RE: Cross-validation script in NM

Dear Kajsa and Dennis Thank you for your thoughts on this. I know of (and have used several times in the past) the mentioned functionalities in PsN and PLT-tools. However, due to the specific nature of my problem, I'm afraid these will not work for me. Allow me to further clarify my problem. (For clarity, I've included a piece of my control stream at the bottom of this message.) As Dennis pointed out, I'm fitting a training group and use the final parameter estimates in a subsequent run to predict the plasmaconcentrations of the validation group. I failed to clarify this in my previous message, but I'm predicting the plasmaconcentrations for the validation group according to a TDM setting. This means that for the validation group MAXEVAL=0 and only the first through sample per ID is included in the dataset as an observation event(EVID=0 and MDV=0). It goes without saying that the objective is to accurately predict the other plasmaconcentrations (EVID=2 and MDV=1) for the IDs in the validation group. Now to get to the problem. I tried this approach with two separate control streams and it works. I.e. plasmaconcentrations are predicted for the validation group based on the post-hoc corrected final parameter estimates of the training group. However, when I combine these in a single control stream (as shown below) the time-varying covariates are not taken into account for the validation group. More specifically, the following statement (under $PK) is not evaluated for the IDs in the validation group (statement used to switch on/off an additional CL due to hemodialysis). CL_DIA = 0 IF(DIALYSIS.EQ.1) CL_DIA = THETA(6) IND=0 IF(IND_DIA.EQ.1) IND=1 This causes the hemodialysis moments to be ignored by NM in the validation group when using the control stream as shown below. Since it worked for me using separate control streams, it seems that the problem is associated with the use of MSFO=... and $MSFI in the training and validation set, respectively. Do any of you have a specific solution for this problem or could shed some light on specific behavior of the $MSFI option in NM which might be causing this? Kind regards, Pieter Colin $PROBLEM No covariates ;; 1. Based on: ;; COMMENT: ;--------------------------------------------------------------------------------- ;----------------------- FIT XVAL -------------------------------------------- ;--------------------------------------------------------------------------------- $INPUT ID TIME DV CMT AMT RATE EVID MDV UVOL EXTRA IND_DIA OCC DIALYSIS ANALYSIS BV MISSING AGE WGT HGT BMI BSA SOFA M1F2 GFR XVAL $DATA RawdataCFP_cov_ext.csv IGNORE=@ IGNORE(MISSING.EQ.1) ;Exclude missing values IGNORE(CMT.GT.3) ;Exclude CSF sample IGNORE(XVAL.EQ.1) REWIND $SUBROUTINE ADVAN13 TOL=12 $MODEL COMP(CENTRAL,DEFOBS,DEFDOSE) COMP(PERIPH) COMP(URINE,INITIALOFF) $PK ;------------- Calculation of Time After Dose ------------ IF (EVID.EQ.1.OR.EVID.EQ.4) THEN TDOS=TIME TAD=0.0 ENDIF IF (EVID.NE.1.AND.EVID.NE.4) TAD=TIME-TDOS TVCLOTHER =THETA(1) CLOTHER =TVCLOTHER*EXP(ETA(4)) TVCL = THETA(2) CL = TVCL*EXP(ETA(1)) TVV1 = THETA(3) V1 =TVV1*EXP(ETA(2)) TVV2 =THETA(4) V2 =TVV2*EXP(ETA(3)) TVQ =THETA(5) Q =TVQ ;------------- Dialysis submodel ------------------------ CL_DIA = 0 IF(DIALYSIS.EQ.1) CL_DIA = THETA(6) IND=0 IF(IND_DIA.EQ.1) IND=1 S1=V1 S3=UVOL K10=CLOTHER/V1 K12=Q/V1 K21=Q/V2 K13=CL/V1 K11=CL_DIA/V1 $DES DADT(1)=-K12*A(1)+K21*A(2)-K10*A(1)-K13*A(1)-K11*A(1)*IND DADT(2)=K12*A(1)-K21*A(2) DADT(3)=K13*A(1) $ERROR IPRED = 1E-3 IF(F.GT.0) IPRED=F Y = IPRED*(1+EPS(1)) IRES = DV-IPRED IWRES = IRES/(IPRED*SQRT(SIGMA(1,1))) IF(CMT.EQ.3) THEN Y = IPRED*(1+EPS(2)) IRES = DV-IPRED IWRES = IRES/SQRT(IPRED*IPRED*SIGMA(2,2)) ENDIF $THETA (1E-9,1.097450) ; CLOTHER; L/h (1E-9,2.124530) ; CL; L/h (1E-9,8.640870) ; V1; L (1E-9,18.58180) ; V2; L (1E-9,34.13580) ; Q; L/h (1E-9,4.046690) ; CL_DIA; L/h $OMEGA 1.265890 ; IIV_CL 0.387112 ; IIV_V1 0.186287 ; IIV_V2 0.371892 ; IIV_CLOTHER $SIGMA 0.090199 ; Proportional plasma 0.106711 ; Proportional urine $ESTIMATION SIG=2 MAX=9999 METHOD=1 SORT INTERACTION POSTHOC PRINT=1 MSFO=run61.msf ;--------------------------------------------------------------------------------- ;----------------------- POST HOC -------------------------------------------- ;--------------------------------------------------------------------------------- $PROBLEM PREDICT XVAL1 $INPUT ID TIME DV CP CMT AMT RATE EVID MDV UVOL EXTRA IND_DIA OCC DIALYSIS ANALYSIS BV MISSING AGE WGT HGT BMI BSA SOFA M1F2 GFR TDM XVAL $DATA RawdataCFP_xval_ext.csv IGNORE=@ IGNORE(MISSING.EQ.1) ;Exclude missing values IGNORE(CMT.GT.3) ;Exclude CSF sample IGNORE(XVAL.NE.1) REWIND $MSFI run61.msf $ESTIMATION SIG=2 MAX=0 METHOD=1 SORT INTERACTION POSTHOC PRINT=1 ...