(This is the first in a two-part blog. Read tomorrow when we look at how industry and other stakeholders weighed in.)

How clear does risk information need to be in direct-to-consumer drug ads? That’s the question the FDA is getting closer to answering as stakeholders weighed in this week on the agency’s proposed rules for presenting risk in broadcast ads.

Twenty-two members (see end of the blog for a complete list) of Community Catalyst’s Prescription Access Litigation Coalition and other supporting groups joined PAL in submitting comments that support the agency’s new proposal to make risk information clear, conspicuous, and neutral in TV ads. The groups also suggested the FDA require that risks be quantified in ads and that the overly-scientific talk be toned down to match the comprehension of the viewer who would have the most trouble understanding the ad.

Many of the provisions in this year’s proposed rule do reinforce the handling of risk information that FDA proposed in last year’s draft guidance. But they are clearer and more concrete, and would go further than the agency’s current standard of “fair balance,” in which drugmakers are only required to present risk as clearly as they present benefits. Specifically, the proposed rules would require that ads use everyday language that is easily readable when in writing and is presented slow enough and prominent enough, whether in writing or audio form, to be easily understood by a consumer viewing the ad. The FDA also proposed a rule that would ban any distracting sounds or images in broadcast prescription drug advertisements.

A step back on why all this matters: remember that the U.S. is one of only two countries that allows drugs to be advertised on TV at all (New Zealand is the other).  And it’s a relatively recent allowance—only in 1997 did the loosening of an FDA regulation about how the major statement about a drug is presented open the floodgates to the sleep butterflies, allergy bees, and PMS symptom balloons.

As was shown by the PAL cases on Vytorin-Zetia, Nexium, Vioxx and Ketek, those changes came with controversy and human costs. Rofecoxib, or Vioxx, was heavily advertised to consumers and physicians in its first year before it was pulled from market after being linked to between 35,200 to 52,800 deaths and 88,000 to 140,000 heart attacks in the US. This caused the Institute of Medicine and other experts to call for an end to DTCA for new drugs, whose side effects are often not known (or in Vioxx’s case, suppressed) until years after they appear on the market.

The link between DTCA and increased prescribing of newer, less-tested drugs has been well-documented, and policymakers, regulators and academics have all expressed concern that the FDA’s inability to regulate and oversee broadcast ads has put the public’s health at unnecessary risk.

But despite this concern and growing evidence that drug ads carry risks beyond the speed-read ones, drug companies came up short on proving public health benefits to their current ad style or offering new evidence-based ideas for presenting risk info in a clear and neutral way. We’ll take a look at what they said tomorrow. Short of all out banning DTCA, the FDA must determine the appropriate standards to best protect the public.

What else could the FDA do?
In addition to offering support to the proposed rules, PAL suggested additional steps that could further enhance the clarity of ads and thus further protect consumers. PAL urged the FDA to address the widely-held myths that the FDA approves all TV ads, and that the government only lets drugs that are “really safe” be advertised on TV, by requiring a disclaimer that “FDA has not approved this ad” for all ads that have not been pre-approved, and including the adverse event hot-line “Medwatch” number in all TV ads.

Though PAL fully supports FDA’s increased vigilance in regulating prescription drug ads, we noted in our comments that there are far more new ads being produced than there are FDA staff members to review these ads. It’s a big imbalance, and though increased funding and staffing of the FDA would help, delayed warning letters that appear long after an ad-buy—such as this Lunesta one–will probably still happen.

To address this issue, the FDA should start using their authority to fine drug companies for ads that violate FDA regulations. Though fining will not increase the speed at which the FDA is able to review ads, it could potentially increase pharma’s compliance with these regulations and exact a price from noncompliant companies, even if the ad in question is no longer being aired.

