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

From: Nick Holford <n.holford>
Date: Fri, 10 Mar 2017 17:25:22 +1300

Penny,

When I use a PKPD model with the PD compartment initialized at TIME=0 I
find that PRED for the PD compartment is initialized to the same value
whether EVID=1 or EVID=4 and has identical values at subsequent times.
So it seems that with an EVID=4 event the compartments are
re-initialized after they are reset.

Perhaps you should try EVID=4 with your more complex model and see what
happens.

Best wishes,

Nick


On 10-Mar-17 16:41, Zhu, Penny wrote:
> 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
> <mailto:n.holford
>
>> 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
>>> [mailto:owner-nmusers
>>> *Sent:* donderdag 9 maart 2017 19:19
>>> *To:* nmusers
>>> *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
>>>
>>> PD Bio-Pharma CDMA
>>>
>>> Sandoz
>>>
>>> 1N025, 100 College Road West
>>>
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>>
>> --
>> Nick Holford, Professor Clinical Pharmacology
>> Dept Pharmacology & Clinical Pharmacology, Bldg 503 Room 302A
>> University of Auckland,85 Park Rd,Private Bag 92019,Auckland,New Zealand
>> office:+64(9)923-6730 mobile:NZ+64(21)46 23 53 FR+33(6)62 32 46 72
>> email:n.holford
>> http://holford.fmhs.auckland.ac.nz/
>> http://orcid.org/0000-0002-4031-2514
>> Read the question, answer the question, attempt all questions

--
Nick Holford, Professor Clinical Pharmacology
Dept Pharmacology & Clinical Pharmacology, Bldg 503 Room 302A
University of Auckland,85 Park Rd,Private Bag 92019,Auckland,New Zealand
office:+64(9)923-6730 mobile:NZ+64(21)46 23 53 FR+33(6)62 32 46 72
email: n.holford
http://holford.fmhs.auckland.ac.nz/
http://orcid.org/0000-0002-4031-2514
Read the question, answer the question, attempt all questions

Received on Thu Mar 09 2017 - 23:25:22 EST

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