Where ED90 is defined as the dose to achieve 90% of maximum DAS28 response. In this calculation the maximum response is estimated from the maximal DAS28 effect at all doses. The 90% (ED90) of maximum response is then calculated as the lowest nominal dose in which is closest to the estimated dose that achieves 90% of maximal efficacy. A factor of 1.1513 maps the dose level (dose level 1-10) to dose in mg/kg on the scale of interest (0.001–30 mg/kg). The slope of the model has been fixed at 1 so the slope is removed. The Emax planned clinical doses are 0.001, 0.003, 0.01, 0.03, 0.1, 0.3, 1, 3, 10, and 30, which are the nominal doses with a rate of half log increase. Therefore, a factor of clinical doses “exp(1.1513)” converts to dose levels with 1 to 1 mapping as illustrated in below table. Dose level in Clinical doses= β3: Eqn Exp(1.1513*( β3-7) 4.x 1 0.001 2 0.003 3 0.010 4 0.030 5 0.100 6 0.300 7 1.000 8 3.000 9 10.000 10 30.000 The model parameter a broader range of doses, it also prevents the clinical dose from β3 covers being negative by taking the exponential transformation. The estimate of is then approximated β3 at the lowest nominal dose level that is close to ED90. If the estimate of is outside range, i.e. β3 the maximal estimate of in the dose range is used i.e. the patients will be assigned to maximal β3 dose at 30 mg/kg. The Bayesian dose response model for the GSK123456 PoC study was ,
Where ED90 is defined as the dose to achieve 90% of maximum DAS28 response. In this calculation the maximum response is estimated from the maximal DAS28 effect at all doses. The 90% (ED90) of maximum response is then calculated as the lowest nominal dose in which is closest to the estimated dose that achieves 90% of maximal efficacy. A factor of 1.1513 maps the dose level (dose level 1-10) to dose in mg/kg on the scale of interest (0.001–30 mg/kg). The slope of the Emax model has been fixed at 1 so the slope is removed. The planned clinical doses are 0.001, 0.003, 0.01, 0.03, 0.1, 0.3, 1, 3, 10, and 30, which are the nominal doses with a rate of half log increase. Therefore, a factor of “exp(1.1513)” converts clinical doses to dose levels with 1 to 1 mapping as illustrated in below table. β3: Dose level in Eqn 4.x Clinical doses= Exp(1.1513*( β3-7) 1 0.001 2 0.003 3 0.010 4 0.030 5 0.100 6 0.300 7 1.000 8 3.000 9 10.000 10 30.000 The model parameter β3 covers a broader range of doses, it also prevents the clinical dose from being negative by taking the exponential transformation. The estimate of β3 is then approximated at the lowest nominal dose level that is close to ED90. If the estimate of β3 is outside range, i.e. the maximal estimate of β3 in the dose range is used i.e. the patients will be assigned to maximal dose at 30 mg/kg. The Bayesian dose response model for the GSK123456 PoC study was ,
PhD%20Dissertation%20Feng%20Liu%20Final%20Clean.docx