A three-outcome design for randomized comparative phase II clinical trials

@article{citeulike:2465054, abstract = {Randomized designs have been increasingly called for use in phase II oncology clinical trials to protect against potential patient selection bias. However, formal statistical comparison is rarely conducted due to the sample size restriction, despite its appeal. In this paper, we offer an approach to sample size reduction by extending the three-outcome design of Sargent et al. (Control Clin. Trials 2001; 22:117-125) for single-arm trials to randomized comparative trials. In addition to the usual two outcomes of a hypothesis testing (rejecting the null hypothesis or rejecting the alternative hypothesis), the three-outcome comparative design allows a third outcome of rejecting neither hypotheses when the testing result is in some ?grey area? and leaves the decision to the clinical judgment based on the overall evaluation of trial outcomes and other relevant factors. By allowing a reasonable region of uncertainty, the three-outcome design enables formal statistical comparison with considerably smaller sample size, compared to the standard two-outcome comparative design. Statistical formulation of the three-outcome comparative design is discussed for both the single-stage and two-stage trials. Sample sizes are tabulated for some common clinical scenarios. Copyright {\copyright} 2007 John Wiley \& Sons, Ltd.}, address = {Eli Lilly and Company, Indianapolis, IN 46285, U.S.A.}, author = {Hong, Shengyan and Wang, Yanping }, citeulike-article-id = {2465054}, doi = {http://dx.doi.org/10.1002/sim.2824}, journal = {Statistics in Medicine}, keywords = {clinical\_trial, phase\_ii, three\_outcome\_design}, number = {19}, pages = {3525--3534}, posted-at = {2008-03-04 14:57:28}, priority = {2}, title = {A three-outcome design for randomized comparative phase II clinical trials}, url = {http://dx.doi.org/10.1002/sim.2824}, volume = {26}, year = {2007} }

TY - JOUR ID - citeulike:2465054 L3 - citeulike-article-id:2465054 TI - A three-outcome design for randomized comparative phase II clinical trials JF - Statistics in Medicine VL - 26 IS - 19 SP - 3525 EP - 3534 AD - Eli Lilly and Company, Indianapolis, IN 46285, U.S.A. N2 - Randomized designs have been increasingly called for use in phase II oncology clinical trials to protect against potential patient selection bias. However, formal statistical comparison is rarely conducted due to the sample size restriction, despite its appeal. In this paper, we offer an approach to sample size reduction by extending the three-outcome design of Sargent et al. (Control Clin. Trials 2001; 22:117-125) for single-arm trials to randomized comparative trials. In addition to the usual two outcomes of a hypothesis testing (rejecting the null hypothesis or rejecting the alternative hypothesis), the three-outcome comparative design allows a third outcome of rejecting neither hypotheses when the testing result is in some ?grey area? and leaves the decision to the clinical judgment based on the overall evaluation of trial outcomes and other relevant factors. By allowing a reasonable region of uncertainty, the three-outcome design enables formal statistical comparison with considerably smaller sample size, compared to the standard two-outcome comparative design. Statistical formulation of the three-outcome comparative design is discussed for both the single-stage and two-stage trials. Sample sizes are tabulated for some common clinical scenarios. Copyright © 2007 John Wiley & Sons, Ltd. KW - clinical_trial KW - phase_ii KW - three_outcome_design AU - Hong, Shengyan AU - Wang, Yanping PY - 2007/// UR - http://dx.doi.org/10.1002/sim.2824 ER -