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From: Bauer, Robert <Robert.Bauer>
Date: Mon, 13 Apr 2015 15:42:01 +0000

Dear Xinting:
Well, in NONMEM 7.3, because ISAMPLE is used for both SAEM and IMP, it is filtered such that if the user sets ISAMPLE for SAEM higher than ISAMPLEMAX, it is not changed from the default of 2 for SAEM. Your NONMEM report file will tell you the actual ISAMPLE used for the SAEM step. Please refer to that. Of course, $SIZES ISAMPLEMAX=??? will allow you to increase ISAMPLEMAX, should you actually needed higher than 10. Typically, however, ISAMPLE should not be greater than 10 for SAEM.

Your convergence success may be serendipitous, as it sometimes is with Monte Carlo matters.

Meanwhile, I am afraid I did not understand your last sentence.

Robert J. Bauer, Ph.D.
Vice President, Pharmacometrics R&D
ICON Early Phase
Office: (215) 616-6428
Mobile: (925) 286-0769
Robert.Bauer m><>

From: Xinting Wang [mailto:wxinting1986
Sent: Sunday, April 12, 2015 9:57 PM
To: Bauer, Robert; Leonid Gibiansky; hnyberg
Cc: nmusers m
Subject: Re: [NMusers] ISAMPLE under SAEM and IMP

Dear all,
Thanks very much for your explanation.
I tried to manipulate different ISAMPLE options after your suggestion, and found that raising ISAMPLE from 2 to 5 would not produce a convergence [CTYPE=3], but if the number is 300, then a convergence is rapidly achieved. Additionally, this does not have an untolerable prolongation of computation time. While I understand that this is only a guidance, and judgement should be made based on the outcome from .ext file produced, it seems to me that raising the number could actually help with convergence.
A follow-up question is, does the convergence criteria in IMP meaniningful, or similar to SAEM, a reference to .ext file is also the preferred method to evaluate if the method is appropriate? Many thanks!
Best Regards

On 9 April 2015 at 01:02, Bauer, Robert <Robert.Bauer
Xinting Wang:
Generating each sample in SAEM is computationally more expensive in SAEM, and so ISAMPLE of 2-10 is generally done. You may try increasing ISAMPLE=3 or 5 in SAEM. Furthermore, convergence testing is only a guide, Review the .ext file and be satisfied by visual inspection that the parameters are not directionally changing, and are just randomly fluctuating.

Robert J. Bauer, Ph.D.
Vice President, Pharmacometrics R&D
ICON Early Phase
Office: (215) 616-6428<tel:%28215%29%20616-6428>
Mobile: (925) 286-0769<tel:%28925%29%20286-0769>
Robert.Bauer ilto:Robert.Bauer<>

From: owner-nmusers to:owner-nmusers
Sent: Tuesday, April 07, 2015 7:42 PM
To: nmusers om>
Subject: [NMusers] ISAMPLE under SAEM and IMP

Dear all,
I have a question regarding the setting of ISAMPLE under SAEM and IMP method in Nonmem 7.2.
I have noticed that in the NONMEM manual, the default setting of ISAMPLE for IMP is 300, and 2 for SAEM. Well it was well explained about the general guidance of ISAMPLE for IMP, i.e. might need to float to 1000-3000 in case of sparse samples. However, the setting for ISAMPLE under SAEM is not explained that much.
Additionally, in the examples provided in the manual most of ISAMPLE setting is in its hundreds or more for IMP, this option under SAEM is mostly 2. I understand that with a lower value the computation is fast, but why is there's such a big difference in terms of setting sample number per subject?
The reason I am asking this is because of a diffitulty to achieve convergence in the burn-in step using below estimation method:

SEED=150159 FILE=Saem.ext

Thanks very much for your explanation.
Best Regards


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Received on Mon Apr 13 2015 - 11:42:01 EDT

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