(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provisions in this year’s proposed rule do reinforce the handling of risk information that FDA proposed in last year’s draft guidance.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

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.