The Association of American Medical Colleges released a set of recommendations this week urging its 129 North American member medical schools to ban all industry gifts to faculty, staff and students, as well as to prohibit ghostwriting arrangements and industry-funded meals and travel.

The recommendations, the result of a two-year task force process on industry funding of medical education, align closely with those of the Prescription Project.

“Most medical schools do not have strong conflict-of-interest policies,” RxP director Rob Restuccia told the New York Times, “and this report will change that.”

Read the Times editorial here, which calls for the policies to be immediately adopted and in some cases, strengthened.

For medical schools writing or revising conflict-of-interest policies, the Prescription Project has developed toolkits describing best practices and practical considerations. Check them out at the RxP website.

The Prescription Project, National Physicians Alliance, Prescription Access Litigation (PAL) and US PIRG have submitted public comments opposing an FDA Draft Guidance that would allow drug companies and their salespeople to distribute reprints of medical journal articles discussing off-label uses to physicians.

The groups outline numerous reasons why the distribution of reprints by pharmaceutical representatives does not facilitate evidence-based decision making and could jeopardize patient safety and public health. They urge the FDA not to issue the Draft Guidance in its current form and to hold public hearings on industry marketing of products for off-label purposes.

Off-label prescribing, the prescribing of drugs for non-FDA approved purposes, is legal. However, the marketing of drugs by pharmaceutical companies for off-label purposes is not legal. Currently, pharmaceutical companies can provide medical journal articles discussing off-label uses to physicians only if the physician asks for the information. The FDA guidance would loosen that restriction.

A whole lot of bloggers have taken on last week’s ghostwriting study in JAMA. Here are a few of our faves:

National Physician’s Alliance, the RxP partner group of physicians to which JAMA author Joseph Ross belongs, has this analysis of the latest chapter in the Vioxx saga.

Here’s NPA member Howard Brody’s take at the Hooked blog.

And in other blogs:

Daniel Carlat at the Carlat Psychiatry Blog compares the Pentagon’s use of thought-leaders (in this exhaustive New York Times investigative report) with Pharma’s strategy to push its message through ‘hired gun’ physicians.

Researcher and watchdog Aubrey Blumsohn has built a Scientific Misconduct Wiki to pair with his Scientific Misconduct blog.  Blumsohn writes:

Hopefully this will form the seed of a peer reviewed online journal devoted to Scientific Integrity. For the moment, it will serve as a non-collaborative repository for reports and academic analysis of the integrity scandal involving Procter and Gamble and the drug Actonel (including the serious implications of the failed but rather sad attempts at coverup and delay by ‘regulators.’”

And here’s a real time example of a university enforcing its policy of financial disclosure for physicians.  Pharmagossip and Pharmalot posted on a story in The Cincinnati Enquirer that the University of Cincinnati has a closer eye on psychiatry professor Melissa Delbello these days after big discrepancies in the size of her paycheck from AstraZeneca came to light.  The letter from Sen. Grassley probably helped things along, but it’s good to see an academic medical center acting on its conflict of interest policies.

Ghostwriters…

The big story from the Pharm Country this week is ghostwriting, in the wake of reports that some of the papers published about Vioxx were penned by Merck but attributed to physician authors.  If you haven’t seen the story, you need not look very far — it’s everywhere.  The Baltimore Sun and CNN here, plus some more in an earlier blog post.

Sen. Chuck Grassley (R-IA), sponsor of the Physician Payments Sunshine Act, wasted no time writing Merck a letter.

As FDA deadline approaches, so do lobbyists

And as the deadline for public comment on the FDA’s proposal to loosen restrictions on off-label marketing materials, pharma lobbyists descend on Washington.  The story is in the Wall Street Journal.  The approaching guidance would allow pharmaceutical salespeople to distribute journal articles about off-label uses of their drugs to doctors – but this review of Neurontin off-label use (spoiler alert: it’s dismal) is a good case study in why some worry about the legalization of such off-label promotion.

Massachusetts Senate cost control bill moves to House

In Massachusetts, the state Senate has passed a comprehensive cost-control bill that includes a gifts ban and academic detailing provision.  Now it moves on to the House.

But not before veteran pharma champion and biotech director Thomas Stossel MD of Harvard Medical School and co-writer and Harvard doc Dennis Ausiello MD got their word on the gift ban in.

“We believe that the best approach to optimize cost effectiveness of product prescribing is to promote more, not less, interaction among all stakeholders involved in health-care delivery, including company marketing reps,” Stossel and Ausiello wrote in the Boston Herald.

