question about random seed for simulation

From: owner-nmusers_at_globomaxnm.com [mailto:owner-nmusers_at_globomaxnm.com] On Behalf Of Zhu, Penny Sent: den 9 mars 2017 19:19 To: 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 PD Bio-Pharma CDMA Sandoz 1N025, 100 College Road West Princeton, NJ 08540 ________________________________ Confidentiality Notice: This message is private and may contain confidential and proprietary information. If you have received this message in error, please notify us and remove it from your system and note that you must not copy, distribute or take any action in reliance on it. Any unauthorized use or disclosure of the contents of this message is not permitted and may be unlawful.

From: [email protected] [mailto:[email protected]] On Behalf Of Zhu, Penny Sent: den 9 mars 2017 19:19 To: [email protected] 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 Princeton, NJ 08540 ________________________________ Confidentiality Notice: This message is private and may contain confidential and proprietary information. If you have received this message in error, please notify us and remove it from your system and note that you must not copy, distribute or take any action in reliance on it. Any unauthorized use or disclosure of the contents of this message is not permitted and may be unlawful.

From: [email protected] [mailto:[email protected]] On Behalf Of Zhu, Penny Sent: donderdag 9 maart 2017 19:19 To: [email protected] 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 Princeton, NJ 08540 Information in this email and any attachments is confidential and intended solely for the use of the individual(s) to whom it is addressed or otherwise directed. Please note that any views or opinions presented in this email are solely those of the author and do not necessarily represent those of the Company. Finally, the recipient should check this email and any attachments for the presence of viruses. The Company accepts no liability for any damage caused by any virus transmitted by this email. All SGS services are rendered in accordance with the applicable SGS conditions of service available on request and accessible at http://www.sgs.com/en/Terms-and-Conditions.aspx

On 3/9/2017 6:11 PM, 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:*[email protected] > [mailto:[email protected]] *On Behalf Of *Zhu, Penny > *Sent:* donderdag 9 maart 2017 19:19 > *To:* [email protected] > *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 > > Princeton, NJ 08540 > > Information in this email and any attachments is confidential and > intended solely for the use of the individual(s) to whom it is addressed > or otherwise directed. Please note that any views or opinions presented > in this email are solely those of the author and do not necessarily > represent those of the Company. Finally, the recipient should check this > email and any attachments for the presence of viruses. The Company > accepts no liability for any damage caused by any virus transmitted by > this email. All SGS services are rendered in accordance with the > applicable SGS conditions of service available on request and accessible > at http://www.sgs.com/en/Terms-and-Conditions.aspx

On Thu, Mar 9, 2017 at 5:11 PM, Faelens, Ruben (Belgium) < Ruben.Faelens_at_sgs.com> 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] > *On Behalf Of *Zhu, Penny > *Sent:* donderdag 9 maart 2017 19:19 > *To:* 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 <(862)%20926-9079> > > > > PD Bio-Pharma CDMA > > Sandoz > > 1N025, 100 College Road West > > Princeton, NJ 08540 > > > > > > > Information in this email and any attachments is confidential and intended > solely for the use of the individual(s) to whom it is addressed or > otherwise directed. Please note that any views or opinions presented in > this email are solely those of the author and do not necessarily represent > those of the Company. Finally, the recipient should check this email and > any attachments for the presence of viruses. The Company accepts no > liability for any damage caused by any virus transmitted by this email. All > SGS services are rendered in accordance with the applicable SGS conditions > of service available on request and accessible at > http://www.sgs.com/en/Terms-and-Conditions.aspx > -- Kyle Baron, PharmD, PhD Senior Scientist Metrum Research Group

