RE: [NMusers] Intra-species PK scaling from adults to infantsfor antibody drugs

Hi Huadong, You say that you do not think that the allometry law should be fixed to 1 for volume-based parameters. I think that we all agree to that the apparent volumes are sometimes not proportional to body weight. However, when this happens it is because something else is confounded with body si

RE: [NMusers] Indirect response model

Dear all, I agree, implementing the actual PK model (i.e. IPP) or using linear interpolation to describe the individual PK profiles as suggested by Juergen and David is necessary in this example. However, for understanding when input concentrations can be used directly as a reasonable approximati

Re: [NMusers] Additive plus proportional error model for log-transform data

our problem. Best regards Jakob Jakob Ribbing, Ph.D. Senior Consultant, Pharmetheus AB Cell/Mobile:+46 (0)70 514 33 77 jakob.ribb...@pharmetheus.com www.pharmetheus.com Phone, Office: +46 (0)18 513 328 Uppsala Science Park, Dag Hammarskjölds väg 52B SE-752 37 Uppsala, Sweden T

Re: [NMusers] Additive plus proportional error model for log-transform data

Sorry, an error in what I wrote below: It should be EXP(0)=1 concentration unit Jakob Ribbing, Ph.D. Senior Consultant, Pharmetheus AB Cell/Mobile:+46 (0)70 514 33 77 jakob.ribb...@pharmetheus.com www.pharmetheus.com Phone, Office: +46 (0)18 513 328 Uppsala Science Park, Dag

Re: [NMusers] Can you post this question?

what you need from this variable is the previous DV value? I did not find time to check your control steam, but if there is any obvious error I am sure someone else will spot that. Best wishes Jakob Jakob Ribbing, Ph.D. Senior Consultant, Pharmetheus AB Cell/Mobile:+46 (0)70 514 33

Re: [NMusers] $PRIOR with normal for OMEGA?

und limitations/features with NWPRI, since that is clearly out of scope for the topic in this tread :>) Best regards Jakob Jakob Ribbing, Ph.D. Senior Consultant, Pharmetheus AB Cell/Mobile:+46 (0)70 514 33 77 jakob.ribb...@pharmetheus.com www.pharmetheus.com Phone, Office: +46 (0)

Re: [NMusers] Different results with ADVAN4 and ADVAN6

Hi Hanna, I did not check the whole model code, but could it be a typo in the rate for re-distribution that produces the difference? DADT(3) = K23*A(2) - K23*A(3) Kind regards Jakob Jakob Ribbing, Ph.D. Senior Consultant, Pharmetheus AB Cell/Mobile:+46 (0)70 514 33 77 jakob.ribb

Re: [NMusers] Simplified Bateman equation where Ka=Ke

: 10.1007/s10928-012-9274-0. Epub 2012 Sep 23. Longitudinal FEV1 dose-response model for inhaled PF-00610355 and salmeterol in patients with chronic obstructive pulmonary disease. Nielsen JC, Hutmacher MM, Cleton A, Martin SW, Ribbing J. DS. Jakob Ribbing, Ph.D. Senior Consultant, Pharmetheus AB

Re: [NMusers] Inherit past calculation of parameter in NONMEM

covariate effects so that a covariate may not reduce by more than 100%, or use e.g. a power model, if covariate values are >0. Best regards Jakob Jakob Ribbing, Ph.D. Senior Consultant, Pharmetheus AB Cell/Mobile:+46 (0)70 514 33 77 jakob.ribb...@pharmetheus.com www.pharmetheus.

[NMusers] The Pharmetheus team is expanding!

Dear all, The Pharmetheus team is expanding! Pharmetheus is a pharmacometrics consultancy company supporting drug development of compounds in all phases and in most therapeutic areas, through strategic support as well as hands on modelling and simulation performed within a reproducible report

Re: [NMusers] W for time varying covariates

). DS. Example code for estimating additive error model with sigma estimated. IPRED = [Model specific equation, or F] IRES = DV-IPRED ADD= SQRT(SIGMA(1,1)) SD = ADD IWRES = IRES/SD Y = IPRED + EPS(1) Jakob Ribbing, Ph.D. Senior Consultant, Pharmetheus AB Cell/Mobile:

