Failure to Account for Clinical Trial Drop-Outs Skews Results

Elie A. Akl, MD, PhD.

Elie A. Akl, MD, PhD

Published July 2, 2012

One in three claims of effective interventions made in top general medical journals may be wrong because investigators didn’t account for clinical trial participants who dropped out, according to an international study led by a UB researcher.

“We found that results reported as statistically significant in up to a third of trials would become statistically insignificant if the investigators had taken into consideration those participants who were lost to follow-up. ”
Elie A. Akl, MD, PhD
Associate professor of medicine, family medicine and social and preventive medicine
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“We found that results reported as statistically significant in up to a third of trials would become statistically insignificant if the investigators had taken into consideration those participants who were lost to follow-up,” says Elie A. Akl, MD, PhD, lead author and associate professor of medicine and family medicine.

Researchers Reviewed 235 Clinical Trials

A team of researchers reviewed 235 clinical trials published in the world’s top five general medical journals between 2005 and 2007 that claimed a statistically significant effect.

In one example, a trial comparing two surgical techniques for treating stress urinary incontinence determined one technique was superior. But in the analysis, it was found that 21 percent of participants were lost to follow-up.

“When we reanalyzed that study by taking into account those drop-outs, we found that the trial might have overestimated the superiority of one procedure over the other,” Akl says.

Methodology Provides Better Way to Judge Risk of Bias

It has long been suspected, but never proven, that loss to follow-up introduces bias into the results of clinical trials.

“The methodology we developed provided that proof,” says Akl, who also is on faculty in the UB School of Public Health and Health Professions and at McMaster University.

“It will allow those who conduct the trials and those who use their results—such as clinicians, other scientists, developers of clinical guidelines, policymakers and agencies like the Food and Drug Administration—to better judge the risk of bias.”

Global Collaboration of Epidemiologists

Twenty clinical epidemiologists from around the world collaborated with Akl on the study, which was funded by Pfizer.

The British Medical Journal published the results in an article titled “Potential impact on estimated treatment effects of information lost to follow-up in randomised controlled trials (LOST-IT): systematic review.

The clinical trial results analyzed had previously been published in Annals of Internal Medicine, British Medical Journal, the Journal of the American Medical Association, Lancet and the New England Journal of Medicine.