On Thu, Mar 9, 2017 at 5:11 PM, Faelens, Ruben (Belgium) < [email protected]> 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:* [email protected] [mailto:[email protected]] > *On Behalf Of *Zhu, Penny > *Sent:* donderdag 9 maart 2017 19:19 > *To:* [email protected] > *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 <(862)%20926-9079> > > > > PD Bio-Pharma CDMA > > Sandoz > > 1N025, 100 College Road West > > Princeton, NJ 08540 > > > > > > > Information in this email and any attachments is confidential and intended > solely for the use of the individual(s) to whom it is addressed or > otherwise directed. Please note that any views or opinions presented in > this email are solely those of the author and do not necessarily represent > those of the Company. Finally, the recipient should check this email and > any attachments for the presence of viruses. The Company accepts no > liability for any damage caused by any virus transmitted by this email. All > SGS services are rendered in accordance with the applicable SGS conditions > of service available on request and accessible at > http://www.sgs.com/en/Terms-and-Conditions.aspx > -- Kyle Baron, PharmD, PhD Senior Scientist Metrum Research Group

On Thu, Mar 9, 2017 at 3:56 PM, Kyle Baron <[email protected]> wrote: > > To Ruben's question: mrgsolve simulates the subjects up front as well. > The subjects are identical across runs if the seed and number of subjects > does not change. > > An illustration: > http://mrgsolve.github.io/2017/03/09/reproducible-results-with-set.seed/ > > Best regards, > Kyle > > > On Thu, Mar 9, 2017 at 5:11 PM, Faelens, Ruben (Belgium) < > [email protected]> 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:* [email protected] [mailto:[email protected]] >> *On Behalf Of *Zhu, Penny >> *Sent:* donderdag 9 maart 2017 19:19 >> *To:* [email protected] >> *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 <(862)%20926-9079> >> >> >> >> PD Bio-Pharma CDMA >> >> Sandoz >> >> 1N025, 100 College Road West >> >> Princeton, NJ 08540 >> >> >> >> >> >> >> Information in this email and any attachments is confidential and >> intended solely for the use of the individual(s) to whom it is addressed or >> otherwise directed. Please note that any views or opinions presented in >> this email are solely those of the author and do not necessarily represent >> those of the Company. Finally, the recipient should check this email and >> any attachments for the presence of viruses. The Company accepts no >> liability for any damage caused by any virus transmitted by this email. All >> SGS services are rendered in accordance with the applicable SGS conditions >> of service available on request and accessible at >> http://www.sgs.com/en/Terms-and-Conditions.aspx >> > > > > -- > Kyle Baron, PharmD, PhD > Senior Scientist > Metrum Research Group > >

On Thu, Mar 9, 2017 at 7:01 PM Kyle Baron <[email protected]> wrote: > > To Ruben's question: mrgsolve simulates the subjects up front as well. > The subjects are identical across runs if the seed and number of subjects > does not change. > > An illustration: > http://mrgsolve.github.io/2017/03/09/reproducible-results-with-set.seed/ > > Best regards, > Kyle > > > On Thu, Mar 9, 2017 at 5:11 PM, Faelens, Ruben (Belgium) < > [email protected]> 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:* [email protected] [mailto:[email protected]] > *On Behalf Of *Zhu, Penny > *Sent:* donderdag 9 maart 2017 19:19 > *To:* [email protected] > *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 <(862)%20926-9079> > > > > PD Bio-Pharma CDMA > > Sandoz > > 1N025, 100 College Road West > > Princeton, NJ 08540 > > > > > > > Information in this email and any attachments is confidential and intended > solely for the use of the individual(s) to whom it is addressed or > otherwise directed. Please note that any views or opinions presented in > this email are solely those of the author and do not necessarily represent > those of the Company. Finally, the recipient should check this email and > any attachments for the presence of viruses. The Company accepts no > liability for any damage caused by any virus transmitted by this email. All > SGS services are rendered in accordance with the applicable SGS conditions > of service available on request and accessible at > http://www.sgs.com/en/Terms-and-Conditions.aspx > > > > > -- > Kyle Baron, PharmD, PhD > Senior Scientist > Metrum Research Group > >