Doctor Tells Pfizer Sales Rep who promoted Celebrex: “Have You No Shame?”

Sun, 26 Dec 2004

An opinion piece by Dr. Marc Siegel, an internist and professor at New York University School of Medicine, expresses the anger and dismay many physicians in the US feel about having been misled by the FDA and its hasty approval of unsafe drugs. At the same time, physicians are being besieged by patients who are influenced by drug manufacturers’ deceptive advertising campaigns.

Dr. Siegel admonishes the FDA to revise its focus and emphasis to offset industry’s influence on consumers “by putting much greater emphasis on drug safety.”

“If the FDA stops greasing the wheels to approval and starts concentrating on the post-approval period, when millions of people take a drug, the current kind of information crisis could be avoided. The agency needs to organize and support independently funded drug safety trials after approval.”

While acknowledging that some side effects are rare and can’t be anticipated, “instead of looking out for these problems, the FDA is being wined and dined to overlook them. As was reported earlier this month in The Post, almost one-fifth of 400 FDA scientists surveyed two years ago by the Health and Human Services Department’s inspector general said they had been pressured by the manufacturer to recommend approval of a drug despite reservations about its safety or effectiveness.”

Of note: A former FDA medical officer who participated in that HHS survey two years ago, called The Alliance for Human Research Protection, informing us that the survey does not begin to reflect the actual pressure brought to bear on FDA medical officers. For starters, he pointed out, the survey was not confidential: the responders had to respond from their government computers–which they knew management could tap. Thus, the answers were shaped by fear of retribution.

Contact: Vera Hassner Sharav
212-595-8974

The Washington Post Company
Put the Brakes on the Wonder Drug Express
By Marc Siegel

The very day that the arthritis painkiller Vioxx was removed from the market in September, the Pfizer representative was stationed in my office hallway trying to convert me to the Celebrex faith. “Have you no shame?” I asked her. “Don’t you realize that these drugs have similar effects?”

“Celebrex doesn’t have that problem,” she retorted, referring to the increased risk of heart attack and stroke that had given Vioxx a black eye. She made this assertion even though there was no scientific certainty to back it up.

Two weeks ago, Pfizer pulled its advertising on Celebrex — though it stopped short of withdrawing the drug itself — after a single study found that it, too, possibly raised the risk of heart disease. Then last week, concerns were raised about the heart disease risk of naproxen, best known as the over-the-counter drug Aleve.

All at once, three drugs that had been heavily promoted as ultra-effective treatments for arthritis were causing anxiety attacks, as many of my patients went overnight from being true believers to thinking that any drug for their ailment could kill them. In truth, it’s not that simple. The risks for most people who take these drugs are really quite small. But this current wave of concern does reveal the truth about the way we develop and market drugs: There is an inadequate concern for public safety, masked by overblown promises.

The public doesn’t receive clear, unfiltered information. Drug companies inflate the balloon of expectations, which then bursts when an unexpected side effect is found. As a result, our response to new medications swings from embracing a panacea to giving in to panic. Yet neither one reflects reality. We need a better brake on drug companies’ hype, and an ability to rein in potent drugs that are being overused.

What isn’t clear to the public is that drugs like Celebrex are largely safe when taken for shorter periods at lower doses, which is the way they’re generally intended to be used for common joint inflammation. The increased risk to the heart is due to taking them at high doses over a prolonged period of time. Celebrex diminishes an enzyme that prevents clotting, which is associated with heart attacks. The prolonged use of Aleve, and perhaps all non-steroidal anti-inflammatory drugs, can lead to fluid retention and elevated blood pressure, itself a risk factor to the heart.

Yet these drugs are being overprescribed by doctors and overused by patients who consider them safe and effective. Public expectation regarding Celebrex and Vioxx was ramped up by direct-to-consumer advertising, a process that is not adequately overseen by the Food and Drug Administration. The public was told that these so-called Cox 2 inhibitors protect the stomach in a way that other non-steroidal drugs, all of which can cause bleeding ulcers or gastritis, don’t. Thinking of Celebrex as a wonder drug, the public naturally feels betrayed now that it understands that the stomach-sparing qualities, though they may exist, were not actually proven, and now that it knows about the elevated heart risk, which FDA scientists suspected from the outset.

The FDA is responsible for providing contextual information to the public and for overseeing all drugs, which should be analyzed according to a risk-benefit model. What is a drug’s risk vs. the benefit it provides? How well would the patient do without it? Unfortunately, this pure model has fallen into disuse.

Thanks to a policy initiated in the early 1990s and intended to help dying AIDS patients, promising drugs are rushed through the pipeline with much more emphasis on whether they work than on whether they’re safe. Once in the marketplace, drugs like Celebrex — which are given to only thousands of test subjects before being approved — are prescribed to millions. U.S. physicians wrote more than 20 million prescriptions for Celebrex last year.

