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Thursday, January 9, 2014

Nearly One-Third of Large Clinical Trials Go Unpublished — in Neurology, Too

By Gina Shaw

Nearly one-third of large clinical trials remain unpublished some five years after completion, according to an October 2013 analysis published in the British Medical Journal (BMJ). Using the database, the authors identified 585 trials involving 500 or more participants that were completed prior to January 2009. Published results could not be found in the literature for 171 (29 percent) of those trials, involving nearly 300,000 study participants. Industry-sponsored trials were significantly more likely to go unreported than those that had no industry funding (32 percent vs. 18 percent, p=0.003).

           Although authors did not break down their findings by specialty, lead author Christopher W. Jones, MD, now an attending physician in the department of emergency medicine at Cooper Medical School of Rowan University in New Jersey, reviewed the study data at Neurology Today’s request.

He found 29 neurology-specific trials, eight of which remained unpublished — a non-publication rate of 28 percent. “The non-publication rate for Alzheimer trials was particularly bad, with five of the eight trials being unpublished,” Dr. Jones said.

These findings aren’t particularly surprising: “publication bias” is a longstanding problem in biomedical science. It’s well known that studies with negative findings, especially those sponsored by industry, often never see the light of PubMed, the National Library of Medicine database of biomedical abstracts.

The problem isn’t limited to any one specialty. A 2008 New England Journal of Medicine analysis of antidepressant studies filed with the Food and Drug Administration (FDA) found that 67 percent of trials deemed negative by the agency went unpublished. And it’s been estimated that only one in five oncology drug trials ever has its results published.

But the new analysis adds to this picture by focusing only on large trials involving 500-plus participants. “This hasn’t really been done before, and we weren’t sure if it would be an issue in really large studies,” said Dr. Jones. “We were hoping that it wouldn’t be as big a problem, because in general, these are studies that have been intended to be published all along. They are going to be attractive to journal editors and shouldn’t be prohibitively difficult to get published, and they are very important in terms of informing clinical practice. The considerable time and expense involved in running trials of this size suggests that non-publication is a conscious decision by the sponsors.”

Pressure from drug and device manufacturers to withhold negative data about their products is a longstanding problem. Walter Koroshetz, MD, deputy director of the National Institute of Neurological Disorders and Stroke, recalled a stroke trial from more than a decade ago that was particularly controversial. “The investigator stood up at a national meeting to say that he’d been warned by legal professionals that he could not present the data that he had planned to present. And then he sat down. Everyone present was very upset.”

The creation of journals that are specifically focused on publishing negative results — such as the Journal of Negative Results in Biomedicine — may help to assuage the lack of interest among the usual array of journals in publishing such findings.

For an extended discussion of the BMJ study and its implications, as well proposed solutions to low publication rates for “negative” trial data, see the upcoming Jan. 16 issue of Neurology Today.


On Jan. 7, Neurology joined the ranks of medical journals willing to publish negative studies. In their call to action for “negative” outcome studies, Neurology Deputy Editor David K. Knopman, MD, and Editor-in-chief Robert A. Gross, MD, PhD, wrote: Neurology® believes it is important to advance research related to neurologic disease and that well-designed studies on important clinical topics should be published, whether or not the results are ‘positive.’" In fact, the publication has “committed additional space” expressly for this purpose.