Re: [NMusers] ETAs & SIGMA in external validation

PARA = TVPARA * (1+ETA(1)) ENDDO ENDIF ;Etas that do not need resampling should be declared after the above DO WHILE block. They should follow below […] $SIMULATION (123456 NEW) (7891011 UNIFORM) ONLYSIMULATION […] ; The SIMETA requires an additional seed number, see nmhelp for more info

Re: [NMusers] ETAs & SIGMA in external validation

Hi Tingjie, It does not: Sigma squared is the sum of all error variances, and assay error in most cases is only a small contribution to this sum. There are exceptions, but when applying a previous model to new data it is rarely the first modification that comes to my mind. Given your objectives

Re: [NMusers] ETAs & SIGMA in external validation

Hi Ruben, I think I misread Tingjies original posting as taking ABS(ETA), whereas his initial attempt was actually ABS(1+ETA), which is less problematic. The latter would not bias simulations much if IIV is e.g. 30% CV, agreed. However, as Tingjies is mainly interested in estimation, I believe t

Re: [NMusers] ETAs & SIGMA in external validation

possible on these covariate-parameter data. Best wishes Jakob Jakob Ribbing, Ph.D. Senior Consultant, Pharmetheus AB Cell/Mobile:+46 (0)70 514 33 77 jakob.ribb...@pharmetheus.com www.pharmetheus.com <http://www.pharmetheus.com/> Phone, Office: +46 (0)18 513 328 Uppsala Scienc

Re: [NMusers] In covariate analysis, should we use p-value or OFV to decide which model is better when comparing?

on and instead specify p-values for forward and backward selection. The gof option is only used in special cases, where one does not want to assume that delta-OFV follows a chi-square distribution (or if one wants to use p-values lower than 0.0001). Best regards Jakob Jakob Ribbing

Re: [NMusers] inclusion of covariates with $PRIOR

these questions? Best regards Jakob Jakob Ribbing, Ph.D. Senior Consultant, Pharmetheus AB Cell/Mobile:+46 (0)70 514 33 77 jakob.ribb...@pharmetheus.com www.pharmetheus.com <http://www.pharmetheus.com/> Phone, Office: +46 (0)18 513 328 Uppsala Science Park, Dag Hammarskjöl

Re: [NMusers] inclusion of covariates with $PRIOR

good to check manually. Best regards Jakob Jakob Ribbing, Ph.D. Senior Consultant, Pharmetheus AB Cell/Mobile:+46 (0)70 514 33 77 jakob.ribb...@pharmetheus.com www.pharmetheus.com <http://www.pharmetheus.com/> Phone, Office: +46 (0)18 513 328 Uppsala Science Park, Dag Hammars

Re: [NMusers] Free speed consulting with Pharmetheus at PAGE in Stockholm

services later - this is open to everyone. Please use this link to get in contact with us for this matter: Pharmetheus.com/speed-consulting <http://pharmetheus.com/speed-consulting> Looking forward to seeing you at PAGE! Jakob Jakob Ribbing, Ph.D. Senior Consultant, Pharmetheus AB

Re: [NMusers] Lognormal survival in NONMEM?

AGE%20_2014_tte_sim_joakim_nyberg_with_code.pdf> These include the log-normal distribution, as well as Gompertz and Weibull. Best regards Jakob Jakob Ribbing, Ph.D. Senior Consultant, Pharmetheus AB Cell/Mobile:+46 (0)70 514 33 77 jakob.ribb...@pharmetheus.com www.pharmetheus.com <http://www.pharmetheus.com

Re: [NMusers] Stepwise covariate modeling

Hi Sumeet, If you have rich sampling (and rich information on all parameters of interest) then one would not expect much difference between the individual parameter estimates with/without covariates in the model. This does not make the covariate model meaningless, since future patients may be s

Re: [NMusers] Error in Power-model for covariate selection

Hi Sumeet, It is great that you have considered already that covarite values do not include zero or negative values, as that would not work with the power model. Did you have any missing values, and how were they coded? I would recommend to code these (in your data file) using the default -99 in

Re: [External] Re: [NMusers] Error in Power-model for covariate selection

e value, I thought it doesnt make sense, and instead I provided median > BMI in place of missing values. Didn’t work that way either. > > Regards, > Sumeet Singla > > > >> On Nov 19, 2019, at 11:10 PM, Jakob Ribbing >> wrote: >> >>  Hi Sumeet, &

