Drug Recalls Put FDA on the Hot Seat

[Guest guest]

Drug Recalls Put FDA on the Hot Seat

Apr. 3 (The Star-Ledger/KRTBN)--Another new drug, another recall. Or so it

would

appear.

Last month, drug makers yanked two widely used medicines from pharmacy shelves:

the controversial Rezulin diabetes pill and the Propulsid heartburn medication.

The withdrawals marked the sixth time in three years that relatively new drugs

were taken off the market after causing deaths or very serious side effects.

The string of recalls, which began in the fall of 1997 with two popular diet

pills, raises anew questions about whether the speedy approval process demanded

in recent years by Congress and the pharmaceutical industry is flawed -- and

unnecessarily exposing more consumers to drugs that later prove to be especially

harmful.

The episode is also training a harsh spotlight on the Food and Drug

Administration, which is being chastised for not moving faster to remove

problematic drugs. Although the agency maintains the number of withdrawals

proves it's getting tough on troubled drugs, critics charge the FDA is actually

beholden to drug makers.

" These withdrawals, and there are nine of them when you include older drugs

recently withdrawn, are just evidence that an unprecedented number of Americans

are being subjected to unsafe drugs, " said , a health policy analyst

at Washington Medical Center who wrote " Prescription for Disaster, " a

book about drug safety.

" I believe there's been a policy change here. The FDA is more interested in

listening to industry rather than their own experts. And the policies are very

beneficial to the industry's bottom line. Even after the problems (with certain

recalled drugs) became known, they remained on the market for a time and sold at

a huge clip. "

In particular, the circumstances surrounding Rezulin have prompted a flurry of

finger-pointing. The FDA is investigating whether Warner-Lambert Co., which sold

the drug, withheld data about its toxic effect on the liver. And members of

Congress want hearings into FDA conduct after the agency investigated its own

employees for leaking information.

Approved in 1997, Rezulin was hailed as a breakthrough drug that did a better

job of controlling Type II diabetes than existing treatments. It was used by

nearly 1.9 million Americans and eventually racked up $1.8 billion in sales. But

it was also quickly linked to a number of deaths and liver failures, sparking an

unusually heated debate within the FDA.

The bureaucratic brawl -- which was made public by an FDA whistleblower -- has

riveted Congress, Wall Street, the medical community and the drug industry.

After all, nothing less than the careers of regulators, the fortunes of company

chieftains and the lives of millions of patients are at stake in shaping the

drug-approval process.

" It's all just incredible, " said Hemant Shah, an independent securities analyst

who tracks the drug industry, following the back-to-back recalls two weeks ago

of Rezulin and Propulsid. " Here, you have nine recalls in three years. This has

to have an impact on the way drugs are approved. "

For the moment, it's not clear whether these incidents will alter the approval

process. But the FDA is clearly on the defensive. Last year, top agency

officials defended their track record in an article in the Journal of the

American Medical Association. Next month, they plan to make a public

presentation to explain their actions regarding Rezulin.

" I think we made the right decision on Rezulin, " said Janet Woodcock, who heads

the FDA's Center for Drug Evaluation and Research, which approves medicines.

" The drug was labeled and people got information that the drug could cause

serious liver problems and death.

" You could say that any drug we put on the market causes serious harm, and so

you could say the toll is going to grow for every day a drug is left on the

market. But every time we approve a drug, we know it's going to harm people.

Many will benefit, and a few will have serious side effects. That's what we have

to live with. "

Certainly, the issue is complicated. Dozens of drugs, some representing genuine

breakthroughs, are approved each year to treat or cure a wide array of maladies.

During the 1990s, 370 medicines were approved, up 55 percent from 239 in the

previous decade, according to the Pharmaceutical Research and Manufacturers of

America, the industry trade group.

" The industry's ever-increasing investment in research, the improving efficiency

of the FDA, the quantum leaps in science now being made and the already full

pharmaceutical pipeline provide concrete hope of continuing and accelerated

progress against disease, " said Alan Holmer, the trade group's director, in a

recent statement touting the approvals.

But drug makers must also please investors with hot-selling medicines that can

quickly bolster profits. And faced with rising costs to develop drugs, they're

working overtime to pitch doctors, health plans and consumers, while also

pushing for legislation to extend patents. All this makes it crucial to win

faster approval for new drugs.

Industry leaders, however, say they aren't surprised by the rising number of

withdrawals. Rather, they see this development as the logical outcome of a

delicate balancing act between the public's desire for more and better

medications, and the risks inherent in allowing a growing stable of drugs on the

market in a relatively short period of time.

