Clinical trials ended early due to positive treatment effects likely exaggerate those effects, according to a new review published in JAMA. The authors caution that researchers should resist pressures to end clinical trials early because of the potential risk to patients in the trials.
The clinical trials reviewed were ended early because of a convincing -- and usually large -- apparent difference between an experimental treatment and an existing standard therapy. The studies were ended so participants taking a placebo or less effective medications could also take the studied drug.
It usually also allows physicians to prescribe the therapy sooner because it will reach the market earlier. Almost everyone involved benefits from a trial ending early -- doctors, researchers, funding sources, pharmaceutical firms, scientific journals, even reporters -- everyone except the patient, who may end up receiving a therapy on the basis of misleading information about its benefits.
The review examined 63 medical questions regarding 91 truncated trials and compared them to 424 comparable trials that were not stopped early. Results showed that the studies that were stopped -- especially smaller trials of a few hundred participants -- had exaggerated or misleading treatment effects. Those misleading findings are often compounded downstream because researchers are less likely to return to the topic after what is perceived as a significant successful finding.
Researchers should be cautious, the review warns, and truncate clinical trials only near the end of a study and then only with "a very good reason." Otherwise, says Dr. Montori, patients and physicians will be making treatment choices based on inaccurate information, or worse, opting for one treatment when another may be more appropriate.
"Our research shows that in most cases early stopping of clinical trials resulted in misleading estimates of treatment effects. These misleading estimates are likely to result in misguided decisions about the trade-off between risks and benefits of a therapy," says Victor
Montori, M.D., Mayo Clinic endocrinologist and corresponding author of the study.
"On average, treatments with no effect would show a reduction in relative risk of almost 30 percent in stopped early trials. Treatments with a true relative risk reduction of 20 percent would show a reduction of over 40 percent."
Bassler et al., 'Stopping Randomized Trials Early for Benefit and Estimation of Treatment Effects', JAMA, March 2010, 303(12):1180-1187
Shortened Clinical Trials Exaggerate Treatment Effects
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