Prescription anxiety

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Tue, 21 Sep 2004 23:15:28 -0400

[sSRI-Research] Prescription anxiety

 

 

 

Prescription anxiety

 

By Jerry Avorn | September 20, 2004

 

 

http://www.boston.com/news/globe/editorial_opinion/oped/articles/2004/09/20/pres\

cription_anxiety?mode==PF

 

THE CONTROVERSY over whether antidepressants increase the risk

of suicide in young people is evidence of major flaws in how we

develop, evaluate, promote, and use prescription drugs. The first

medicine in this class was introduced more than 15 years ago; they

have since become some of the most widely ingested medications in

America. Why did it remain unclear for so long whether these products

can cause a potentially fatal side effect in children?

 

Most Americans are surprised to learn that the Food and Drug

Administration does not test drugs itself; instead, it nearly always

relies on studies conducted by their manufacturers. These

pre-marketing trials are usually held to standards so low that their

results just can't provide the information that I as a doctor need in

order to think intelligently about giving prescriptions.

 

In general, a company can win FDA approval for a new drug by

showing that it works better than a sugar pill over a time frame that

can be remarkably brief -- as short as eight to 12 weeks, even for

drugs that may be taken for years. A manufacturer can conduct multiple

studies, many of which might produce negative results. But as long as

it can submit two positive trials, the agency is likely to approve

marketing. (The results of the other studies may be buried.)

Complicated patients, such as the elderly, the chronically ill, and

children are often underrepresented in such clinical trials -- or left

out entirely.

 

Side effects can be missed if they occur only with prolonged

use, in combination with other drugs, or in vulnerable populations.

And such studies don't begin to answer whether a new drug is better

than existing alternatives or what its effects will be over a lifetime

of use.

 

The very questions I most need answered in choosing a medication

are ignored in such quick pre-approval studies, because the FDA does

not require that they even be asked. This approach may not be ideal

for doctors or patients, but it works well for pharmaceutical

companies in several ways: It holds down the costs of clinical trials

and avoids revealing that a new product is no better than existing

medicines, which is often the case.

 

After a drug is approved, the FDA does sometimes ask

manufacturers to perform systematic post-marketing studies of the

effects of their products once they are in widespread use. But in a

report last year assessing its portfolio of active surveillance

projects, the agency admitted that fully half the studies it mandated

had not even been started.

 

All drugs that work have risks, and the goal of wise prescribing

-- and of wise public policy -- is to understand those risks so they

can be weighed against a drug's benefits. Here again our regulatory

apparatus and the pharmaceutical industry have let us down. In order

to persuade (some would say bribe) companies to measure the effects of

their products in children, the federal government agreed to give

lucrative six-month patent extensions to companies if they tested

their drugs in this age group. All that was required was testing --

again, against placebo. Patent extension was granted regardless of

what those tests showed. Many of these trials were small, brief, and

underpowered. For drugs like Paxil and Zoloft, they failed to provide

evidence of a clinical benefit against which the emerging information

on risk could have been compared.

 

The problem runs even deeper. Just as the pharmaceutical

industry has hegemony over most drug testing, it also controls much of

the information that doctors and patients see about the safety and

effectiveness of its products. This is usually accomplished through

the ubiquitous din of promotion to physicians and consumers that

drives so much drug prescribing and taking. But now we learn that

there is also a larger problem. Doctors and the public never got to

see vital negative information about antidepressants in adolescents

that was present in company-sponsored trials.

 

Several of those studies found that the drugs failed to help

patients and increased the risk of suicide. Even more shamefully, the

FDA discounted a thorough analysis of clinical trial data that was

performed last year by one of its own scientists, documenting a higher

risk of self-harm in young people assigned to take antidepressants

rather than placebo. This finding has now been confirmed in an

analysis by researchers at Columbia University that was released at

last week's FDA hearings.

 

Ironically, the antidepressant-suicide debate follows a recent

Bush administration proposal that would prohibit legal action against

drug companies over any product the FDA had approved. The lapses now

being uncovered in companies' disclosures of their own antidepressant

trial data, and the FDA's occasional tendency to underestimate drugs'

potential for lethal side effects, make it clear how counterproductive

this policy would be. Some of the most relevant hidden information on

adverse drug effects can be discovered by attorneys in the course of

litigation on behalf of patients who have been harmed. This may be a

weird way for a nation to conduct drug safety research, but unless we

do a better job through conventional means, it isn't one we should

discard.

 

The FDA continues to devote inadequate attention to measuring

the risk-benefit relationships of the drugs it approves. The nation

requires a more effective approach to these vital questions, beginning

with more head-to-head comparisons of drugs for effectiveness and

safety, and continuing with a robust system of post-marketing

surveillance.

 

The public also deserves access to a complete reckoning of the

findings of all clinical trials conducted by companies in testing

their products; no results should be hidden in the name of corporate

prerogative. In a healthcare system as rich as ours, we physicians

should not have to rely on attorneys general, tort lawyers,

journalists, and whistleblowers to uncover the facts we need about the

risks and benefits of the medications we prescribe.

 

Dr. Jerry Avorn, an internist and associate professor of

medicine at Harvard Medical School, is the author of " Powerful

Medicines: the Benefits, Risks, and Costs of Prescription Drugs. "