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  • [NMusers] Pre-release of PsN version 2.2
    or in your own perl scripts For more information visit the the PsN homepage http psn sourceforge net PsN is described in Lindbom L Ribbing J Jonsson EN Perl speaks NONMEM PsN a Perl module for NONMEM related programming Comput Methods Programs Biomed 2004 Aug 75 2 85 94 The implementation of the statistical methods is described in Lindbom L Pihlgren P Jonsson EN PsN Toolkit A collection of computer

    Original URL path: http://nonmem.org/nonmem/nm/99mar042005.html (2016-04-25)
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  • [NMusers] Plcebo Corrected PK/PD
    The drug effect beta ce t will be superimposed on the disease progress line and with a suitable design and reasonable parameters then the observed status could be used to estimate the parameters of this model with random effects i e BSV on each parameter Of course with the over sparse designs that are commonly used in clinical trials or if the time course of disease progression is too closely correlated with the time course of drug effect then there may be an a posteriori identifiability problem but in theory the parameters are a priori identifiable Nick Nick Holford Dept Pharmacology Clinical Pharmacology University of Auckland 85 Park Rd Private Bag 92019 Auckland New Zealand email n holford auckland ac nz tel 64 9 373 7599x86730 fax 373 7556 http www health auckland ac nz pharmacology staff nholford From Mats Karlsson Mats Karlsson farmbio uu se Subject Re NMusers Plcebo Corrected PK PD Date Fri March 4 2005 3 13 pm Nick Would the model not be identifiable only if you assume that the covariance of the random effects for alpha and beta is zero At least if Ce is constant If it is variable and variable enough it starts to resemble a cross over experiment at least when you have frequent measurement Mats From Bhattaram Atul BhattaramA cder fda gov Subject RE NMusers Plcebo Corrected PK PD Date Fri March 4 2005 4 05 pm Hello Nick I dont think you can estimate the true variability unless one does a cross over design If you dont have placebo data in the same subject for symptomatic drugs anti hypertensives how would you estimate the true variability Venkatesh Atul Bhattaram Pharmacometrics FDA From Bachman William MYD bachmanw iconus com Subject RE NMusers Plcebo Corrected PK PD Date Fri March 4 2005 4 23 pm This is done all the time measure the placebo effect in some subjects and the drug effect in others at least where ethical Look at all those analgesic studies that have been done It s clear you don t have the variability in the same subjects but in a well designed study with sufficient power the estimate of variability in placebo effect is sufficiently accurate for the purpose In many cases there is no other way to do it Obviously the study design is dependent on the indication severity of disease state and practicality ethicality you can t pull teeth from a subject without medication one week and with medication the next From Nick Holford n holford auckland ac nz Subject Re NMusers Plcebo Corrected PK PD Date Fri March 4 2005 5 47 pm Atul It all depends on the model you have in mind If the time course of the placebo effect is essentially the same as the time course of the drug effect then I agree that the two components of the overall response cannot be distinguished as I indicated in my previous posting But if the placebo response or disease progress is different

    Original URL path: http://nonmem.org/nonmem/nm/99mar022005.html (2016-04-25)
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  • [NMusers] Model building question
    Wade demonstrated the same to be true for structural effects and our local experience with more robust search methods suggests that the same is true of residual error and interindividual error terms The outcome is always very sensitive to the sequence of hypothesis tests I ve been told by those who formally study combinatorial optimization which is what we are doing in our model building that our algorithm is really really naive Mark Sale M D Global Director Research Modeling and Simulation GlaxoSmithKline 919 483 1808 Mobile 919 522 6668 From jeffrey a wald gsk com Subject Re NMusers Model building question Date Tue March 1 2005 10 29 am From a formalistic perspective I d have to agree with Mark From a pragmatic perspective I would agree with a reworded version of Nick s statement The sequence of model building should not affect substantial inferences However this thread raises a question in my mind Is the coda of Nick s statement but sometimes it does really true when we limit ourselves to consideration of substantial inferences i e drug label changes dose adjustments etc I would be curious to learn of real life examples in which different model building sequences have led to equivalent models with substantially different clinical manifestations I think the field of combinatorial optimization offers the possibility for increased automation of model building which in and of itself might yield great benefits However in my somewhat intentionally provocative opinion IMSIPO I am not convinced that when we do what we do already with adequate expertise that we are somehow failing to identify clinically meaningful actionable conclusions Jeff Jeff Wald PhD jeffrey a wald gsk com Clinical Pharmacokinetics Modeling and Simulation Neurology and GI RTP NC From Harry Mager harry mager bayerhealthcare com Subject Re NMusers Model building question Date 01 Mar 2005 10 22 Mark Of course I totally agree with you one minor remark however Even if the information content in 2 covariates it is nearly the same it may well happen that both are retained in a relationship In this case you may end up with a very high measure for the association between DV and the model predictiions but the regression coefficients tend to be very large pretending a strong relationship but with opposite signs very strong opposite influence of the covariates on the the dependent variable There seems to be no way to avoid a careful examination of the covariate structure and its potential implications on regression coefficient variabilities Harry Dr Harry Mager Head Global Pharmacometrics Bayer Healthcare AG BHC PH PD GMD GB Biometry Pharmacometry D 42096 Wuppertal Bldg 470 Telefon 49 0 202 36 8891 Telefax 49 0 202 36 4788 eMail Harry Mager HM Bayer AG de From mark e sale gsk com Subject Re NMusers Model building question Date Tue March 1 2005 10 37 am Harry Absolutely careful and thorough and thoughtful i e what make biological sense does BSA make more sense than body weight does