Those joining Community Catalyst’s and PAL’s comments were:

The Alliance for Retired Americans
The American Federation of State, County and Municipal Employees (AFSCME)
The American Medical Student Association (AMSA)
Breast Cancer Action
California Alliance for Retired Americans (CARA)
CALPIRG
The Coalition of Wisconsin Aging Groups
Connecticut Center for Patient Safety
Connecticut Citizen Action Group
Consumers Advancing Patient Safety (CAPS)
Health Care for All
IUOE Local 4 Funds
Long Island Health Access Monitoring Project
MASSPIRG
New England Carpenters Health Fund
National Legislative Association on Prescription Drug Prices (NLARx)VPIRG
National Women’s Health Network
Oregon Health Action Campaign
Prescription Policy Choices
TeamstersCare
US PIRG

–Emily Cutrell, Prescription Access Litigation

The unconventional thank you note: GSK exec demonstrates

Yesterday Chris Viehbacher, head of GlaxoSmithKline’s U.S. Division, sent a wouldn’t-it-be-a-shame note to legislators considering a Massachusetts bill that would ban pharmaceutical vendors from giving gifts to physicians.  In the letter, Viehbacher expressed his displeasure at the prospective law and reminded them of Glaxo’s recent job creation in the Bay State. Considering that the same legislators have proposed $1B to help boost the state’s biotech cluster, we wonder just how much Viehbacher wants before he’d be content ditching the bribes to physicians and sticking to the science.

Here’s the original story in the Boston Herald, and today’s follow-up, which includes interviews with two legislators who weren’t amused. We were, though, to read that state Sen. Mark Montigny (D-New Bedford) called the letter ‘baloney.’

Speaking of the Boston broadsheets, Pharmalot says supporters of physician/industry relations have enjoyed some column inches lately on the op-ed pages of the Herald and Globe. Chief of medicine at Mass General Hospital Dennis Ausiello, M.D. coauthored both, in which he calls for “more, not less, interaction between academic physician scientists and their counterparts in industry, engagement that should occur at every stage of the drug development process.”

When last we checked, that engagement was happening at every stage of the process – and look how good Vytorin turned out.

We’d like to hear from you

Today, Big Pharma goes to the Hill, but not for lobbying (ok, well maybe for that too.) The House and Energy Oversight and Investigations subcommittee will be hearing from Pfizer, Johnson & Johnson, Merck, and Schering-Plough about direct-to-consumer advertising.

The baby in the bathwater, and Texaco treats at school:

A doc–off over AAMC recommendations

Over at MSNBC, Art Caplan Ph.D., a renowned bioethicist at University of Pennsylvania squares off against Cornell surgeon Edward Craig M.D. M.P.H.  about why the new AAMC recommendations are a good thing – or not.

Caplan writes:

Business has no business selling or promoting in the middle of classrooms or other academic settings. Academic medical centers, if they want to teach their students how best to think about the medicines they prescribe and to retain the trust of the American people about evaluating them objectively, should do everything they can to keep the marketing, sales pitches, promotions and bribes — large and small — away from campus.

Craig, however, says that the prescribed ban, which includes things as big as foreign travel and as small as pens, lacks subtlety, and insults hungry doctors.  “When was the last time you were bribed by a piece of pizza or a logo pen with five days worth of ink?” Craig writes.

Ah, the old if-it-were-you argument.  More than a few fables and aphorisms have been written to warn us against that reasoning, but perhaps Jane Austen did it best in her novel, Persuasion: “How quick come the reasons for approving what we like!”

(And we like the pens a lot.)

Airing on the side of secrecy

Slate.com reported on some undisclosed industry relationships on the airwaves.  Neither the hosts nor the medical experts interviewed during a program on the depression meds SSRIs announced the experts’ consultant and advisory capacities for makers of the drugs.  More here.

A few weeks ago, we posted on the curious persistence – and size — of propaganda for Vytorin, the combo cholesterol drug that’s efficacy went the way of its clinical trial results – into thin air – after a panel of cardiologists rendered its cholesterol-lowering powers null and void at the American College of Cardiologists meeting in March.

But Gary Giorgio, MD, a doctor of emergency medicine in Akron, Ohio, said it better than we could have in this letter to the editor of the Akron Beacon-Journal, which ran two full-page Vytorin ads like the ones we saw in the Globe.

“The ads follow fast and furious on the heels of a study published in the New England Journal of Medicine that showed no benefit of the combination drug in reducing plaque,” Giorgio wrote.

“Given these facts, why would any intelligent physician prescribe this medication? Is it because industry-tainted guidelines keep pushing for lower and lower cholesterol targets despite a lack of evidence that this is beneficial? Is it because pharmaceutical giants Merck and Schering-Plough, which stand to make billions more dollars if patients are switched to or kept on Vytorin, have duped physicians and their patients? You be the judge.

“If you’re taking Vytorin, maybe, as the ad suggests, you should be talking more to your physician.”

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.

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.