The mostly beneficent motives that drove the push to get HIV-AIDS drugs onto the market, meanwhile, have been largely supplanted by marketing pressures to simply replace an existing drug that works with a new and more expensive pill. And to sell these medications, drug manufactures use direct-to-consumer advertising.

Among the industrialized nations, direct-to-consumer advertising is legal only in New Zealand and the United States. A 2002 study in the New England Journal of Medicine showed that this advertising amounts to 16 percent or more of all spending on drug promotion. In 1997, the FDA issued a series of feeble guidelines that allowed TV ads with only a brief mention of side effects. According to RX Insight, a drug company consulting firm, the drug manufacturers refer to the day these guidelines were issued as “liberation day.”

Since then, the pharmaceutical companies have had largely free rein to create name recognition using extensive TV and magazine ad campaigns. The FDA receives approximately 32,000 requests yearly from drug companies for approval of television ads alone, and can’t possibly be discerning about the quality of information in them.

Meanwhile, physicians — who certainly can’t be excused for prescribing irresponsibly — have been largely removed as effective filters of information as the drug manufacturers bombard them with biased data, free lunches and free drug samples. Doctors find themselves compelled to respond to nervous ad-driven questions from their patients, rather than those of fundamental medical importance. A UCLA report in 2000 described the future consequences of this process as “a world of aggressive, distrustful and only partially informed patients and cowed physicians.”

Surveys conducted by the FDA in 1999 and 2003 and by the Kaiser Family Foundation in 2001 showed that more than 50 million people respond to drug ads by asking their doctors about whether the medication might work for them, just as the ads urge. But the same two studies revealed that almost 60 percent of consumers feel that the side-effect warnings communicated by these ads are inadequate.

How can the FDA compete with these pressures? It can start with a much greater emphasis on drug safety. If the FDA stops greasing the wheels to approval and starts concentrating on the post-approval period, when millions of people take a drug, the current kind of information crisis could be avoided. The agency needs to organize and support independently funded drug safety trials after approval.

It’s true that some side effects are rare and can’t be anticipated, but instead of looking out for these problems, the FDA is being wined and dined to overlook them. As was reported earlier this month in The Post, almost one-fifth of 400 FDA scientists surveyed two years ago by the Health and Human Services Department’s inspector general said they had been pressured by the manufacturer to recommend approval of a drug despite reservations about its safety or effectiveness. The survey also found that a majority had doubts about the adequacy of federal programs to monitor prescription drugs on the market and that more than a third were not confident of the agency’s ability to assess a drug’s safety.

With 700,000 people dying every year in the United States of heart disease, it is dismaying to consider that scientists in the lab knew of the mechanism by which Celebrex, despite its relative safety for the vast majority of people, increases clotting . Similarly, the FDA had been aware of the cardiovascular risks associated with Vioxx since at least 2000, when a study revealed the problem; despite these concerns, it yielded to the manufacturer’s arguments to keep the drug on the market.

The problem of naproxen is even more difficult to address. Here is a drug that is available over the counter and may be used without a physician’s guidance. Doctors issue 70 million prescriptions for non-steroidal anti-inflammatories every year, which is bad enough, but more than 30 billion over-the counter tablets are sold annually in the United States alone. This is clearly overuse, and if further study shows that unregulated use of these drugs causes a significant risk of heart attack or stroke, the FDA will have to rethink whether to allow an effective pain and anti-inflammatory drug like naproxen to be available without a prescription.

But the FDA that engages in that analysis will have to be a much stronger and more effective agency than the one in place now. In an editorial in the Nov. 30 issue of the Journal of the American Medical Association, deputy executive editor Phil Fontanarosa discussed the creation of a new office of drug safety to ensure a more independent and extensive evaluation of drugs than the FDA can provide. It would seem that a better first step would be to try to strengthen the FDA itself, to make it a more effective regulatory agency less dependent on drug company money and political appointments.

What’s clear is that our current method for informing the public and dispensing prescription drugs is distorted. First patients are seduced and later they are frightened. A drug is shoved down patients’ throats before it is completely studied. Influenced by advertising pressures, doctors replace a perfectly good generic drug that costs pennies with the latest and greatest new pill that costs dollars, and patients clamor for medications that they really know little about.

As a doctor, I feel a responsibility not to betray my patients’ safety. But it will take more than a feeling of responsibility if we’re going to put the brakes on this speeding train.

Marc Siegel is an internist and an associate professor of medicine at New York University School of Medicine.

C 2004 The Washington Post Company