Constant and Proportional Error with Log transformed data with single data point per subject

From: Garry Boswell GBoswell@pcyc.com Subject: [NMusers] Constant and Proportional Error with Log transformed data with single data point per subject Date: Thu, May 20, 2004 6:53 pm NM Users, I have a PK study in mice in which I have a single blood sample per mouse, groups of 6 mice per time point. I have both IP and IV data from both single and multiple dose administration. During the model building process it appeared that an additive plus proportional error structure provided a better "fit" than other error structures. As noted by Ette et al (JPP 23(5), 1995) with only a single sample per animal I could not separately estimate interanimal and residual variability. Therefore I fixed Omega =0. Using the code below (error code suggested by Leonid Gibiansky in an earlier List Serve post), I was able to fit the non-log transformed data but the model was not adequate based on the diagnostic plots, etc. I was able to fit the log transformed data using Y=log(F)+Err(1) as described in NONMEM Tip #9. However I wanted to try the additive plus proportional error structure but with log transformed data. NONMEM Tips #9 and #10 nicely address the method of doing this with log transformed data but with what I believe is for data with multiple samples from each individual. My question is, can the methods described in these tips be applied to my model with Omega =0 FIXED? TIA for any assistance. Garry $PROB DRUG X PK STUDY $INPUT ID DAY=DROP TIME AMT MDV EVID DV LNDV WT SEX CMT SS II $DATA Dataset_04.csv IGNORE=# $SUBROUTINES ADVAN2 TRANS2 $PK TVCL = THETA(1) TVV = THETA(2) TVKA = THETA(3) TVF2 = THETA(4) CL =TVCL* EXP(ETA(1)) V =TVV KA=TVKA F2 =TVF2 K = CL/V HALF = (0.693/K) S2 = V $ERROR IPRED=F IRES=DV-IPRED IWRES=(DV-IPRED)/SQRT(F*F*THETA(1)*THETA(1)+THETA(2)*THETA(2) ) Y=F*(1+THETA(5)*EPS(1))+THETA(6)*EPS(2) $THETA (0, 15) $THETA (0, 10) $THETA (0, 0.8) $THETA (0, 0.7) $THETA (0, 0.5) $THETA (0, 0.01) $OMEGA 0 FIXED $SIGMA 1 FIXED $SIGMA 1 FIXED $EST MAXEVALS = 9900 NOABORT SIGDIGITS =3 PRINT =10 POSTHOC METHOD=CONDITIONAL $COV PRINT=E $TABLE NOPRINT ONEHEADER ID SEX TIME CL V KA F2 HALF WT FILE=Outfile_04.txt