    Original URL path: http://nonmem.org/nonmem/nm/99feb282005.html (2016-04-25)
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  • [NMusers] NONMEM question.
    you can give me an example to show how its being done Many thanks Philip From Joel Owen Subject Re NMusers NONMEM question Date Fri March 18 2005 12 32 pm Dear Phil A workshop on model validation evaluation was held as part of the 2004 East Coast Population Analysis Group meeting Slides from the workshop are available on the ECPAG website at the following link http www ecpag org

    Original URL path: http://nonmem.org/nonmem/nm/99feb222005.html (2016-04-25)
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  • [NMusers] New NMTRAN bug list with a new Bug # XXVIII
    in the SUBROUTINES record XIV NM TRAN translation of clock times to elapsed times can be faulty All elapsed times resulting from clock time translation should have two digits to the right of the decimal point Certain elapsed times greater than 999 99 hours 41 6 days are unpredictably and mistakenly truncated so that they contain only one digit to the right of the decimal point See discussion in the NONMEM Archive http www cognigencorp com nonmem nm 99apr192002 html Fix In routine READ3 replace the line ELSEIF VALUE KK J GE 1000 0 AND WIDE NE Y THEN with ELSEIF VALUE KK J GE 1000 0 AND WIDE NE Y AND NSP EQ 1 THEN XV The error message DATA WIDE CANNOT BE USED FILE CONTAINS MORE THAN 9999 RECS may appear but it should not appear when 1 the WIDE option appears on the DATA record 2 there are more than 9999 records in the data set 3 the control stream consists of a single problem Fix In routine READF insert these two statements anywhere among the other declaration statements COMMON COMEND ENDFIL LOGICAL ENDFIL and change the statement IF INOBS GT 9999 AND WIDE EQ Y CALL ERRMSG 283 1 to IF INOBS GT 9999 AND WIDE EQ Y AND NOT ENDFIL X CALL ERRMSG 283 1 In routine GETITM insert this statement anywhere among the other declarations COMMON COMEND ENDFIL In routine CHKDAT change the statement IF MKFDAT AND INOBS GT K9999 THEN to IF MKFDAT AND INOBS GT K9999 AND WIDE NE Y THEN XVI NM TRAN translation of TIME data items is faulty when 1 NM TRAN infers that the data are single subject data 2 the name ID is listed in the INPUT record as ID or ID L1 3 some synonym A B and or DATE DROP preceeds ID in the INPUT record Time translation occurs when either clock times are present in the NM TRAN data set or DATE items appear Usually when time translation occurs with single subject data ID does not appear in the INPUT record though L1 may appear in which case the TIME data item on the first record of the data set is translated to 0 and subsequent TIME data items are translated to times relative to 0 When ID is listed in the INPUT record with every data record where the ID data item changes value the TIME data item is translated to 0 and subsequent TIME data items up to the next change in ID value are translated to times relative to 0 Due to the bug if ID is listed near the beginning of the INPUT record different data from the ID data items are used in the process of time translation If the ID is listed near the end of the INPUT record the ID data items are ignored in the process of time translation i e all TIME data items subsequent to the one on the first data record are translated to times relative to 0 Work around Construct a new data set such that 3 above will not happen That is the new data set will be exactly like the old data set except for having a new column that is exactly like the column in the original data set with the ID data items column C and the new column will be placed before the columns with the A type data items and or the DATE data items Actually column C itself can be deleted but if it is not give this column a name N different from ID and use N DROP Work around Avoid using the synonym A B XVII The constant LNP4 in files TSIZES is set at installation time to the default value of 1000 An error occurs during compilation of generated code when LNP4 is set to a value greater than 9999 However a value greater than 9999 is of little practical value When the option COMRES n n 0 is used in the ABBREVIATED record or when verbatim code is used and when LNP4 is set to a value greater than 1000 an error occurs during compilation of generated code Fix In routine GENCOM replace the two lines of code WRITE LINE A I4 4 A DIMENSION COM COMMAX LL 19 with WRITE LINE A I6 6 A DIMENSION COM COMMAX LL 21 XVIII The data may be mistakenly interpreted as single subject data when 1 there are multiple problem specifications 2 in the second or subsequent problem specification a MSFI record appears without the NPOP option With the problem specification where the MSFI record appears without the NPOP option the data are misinterpreted as single subject data An error message will make it clear that the data are being misinterpreted Work around Include the NPOP option XIX Fatal error message 386 spuriously arises when abbreviated code such as IF condition statement is used where 1 the condition includes a test of ICALL or COMACT and either 2a the statement is a WRITE PRINT statement that uses either ICALL or COMACT in the output list or 2b the statement is an assignment statement that uses either ICALL or COMACT as a right hand quantity Work around Instead of the above IF statement use IF condition THEN statement ENDIF XX There arises a faulty end of record condition when 1 a superproblem is used 2 the data set is too large Work around Try reinstalling NONMEM setting LIM1 the size of buffer 1 to a value large enough that for each of the problems in the superproblem the entire data set for the problem can be stored in computer memory throughout the NONMEM run See Guide III chapter III section 2 9 4 XXI A constant used in abbreviated code may not be translated into a double precision constant when 1 neither the SP nor LIBRARY options appear in the SUBROUTINE statement 2 a statement of form IF condition1 AND condition2 or IF condition1

