From: wu kehua <*zckehua*>

Date: Tue, 17 Nov 2009 14:19:34 -0600

Dear Joseph,

Sorry for so delayed response. I build the model as your recommendations,

and the model works very well.

But there is another problem when the number of subgroups scales up to 12.

PDx-pop shows a problem with my model: "332 $MIX: NSPOP OR INDEX I OF P(I)

EXCEEDS CONSTANT "MMX" IN SIZES. "

It seems that I should change the value of 'MMX'. I searched at the help

files and did not find how to change it.

I appreciate your and your colleagues' help.

Best regards,

Kehua

2009/10/20 Joseph Standing <joseph.standing

*> Dear Kehua,
*

*>
*

*>
*

*>
*

*> We discussed your question in the Uppsala pharmacometrics meeting
*

*> yesterday. If I understood your original question correctly, it was that
*

*> there were two possible conditions for ALPHA and BASE, and that each
*

*> combination was possible. A general principle for coding this:
*

*>
*

*>
*

*>
*

*> ….
*

*>
*

*> $MIX
*

*>
*

*>
*

*>
*

*> P(1) = Theta(alph) * Theta(Base)
*

*>
*

*> P(2) = (1 – Theta(alph)) * Theta(Base)
*

*>
*

*> P(3) = Theta(alph) * (1 - Theta(base))
*

*>
*

*> P(4) = (1 – Theta(alph)) * (1-Theta(base)) ; = 1 – P(1=
*

) – P(2) –

*> P(3)
*

*>
*

*>
*

*>
*

*> …
*

*>
*

*>
*

*>
*

*> $THETA (0,x,1) ; Theta(alph)
*

*>
*

*> $THETA (0,y,1) ; Theta(base)
*

*>
*

*>
*

*>
*

*>
*

*>
*

*> You should be able to extend this general principle to suit your specific
*

*> case.
*

*>
*

*> Best wishes,
*

*>
*

*>
*

*>
*

*> Joe Standing
*

*>
*

*>
*

*> ------------------------------
*

*>
*

*> *From:* owner-nmusers *

]

