[OT] Antidepressants Under Scrutiny Over Efficacy

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Antidepressants Under Scrutiny Over Efficacy

Sweeping Overview Suggests Suppression of Negative Data Has Distorted View of

Drugs

By DAVID ARMSTRONG and KEITH J. WINSTEIN

January 17, 2008; Page D1

The effectiveness of a dozen popular antidepressants has been exaggerated by

selective publication of favorable results, according to a review of unpublished

data submitted to the Food and Drug Administration.

As a result, doctors and patients are getting a distorted view of how well

blockbuster antidepressants like Wyeth's Effexor and Pfizer Inc.'s Zoloft really

work, researchers asserted in this week's New England Journal of Medicine.

Since the overwhelming amount of published data on the drugs show they are

effective, doctors unaware of the unpublished data are making inappropriate

prescribing decisions that aren't in the best interest of their patients,

according to researchers led by k , a psychiatrist at Oregon Health &

Science University. Sales of antidepressants total about $21 billion a year,

according to IMS Health.

Wyeth and Pfizer declined to comment on the study results. Both companies said

they had committed to disclose all study results, although not necessarily in

medical journals. GlaxoKline PLC, maker of Wellbutrin and Paxil, said it

has posted the results of more than 3,000 trials involving 82 medications on its

Web site, and also has filed information on 1,060 continuing trials at a federal

government Web site.

Schering-Plough Corp., whose Organon Corp. unit markets Remeron, and Eli Lilly &

Co., which makes Prozac, said their study results were indeed published -- not

individually, but as part of larger medical articles that combined data from

more than one study at a time. The New England Journal study counted a clinical

trial as published only if it was the sole subject of an article. " Lilly has a

policy that we disclose and publish all the results from our clinical trials,

regardless of the outcomes from them, " a Lilly spokeswoman said.

Pharmaceutical companies are under no obligation to publish the studies they

sponsor and submit to the FDA, nor are the researchers they hire to do the work.

The researchers publishing in the New England Journal were able to identify

unpublished studies by obtaining and comparing documents filed by the companies

with the FDA against databases of medical publications.

" There is no effort on the part of the FDA to withhold or to not post drug

review documents, " an FDA representative said. For newer drugs, information is

posted online " as soon as possible. " Older documents aren't always available

online and efforts to add those files to the Web are slowed by " a lack of

resources, " the agency said, acknowledging that there is a backlog in complying

with records requests.

A total of 74 studies involving a dozen antidepressants and 12,564 patients were

registered with the FDA from 1987 through 2004. The FDA considered 38 of the

studies to be positive. All but one of those studies was published, the

researchers said.

The other 36 were found to have negative or questionable results by the FDA.

Most of those studies -- 22 out of 36 -- weren't published, the researchers

found. Of the 14 that were published, the researchers said at least 11 of those

studies mischaracterized the results and presented a negative study as positive.

Five Trials

For example, Pfizer submitted five trials on its drug Zoloft to the FDA, the

study says. The drug seemed to work better than the placebo in two of them. In

three other trials, the placebo did just as well at reducing indications of

depression. Only the two favorable trials were published, researchers found, and

Pfizer discusses only the positive results in Zoloft's literature for doctors.

One way of turning the study results upside down is to ignore a negative finding

for the " primary outcome " -- the main question the study was designed to answer

-- and highlight a positive secondary outcome. In nine of the negative studies

that were published, the authors simply omitted any mention of the primary

outcome, the researchers said.

The resulting publication bias threatens to skew the medical professional's

understanding of how effective a drug is for a particular condition, the

researchers say. This is particularly significant as the growing movement toward

" evidence-based medicine " depends on analysis of published studies to make

treatment decisions.

Full story

http://online.wsj.com/article_print/SB120051950205895415.html