Re: [FORGED] [NMusers] RE: question about random seed for simulation

From: Zhu, Penny <penny.zhu_at_sandoz.com>
Date: Fri, 10 Mar 2017 03:41:21 +0000

Dear Nick and all
I thought about this option before but noted that EVID=4 will clear all compartment.

My MODEL is a pk PD linked model. The starting condition for the PD compartment is non-zero(baseline). Also the pk is a TMDD MODEL and the starting condition for the receptor is also non-zero. I was wondering how EVID=4 would clear/reset all compartments in this case.

Penny Zhu

On Mar 9, 2017, at 6:34 PM, Nick Holford <n.holford_at_auckland.ac.nz<mailto:n.holford_at_auckland.ac.nz>> wrote:


Penny,

A simple solution using NONMEM is to put the different designs one after the other and separate them with an EVID=4 data item on the first dosing record for each design. You can a DESIGN data item value for each design which then makes it simple to use the simulated data in a subsequent NONMEM estimation run using ACCEPT or IGNORE on the $DATA record.

That way you can do the simulation just once and be sure to have all the random effects (ETA) identical for each subject.

Best wishes,

Nick

On 10-Mar-17 12:11, Faelens, Ruben (Belgium) wrote:
Hi Penny,

Nonmem indeed calculates each subject one after the other. The random values will therefore change. Maybe you can set the random seed every time you simulate t=0, based on the subject ID?
This may also depend on your data file; have you tried ordering on time (so the first 50 rows are all t=0 for subject 1 to 50) ?

This largely depends on the simulation software and its design:
As an example: Simulo samples all subjects together at simulation start, after which it runs the trial design; so the same subjects are sampled independent of subsequent trial design.

I do not know about other tools (TS.2, simulx, mrgsolve), maybe the authors of these tools can specify?

Kind regards,
Ruben Faelens

From: owner-nmusers_at_globomaxnm.com<mailto:owner-nmusers_at_globomaxnm.com> [mailto:owner-nmusers_at_globomaxnm.com] On Behalf Of Zhu, Penny
Sent: donderdag 9 maart 2017 19:19
To: nmusers_at_globomaxnm.com<mailto:nmusers_at_globomaxnm.com>
Subject: [NMusers] question about random seed for simulation

Dear All
I have finished a multiple dose simulation for 600 subjects and want to perform a single dose simulation (different sampling time) on the same subjects (same ETA as the first simulation). I used the same seed for the simulation step, it turned out the first subject was the same and the rest of the subjects are not and I am not sure whether this was due to the fact that the two simulation has different number TIME records. If so, I wonder what is the proper way to set the simulation seed so that the ETAs for the second simulation will be identical to the first one.

I know that I could output the individual parameter estimate from the first simulation and import them into the second one. But I was thinking if the random seed can be synchronized between the two simulation, it could be an easier solution.

Your help is very much appreciated!

Thank you very much and best regards!

Penny (Peijuan) Zhu, Ph.D.
Associate Director Clinical Pharmacology

Cell: 862-926-9079

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Sandoz
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Received on Thu Mar 09 2017 - 22:41:21 EST

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