The Problem With Drug Clinical Trials

It’s bad enough when a medication for asthma, hypertension or anything else doesn’t do what it’s supposed to. Even more exasperating is knowing that the way the system of drug discovery and testing is set up, it’s practically guaranteed to produce medications that will not help a lot of the people they’re aimed at.

The reason is that, in order to participate in a clinical trial that the manufacturer runs to test whether an experimental compound is effective, you need to be sick but not too sick. Often, if you have something other than the illness the drug is targeted at, you don’t qualify. Thanks to this and other problems, conclude scientists at the University of Pittsburgh Graduate School of Public Health, the results of clinical studies used to get federal approval for common antidepressants do not apply for most patients with depression.

For their paper in the May issue of the, epidemiologist Stephen Wisniewski and his colleagues compared depressed patients who met the criteria for joining a phase III clinical trial (which compares the experimental compound to a placebo) of antidepressants to those who did not. Although the inclusion criteria vary from study to study and are not subject to federal guidelines (the manufacturer gets to decide who’s in and who’s out),  patients with milder forms of depression are typically excluded (they’re more likely to respond to the placebo, making the experimental drug look less effective by comparison). Excluded, too, are patients with chronic depression (they're harder to get a response from, also making the new drug look ineffective) or with additional psychiatric and medical illnesses (who might show dangerous side effects or not respond to the drug).

So, how many patients with depression are thereby excluded? Assessing 2,855 patients treated with citalopram (sold by Forest Labs as Celexa), the scientists find that only 22 percent of people with depression qualify for phase III clinical trials of antidepressants. That means that 78 percent of people with depression are getting the supposedly helpful drug, even though there are no data on whether it is safe and effective in people like them. “This raises major concerns about whether results from traditional phase III studies can be generalized to most people with depression, who also often suffer from anxiety, substance abuse and other medical and psychiatric problems,” said Wisniewski.

The concern is not merely hypothetical. When the scientists assessed how well patients did on antidepressants, they found that those few who would have been eligible for the clinical trial had higher remission rates (34 percent vs. 25 percent for the ineligible patients), and fewer serious side effects and adverse events. The clinical trials that serve as the basis for getting a new drug approved—and that the press trumpets as indicating how effective a drug is—“suggest more optimistic outcomes than may exist for real-world patients” with depression,” said Wisniewski.

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