" You can debate whether the FDA acted fast enough in withdrawing Rezulin or any

other drug, " said Fred Hassan, chief executive of Pharmacia & Upjohn Inc. " The

problem is that if you want medicines fast, you're going to have unexpected

findings with some products. Ultimately, I believe the problems depend on the

quality of the products. "

This debate first flared two years ago, shortly after the Duract painkiller and

the Posicor heart drug were pulled off the market, each within a year of being

approved. Those recalls followed the fall 1997 withdrawal of the Redux diet

pill, along with one of the drugs in the fen-phen combination. Redux had been

approved by the FDA only a year earlier.

Meanwhile, warnings were issued over other newly approved drugs, such as the

Viagra impotence pill, which became available in 1998 and has since been linked

to cardiovascular side effects. And Rezulin consistently made headlines as

serious new warnings were issued by the FDA no less than four times as the

number of deaths and cases of liver failures rose.

The rash of withdrawals and warnings sparked an outcry over the wisdom of a 1992

law passed by Congress, and renewed in 1997, to facilitate faster drug

approvals. Under that law, the drug industry agreed to pay the tab for more FDA

staff to review new drugs, along with a guarantee that decisions be made quicker

every year.

But critics compare the number of recalls with just eight between 1980 and 1993,

and none between 1994 and 1996. The list is growing -- last year, the Raxar

antibiotic was recalled, and the Trovan antibiotic was restricted to hospitals

and nursing homes. Both were approved in 1997. And Hismanal, a 10-year-old

antihistamine, was yanked.

Nothing, though, has galvanized attention as much as Rezulin. While two similar,

apparently safer drugs were approved last year, the diabetes pill remained on

the market until March 21. But behind the scenes FDA officials and some of their

own medical reviewers spent months fighting about the damage caused by the drug.

The battle intensified as agency e-mail notes and memos found their way to

Congress and, later, the media. Meanwhile, Sobel, a long-standing FDA

supervisor who oversaw the approval of Redux and Rezulin, was kicked upstairs to

a senior administrative post, a move FDA sources interpreted as a means of

shifting blame for problem drugs.

And last month, the FDA began investigating Misbin, one of its own

medical reviewers, for leaking agency documents about Rezulin. Another reviewer,

Leo Lutwak, was recently interrogated by FDA investigators and threatened with a

five-year jail term in connection with the inquiry into Misbin. Lutwak was also

involved in reviewing Redux.

Public Citizen Health Research Group, a nonprofit organization and outspoken FDA

critic, cited these developments in a recent letter to Donna Shalala, who heads

U.S. Health and Human Services, charging the regulatory agency with conducting

the equivalent of a witch hunt instead of investigating problem drugs.

" For many dedicated FDA scientists, the atmosphere has become poisoned and

repressive, " wrote Sidney Wolfe, who heads the group and demanded the agency

implement the government code of ethics. " Until this is done, the FDA will

continue to make additional serious mistakes regarding drug safety. "

Similarly, U.S. Rep. Tom Bliley, who heads the House Commerce Committee, which

oversees the agency, wrote FDA commissioner Jane Henney to complain about

retaliation against Misbin. " Misbin has been a public FDA critic for years, but

it appears that only after Misbin wrote to certain members of Congress has he

now been targeted, " Bliley wrote.

The FDA's Woodcock declined to comment specifically about what she called

" personnel matters. " But she did offer that agency employees are " free to speak

their minds, if they don't identify themselves as agency spokespeople. But

agency people can't release information. It's against the law. "

As for the agency's recent track record in approving -- and handling -- problem

drugs, Woodcock went on the offensive.

" I feel the obsession with counting withdrawals is a red herring, " she said.

" I'm really baffled why people think it'd be safer if we took longer to approve

drugs. Do you think we can make drugs safer by reviewing them slower?

" The percentage of drugs withdrawn versus approved is down, and the number of

serious events that have had to be added to the labels dropped from 50 percent

to 30 percent, " she continued. " It's so easy for people to say we're going down

the tubes. But the idea that we're doing a worse job is wrong. We're finding

problems earlier.

" We're changing our posture. We're becoming more aggressive. We're taking a

stronger role and that's why more drugs are being taken off the market. You

know, over time, in different fields, standards change. It's ironic, though,

that the very same statistic is being used as a measure of failure. "

But Tom , of the Washington Medical Center, disagreed. " They're

playing a numbers-crunching game. Look at Hismanal, Seldane, Propulsid, not just

Rezulin. They knew about problems associated with these drugs for months. They

had the knowledge to act and they failed to act.

" Instead, we have an FDA investigating leaks and engaging in spin control --

they routinely release important information after the deadline for major media.

Until their priority is shifted in a major way, we're going to continue to have

dangerous drugs. "

By R. Silverman