because you have to prove intend to defraud, the FDA is empowered by current law to engage in misdemeanor prosecutions, which require a much lower burden of proof. By those means, Woolner says, you might actually get some of the responsible parties to do a little jail time. And maybe that would grab the industry's attention in a way we have so far failed to do.

Pfizer Assessed Record Fine--Why We Need a Reminder of Our Mission

The AP has released the details of the record $2.3B fine assessed against Pfizer for off-label marketing of Bextra and other drugs:

http://finance.yahoo.com/news/Pfizer-to-pay-record-23B-apf-1176280604.html?x=0

Readers of this blog, all half dozen of you, might be wondering what my reaction to this news is. A few more recent readers of the blog might imagine that I'd be chortling about the evil drug industry finally getting their just desserts.

So it may be time to stop, take a deep breath, and remind ourselves of why we are here. As the old saying goes, we have been up to our ass in alligators for a good while now--anyone recall which swamp we came to drain?

One major point to be followed by a minor point.

Major point: My purpose in writing HOOKED and later in starting this blog has never been to vilify the pharmaceutical industry. I take for granted that we live in a capitalist society and that in such a society it is a good thing to make a profit by selling products or services that people want. Moreover, the drug companies could have chosen to be Philip Morris, or run gambling casinos. Instead they have chosen to try to make a profit by selling substances that can contribute, sometimes in very significant ways, to improving human health. They have also undertaken some degree of risk by not only selling old substances but trying to discover new, helpful and safe substances. All that is behavior ideally to be rewarded and honored.

Like most institutions that intend to do good, the drug companies also occasionally do wrong. When they do so, we should make note of it and there should be appropriate consequences. The new $2.3 hit on Pfizer is presumably such an instance of serious wrongdoing that we hope is being appropriately punished. (You might argue that for the major players in the U.S. drug industry, even $2.3B is peanuts, but that is another discussion.) But that is a very different matter from saying that an entire industry, and the people who work for it, are all evil.

This blog exists for an entirely different reason--to hold an ethical mirror up before the medical profession and to ask what our relationship is and should be with the pharmaceutical industry. When we became doctors, we did not get up and swear an oath to maximize sales and profits. We got up and took an oath to put the patient's interests, and by implication the public's health, ahead of our own. To what extent, then, can professionals be true to that oath and still engage in activities that suggest a very close tie with the interests of the pharmaceutical industry?

After doing the 6-7 years of research that went into HOOKED, I concluded that physicians lining their stomachs and pockets with the largesse frequently provided by the industry was behavior ultimately inconsistent with that professional obligation. I concluded that this did not mean, "medicine = good, pharmaceutical industry = bad." Rather it meant: "Medicine and pharmaceutical industry = different interests." There may be a significant conflict of interest between what is good for drug company sales and what is good for the public health. This conflict is not ubiquitous; but it occurs often enough so that it is an important feature of the ethical landscape. That led me to conclude that how physicians relate to the industry should be reformed in major ways--some of which, since HOOKED was published 2-1/2 years ago, have actually come to pass.

In passing I will note that this is one of the biggest bones I have to pick with the ACRE crowd as discussed in a number of previous posts. My ability to say that I am not accusing the drug industry of being evil, just pointing out that the professional ethics of medicine requires that we not identify our interests with theirs, depends totally on the ethical meaningfulness of the idea of conflict of interest. ACRE has been doing its level best to trash that idea--to say that if you see COI at the medicine-Pharma interface, you are either prejudiced, or logically muddled, or envious. If I did not have the concept of COI to employ as an ethical tool, then I would be forced into the silly position of arguing, "medicine = good, pharmaceutical industry = bad." Myself, I would rather have COI.

So when I read about the $2.3B Pfizer fine, my question is--where and how were the docs involved? What role did we play? It would be wrong if Pfizer ended up with egg on its face and the docs who all made this possible--the hired shills/speakers, the "key opinion leaders," the researchers all too happy to spin or doctor the research data, the docs who put their names on ghostwritten articles if there were any-- walked away smelling like roses.

OK, are we clear now on what the basic issues are?

Minor point--at the risk of appearing to contradict what I have just said at length, I will focus on one sentence out of the AP article. I mention it lest you think I was being overly critical of the industry in a recent post (yesterday to be precise) when I wrote the following:

Even as far back as 1984, before the really cutthroat era of marketing competition we have seen since then, we did not have an industry that aimed to keep well within the bounds of law and ethics, and where only a few bad apples transgressed. Instead we had an industry, and apparently still do today, where skating as close to the edge of the ethical and legal thin ice as possible is the day-to-day business plan. When a skater falls through the ice we cannot dismiss it as an unfortunate aberration. We must see that this is a predictable outcome of deliberately chosen corporate strategy.

