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  • [NMusers] updated NONMEM bug list [23MAY2005]
    table is really seen by the user Discussion The following helpful fact is undocumented There is an exception as to when the NOFORWARD option is the default option With a series of contiguous TABLE records in a given problem specification each having a FILE option that uses the same file name the second and subsequent TABLE records in the series are always treated as though the FORWARD option appears on these records because otherwise the presence of these records makes no sense It also really makes no sense to use the NOFORWARD option with any TABLE record regardless of the file name used by the FILE option in a problem specification with an NSUBS value of 2 or more So with NONMEM Version VI this will constitute another exception as to when the NOFORWARD option is the default option VI When each of two different problems within the scope of a superproblem use the same file as either a NONMEM data file Model Specification Input file or Model Specification Output file or table file an abnormal operating system termination may arise If these circumstances do not lead to such a termination the user should not be concerned Fix Before each of the two instances of the statement I2 0 in routine SUPER insert the statement IF I2 EQ 1 CLOSE UN 2 Before each of the two instances of the statement I3 0 in routine SUPER insert the statement IF I3 EQ 1 CLOSE UN 3 Before each of the two instances of the statement I4 0 in routine SUPER insert the statement IF I4 EQ 1 CLOSE UN 4 Work around Avoid such circumstances An example of where these circumstances arise may be found in the Help Guide Superproblem Example 1 For this example the file simulation is used as a table file in problem 2 and as a NONMEM data file in problem 3 This can be avoided by taking the data set of problem 3 to be the internal data set created with problem 2 remove both the TABLE record of problem 2 and the DATA record of problem 3 VII When a mixture model is used estimates of etas available to the PRED routine during problem finalization i e when ICALL 3 are always those for the first submodel With each individual they should be those for the submodel to which the individual is classified VIII The statistic ETABAR and results from the Centering First Order Conditional Estimation method are incorrect when 1 a mixture model is used 2 the mixture probability of either the first or last subpopulation is set to 0 Work around Usually if a mixture probability is being set to 0 this is being done for all individuals and for all values of the population parameters In this case simply remove any reference to the first or last subpopulation from routine MIX Otherwise try to keep the first and last subpopulation from being one with a mixture probability equal to 0 IX

    Original URL path: http://nonmem.org/nonmem/nm/99jun012005.html (2016-04-25)
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  • [NMusers] RES and WRES
    found out that for some observations RES and WRES have different signs METHOD 1 INTERACTION combined error model implemented in log transformed variables Y F SQRT THETA 1 THETA 2 F 2 ERR 1 So the question is when it happens and what does it mean Thanks Leonid WRES The weighted residuals for an individual are formed by transform ing the individual s residuals so that under the population model assuming the true values of the population parameters are given by the estimates of those parameters all weighted residu als have unit variance and are uncorrelated As with the predic tion and residual the weights are also computed at eta 0 From Andrew Hooker Andrew Hooker farmbio uu se Subject RE NMusers RES and WRES Date Sat May 28 2005 5 33 am Hi Leonid The weighted residuals are calculated by dividing the vector of each individual s residuals res i by the square root of the matrix of covariances of that individual s data conditional on the population model WRES i RES i SQRT COV data i F pop This means that for each WRES calculated we include covariances between data points of an individual If the correlations between

    Original URL path: http://nonmem.org/nonmem/nm/99may272005.html (2016-04-25)
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  • [NMusers] CONT data item tip
    using the CONT data item I cannot locate this posting now it s not in the Globomax list of NONMEM Tips nor visible by searching the Cognigen archive I would be grateful if Bill or anyone else would send it to me In particular I would like to know what verbatim code is needed to access data items in a record with CONT 1 Thanks Nick Nick Holford Dept Pharmacology

    Original URL path: http://nonmem.org/nonmem/nm/99may262005.html (2016-04-25)
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  • [NMusers] a question about control file
    PROB RUN cbzcontrol69tets70 INPUT C ID SEX AGE WT EVID TIME AMT SS II DV MDV VAL PHE PHB MD DATA datacbz1 csv IGNORE C SUBR ADVAN2 TRANS2 PK TVCL1 THETA 1 AMT THETA 4 WT THETA 5 AGE THETA 6 TVCL2 THETA 7 VAL THETA 8 PHE THETA 9 PHB THETA 10 SEX TVCL TVCL1 TVCL2 TVV THETA 2 TVKA THETA 3 CL TVCL EXP ETA 1 Clearance mL kg d V TVV EXP ETA 2 Central volume mL kg KA TVKA Absorption rate d S2 V Scale factor ERROR Y F EXP ERR 1 From Jakob Ribbing Jakob Ribbing farmbio uu se Subject RE NMusers a question about control file Date Wed May 25 2005 11 25 am Dear Chang A good guess at initial estimates is easier to make if the parameters that you estimate actually mean something The current interpretation of TVCL or THETA 1 is the typical value of clearance for an individual which has been given a dose of 1 mg weights 1 kg is 1 year old of SEX 0 and on no concomitant medication It is very hard to tell what clearance this rather untypical individual might have Center your covariates on

    Original URL path: http://nonmem.org/nonmem/nm/99may252005.html (2016-04-25)
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  • [NMusers] Neutrophil transit models
    instances where the neutrophil transit models developed by Friberg and Karlsson for cytotoxic agents have been used to actually develop alternative dosing regimens for those drugs and if so what are the status of those trials Thanks Pete Bonate Peter

