Unfavorable Drug Studies Don’t Get Published

As this story by Reuters reports and this more in-depth analysis by the Wall Street Journal notes, negative studies rarely get published. Without such information being made available to the public, the public — including doctors who do the prescribing — get a skewed view on a drug’s effectiveness.

The Wall Street Journal article puts the blame squarely on drug companies’ failure to submit such studies for publication. But the story is more complex than that, as the researchers themselves note.

The new study, published in this week’s New England Journal of Medicine, found that, “Nearly a third of antidepressant drug studies are never published in the medical literature and nearly all happen to show that the drug being tested did not work. In some of the studies that are published, unfavorable results have been recast to make the medicine appear more effective than it really is.”

“Of the 74 studies that started for the 12 antidepressants, 38 produced positive results for the drug. All but one of those studies were published. However, when it came to the 36 studies with negative or questionable results, as assessed by the FDA, only three were published and another 11 were turned around and written as if the drug had worked.”

Because this information was hidden from public view and not readily available to other researchers, it had a real influence on the impression of a drug’s effectiveness. This graphic says it all:

The overall impression of the effectiveness of antidepressant drugs like Serzone, Zoloft, Remeron and Wellbutrin were inflated because of the lack of information about the negative studies.

Some companies have since changed their policies, as the WSJ article notes. GlaxoSmithKline (maker of Paxil and Wellbutrin) makes all of its study results available on its website. Two other companies, Schering-Plough and Eli Lilly, noted that all of their clinical trials data were indeed published, just not as individual studies (somebody would actually have go and do some additional research to see whether these claims are true). Wyeth and Pfizer had no comment and apparently have no policy of ensuring all of its clinical trial data — positive or negative — see the light of day.

The article notes that the problem isn’t just with the drug companies, but also with journal editors and publishers, who rarely accept for publication studies that show no positive impact of the treatment under study.

This finding shouldn’t be surprising to professionals within the field, as studies that show no effectiveness have long sat on the sidelines of journals. Journals want to publish stuff that shows XYZ treatment works, not that stuff doesn’t work. In fact, it would be interesting if someone did a parallel study to examine how many negative-effects antidepressant drug studies were submitted to journals only to be rejected.

If more companies take it upon themselves to ensure all negative results also find a way to publication (whether in a journal or not really isn’t as important as simply providing the information and making it available through some public means), this problem will likely be resolved. And if the companies don’t want to take it upon themselves to do so, the FDA should make it a new requirement before accepting any new drug applications from the company.