As we reported earlier today, new research has discovered that pharmaceutical companies withheld a handful of nonsignificant and negative data from publication when working to get the U.S. Food and Drug Administration (FDA) to approve atypical antipsychotics. However, the problem was significantly less severe than the publication bias researchers found when looking at antidepressants.
Antidepressants have been especially hard hit when looking at the FDA pre-approval research. In fact, in Lesley Stahl’s recent 60 Minutes report on antidepressant research, she walked away completely baffled by the meaning of it all. What does it mean when researchers find such negative findings that were never published?
Let’s find out…
In the current research, scientists examined 24 FDA pre-marketing studies for eight second-generation antipsychotics (also referred to as atypical antipsychotics):
- aripiprazole (Abilify)
- iloperidone (Fanapt)
- olanzapine (Zyprexa)
- paliperidone (Invega)
- quetiapine (Seroquel)
- risperidone (Risperdal)
- risperidone long-acting injection (Consta)
- ziprasidone (Geodon)
The researchers then compared the results in the FDA’s review documents to the results presented in medical journals. Ideally, they would expect to find 24 published studies, but instead they could only find 20:
[… F]our premarketing trials submitted to the FDA — which yielded unflattering results — remained unpublished. Three showed the new antipsychotic drugs had no significant advantage over a placebo.
In the fourth, the drug was superior to a placebo, but it was significantly inferior to a much less expensive competing drug, the researchers note.
Just 17 percent of studies were not published, which is actually lower than the industry average for new drug approvals winding their way through the FDA process.
And this isn’t nearly as bad as the data — 40 percent of the studies were never published — surrounding antidepressants:
In 1998 Moore used the Freedom of Information Act to pry such data from the FDA. The total came to 47 company-sponsored studies—on Prozac, Paxil, Zoloft, Effexor, Serzone, and Celexa—that Kirsch and colleagues then pored over. (As an aside, it turned out that about 40 percent of the clinical trials had never been published. That is significantly higher than for other classes of drugs, says Lisa Bero of the University of California, San Francisco; overall, 22 percent of clinical trials of drugs are not published. “By and large,” says Kirsch, “the unpublished studies were those that had failed to show a significant benefit from taking the actual drug.”)
In just over half of the published and unpublished studies, he and colleagues reported in 2002, the drug alleviated depression no better than a placebo. “And the extra benefit of antidepressants was even less than we saw when we analyzed only published studies,” Kirsch recalls. About 82 percent of the response to antidepressants — not the 75 percent he had calculated from examining only published studies — had also been achieved by a dummy pill.
The important thing to keep in mind is that pre-marketing research is conducted primarily in order to get a drug through the FDA process. It is not the final word on a drug’s effectiveness, it is simply a bureaucratic hurdle drug companies must cross in order to get their drug on the market.
Once on the market, dozens — and in the case of antidepressants, hundreds — of additional studies are carried out. These studies, which are often more varied, independent, and done by a wider range of researchers, eventually make up the majority of a drug’s efficacy research.
So the silver lining on this latest research is that the percentage of studies never published is actually lower than the industry average, and significantly lower than the number of studies never published before antidepressants were approved.
Read the full news article: Publication Bias May Give MDs an Incomplete Picture of Antipsychotics
Turner, E.H., Knoepflmacher, D., & Shapley, L. (2012). Publication Bias in Antipsychotic Trials: An Analysis of Efficacy Comparing the Published Literature to the US Food and Drug Administration Database. PLoS Medicine, 9(3): e1001189. doi:10.1371/journal.pmed.1001189