Problem in using $PRED

From: TBTZENG@aol.com Subject: [NMusers] Problem in using $PRED Date: Fri, 22 Mar 2002 07:50:05 EST Dear NONMEM Users: I am exploring the function of user-written using $PRED and find that the program appears not to function right in $PRED as compared to $PREDPP in the same set of data. Under $PREDPP, the parameter estimates and program iteration are reasonable and normal with 1779 iterations and MOF value of -460.51. However, under $PRED , program appears to reach local convergence (minimization was successful with no warning signs) with only 16 iterations, MOF value of 1708.311 and the parameter estimates are exactly the same as the initial estimates. Included here are my two control streams and one partial data set. Any clue about the problems in my control stream and/or data format using $PRED is appreciated. Data are from a cross-over oral bioequivalence study for two formula with same active ingredient. Plasma concentrations were transformed into log scale. Thanks a lot! Tsang-Bin Tzeng MegaMed PRI/PPC USA (609) 870-0248 Here are my two control streams $PROB Test1 bioavailability $INPUT FORM ID TIME CON MDV AMT LCON=DV $DATA TEST1BIO.PRN $PRED ;$SUBROUTINES ADVAN2 TRANS2 ;$PK CALFL=1 ; once per individual CL = THETA(1) * EXP(ETA(1)) V = THETA(2) * EXP(ETA(2)) IF (FORM.EQ.1) THEN KA = THETA(3) * EXP(ETA(3)) ALAG1 = THETA(4) * EXP(ETA(4)) F1 = THETA(5) * EXP(ETA(5)) ELSE KA = THETA(6) * EXP(ETA(6)) ALAG1 = THETA(7) * EXP(ETA(7)) F1 = 1.0000 ENDIF DT=TIME-ALAG1 S2 = V/1000 F=KA*F1*AMT/S2/(KA-CL/V)*(EXP(-CL/V*DT)-EXP(-KA*DT)) ;$ERROR CALLFL=0 IF (F.GT.0) THEN IPRE=LOG(F) ELSE IPRE=LOG(10) ENDIF IRES= DV - IPRE QQ=1 IF(FORM.EQ.1) QQ=0 Y=IPRE + (1-QQ)* ERR(1)+ QQ*ERR(2) $THETA (0 4.7 100); 1 CL (1 129 400); 2 V (0 2 10); 3 KA1 (0 0.1 5); 4 TLAG1 (0 1 3); 5 F (0 2 10); 6 KA2 (0 0.1 5); 7 TLAG2 $OMEGA 0.1 0.1 0.1 0.2 0.1 0.1 0.2 $SIGMA 0.01 0.01 $EST MSFO=msf MAX=9990 PRINT=10 POSTHOC; METHOD=1 ;$COV $SCATTER IPRE VS DV $PROB Test1 bioavailability $INPUT FORM ID TIME CON MDV AMT LCON=DV $DATA TEST1BIO.PRN $SUBROUTINES ADVAN2 TRANS2 $PK CALFL=1 ; once per individual CL = THETA(1) * EXP(ETA(1)) V = THETA(2) * EXP(ETA(2)) IF (FORM.EQ.1) THEN KA = THETA(3) * EXP(ETA(3)) ALAG1 = THETA(4) * EXP(ETA(4)) F1 = THETA(5) * EXP(ETA(5)) ELSE KA = THETA(6) * EXP(ETA(6)) ALAG1 = THETA(7) * EXP(ETA(7)) F1 = 1.0000 ENDIF S2 = V/1000 $ERROR CALLFL=0 IF (F.GT.0) THEN IPRE=LOG(F) ELSE IPRE=LOG(10) ENDIF IRES= DV - IPRE QQ=1 IF(FORM.EQ.1) QQ=0 Y=IPRE + (1-QQ)* ERR(1)+ QQ*ERR(2) $THETA (0 4.7 100); 1 CL (1 129 400); 2 V (0 2 10); 3 KA1 (0 0.1 5); 4 TLAG1 (0 1 3); 5 F (0 2 10); 6 KA2 (0 0.1 5); 7 TLAG2 $OMEGA 0.1 0.1 0.1 0.2 0.1 0.1 0.2 $SIGMA 0.01 0.01 $EST MSFO=msf MAX=9990 PRINT=10 POSTHOC; METHOD=1 ;$COV $SCATTER IPRE VS DV My data file is (The first 4 subjects are provided here): 1 1 0 . 1 100 . 1 1 0 . 1 0 . 1 1 0.5 20 0 0 2.995732 1 1 1 33.6 0 0 3.514526 1 1 1.5 45.6 0 0 3.819908 1 1 2 60.9 0 0 4.109233 1 1 2.5 116 0 0 4.75359 1 1 3 153 0 0 5.030438 1 1 4 245 0 0 5.501258 1 1 6 375 0 0 5.926926 1 1 8 364 0 0 5.897154 1 1 10 360 0 0 5.886104 1 1 12 341 0 0 5.831882 1 1 24 285 0 0 5.652489 1 1 36 319 0 0 5.765191 1 1 48 235 0 0 5.459586 1 1 72 76.8 0 0 4.341205 1 1 96 26 0 0 3.258097 1 2 0 . 1 100 . 1 2 0 . 1 0 . 1 2 0.5 . 1 0 . 1 2 1 28.8 0 0 3.360375 1 2 1.5 38.5 0 0 3.650658 1 2 2 59.8 0 0 4.091006 1 2 2.5 83 0 0 4.418841 1 2 3 132 0 0 4.882802 1 2 4 146 0 0 4.983607 1 2 6 346 0 0 5.846439 1 2 8 421 0 0 6.042633 1 2 10 472 0 0 6.156979 1 2 12 439 0 0 6.084499 1 2 24 420 0 0 6.040255 1 2 36 285 0 0 5.652489 1 2 48 163 0 0 5.09375 1 2 72 40.5 0 0 3.701302 1 2 96 16.3 0 0 2.791165 1 3 0 . 1 100 . 1 3 0 . 1 0 . 1 3 0.5 11.6 0 0 2.451005 1 3 1 22.5 0 0 3.113515 1 3 1.5 37.8 0 0 3.632309 1 3 2 57.1 0 0 4.044804 1 3 2.5 104 0 0 4.644391 1 3 3 124 0 0 4.820282 1 3 4 172 0 0 5.147494 1 3 6 184 0 0 5.214936 1 3 8 191 0 0 5.252273 1 3 10 235 0 0 5.459586 1 3 12 319 0 0 5.765191 1 3 24 206 0 0 5.327876 1 3 36 . 1 0 . 1 3 48 118 0 0 4.770685 1 3 72 49.7 0 0 3.906005 1 3 96 26.2 0 0 3.265759 1 4 0 . 1 100 . 1 4 0 . 1 0 . 1 4 0.5 . 1 0 . 1 4 1 14.3 0 0 2.66026 1 4 1.5 18.4 0 0 2.912351 1 4 2 28 0 0 3.332205 1 4 2.5 45.7 0 0 3.822098 1 4 3 73 0 0 4.290459 1 4 4 127 0 0 4.844187 1 4 6 159 0 0 5.068904 1 4 8 177 0 0 5.17615 1 4 10 200 0 0 5.298317 1 4 12 237 0 0 5.46806 1 4 24 256 0 0 5.545177 1 4 36 118 0 0 4.770685 1 4 48 112 0 0 4.718499 1 4 72 29.3 0 0 3.377588 1 4 96 15 0 0 2.70805