FDA Deputy Commissioner Scott Gottlieb on Monday likely will announce that the agency plans to develop guidelines to allow the use of adaptive clinical trials -- studies that are modified prior to completion based on early results -- in the prescription drug approval process, the Wall Street Journal reports. FDA has assembled an internal team that will collaborate with agency drug review divisions to develop guidelines for adaptive trials. Robert O'Neill, director of the Office of Biostatistics at the FDA Center for Drug Evaluation and Research, said that the agency has begun to compile examples of adaptive trials. Each FDA drug review division has received at least one adaptive trial submission in the past year, he said. According to O'Neill, FDA will develop a "concept paper" on adaptive trials and likely will release guidelines for the studies next year. "We think it's time to start exploring the appropriate use of these designs in the appropriate situations," he said (Wilde Mathews, Wall Street Journal, 7/10).

Potential Benefits
According to the Journal, adaptive trials allow researchers to make modifications based on early results to direct a larger percentage of participants to treatments that appear the most effective; to eliminate treatments that appear ineffective; to add more participants who appear to benefit from certain treatments; or to combine two phases of prescription drug development into one study (Wall Street Journal chart, 7/10). Pharmaceutical companies hope that adaptive trials will produce "more efficient tests that could save millions of dollars" in prescription drug development costs, and some have begun to conduct such studies, the Journal reports. Supporters of adaptive trials maintain that such studies can reduce the number of participants by 30% or more. In addition, adaptive trials reduce the likelihood that participants will receive ineffective treatments, according to supporters.

Concerns, Comments
The plan to allow the use of adaptive trials in the prescription drug approval process "has sparked controversy among researchers" because of concerns about the ethicality and statistical accuracy of such studies, the Journal reports. One concern is that adaptive trial sponsors, researchers or participants who receive information about early results might "consciously or unconsciously change their conduct on an ad hoc basis," according to the Journal. "Another worry is that preliminary finding could leak out to investors," the Journal reports. According to Thomas Fleming, a statistics professor at the University of Washington, early results from trials are "not always a reliable clue," and they might prompt researchers to make modifications that reduce the efficiency of studies or make the results more difficult to interpret. He added that the use of late-stage adaptive trials raises "very serious ethical and scientific concerns." O'Neill said that FDA hopes to address concerns about adaptive trials, adding that "the last think we want to have happen is for the enthusiasm for these designs to run ahead of the ability to carry them out with integrity" (Wall Street Journal, 7/10).

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