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Research Development & Clinical Trials incorporated in the design for a future large Phase 3 study. "The Bayesian adaptive trial design will teach us what to do in Phase 3," said Dr. Satlin. Because the current Phase 2 study is blinded, Dr. Satlin and his team members at Eisai and the investigators at the trial sites are unaware of the trial data, including any modifications to the trial design that result from the interim analyses of the data. ONLY THE COMPUTER "KNOWS" In the Eisai study, only the computer system running the trial has access to the unblinded patient data, and it uses sophisticated computation algorithms to direct the analysis of the data and modify the trial if specific contingencies occur, Dr. Satlin said. The algorithms are based on the extensive pretrial simulations and scenario planning by Dr. Satlin and his staff. "We thought through the possible outcomes that could occur if we evaluated five dosages," he said. The biostatistics experts on Dr. Satlin's team calculated probability distributions for the effects of the different dosages. The algorithms use these probability distributions during the multiple planned interim analyses. Also during the analyses, the trial's longitudinal model adjusts the probability distributions based on all of the patient outcome data up to that point in the trial. If an interim analysis reveals that the highest dosage is the most effective, and the lowest dosage is the least effective, the randomization process adapts by assigning fewer patients to the least-effective dosage arm. "Another possible outcome is that none of the dosages will work," he said. If futility is determined, the trial's computer system is programmed to alert Dr. Satlin's team so that the trial can be terminated. The trial's computer system also informs Dr. Satlin and his staff if an interim analysis indicates an obvious clinical benefit of the drug. If this occurs before the completion of the trial (cutoff point for the estimated meaningful difference in change from baseline on primary end point for BAN2401 compared to placebo is 25 percent), Eisai will be able to trim development time and cost by initiating a Phase 3 trial while the Phase 2 trial is ongoing, he said. If a Phase 3 trial occurs, its design will be conventional, he said. "Once we learn from the Phase 2 study everything we need to do to design a Phase 3 trial so it will be successful, there is no longer the need for a Bayesian adaptive design, and we avoid the complexities and added work associated with a Bayesian adaptive design," said Dr. Satlin. "Also, regulators are more comfortable with a traditional design for Phase 3 because there is no possibility that trial modifications have been done, and therefore the results are easier to interpret." The BAN2401 study is the first, but will not be the only, Bayesian adaptive trial sponsored by Eisai. A new insomnia drug and another Alzheimer's disease drug soon will be evaluated in Bayesian design trials. In the big world of clinical trials, it's the small stuff that counts. WZƐĞƌǀĞƐĂƐĂƚƌƵĞĞdžƚĞŶƐŝŽŶŽĨŽƵƌĐůŝĞŶƚƐ tĞƚĂŝůŽƌĞĂĐŚƉĂƌƚŶĞƌƐŚŝƉƚŽLJŽƵƌƐŝnjĞ ĐƵůƚƵƌĂůďĂĐŬŐƌŽƵŶĚ ƉŝƉĞůŝŶĞ ƐĞƌǀŝĐĞ ĂŶĚŽƉĞƌĂƟŽŶĂůƌĞƋƵŝƌĞŵĞŶƚƐ͘ clearlypra.com >ĞĂƌŶŵŽƌĞ WŚĂƐĞ/ /s &Ƶůů ^ĞƌǀŝĐĞŝŽƉŚĂƌŵĂĐĞƵƟĐĂůƌƵŐĞǀĞůŽƉŵĞŶƚ about our dƌĂŶƐĨŽƌŵŝŶŐůŝŶŝĐĂůdƌŝĂůƐƚŚƌŽƵŐŚ KƵƌWĞŽƉůĞ /ŶŶŽǀĂƟŽŶ dƌĂŶƐƉĂƌĞŶĐLJ ƚĂŝůŽƌĞĚƐŽůƵƟŽŶƐ © PRA 2013. All Rights Reserved. 10.13 October 2013 LifeScienceLeader.com 55