Cloning Kessler
A bad choice for the FDA.

n a remarkable scientific achievement that would seem a reversal of its opposition to human cloning, the Bush administration is prepared to create a carbon copy of David Kessler to run the Food and Drug Administration. He may not look like Kessler, but Vanderbilt University Vice Chancellor Alastair Wood has exactly the same political genes. Like Kessler, he is a doctor sponsored by a Republican senator — and a buddy of Senator Ted Kennedy, the guy who really nominates FDA commissioners. (Kessler's godfather with Kennedy ties was Orrin Hatch. Wood's is Senator Frist.)

And — thanks to advances in genetic technology — Wood will have something Kessler never had: the enthusiastic endorsement of Sidney Wolfe, who heads up Health Research, Public Citizen, an organization which, among other things, is devoted to undoing FDA reforms that require the agency to get lifesaving drugs to Americans faster. Wolfe has said: "This guy is clearly qualified… Wood has shown in his writings that he is willing to criticize the FDA and the pharmaceutical industry. That's exactly what we need."

Here's a little of what Wood wrote (in case the White House hasn't read it yet) and that has Wolfe so happy. In an article for The Journal of the American Medical Association (volume 281, May 12, 1999), entitled "The Safety of New Medicines: Asking the Right Questions," Wood wonders why so "many" people were "exposed" (his words — not mine) to drugs associated with serious and even fatal events before the drugs were withdrawn from the market. He further wonders why these drugs were even approved at all, since he believes that "none of the drugs was indicated for a life-threatening condition nor, in many cases, were they the only drugs available for that indication."

In doing so, Wood reveals a misunderstanding of medical practice and, more disturbingly, a willingness to assume that drug companies ignore deadly side effects in the development process, deliberately marketing those drugs because they place profits above the health of patients.

He writes: "For example, in the 11 months that bromfenac was available, it is remarkable that physicians prescribed this new nonsteroidal, known to elevate liver enzymes, to 2.5 million patients with acute pain, even though many well-tested similar drugs were available. How could a nonsteroidal for the treatment of pain, with a restriction that patients take it for no more than 10 days, be cost-effective for a pharmaceutical manufacturer to market?"

The implication here, of course, is that such a drug couldn't have been cost-effective unless it was marketed to be used beyond ten days, where elevated liver enzymes would be a serious problem. In other words, Wood was suggesting that the drug company can only make money by deliberately poisoning people.

Here are the rest of the facts, however. After a standard-time-track review — not the fast-track review Sid Wolfe fears — bromfenac was approved for acute pain only, and carried a warning about liver-enzyme elevation with prolonged use. Such elevations are "consistent with experience with other agents of its class," according to an article in the September 1999 issue of The Annals of Pharmacotherapy. Despite a strengthened warning of liver failure after extended use, physicians kept prescribing the drug for more than ten days at a time. The total number of liver failures, out of 2.5 million patients? Twelve — or .00048 percent of all patients. And as for a conspiracy to promote the drug for use beyond the ten-day period — thereby making it more "cost-effective" to market — it turns out that almost all of these cases occurred among an estimated 200,000 to 400,000 patients who took the drug for longer periods of time. That included patients who took the drug after a stronger warning about its side effects went out from both the FDA and the company.

Wood calls it "surprising" that Seldane, an allergy drug, was — as he put it — "removed from the market, not when the adverse events were identified, but after the manufacturer had developed a new product to substitute for it." Yet the first adverse event, ventricular tachycardia, was identified in 1990. At the time, it was assumed that tachycardia was a result of an interaction between Seldane and certain antibiotics and antifungals.

Thereafter, nearly a hundred articles researched and discussed the possible hazards of this combination. Seldane's developers issued warning letters and sponsored research into possible other interactions. As a result, use of Seldane with drugs that might cause the deadly reaction declined by nearly 60 percent. The rate of Seldane prescribing dropped as well. The drug was withdrawn from market because despite these efforts, the combined use and prescribing of Seldane and certain antibiotics and antifungals continued.

What is remarkable is that while prescription-drug use has increased in the past decade, the number of adverse events as a percentage of total prescriptions has hardly budged. Drug withdrawals as a percentage of new drugs remains at about 3 percent, essentially the same ratio from decades ago.

Wood ignores this safety record. Instead, he calls for companies to adhere to an impossible safety standard: "Manufacturers should behave responsibly in the promotion of new drugs for which toxicity is, by definition, currently unknown." Further, "to encourage such responsibility direct to consumer advertising should be permitted only for drugs that have undergone a monitored post marketing testing process that would include a sufficient number of patients to provide adequate confidence in their safety for widespread clinical use. This step could help prevent the excessively rapid uptake of new drugs at a rate that exceeds the capacity available to review their safety in practice."

Translation: FDA to patients: Drop dead. It's troubling enough that a proposal to link marketing to an unclear and shifting post-marketing safety standard would likely be unconstitutional and smacks of regulatory overreach. Worse, it would compromise the public health.

In Wood's world, doctors shouldn't get access to new drugs and shouldn't learn about them because drug companies have no idea what side effects lie ahead as a drug moves from the pristine environment of a clinical trial into the real world. So for example, if a new drug for diabetes, depression, cancer, AIDS, or heart failure had some terrific benefits, but months or years after it was on the market some questions about side effects came up that no one could anticipate, patients would be denied direct access to information about these drugs until companies went through yet another round of clinical trials or studies — a process that could take months. It would also mean that new dosing levels and new uses for existing drugs could not be promoted or widely disseminated unless companies provided his FDA "adequate confidence in their safety for widespread clinical use."

Finally Wood questions the value of bringing another drug for the same illness to market. But if one or more drug has side effects that are dangerous to a group of patients or if some people don't respond to a particular drug, isn't that reason enough to for people to be free to have it available. Or does Dr. Wood, like Kessler before him, believe that the FDA is the best arbiter of whose life is worth living or cutting short? Like his cheering section in the Public Citizen, does he have contempt for private pharmaceutical profits that blinds and biases him against the right of companies to develop and market products based on their ability to make a clinical difference in people's lives? These are questions the Bush administration should have asked before they decided to clone another Kessler.