Hi Alan, Like Bill mentioned above, the reason why the simultaneous approach rasises questions is that the PK fitted with the simultaneous method can be quite sensitive to PD model misspecification. The publicatiosn below discussed the robusteness and performance of several secinarios within the two methods (simultaneous vs. sequential):
1: Zhang L, Beal SL, Sheinerz LB. Simultaneous vs. sequential analysis for population PK/PD data II: robustness of methods. J Pharmacokinet Pharmacodyn. 2003 Dec;30(6):405-16. 2: Zhang L, Beal SL, Sheiner LB. Simultaneous vs. sequential analysis for population PK/PD data I: best-case performance. J Pharmacokinet Pharmacodyn. 2003 Dec;30(6):387-404. *Murad Melhem, PhD* *assistant Director Pk/PD* *Cognigen Corp.* *Buffalo, NY* ** Dear All, > > I know this is an old topic but would like to see the statistics. > > When you have to develop a pop PK model for both parent and active > metabolites, which approach do you prefer or have you used most: > simultaneous or sequential? Which way do you think is more scientific? I > heard comments saying that the simultaneous approach is not scientific. > > Thanks, > > Alan >
