Re: [NMusers] RE: Link different thetas to same omega using mu referencing

From: Emmanuel Chigutsa <>
Date: Wed, 13 Apr 2016 17:00:50 +0000 (UTC)

I think the following code should work:
CL = EXP(MU_1+ETA(1))*(1+CLCOV)

      From: Rupert Austin <>
 To: "'Sadler, Brian'" <>;
 Sent: Wednesday, April 13, 2016 11:44 AM
 Subject: RE: [NMusers] RE: Link different thetas to same omega using mu re=
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m not sure that Brian’s suggestion is acceptable due to the foll=
owing constraint I quote from one of the NONMEM manuals:  “Tim=
e dependent covariates cannot be part of the MU_ equation”  If=
 CAT is time-varying (as suggested by Jacob) then “MU_1 = CAT1*TH=
ETA(1) + CAT2*THETA(2) + CAT3*THETA(3)” includes time dependent cov=
ariates. Rather worryingly, I don’t think NONMEM will trap this pro=
blem since I have fallen foul of it with no resulting NONMEM warnings, and =
I have no idea what the consequences are for the resulting NONMEM run and r=
esults.  Rupert  Rupert Austin, PhDSenior ScientistBAST Inc Limit=
edLoughborough University Science and Enterprise ParkCharnwood WingHolywell=
 ParkAshby RoadLoughborough, LE11 3AQ, UKTel: +44 (0)1509 222908  From=
: [] On Beh=
alf Of Sadler, Brian
Sent: 13 April 2016 13:26
Subject: [NMusers] RE: Link different thetas to same omega using mu referen=
cing  Hi Jacob,  I suggest:CAT1=0CAT2=0CAT3=0IF(CAT.EQ.1) C=
AT1=1IF(CAT.EQ.2) CAT2=1IF(CAT.EQ.3) CAT3=1MU_1 = CAT1*THETA(1) + C=
AT2*THETA(2) + CAT3*THETA(3)CL = EXP(MU_1+ETA(1))  That way you have=
 only one OMEGA. This could be more flexible when expanding OMEGA for addit=
ional IIV in block format.  Cheers… Brian    From: o= [] On Behalf=
 Of Michael Fossler
Sent: Wednesday, April 13, 2016 7:56 AM
To: Leander, Jacob;
Subject: [NMusers] RE: Link different thetas to same omega using mu referen=
cing  This looks like it would work – it seems to obey the rul=
es around mu-referencing. You can simplify the $OMEGA by using SAME(3) =
 MikeMichael J. Fossler, Pharm. D., Ph. D., F.C.P.VP, Quantitative=
 SciencesTrevena, Incmfossler_at_trevenainc.comOffice: 610-354-8840, ext. 249C=
ell: 610-329-6636  From: [mailto:owner-nm=] On Behalf Of Leander, Jacob
Sent: Wednesday, April 13, 2016 7:01 AM
Subject: [NMusers] Link different thetas to same omega using mu referencing=
  Hi  Consider the case where we have a categorical (potentially =
time-varying) covariate named CAT that can take several values (e.g. 0,1,2,=
3).Let’s say I want to model CL depending on this categorical covar=
iate (where parameters are estimated on log-scale). A simple solution to th=
is would be  IF(CAT.EQ.1) TVCL = THETA(1)IF(CAT.EQ.2) TVCL = THETA=
(2)IF(CAT.EQ.3) TVCL = THETA(3)  I let CL be described by a log-norm=
al distribution with the same omega element for all CAT values.  CL =
= EXP(TVCL + ETA(1))  With an omega statement:  $OMEGA 0.1 =
I now want to switch to the mu referencing framework in NONMEM. Each the=
ta needs to be reference to a MU value, and to force it to be described by =
the same eta I apply the following approach.  MU_1 = THETA(1)MU_2 =
= THETA(2)MU_3 = THETA(3)  IF(CAT.EQ.1) CL = EXP(MU_1 + ETA(1))I=
F(CAT.EQ.2) CL = EXP(MU_2 + ETA(2))IF(CAT.EQ.3) CL = EXP(MU_3 + ETA(3))=
  With an omega statement:  $OMEGA BLOCK(1) 0.1$OMEGA BLOCK(1) SA=
ME$OMEGA BLOCK(1) SAME  where I force the omega element corresponding =
to ETA1, ETA2 and ETA3  to be the same.  Is this a valid approach=
 to obtain what I need? Or is there a simpler way in the mu-referencing fra=
mework to link different thetas to the same omega element?  All the be=
st,Jacob  Confidentiality Notice: This message is private and may con=
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Received on Wed Apr 13 2016 - 13:00:50 EDT

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