Re: [External] Re: [NMusers] Error in Power-model for covariate selection

Great to hear it is now working. If you want to set the same limits for all power models, you can even write this in a more generic form: *:*-5 = -5 And if you want to apply only for one parameter or one covariate that is possible as well, e.g.: V2:*-5 = -5 Best regards Jakob > On 21 Nov 20

Re: [NMusers] Block SIZE with SCM

Dear Emeric, The code has negative PD, maybe PsN has problems interpreting this? I am not sure how PD=-100 would be interpreted by NONMEM, but try PD=100, instead. I think this is what you intended to do? As a side note, PsN (mainly to handle old nonmem versions) has functionality for dropping

Re: [NMusers] Block SIZE with SCM

ariates are added during the forward path. > > Best Regards, > > Emeric Sibieude > > Student trainee in Master's degree > > Biopharma | R&D | Global Development | Translational Medicine > > Merck > > Lausanne , Switzerland > > emer

Re: [NMusers] Updating xpose4 stratification headers in VPCs

;=vpcPlot@plotList[[3]], “Dose C"=vpcPlot@plotList[[5]],layout = c(3,1)) That last step one has to be careful, as it is a bit error prone: you manually set the labels and if you get it wrong it will be mislabelled. Best regards Jakob Jakob Ribbing, Ph.D. Senior Consultant, Pharmetheus AB

[NMusers] Free Virtual Speed Consulting with Pharmetheus during ACoP11

limited. Sign up as soon as possible to give us a chance to help you tackle your challenges! Read more about the offer here: https://lnkd.in/dtXjKKg <https://lnkd.in/dtXjKKg> Hope to meet with you during ACoP! Jakob Ribbing, Ph.D. Senior Consultant, Pharmetheus AB Cell/Mobile: +46

Re: [NMusers] SEED status with SAEM method

observations per subject it will be difficult to find support for more than one level. And for a model with only residual error (no IIV), would not the FO Estimation method be sufficient, so why would you need to use SAEM for this data/model? Best regards Jakob Jakob Ribbing, Ph.D. Senior

Re: [NMusers] SEED status with SAEM method

jects with multiple observations? Best regards Jakob Jakob Ribbing, Ph.D. Senior Consultant, Pharmetheus AB Cell/Mobile: +46 (0)70 514 33 77 jakob.ribb...@pharmetheus.com www.pharmetheus.com Phone, Office: +46 (0)18 513 328 Uppsala Science Park, Dag Hammarskjölds väg 36B SE-752 37 Up

Re: [NMusers] Statistical power computation based on the wald test

tps://ascpt.onlinelibrary.wiley.com/doi/abs/10.1016/j.clpt.2003.11.158> Best regards Jakob Jakob Ribbing, Ph.D. Senior Consultant, Pharmetheus AB Cell/Mobile: +46 (0)70 514 33 77 jakob.ribb...@pharmetheus.com www.pharmetheus.com Phone, Office: +46 (0)18 513 328 Uppsala Science Park, Dag Hammars

Re: [NMusers] Problem with PSN4. 9 - COVARIANCE STEP ABORTED

find e.g. psn.mod. If on a LINUX system you can just run diff or ’sdiff -s’ to compare this file between the two runs with execute Did you change anything else in the configuration of PsN or NONMEM, e.g. the compiler? Best wishes Jakob Jakob Ribbing, Ph.D. Senior Consultant, Pharmetheus AB

Re: [NMusers] Fwd: T in $DES

Dear Matts, Did you get funny results in the way that using T_DAY did now work as intended? If you are unsure you could set up a simple test where you have the analytical solution to the output, as an initial confirmation. Otherwise, for models integrating forward in time, a covariate value at t

Re: [NMusers] Fwd: T in $DES

could include the log of T and in that case you would use: DEL = 1E-12 ...LOG((T+DEL)... Jakob Ribbing, Ph.D. Senior Consultant, Pharmetheus AB Cell/Mobile: +46 (0)70 514 33 77 jakob.ribb...@pharmetheus.com www.pharmetheus.com Phone, Office: +46 (0)18 513 328 Uppsala Science Park, Dag

