Using Adaptive Design
CROs that design and manage clinical trials for pharma and biotech companies believe strongly in the power of a well-designed and executed Phase II trial as part of an overall clinical development plan. “The relatively recent explosion in understanding the molecular pathophysiology of cancer and the identification of new targets is revolutionizing the way we conduct Phase IIa/IIb clinical trials in oncology,” Parexel’s Denis R. Miller, M.D., therapeutic area team leader, oncology/hematology, told GEN.
“The increased cost of clinical research, the intensely completive environment, the limited number of patients available and willing to enroll in clinical trials, the pressures of time and economics on physicians who are engaged in clinical trials, and the identification of validated biomarkers that accurately predict response are major and compelling considerations that that must be incorporated into the design and conduct of early-phase clinical trials,” Dr. Miller noted.
He encourages the use of adaptive designs, enrichment (enrolling only patients whose tumors express the drug target), randomized designs, and selection of endpoints that are surrogates of overall survival. The incorporation of adaptive designs may take a number of forms including changes in eligibility criteria, planned sample size, test statistic or analytic methods, hypothesis, primary endpoint, choice of dose groups or treatment arms, allocation to treatment to achieve balance or assigning fewer subjects to inferior treatment based on interim analysis, and use of an enriched patient population only.
Seamless two-stage designs have been proposed in which Phase I determines safety only via maximal tolerated doses. Phase Ib/IIa would refine that dose by evaluating efficacy and safety to determine the best dose.
Dr. Miller noted that the use of adaptive designs “should go a long way in increasing the likelihood of a successful early-phase clinical trial.” These novel approaches should deliver us more efficiently to the next step of conducting a large-scale, pivotal, randomized Phase III trial and increasing the likelihood of success. No longer can we justify inefficient early-phase clinical trials that are wasteful of the limited and precious resources now available to conduct clinical research in oncology.”