    Original URL path: http://nonmem.org/nonmem/nm/99feb172005.html (2016-04-25)
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  • [NMusers] Difficulty with ADVAN6
    error do not see the change being reflected NUMERICAL DIFFICULTIES WITH INTEGRATION ROUTINE MAXIMUM NO OF EVALUATIONS OF DIFFERENTIAL EQUATIONS 100000 EXCEEDED I appreciate your help very much Kind Regards Partha Partha Nandy BMS Clinical Discovery Lawrenceville NJ From phil lowe pharma novartis com Subject Re NMusers Difficulty with ADVAN6 Date Wed February 16 2005 1 38 pm Dear Partha I had this problem some years ago and asked nmusers

    Original URL path: http://nonmem.org/nonmem/nm/99feb162005.html (2016-04-25)
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  • [NMusers] Error message: floating divide by zero
    a NONMEM project Both the data and the code has been working fine in anohter machine both are in Version 1 1 Strange enough other NONMEM codes are working in one computer but not the other with similar floating point invalid error message I appreciate any kind answers and the solutions very much Liang From Bachman William MYD bachmanw iconus com Subject RE NMusers Error message floating divide by zero

    Original URL path: http://nonmem.org/nonmem/nm/99feb152005.html (2016-04-25)
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  • [NMusers] Installation of NONMEM
    installed Wings yet but plan to Any help would be appreciated Lai San THAM National University Hospital From Bachman William MYD bachmanw iconus com Subject RE NMusers Installation of NONMEM Date Tue February 15 2005 8 01 am Lai San Follow the directions in the readme doc on the installation cd 1 Read Appendix 3 section 3 3 and Appendix 5 in NONMEM Users Guide Part III NONMEM Installation Guide 2 Open a MS DOS window by double clicking the MS DOS icon or the Start Programs Command Prompt on Window NT or the Start Programs Accessories Command Prompt on Windows 2000 The menu path may be different for other versions of Windows 3 Insert disk 1 Double Precision NONMEM and PREDPP into the floppy drive or place the CD in the CD drive 4 Change to the appropriate floppy or CD ROM drive by typing x where x is the appropriate drive letter 5 At the command prompt type the setup command and appropriate options The setup command is described in Appendix 5 Guide III If the Compaq Digital Visual Fortran compiler is used and NONMEM is to be installed from the floppy drive labeled a into the nmv

    Original URL path: http://nonmem.org/nonmem/nm/99feb142005.html (2016-04-25)
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