*> *On Behalf Of *Fidler,Matt,FORT WORTH,R&D
*

*> *Sent:* den 13 oktober 2009 21:33
*

*> *To:* wu kehua
*

*> *Cc:* nmusers *

*> *Subject:* RE: [NMusers] a question about the mixture distribution
*

*>
*

*>
*

*>
*

*> Kehua,
*

*>
*

*>
*

*>
*

*> The number of subgroups depend on how you view the subgroups.
*

*>
*

*>
*

*>
*

*> There are three subgroups for ALPH, and there are two subgroups for BASE.
*

*> Therefore, there could be
*

*>
*

*>
*

*>
*

*> 3*2 = 6 subgroups
*

*>
*

*>
*

*>
*

*> or
*

*>
*

*>
*

*>
*

*> 3+2 = 5 subgroups -- 3 for ALPH and 2 for BASE.
*

*>
*

*>
*

*>
*

*>
*

*>
*

*> While technically there are 6 groups, you only code for 5, and each of
*

*> these five have sufficient information to determine which group each
*

*> individual is a member of.
*

*>
*

*>
*

*>
*

*> Matt.
*

*>
*

*>
*

*>
*

*>
*

*> ------------------------------
*

*>
*

*> *From:* wu kehua [mailto:zckehua *

*> *Sent:* Tuesday, October 13, 2009 11:58 AM
*

*> *To:* Fidler,Matt,FORT WORTH,R&D
*

*> *Cc:* nmusers *

*> *Subject:* Re: [NMusers] a question about the mixture distribution
*

*>
*

*> Hi Matt,
*

*>
*

*> Thank you very much for your kindly reply. It is very helpful.
*

*>
*

*> I still have another question about this issue. I have tried the first
*

*> option. I applied three subgroups on ALPH and two subgroups on BASE. I th=
*

ink

*> there should be six subgroups in total, right? But in the resulting data,
*

*> there are just five subgroups. The code follows,
*

*>
*

*> $PRED
*

*>
*

*> CALLFL =1
*

*> EST = MIXEST
*

*> IF (MIXNUM.EQ.3) THEN
*

*> ALPH = (THETA(3))
*

*> END IF
*

*> IF (MIXNUM.EQ.2) THEN
*

*> ALPH = (THETA(2))
*

*> END IF
*

*> IF (MIXNUM.EQ.1) THEN
*

*> ALPH = (THETA(1))
*

*> ENDIF
*

*>
*

*>
*

*> IF (MIXNUM.EQ.4) THEN
*

*> BASE=THETA(4)
*

*> ELSE
*

*> BASE=THETA(5)
*

*> END IF
*

*>
*

*>
*

*>
*

*> $MIX
*

*>
*

*> P(1) = THETA(6)
*

*> P(2)=THETA(7)
*

*> P(3) = 1-THETA(7)-THETA(6)
*

*> P(4)=THETA(8)
*

*> P(5)=1-THETA(8)
*

*> NSPOP = 5
*

*>
*

*> Sorry to bother you and thank you very much. I will try that one mentione=
*

d

*> in your mail and let you know the results.
*

*> I appreciate your helps.
*

*>
*

*> Best regards,
*

*>
*

*> Kehua
*

*>
*

*> 2009/10/13 Fidler,Matt,FORT WORTH,R&D <Matt.Fidler *

*>
*

*> Kehua,
*

*>
*

*>
*

*>
*

*> Option 1 is definitely better. This states that there is a possibility
*

*> that a population falls into ALPH1 or ALPH2. Within that same population
*

*> there are two populations for BASE.
*

*>
*

*>
*

*>
*

*> The other option states that each person in the has distinct parameters
*

*> that four populations fall into: ALPH - Pop1, ALPH - Pop 2, Base -Pop 1, =
*

or

*> Base -Pop2. Therefore, if you selected ALPH - pop1, you wouldn't have th=
*

e

*> parameter base. (You require this by having P1 - P4 to add up to be one -
*

*> the total probability).
*

*>
*

*>
*

*>
*

*> A third option you may consider is if you have reason to believe that the
*

*> populations that have ALPH1 and Base1 are the same:
*

*>
*

*>
*

*>
*

*> $PRED
*

*> IF (MIXNUM.EQ.2) THEN
*

*> ALPH =THETA(1)
*

*>
*

*> ELSE
*

*> ALPH = THETA(2)
*

*> ENDIF
*

*>
*

*> IF (MIXNUM.EQ.2) THEN
*

*>
*

*>
*

*> BASE=THETA(3)
*

*> ELSE
*

*> BASE=THETA(4)
*

*> END IF
*

*>
*

*> $MIX
*

*>
*

*> P(1) = THETA(5)
*

*> P(2) = 1-THETA(5)
*

*>
*

*> NSPOP = 2
*

*>
*

*>
*

*>
*

*> I haven't run anything like Option 1, and am unsure if NONMEM supports tw=
*

o

*> separate populations for ALPH and BASE. Has anyone tried this?
*

*>
*

*>
*

*>
*

*> Matt.
*

*>
*

*>
*

*> ------------------------------
*

*>
*

*> *From:* owner-nmusers *

]

*> *On Behalf Of *wu kehua
*

*> *Sent:* Tuesday, October 13, 2009 10:58 AM
*

*> *To:* nmusers *

*> *Subject:* [NMusers] a question about the mixture distribution
*

*>
*

*> Hi,
*

*>
*

*> I am a new NONMEM user. I have a question about mixture distribution.
*

*>
*

*> I have two parameters. How to apply mixture distribution on the both
*

*> parameters? I should use the first one or the second one?
*

*>
*

*> *First,*
*

*> $PRED
*

*> IF (MIXNUM.EQ.2) THEN
*

*> ALPH =THETA(1)
*

*> END IF
*

*> IF (MIXNUM.EQ.1) THEN
*

*> ALPH = THETA(2)
*

*> ENDIF
*

*>
*

*> IF (MIXNUM.EQ.3) THEN
*

*> BASE=THETA(3)
*

*> ELSE
*

*> BASE=THETA(4)
*

*> END IF
*

*>
*

*> $MIX
*

*>
*

*> P(1) = THETA(5)
*

*> P(2) = 1-THETA(5)
*

*> P(3)=THETA(6)
*

*> P(4)=1-THETA6)
*

*> NSPOP = 4
*

*>
*

*>
*

*> *Second,*
*

*>
*

*> IF (MIXNUM.EQ.1) THEN
*

*> ALPH =THETA(1)
*

*> BASE=THETA(3)
*

*> END IF
*

*> IF (MIXNUM.EQ.2) THEN
*

*> ALPH = THETA(1)
*

*> BASE=THETA(4)
*

*> ENDIF
*

*> IF (MIXNUM.EQ.3) THEN
*

*> ALPH = THETA(2)
*

*> BASE=THETA(3)
*

*> ELSE
*

*> ALPH = THETA(2)
*

*> BASE=THETA(4)
*

*> END IF
*

*>
*

*> $MIX
*

*>
*

*> P(1) = THETA(5)
*

*> P(2) = THETA(6)
*

*> P(3)=THETA(7)
*

*> P(4)=1-THETA(5)-THETA(6)-THETA(7)
*

*> NSPOP = 4
*

*>
*

*> Thank you very much!
*

*>
*

*> Best regards,
*

*>
*

*> Kehua
*

*>
*

*>
*

*> This e-mail (including any attachments) is confidential and may be
*

*> legally privileged. If you are not an intended recipient or an authorized
*

*> representative of an intended recipient, you are prohibited from using,
*

*> copying or distributing the information in this e-mail or its attachments=
*

.

*> If you have received this e-mail in error, please notify the sender
*

*> immediately by return e-mail and delete all copies of this message and an=
*

y

*> attachments.
*

*>
*

*> Thank you.
*

*>
*

*>
*

*>
*

*> This e-mail (including any attachments) is confidential and may be legall=
*

y

*> privileged. If you are not an intended recipient or an authorized
*

*> representative of an intended recipient, you are prohibited from using,
*

*> copying or distributing the information in this e-mail or its attachments=
*

.

*> If you have received this e-mail in error, please notify the sender
*

*> immediately by return e-mail and delete all copies of this message and an=
*

y

*> attachments.
*

*>
*

*> Thank you.
*

*>
*

Received on Tue Nov 17 2009 - 15:19:34 EST

Date: Tue, 17 Nov 2009 14:19:34 -0600

Dear Joseph,

Sorry for so delayed response. I build the model as your recommendations,

and the model works very well.

But there is another problem when the number of subgroups scales up to 12.

PDx-pop shows a problem with my model: "332 $MIX: NSPOP OR INDEX I OF P(I)

EXCEEDS CONSTANT "MMX" IN SIZES. "

It seems that I should change the value of 'MMX'. I searched at the help

files and did not find how to change it.

I appreciate your and your colleagues' help.

Best regards,

Kehua

2009/10/20 Joseph Standing <joseph.standing

) – P(2) –

]

ink

d

or

e

o

]

.

y

y

.

y

Received on Tue Nov 17 2009 - 15:19:34 EST