Clinicans warned about randomized clinical trials

A review article in the November 2 issue of JAMA: The Journal of the American Medical Association, suggests clinicians ought to view with skepticism the results of randomized clinical trials stopped early because of apparent benefit.

Victor M. Montori, M.D., M.Sc., from McMaster University, Hamilton, Ontario, and colleagues conducted a review of the medical literature to identify randomized clinical trials (RCTs) of any intervention reported as having been stopped earlier than planned because of results favoring the experimental intervention.

"Of 143 RCTs stopped early for benefit, the majority (92) were published in 5 high-impact medical journals. Typically, these were industry-funded drug trials in cardiology, cancer, and human immunodeficiency virus/AIDS," the authors found. "The proportion of all RCTs published in high-impact journals that were stopped early for benefit increased from 0.5 percent in 1990 – 1994 to 1.2 percent in 2000 – 2004. On average, RCTs recruited 63 percent of the planned sample and stopped after a median (mid-point) of 13 months of follow-up, one interim analysis, and when a median of 66 patients had experienced the end point driving study termination (event)." The authors also note that "trials with fewer events yielded greater treatment effects."

The authors conclude: "RCTs stopped early for benefit are becoming more common, often fail to adequately report relevant information about the decision to stop early, and show implausibly large treatment effects, particularly when the number of events is small. These findings suggest clinicians should view the results of such trials with skepticism."

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