Re: [NMusers] computation of exponential error model for RUV

Dear Monia, Yes, that is correct. So if one were to use this parameterization for FOCE then one would effectively get a proportional (symmetric) error distribution, exactly according to what you suggested: Y=F*(1+EPS(1)) For this reason, the standard approach in NONMEM (for FOCE and exponential

Re: [NMusers] computation of exponential error model for RUV

Dear all, For simulation, the EXP(EPS(1)) would be a log-normal distribution as intended, so either or would work in simulation mode and it is only in estimation (FOCE) the log-transform is necessary. Cheers Jakob > On 19 Jul 2021, at 18:10, Leonid Gibiansky wrote: > > yes, it does at e

Re: [NMusers] data

Dear Andre, Since nonmem warns for the same lines as before it is quite clear the nonmem is reading the old datafile. Did you update the datafile name in the nonmem control stream? Or, if you did not change the name of the datafile, are you sure the datafile is updated on the server where nonmem

Re: [NMusers] flip-flop without absorption information?

Dear Niurys, It would be down to distributional assumptions in that case. For example if you have a very strong predictor (covariate) of either elimination or absorption rate (but not both) - data could be informative to discriminate between flip-flop or not. Had your therapeutic been IgG monoc

Re: [NMusers] OFV by endpoint of joint models?

much value in joint modelling (simultaneous estimation of the two models), since no subject has observations of both endpoints. Or maybe I missed your point? Best regards Jakob Jakob Ribbing, Ph.D. Senior Consultant, Pharmetheus AB Cell/Mobile: +46 (0)70 514 33 77 jakob.ribb

Re: [NMusers] Simulate with parameter uncertainty

Hi Mark, I am assuming that you problem is a little more complex than only one theta, e.g. that you would like to simulate typical CL for a number of subgroups, where several covariate values (impactful on CL) are different across sub groups. In that case Leoid’s nonmem code would be a quick way

Re: [NMusers] Off diagonals in $TABLE

irrelevant, but I do not think that is what you mean. Best regards Jakob Jakob Ribbing, Ph.D. Senior Consultant, Pharmetheus AB Cell/Mobile: +46 (0)70 514 33 77 jakob.ribb...@pharmetheus.com www.pharmetheus.com Phone, Office: +46 (0)18 513 328 Uppsala Science Park, Dag Hammarskjölds väg 36B SE

Re: [NMusers] Off diagonals in $TABLE

). And for summary stats I believe what Leonid suggests (off-diagonal omega) is the more useful correlation, whereas e.g for a diagnostic plot EBE etas may be useful. Cheers Jakob Jakob Ribbing, Ph.D. Senior Consultant, Pharmetheus AB Cell/Mobile: +46 (0)70 514 33 77 jakob.ribb

Re: [NMusers] llp function in PsN

writing a few lines of code, or preparing a whole set of control streams with different fixed values for the parameter in question, but maybe someone else can suggest a PsN command for this? Best regards Jakob Jakob Ribbing, Ph.D. Principal Consultant, Pharmetheus AB > On 7 Feb 2023, at

Re: [NMusers] Combining L2-records configuration with M3 method

acceptable? Best regards Jakob Jakob Ribbing, Ph.D. Principal Consultant, Pharmetheus AB Cell/Mobile: +46 (0)70 514 33 77 jakob.ribb...@pharmetheus.com www.pharmetheus.com Phone, Office: +46 (0)18 513 328 Uppsala Science Park, Dag Hammarskjölds väg 36B SE-752 37 Uppsala, Sweden > On 19 Dec 2

Re: [NMusers] Verbatim Code

does PsN need to do this). Best wishes Jakob Jakob Ribbing, Ph.D. Principal Consultant, Pharmetheus AB Cell/Mobile: +46 (0)70 514 33 77 jakob.ribb...@pharmetheus.com www.pharmetheus.com Phone, Office: +46 (0)18 513 328 Uppsala Science Park, Dag Hammarskjölds väg 36B SE-752 37 Uppsala

Re: [NMusers] NONMEM related implementation question

for both types of records. Best regards Jakob Jakob Ribbing, Ph.D. Principal Consultant, Pharmetheus AB Cell/Mobile: +46 (0)70 514 33 77 jakob.ribb...@pharmetheus.com www.pharmetheus.com Phone, Office: +46 (0)18 513 328 Uppsala Science Park, Dag Hammarskjölds väg 36B SE-752 37 Uppsala, Sweden