Hmm.  A call for more interaction among all stakeholders + a state shortage of primary care docs = Perhaps the reps could see patients themselves, to help the docs out?

We thought we were just poking fun, till we saw this post on Pharmalot – it’s almost happening! In Australia, medical practices have started to ask pharmaceutical companies to help with payroll for their staff.   A total pigs-on-the-runway moment for PostScript.

Pharmalot and the HealthBlog are really good about pointing out relevant ties to industry that may color the opinion columns and letters of pharma’s more prolific defenders like Stossel, which is good, because it seems the original publisher of those pieces rarely get disclosure of his industry ties right on the first try….

The Vytorin Connections

Part of Schering-Plough’s clean-up team for the Vytorin mess is on the board of the New York chapter of the American Heart Association,  as is one of S-P’s compliance officials, reports Pharmalot.  While consumer groups like the AHA taking funding from pharmaceutical companies is nothing new, Pharmalot says there are an awful lot of dots to connect in this picture.

On the street where you live

All politics are local, and now so are drug ads, like this Zyrtec pull-away flyer.  Streetcorner DTC? From what we know about the size of pharma’s marketing budget, we’d say this is cutting more than a few street corners.

Using court documents from lawsuits over Merck’s Vioxx, a study in this week’s Journal of the American Medical Association found that Merck often wrote first drafts or commissioned for-profit ghostwriters to write academic articles on the pain drug, then paid academic thought leaders for claiming primary authorship. Half the time, those doctors did not disclose that payment in publication, and often the corporate ghostwriter was not listed among authors at all. 

In a companion editorial, JAMA editor-in-chief and RxP advisory board member Catherine D’Angelis M.D. decries the practice, writing, “it is clear that at least some of the authors played little direct roles in the study or review, yet still allowed themselves to be named as authors.”  The lead author of the paper, Dr. Joseph Ross of Mount Sinai School of Medicine in New York, is a member of the National Physicians Alliance, a partner of the Prescription Project.

Read more in the Washington Post, the Boston Globe, and the New York Times.

One of the beauty’s of the American marketplace is this: If you can buy ad-space, you can sell your wares, even when those wares have been proved a sham. This week’s proof? Vytorin.  Clinical trials of the combo-cholesterol drug, which were subject to a little data-magic last year, have come up way short in the cholesterol-lowering and plaque-dissolving departments for which it was sold.  But aggressive marketing of the drug, which got the official snake-oil verdict by an expert panel of cardiologists at the American College of Cardiologists conference two weeks ago, steams ahead.  This week, Merck and Schering-Plough, the drug companies that teamed up to bring us Vytorin, ran a double-sided full-page ad touting the drug in a number of top newspaper dailies in the country, including the Boston Globe and the Los Angeles Times.

Another beauty of the American marketplace is this: Bad news doesn’t go unnoticed.  News of Vytorin’s dismal trial results triggered a stock price plummet and ensuing crisis at Schering-Plough, the New Jersey Star-Ledger reported Sunday. In the aftermath of the ACC conference, Schering-Plough announced it would eliminate 5,000 jobs as part of a cost-cutting strategy, the development of which was apparently a Zen-like experience for CEO Fred Hassan, who told the Star-Ledger:

“It’s really very refreshing and energizing to see people just come together and in a very good way,” he said. “We had the whole team there working together.”

Hmmmm. That kumbiya-like description of how well the S-P management team worked together to plan cutbacks may not have been the best story to relay through New Jersey’s top news outlet. We’re pretty sure that the 5,000 Schering-Plough employees – mostly New Jerseyites – whose jobs are on the chopping block, not to mention the five million people who shelled out for Vytorin last year, are feeling anything but refreshed and energized today.

For anyone reading pharmaceutical news, this week was All Vytorin, all the time.

For many, the plot is twisted but familiar. Vytorin is a combination drug of Merck’s Zocor (a cholesterol drug in the simvastatin family) and Schering-Plough’s Zetia, an ezetimibe, which was said to clear arterial plaque in a different way than traditional cholesterol-lowering statins. In October 2007, some reporters noticed that the ENHANCE trials wasn’t registered on ClinicalTrials.gov, even though all trials for FDA-approved drugs are required to be registered there before they enroll participants. In November, calls for the ENHANCE results, which had been completed two years earlier, grew louder. Merck and Schering-Plough, which were splitting the spoils, made the unorthodox announcement that they were changing the primary endpoint (what the trial is measuring), and would have results in time for the 2008 annual meeting of the American College of Cardiologists.