    Original URL path: http://nonmem.org/nonmem/nm/97may192005.html (2016-04-25)
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  • [NMusers] Need help
    EPS 1 THETA 6 F EPS 2 Y F W IPRED F IRES DV IPRED IWRES IRES W SIGMA 1 FIX 1 FIX ESTIMATION MAXEVALS 9999 PRINT 99 METHOD 0 NOABORT POSTHOC COVARIANCE TABLE ID CL V Q VSS IPRED IWRES NOPRINT FILE TABLE1 TABLE ID TIME ETA1 ETA2 ETA3 ETA4 SCATTER PRED VS DV UNIT SCATTER PRED VS TIME SCATTER WRES VS PRED SCATTER IWRES VS IPRED I let nonmem run for more than 5 days but nothing came out Concerning the pharmacodynamic aspects I used the following records let nonmem run for the same delay and again did not succeed to obtain results ID TIME AMT RATE CP MDV RCBF WT 1 0 1 27 0 3 09 65 1 8 480 6 1 1 8 0 89 0 7 53 65 1 16 62 52 0 2 27 65 1 24 166 80 0 0 76 65 1 32 319 33 0 0 99 65 1 40 0 1 53 65 1 48 824 93 0 0 91 65 1 56 1295 18 0 0 83 65 1 64 1339 19 0 7 60 65 1 72 1456 10 0 3 84 65 1 80 1537 57 0 1 92 65 1 88 1336 66 0 2 33 65 2 0 3 51 0 10 85 54 2 8 560 10 1 2 8 14 05 0 6 47 54 etc PROBLEM CMAX INPUT ID TIME AMT RATE CP DROP MDV RCBF DV WT DROP DATA DATACLOKE0 SUBROUTINES ADVAN 6 TRANS 1 TOL 6 MODEL COMP CENTRAL COMP EFFECT COMP CMAX COMP TMAX PK TVK THETA 1 K TVK EXP ETA 1 TVKE0 THETA 2 KE0 TVKE0 EXP ETA 2 TVTMAX LOG TVK LOG TVKE0 TVK TVKE0 TMAX TVTMAX EXP ETA 3 DES DADT 1 K A 1 D2 KE0 A 1 A 2 DADT 2 D2 IF D2 GT 0 THEN DADT 3 D2 DADT 4 1 ELSE DADT 3 0 DADT 4 0 ENDIF THETA 0 01 0 03 ERROR Y1 A 1 Y2 A 2 Y3 A 3 Y4 A 4 Y Y2 1 EPS 1 OMEGA 001 001 001 SIGMA 001 ESTIMATION METHOD 0 MAXEVAL 9999 NOABORT TABLE FILE stream NOPRINT NOHEADER TIME AMT RATE MDV Y1 Y2 Y3 Y4 TMAX Can anyone tell me if I chose the right models or help me resolving this Thanks in advance Vincent Vincent Bonhomme E Mail vincent bonhomme chrcitadelle be From Bachman William MYD bachmanw iconus com Subject RE NMusers Need help Date Thu May 19 2005 10 14 am At first glance your control stream and data file look OK What I would do as a diagnostic in my opinion is to use ESTIMATION MAXEVALS 9999 PRINT 1 MSF runX msf METHOD 0 NOABORT POSTHOC this allows creation of an INTER file that generates output for every iteration that can be read to determine that NONMEM is running and doing something in case the problem is just very slow and not just sitting there

    Original URL path: http://nonmem.org/nonmem/nm/98may192005.html (2016-04-25)
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  • [NMusers] NP4F error
    I have encountered a NONMEM error message which I had not seen before 0MINIMIZATION SUCCESSFUL NO OF FUNCTION EVALUATIONS USED 640 NO OF SIG DIGITS IN FINAL EST 5 5 0PRED RETURNS DIFFERENT OUTPUTS WITH THE SAME INPUTS 0PROGRAM TERMINATED BY NP4F The message is apparently issued at the very end of the run and unfortunately prevents NONMEM from reporting the parameter estimates The table step is also omitted Has

    Original URL path: http://nonmem.org/nonmem/nm/99may192005.html (2016-04-25)
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  • [NMusers] Multiple dosing
    don t you share a representative piece of your data file and control file Then people will be able to help you a lot better best regards Liping Liping Zhang PhD Global PK PD Modeling and Trial Simulation ELi Lilly Company Work 317 277 8687 Fax 317 433 6661 DC 0734 Email zhang liping lilly com From Pravin Jadhav pravinj gmail com Subject Re NMusers Multiple dosing Date Wed May 18 2005 6 01 pm Bharath See if the following case study answers your question http www accp1 org pharmacometrics PDF CSIINONMEMfinal pdf There are some additional codes available in the code library http www accp1 org pharmacometrics codelib htm Hope it helps Pravin From Muralidharan Bharath Bharath Muralidharan STJUDE ORG Subject RE NMusers Multiple dosing Date 05 18 2005 05 11 PM Dear Dr Zhang This is how my data file looks PAT NO COURSE DAY EVID DOSE AMT TIME 201 1 10 3 201 1 10 1 100000 200000 0 201 1 10 1 100000 200000 24 201 1 10 1 100000 200000 48 201 1 10 1 100000 200000 72 201 1 10 1 100000 200000 96 201 1 10 1 100000 200000 120 201 1 10 1 100000 200000 144 201 1 10 1 100000 200000 168 201 1 10 1 100000 200000 192 201 1 10 2 216 201 1 10 2 216 083 201 1 10 2 217 08 201 1 10 2 218 08 201 1 10 2 220 08 201 1 10 2 222 08 201 1 10 2 224 08 201 1 10 2 228 08 Thanking You Kumar From Liping Zhang ZHANG LIPING lilly com Subject RE NMusers Multiple dosing Date Thu May 19 2005 11 00 am Hi Kumar hope this is not a representative piece of your data

    Original URL path: http://nonmem.org/nonmem/nm/99may182005.html (2016-04-25)
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