Drug Rush.

• Author: POMPER, STEPHEN
• Position: Hazards associated with fast new drug approvals

Why the prescription drug market is unsafe at high speeds

THE DRUG WORLD THAT AMERICANS once worried about was a shadowy demi-monde populated by hollow-eyed junkies toting needles, spoons, and Jefferson Airplane LPs. But times have changed, and a new drug culture requires our attention. The pushers in this culture wear lab coats and business suits and move their product through HMOs and family doctors. And although their drugs may be government regulated, that does not make them safe. According to statistics cited by Food and Drug Administration officials, toxic reactions to marketed drugs are estimated to cost more than $30 billion per year and be among the ten leading causes of death in the United States.

You might think that under the circumstances, the government would be pouring enormous resources into evaluating the hows and whys of prescription drug fatalities, but it is not. Industry-supported reforms have provided the FDA major resources to focus on the approval of new drugs, but once these drugs are out in the market, the picture changes dramatically. The group that keeps track of whether these drugs are hurting the people who are taking them is one of the agency's weakest stepchildren. It has limited clout within the FDA. It scrapes by on between $10 and $15 million a year--less than what Eli Lilly was estimated to spend on its 1997 Prozac ad campaign according to The New York Times. It relies on voluntary and unreliable reporting by doctors for most of its information. In the words of Carol Scheman, an FDA deputy commissioner in the 1990s, the nation's system for keeping track of the bad effects of prescription drugs is "appallingly bad."

That's particularly lousy news when you consider the speed at which new drugs are being approved and the remarkably aggressive, almost reckless, promotional efforts that go into making them sell. Consider that six new drugs approved since mid-1996 have been pulled off the market, one of the most recent being the diabetes drug Rezulin. Larry Sasich of Public Citizen's Health Research Group points out that all six of them were "me too" drugs: They treated symptoms that were already treatable with existing medications. Nevertheless, millions of prescriptions were written, and more than 150 deaths were linked to these medicines before they were pulled off the market. And because reporting is unreliable, the actual body count could be up to 100 times greater.

Perhaps you're thinking fine, if the system is imperfect, at least doctors are protecting their patients from unsafe new drugs. But drug companies may push doctors to prescribe their drugs even when they're reported to be unsafe. Rezulin is a case in point. In January 1997, the FDA approved Rezulin under its accelerated "fast track" procedures following six months of testing. But it wasn't long before users started dying, the United Kingdom's Medicines Control Agency revoked its approval, and FDA insiders started working with the media--notably David Willman of the Los Angeles Times--to get the word out that Rezulin was just not safe.(*) In March 1999, with the death toll approaching 30, senior FDA epidemiologist David J. Graham publicly told an FDA advisory board that every single patient taking Rezulin was at risk of sudden liver failure. Given all this, and given that there were drugs on the market that treated the same type of diabetes as Rezulin and did not fry a patient's liver, why would a doctor still prescribe Rezulin?

You'd hate to think the answer could be: "Knicks tickets." In a fax that went out to select New York area physicians in spring 1999, Rezulin's manufacturer, Parke-Davis (a Warner Lambert subsidiary) invited guests to attend a "special scientific lecture" at "the Club Bar and Grille ... Madison Square Garden." After a short lecture and Q & A over dinner, the guests would be ushered down to their seats in the stadium where they would watch a "BASKETBALL GAME!!!! New York Knicks vs. Toronto Raptors." Perhaps you're thinking that it takes a certain amount of chutzpah to throw what is effectively a basketball party for a product that is widely suspected of killing people, but chutzpah is often what good business is all about.

The problem is, it's not always consistent with good medicine.

Maginot Line

As the nation's drug regulator, the Food and Drug Administration should be the first line of defense against drug companies that are pushing dangerous product. But asking the FDA to rein in the pharmaceuticals industry is a bit like sending someone out to catch Niagara Falls in a bucket. The industry has vastly greater resources to press its agenda. And changes in drug laws and regulations have encouraged a boom market for drugs that the agency is not equipped to police.

To get a feel for the mismatch in financial resources, consider the following: The FDAs annual budget for approving, labeling, and monitoring drugs is roughly $290 million. To that figure, add the $2 or $3 million available to Public Citizen's Health Research Group, which was formed to help even the balance between regulators and the drug industry. Now compare those numbers to the $11 billion promotional budget that the drug industry gives itself according to a recent article in the Journal of the American Medical Association.

In order to get a full picture of what the FDA is up against, however, you have to step back and see how dramatically the regulatory landscape has changed in the last decade. Back in the early 1990s, there was a widely shared perception that the FDA was too slow to approve new drugs even when they might offer desperately needed help for people who were dying. AIDS activists were particularly eager to light a fire under the approvals process out of concern that the FDA might be holding up life-saving or life-prolonging treatments. They were well connected and highly committed, and they had the support of an industry that wanted faster approvals for its own reasons. It therefore was no great surprise that in 1992 Congress passed a new law creating the blueprint for a faster approvals process. Under the new law, the FDA would hire more reviewers and take the other steps necessary to speed up reviews without sacrificing rigor, and industry would bear the additional costs by paying "user fees" with every new drug application.

But if AIDS helped to crack open the door for faster drug reviews, the pharmaceutical industry was standing right there to kick it wide open. The new law created a faster review process for all drugs--not just breakthrough treatments for diseases like AIDS. This meant that as approval times have dropped from 30 to 12 months on average, there has been a rush of newly approved drugs which do not offer the public any new treatment benefits, but which could pose new risks.

And to compound the impact of the newly-approved drugs, in 1997 the FDA yielded to years of industry pressure and loosened restrictions on consumer advertising. This made it possible for drug companies to advertise on television without spending huge chunks of time describing risks and side effects. Ads for new drugs like Viagra and Claritin became almost as familiar as Burger King commercials. New products generated blockbuster sales in a matter of months.

But while the changes have been a hit commercially, they have...