We now read from the AP that part of the reason the Pfizer settlement was so high compared to previous legal penalties was that Pfizer was viewed as a repeat offender:

"Mike Loucks, the U.S. attorney in Massachusetts ... said that even as Pfizer was negotiating deals on past misconduct, they were continuing to violate the very same laws with other drugs."

I rest my case.

Celebrex--What Don't We Know Yet about Its Risks?

As summarized in HOOKED, Celebrex (celecoxib) is the only COX-2 selective nonsteroidal antiinflammatory drug left standing in the marketplace, though its sales are way down from its heyday, before its cousins Vioxx and Bextra got yanked. As you no doubt know, the other COX-2s bit the dust due to their excessive risks of cardiovascular disease due to increased blood clotting--the downside of the beneficial mechanism of the COX-2s by which they were supposed to have prevented bleeding from the gastrointestinal tract (a fond hope that was never realized in practice to the extent predicted in the lab).

Pfizer, who makes Celebrex, would love to believe, and to have us believe, that because it's chemically different from Vioxx and Bextra, the big-time cardiovascular risks attendant upon those drugs are either much reduced, or virtually non-existent, with Celebrex. The position I took in HOOKED was that the bulk of the evidence showed that the CV risk is a class effect, and that while Celebrex might be relatively safer than Vioxx or Bextra, it's still riskier than the non-COX-2s like ibuprofen and naproxen. Given that Celebrex has never been shown to have superior pain-relieving properties, and given that it costs ten times as much as the generic nonsteroidals, it seems a no-brainer not to prescribe it. So who's right--me or Pfizer?

The Dynamic Duo of journalists Jeanne Lenzer and Shannon Brownlee recently weighed on the Center for Public Integrity website: http://www.publicintegrity.org/articles/entry/1203/. Their cogent analysis is well worth reading in its entirety. Here are some highlights.

Quite independent of the scientific question of whether Celebrex is heart-risky or not, Pfizer has managed to stage two major public relations coups. The first was handed to them by the FDA. The FDA's scientific advisory panel agreed with my point of view back in 2005. The FDA bigwigs then caved to commercial interests and obscured the issue, by demaning that all nonsteroidals (even naprosyn and ibuprofen who were not part of this dogfight in the first place) carry a warning of increased heart risk. If, by virtue of equal labeling, Celebrex appears to be no more risky than over-the-counter Motrin, then that seems to send a strong message to physicians and the public that whatever low risk Celebrex might carry is not worth worrying about. This, L&B quote an insider, is standard industry strategy. If you can't get the FDA label you want for your own drug, then at least be sure that the bad label is slapped on all your competitor drugs too.

The other big coup for Pfizer, Lenzer and Brownlee continue, is a study called PRECISION. Its lead investigator is Dr. Steve Nissen, cardiologist at the Cleveland Clinic, who is often a hero to the skeptical-of-Pharma crowd, as he was for his work in exposing the heart risks of the diabetes drug Avandia (rosiglitazone). Here he gets to be the goat. PRECISION is designed to answer the question of the relative cardiovascular risks of Celebrex, ibuprofen, and naprosyn, by enrolling 20,000 subjects at 637 international sites (at a cost of a whopping $100M). Subjects will be selected from groups known to be at high risk for heart disease, to make sure that enough adverse events occur to be able to get a good read on which drug causes the most.

Dr. Nissen's take on this according to L&B: there remains a valid open question as to which drug is the lowest risk and so should be preferred in practice. L&B's rejoinder: this issue was settled by the FDA advisory committee back in 2005. The only advantage to doing the PRECISION study now is Pfizer marketing. While the study is ongoing, Pfizer can claim in rebuttal to anyone who accuses Celebrex of carrying excess heart risks, "the data are not in yet." When the data finally are in, and even if PRECISION then shows that Celebrex clearly has higher risks, guess what--that's just about the time that Celebrex is scheduled to go off patent, so the study is low-risk for Pfizer marketing (even if high-risk for the hapless research subjects).

L&B's most telling criticism: the consent form for PRECISION (which Pfizer, Dr. Nissen, and the Cleveland Clinic all refused to release, but which the journalists obtained via a leak) says flat out, “At this time, no studies have shown that celecoxib [Celebrex] causes more heart attacks or strokes than prescription ibuprofen or naproxen in the treatment of patients with chronic arthritis.” That statement, as L&B document and as I showed in HOOKED a couple of years ago, is simply not accurate. If you have to falsify the data to get people to enroll in your study, that says something about how valid the study is.