EDITORIAL - Sidney Wolfe & USA Today on the FDA and drugs approved and removed

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This Editorial appears in USA Today, December 27th, 2004 Page 14A. It

is in response to the newspaper's editorial staff opinion that follows.

Take drugs off the market

By Sidney Wolfe

Amid the furor involving pain drugs, it may be of interest to ponder the

theoretical problem of the Food and Drug Administration prematurely

deciding to ban a drug whose benefits outweigh its risks. But we must

confront the reality that during the past 10 years, there is

overwhelming evidence that the FDA repeatedly delayed withdrawing many

drugs long after clear, unequivocal evidence of risks that outweighed

any demonstrable benefits.

The often-failed FDA strategy of " risk management, " a dangerous interim

alternative to taking drugs off the market, has ensured that thousands

of people were injured or killed after certain drugs should have been

pulled.

A recent example is the diabetes drug Rezulin, first marketed in 1997.

By that December, it was taken off the market in the United Kingdom

because of liver damage, many cases having occurred in the United

States.

In July 1998, Public Citizen petitioned the FDA to ban the drug, which,

although lowering blood sugar by a different mechanism than earlier

diabetes drugs, had no evidence of improved mortality or morbidity. By

July 1998, there were 560 reported cases of liver damage, including 26

deaths.

After failed efforts at " risk management, " Rezulin was withdrawn from

the market in January 2000, by which time there were hundreds of

additional cases of liver damage and 63 deaths. Other belatedly banned

drugs include the painkiller Duract, the blood-pressure drug Posicor and

the cholesterol-lowering drug Baycol.

Decisions to approve or remove drugs must be based on adequate evidence

of both benefits and risks. For Vioxx, Celebrex and Bextra - the three

COX-2 inhibitor pain/arthritis drugs - at approval there was no evidence

that they were more effective than older drugs.

Only Vioxx, now withdrawn because of a significant increase in heart

attacks, proved to be less dangerous to the gastrointestinal tract than

older drugs. Celebrex and Bextra did not. Although at approval there was

no evidence of increased cardiac risk from Vioxx or Celebrex, less than

a year later a 2001 study on Vioxx found it was five times more likely

than naproxen (Aleve) to cause heart attacks, and a Celebrex study

prompted FDA concerns about cardiac risks for that drug.

Removing Celebrex from the market will be a major step forward for

public health. For naproxen, the evidence of its harm is preliminary at

best, and it is unlikely to pose cardiac risks as high as those

documented for Vioxx or Celebrex. There is no basis for removing it from

the market.

Unique risks without unique benefits should always be the algorithm for

removing drugs.

Sidney Wolfe is the director of Public Citizen's Health Research Group

and co-author of the new edition of Worst Pills, Best Pills. Public

Citizen's Web site, www.worstpills.org, lists what it says are safer

alternatives to 181 drugs.

_____________________________________________

The Previous Editorial by Dr. Wolfe was in response to the USA Today

Editorial Staff's opinion that follows:

The Vioxx/Celebrex dilemma: Who should take the risk?

" This is a very confusing situation, " a top Food and Drug Administration

scientist, Kweder, said of the controversy over Celebrex and

other popular pain relievers. If the FDA is confused, imagine the

feelings of doctors and patients caught in the backlash.

The story so far: Celebrex, along with Vioxx and Bextra, were a new

class of drugs that held great promise to relieve suffering from

arthritis without causing the digestive discomfort and bleeding

associated with older medications. They were heavily marketed, and sales

reached billions of dollars.

Three months ago, a study confirmed fears that Vioxx increased the risk

of heart attack and stroke. Now Vioxx is off the market, pulled by its

manufacturer, and last Thursday the FDA urged doctors to limit

prescriptions for Celebrex and Bextra.

The Vioxx debacle exposed a much larger danger: The FDA's monitoring of

new drugs is inept. Even after Vioxx was implicated in up to 40,000

deaths, the agency seemed to react only after one of its scientists,

Graham, turned whistleblower and told Congress that the FDA's

procedures guarantee that unsafe drugs remain on the market.

As we've noted previously, that problem needs to be addressed urgently.

Drugs that show Vioxx-like dangers should be removed, or their use

should be sharply restricted. But another danger is emerging: the risk

that overreaction will make helpful drugs unavailable to seriously ill

patients for whom significant risk is acceptable.

The consumer group Public Citizen, for instance, is urging that 181

drugs be taken off the market. Doing so, no doubt, would save some

lives. It also would relegate many others to pain, disability and

premature death.

Nearly half of Americans take at least one prescription drug, and rarely

are the safety issues clear-cut.

Consider Celebrex. A study released earlier this month found that

patients who received several times the typical dose had an increased

risk of heart attack and stroke. Previous studies showed the opposite.

Another new study found that Celebrex caused fewer heart problems than

naproxen (sold over the counter as Aleve).

If Celebrex were pulled from the market, millions who've found relief

from painful, disabling arthritis would have to switch to other

medicines such as ibuprofen or naproxen. But those drugs cause severe

gastrointestinal problems in some people, resulting in more than 16,000

deaths a year. Patients and doctors have to decide whether the potential

cardiac risk outweighs the drug's benefit.

Certainty about drugs is impossible because clinical trials before FDA

approval involve only a few thousand patients. New risks, or benefits,

can emerge once the drug is prescribed to millions. Vioxx, for example,

was showing promise for preventing precancerous colon polyps.

Overreaction can cause harm by:

*Delaying new drug approvals. Some patient-advocacy groups worry that

the FDA is slowing approval of new drugs for cancer and other deadly

diseases. Marqibo, a pill to treat an aggressive cancer that kills at

least half of all patients with it, was turned down for accelerated

approval earlier this month. That caution may be appropriate, but there

is another side: " The number of people who die because of delayed

approval far exceeds the number hurt by unsafe drugs, " says

of Abigail Alliance, a group that wants quicker access to new

drugs.

*Distorting the level of risk. Clinical studies often contradict each

other, and wide-ranging conclusions are drawn from small samples. In the

recently reported link between naproxen and cardiac risk, fewer than 3%

of the 2,500 elderly patients suffered heart attacks or strokes over

three years, a relatively small number for that age group. " We're being

given flash results based on single trials that haven't been properly

analyzed, " says Weber, associate dean of New York's Downstate

College of Medicine. " There may or may not be a safety problem. At this

point, we don't know. "

*Jeopardizing health. In October, the FDA ordered antidepressants to

carry tough labels warning of increased suicidal behavior in children.

Banning the drugs would have threatened the health of a million kids

getting relief from the agony of depression. The suicide rate in 15

nations has dropped by one-third during the past 15 years since these

drugs were introduced. The FDA was right to urge greater monitoring

instead.

Make no mistake: The FDA is badly off-track. It's not watching closely

enough to see that the drugs it approves are safe as well as effective.

But most often, the right solution will be to restrict a drug's use, not

to ban it.

Risk can be controlled.

It can't be eliminated.

I'll tell you where to go!

Mayo Clinic in Rochester

http://www.mayoclinic.org/rochester

s Hopkins Medicine

http://www.hopkinsmedicine.org