Logistic Mixed models with NONMEM

From: Doug Oman <oman@stat.berkeley.edu> Subject: Logistic Mixed models with NONMEM Date: 23 Jan 1998 12:58:09 -0500 Some questions about using NONMEM for mixed logistic modelling: 1. It seems that in the example PRED record (copied below) from the logistic modelling section in the NONMEM user's archives, that THETA(1) and THETA(3) only appear together, ie, as THETA(1)*EXP(THETA(3)). Therefore the model should not be identifiable (ie, there would be an infinite number of solutions; the way to generate other solutions from one solution would be to add K to THETA(3) and divide THETA(1) by EXP(K)). Surely this can't be correct? 2. I've created a very simple PRED record (also below) for calculation of a global mean in a mixed logistic model (ie, the covariate DOSE is no longer present). Should it work? $SUBROUTINES CONTR=contr CCONTR=ccontr $PRED ; NEXT LINE IS VERBATIM CODE " CALL GETETA(ETA) A = THETA(1)+ETA(1) B = EXP(A) P = B/(1+B) Y = P**DV*(1-P)**(1-DV) 3. The documentation for the PRED record from the NONMEM user's archives (copied below) says that it implements a 'sigmoid emax model'. I know little pharmacology so I don't know what that model is. How can I find out (Online resources, if any, would be especially helpful)? Thank you -Doug Oman ================ EXAMPLE PRED RECORD FROM NONMEM ARCHIVES ============ $PROB POP [>1 OBS/INDIVID] $DATA <your_data_file> $INPUT ID=L1 DOSE DV $SUBROUTINES CONTR=contr CCONTR=ccontr $PRED ; NEXT LINE IS VERBATIM CODE " CALL GETETA(ETA) GAMMA=THETA(1)*EXP(THETA(3)*ETA(1)) IF(GAMMA.GT.10) EXIT D50 = THETA(2)*EXP(ETA(1)) IF(D50.LT..00001) EXIT LDOS= LOG(DOSE) A = GAMMA*LDOS - GAMMA*LOG(D50) B = EXP(A) P = B/(1+B) Y = P**DV*(1-P)**(1-DV) ;$THETA, $OMEGA, as necessary/desired. ;be sure to use METH=1 LAPLACE on $EST -- >From Douglas W. Oman Department of Biostatistics, U.C. Berkeley oman@stat.berkeley.edu (forwards to Home below) Home dougoman@wco.com (707) 878-2573