From: Joseph Standing <*joseph.standing*>

Date: Tue, 20 Oct 2009 09:24:07 +0200

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

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 think

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 mentioned

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 the

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 two

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

Matt.

_____

From: owner-nmusers

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

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

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Thank you.

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,

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

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attachments.

Thank you.

Received on Tue Oct 20 2009 - 03:24:07 EDT

Date: Tue, 20 Oct 2009 09:24:07 +0200

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

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 think

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 mentioned

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 the

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 two

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

Matt.

_____

From: owner-nmusers

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 any

attachments.

Thank you.

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 any

attachments.

Thank you.

Received on Tue Oct 20 2009 - 03:24:07 EDT