And at that ACC meeting this past weekend, an expert panel of five cardiologists finally disrobed the emperor. Even with the changed primary endpoint, Vytorin showed no significant plaque-dissolving benefit over plain ol’ simvistatin. Now it looks as though the drug companies backdated the start date of another Zetia trial, IMPROVE-IT. Emails about suppressed data, vexed researchers, and calls for prescribers to return to older, proven drugs are daily in the news.

Maybe it’s just the times, but we can’t help noticing some similarities between what Forbes.com calls the ‘Vytorin Saga’ and the Bear Stearns bail-out and its myriad financial aftershocks.

Both the Bear and Vytorin nosedives come out of the same economic zeitgeist: in recent years, pharmaceuticals and investment banks have grown profits largely with risky delay tactics – in the case of pharmaceuticals, a cocktail of combo and me-too drugs that magically create new patent exclusivity with the same molecules, and legal battles to keep generics out of the market. In the case of investment banks, those delay tactics included trading on products made up of no-look mortgages given to people without the means to pay. There was time to be bought, and to be sold again at a premium.

As a product, Vytorin is much like a sub-prime mortgage – an unproven way to capture share in a market that had been largely tapped (all the viable mortgage candidates already owned, and were taking out multiple home equity loans to redo their kitchen). With Zocor going off patent, Merck needed a way to keep share in a market that seemed to be expanding infinitely, or at least as far as the shareholders eyes could see. Like homeowners and housing prices, the number of Americans with high cholesterol just kept going up. And up and up. Why not tap into that? Share the profits? The proof – that could come later, once market share was secured. A trial was started, and finished. There was time, certainly time to massage the data – and the start dates, and the end dates, and the primary endpoint. Two years passed, and over $5 billion of Vytorin was sold.

But like Bear’s last few days, Vytorin was brought down when someone finally looked at what was there. “I’m not saying this drug should go away, but it should definitely go to the end of the line,” Dr. Harlan Krumholz told MedPage Today. Dr. Krumholz, a Yale cardiologist, was a member of the panel that spoke on the ENHANCE trial last week. Other prominent cardiologists have called the drug ‘a last resort.’

It’s important to remember that the proof on Vytorin had always been there – or, more accurately, never been there. The key for the subprimes was to buy and sell, but not to ask. The key to Vytorin’s success was, well, not to ask. At least not yet.

But now we are all asking – not just regulators and cardiologists, but homeowners, patients, grocery-shoppers, and members of a public daily medicated but rarely squared with.

Policymakers have begun investigations and hearings. Patients are asking their doctors, and their doctors are retracting their prescribing pens and going back to the basics – in this case, tried-and-true statins. In the contracting financial markets, lending has tightened, and investors are going back to other basics – bonds, banks with demonstrated liquidity. It seems the moment for evidence-based lending and medicine is at hand.

The National Physicians Alliance is calling on doctors to push back on Big Pharma’s marketing machine by just saying “no” to branded tchotchkes, drug samples and sales rep pitches. Launched Tuesday, NPA’s “Unbranded Doctor” campaign urges docs to join a national network of physicians committed to reducing the influence of pharmaceutical marketing on the medical profession.

The campaign features a special website, http://unbrandeddoctor.org/ that offers docs “how tos” on becoming “unbranded,” including clever flyers and posters designed to inform patients why a doctor has chosen not see sales reps or distribute samples as well as sources of independent medical information and industry-free CME. The site also offers “Unbranded Doctor” coffee mugs, back packs, t-shirts and other products to replace the drug company-branded items that pollute doctors’ offices. For more information about the National Physicians Alliance, go to www.npalliance.org.
 

PostScript was delighted to discover DTC-In-Perspective, a blog by the CEO of the company of the same name. DTC is one of those publishing, conference/training, and consulting companies that specializes in soaking pharma for pricey analysis of its own behavior — in this case direct to consumer advertising.  Bob Ehrlich, the aforementioned CEO, ought to know whereof he speaks. Bob is the guy who brought us Lipitor. That is, he advertised the heck out of it when he was VP Consumer Marketing for Parke-Davis. For that, Advertising Age named Bob one of the top 50 marketers in the US.

But all that marketing was strictly educational, right? Not really. Here’s Bob this week: “Drug marketing is designed to sell drugs. Ok, I said it. It is not usually to educate objectively… Does all this drug marketing create demand for products that may have cheaper equally effective alternatives? I am sure it does.”

Thanks for confirming, Bob. We couldn’t have said it better.