of 17% signals that the NDLM model is over-sensitive and inflate the false positive so appropriate adjustment to the test statistics or decision criteria may be needed. The analysis of the and NDLM models on the curve and linear curve also show the Emax Emax same trend. The probability of success is 98% for both and NDLM models if the true Emax response curve follows data and 96% and 95% for log linear curve for and NDLM Emax Emax models respectively. For U-shaped dose response curves, the power measured as the probability of success of the model is 26% and power using the NDLM model is 92%. The NDLM Emax model significantly improves the probability of success compared to the model in the fixed Emax design model. Table 6.6 Probability of final success and failure in fixed design using Bayesian model and Emax NDLM model in Scenario 1. Assumed True Bayesian model Bayesian NDLM model Emax Dose Response Prob. of final Prob. of final Prob. of final Prob. of final success failure success failure Placebo like flat 0.06 0.94 0.17 0.83 curve with 0.98 0.02 0.98 0.02 Emax EC50=3 LogLinear 0.96 0.04 0.95 0.05 Curve U-Shaped curve 0.26 0.74 0.92 0.08 Adaptive Design Simulation Fixed design assumes that all 6 doses are allocated to a fixed number of patients. No adaptations were adopted in this design. In the adaptive simulation, study may stop for futility or success or subjects are allocated to certain dose based on the dose response of the subjects already enrolled in the study.
of 17% signals that the NDLM model is over-sensitive and inflate the false positive so appropriate adjustment to the test statistics or decision criteria may be needed. The analysis of the Emax and NDLM models on the Emax curve and linear curve also show the same trend. The probability of success is 98% for both Emax and NDLM models if the true response curve follows Emax data and 96% and 95% for log linear curve for Emax and NDLM models respectively. For U-shaped dose response curves, the power measured as the probability of success of the Emax model is 26% and power using the NDLM model is 92%. The NDLM model significantly improves the probability of success compared to the Emax model in the fixed design model. Table 6.6 Probability of final success and failure in fixed design using Bayesian Emax model and NDLM model in Scenario 1. Assumed True Dose Response Bayesian Emax model Bayesian NDLM model Prob. of final success Prob. of final failure Prob. of final success Prob. of final failure Placebo like flat curve 0.06 0.94 0.17 0.83 Emax with EC50=3 0.98 0.02 0.98 0.02 LogLinear Curve 0.96 0.04 0.95 0.05 U-Shaped curve 0.26 0.74 0.92 0.08 Adaptive Design Simulation Fixed design assumes that all 6 doses are allocated to a fixed number of patients. No adaptations were adopted in this design. In the adaptive simulation, study may stop for futility or success or subjects are allocated to certain dose based on the dose response of the subjects already enrolled in the study.
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