Much ado about clinical trials

September 1, 2004

How objective are the published results of clinical trials? The question has been simmering for years, but anxieties surrounding the matter recently reached the boiling point in the dispute over a

How objective are the published results of clinical trials? The question has been simmering for years, but anxieties surrounding the matter recently reached the boiling point in the dispute over a possible link between antidepressant medications and suicide. (For a review of the controversy, see Updates in the July 2003 issue of Contemporary Pediatrics.) In brief, critics of the current system charge that:

In the case of selective serotonin reuptake inhibitor (SSRI) antidepressant drugs, British health authorities cited the case of citalopram (Celexa): Positive results of a clinical trial were published in the June 2004 issue of the American Journal of Psychiatry, whereas the only published citation of a different trial that yielded negative results was in a textbook written in Danish-presumably seen by few, if any, clinicians worldwide. Researchers from Britain's National Collaborating Centre for Mental Health have requested a full report of the unpublished study from the Danish manufacturer. British authorities have banned the use of all SSRIs except fluoxetine (Prozac) in patients younger than 18 years. In the United States, New York State Attorney General Eliot Spitzer has sued the manufacturer of paroxetine (Paxil) for failure to publicize negative studies.

The SSRI imbroglio is not the first such situation in the complicated world of clinical trials-only the most recent. Pharmaceutical manufacturers, who foot the bill for clinical trials of the drugs they are developing, naturally have an interest in publicizing positive results and soft-pedaling what is less than positive. Finding a counterweight will not be easy, but one solution that has been publicized is to create a public registry of clinical trials. The American Medical Association has called for an inclusive registry of this kind, so that clinicians who read a glowing report on a new drug would know where to check for potential contradictory results. The federal government already maintains a limited registry ( http://www.clinicaltrials.gov/), which could, possibly, be expanded to include trials funded by manufacturers and educational institutions, as well as those funded by government. The FDA receives such data, but does not make it available to the public.

So strong is the pressure for a corrective that the pharmaceutical industry is eagerly accepting the registry idea. So far, giants GlaxoSmithKline, Merck, Lilly, and Johnson & Johnson have supported the idea, and the industry's lobbying arm, PhRMA, has issued a cautious statement favoring the idea-in principle.

A registry will not solve the problem, but may represent a first step. Next might be full funding for a proposition being pushed by Senator Hillary Rodham Clinton (D-N.Y.): head-to-head testing of drugs intended to treat similar ailments. After all, Senator Clinton has said, "When Consumer Reports reviews cars, they don't compare the performance of a new car to walking. They compare it to other cars in its class. Why can't we have the same type of information for the medications we take?"