Laplacian, BQL and initial estimates

On 7/17/2016 4:28 PM, Mark Sale wrote: > Question: > > NONMEM has a function to run a grid search to obtain initial estimates for THETA. But, when I try to do this with BQL data/Laplacian I get this run time error message: > > 0PROGRAM TERMINATED BY OBJ > WITH INDIVIDUAL 1 ID= 1.00000000000000E+00 DATA REC. 13 > WITH NMPR17, LAPLACIAN ESTIMATION METHOD MUST BE USED > > It seems the Laplacian isn't used for the grid search for initial estimates (even though specified in $EST). > > any ideas? > > Mark Sale M.D. > > Vice President, Modeling and Simulation > > Nuventra Pharma Sciences, Inc. > 2525 Meridian Parkway, Suite 280 > Durham, NC 27713 > > Phone (919)-973-0383 > > [email protected] <[email protected]> > > CONFIDENTIALITY NOTICE The information in this transmittal (including attachments, if any) may be privileged and confidential and is intended only for the recipient(s) listed above. Any review, use, disclosure, distribution or copying of this transmittal, in any form, is prohibited except by or on behalf of the intended recipient(s). If you have received this transmittal in error, please notify me immediately by reply email and destroy all copies of the transmittal. ------------------------------------------------------------------------ Human Predictions Logo < http://www.humanpredictions.com >*William S. Denney, PhD* Chief Scientist, Human Predictions LLC +1-617-899-8123 [email protected]

________________________________ From: Bauer, Robert <[email protected]> Sent: Monday, July 18, 2016 12:19:22 PM To: Mark Sale; Bill Denney; [email protected] Subject: RE: [NMusers] Laplacian, BQL and initial estimates Mark: I have looked at the initial theta evaluation which occurs when a lower and upper bound are supplied, and no initial value (such as (0.001,,100.0), and it seems that this method will only do a search using a First order objective function evaluation. I will see if it can be expanded to FOCE/FOCEI/Laplace for NONMEM 7.4. Robert J. Bauer, Ph.D. Vice President, Pharmacometrics R&D ICON Early Phase 820 W. Diamond Avenue Suite 100 Gaithersburg, MD 20878 Office: (215) 616-6428 Mobile: (925) 286-0769 [email protected]<mailto:[email protected]> http://www.iconplc.com/ From: [email protected] [mailto:[email protected]] On Behalf Of Mark Sale Sent: Sunday, July 17, 2016 2:00 PM To: Bill Denney; [email protected] Subject: Re: [NMusers] Laplacian, BQL and initial estimates pretty standard $EST I think $ESTIMATION METH=1 NUMERICAL SLOW LAPLACIAN INTER NOTHETABOUNDTEST NOOMEGABOUNDTEST MAXEVAL=9999 PRINT=1 NOABORT MSFO=MSF1 and just 1. Mark Sale M.D. Vice President, Modeling and Simulation Nuventra Pharma Sciences, Inc. 2525 Meridian Parkway, Suite 280 Durham, NC 27713 Phone (919)-973-0383 [email protected]<[email protected]> CONFIDENTIALITY NOTICE The information in this transmittal (including attachments, if any) may be privileged and confidential and is intended only for the recipient(s) listed above. Any review, use, disclosure, distribution or copying of this transmittal, in any form, is prohibited except by or on behalf of the intended recipient(s). If you have received this transmittal in error, please notify me immediately by reply email and destroy all copies of the transmittal. ________________________________ From: Bill Denney <[email protected]> Sent: Sunday, July 17, 2016 4:54:05 PM To: Mark Sale; [email protected] Subject: Re: [NMusers] Laplacian, BQL and initial estimates Hi Mark, Might you have more than one $EST step where Laplacian is not used in one of them? And, can you share your $EST step options? Thanks, Bill On 7/17/2016 4:28 PM, Mark Sale wrote: Question: NONMEM has a function to run a grid search to obtain initial estimates for THETA. But, when I try to do this with BQL data/Laplacian I get this run time error message: 0PROGRAM TERMINATED BY OBJ WITH INDIVIDUAL 1 ID= 1.00000000000000E+00 DATA REC. 13 WITH NMPR17, LAPLACIAN ESTIMATION METHOD MUST BE USED It seems the Laplacian isn't used for the grid search for initial estimates (even though specified in $EST). any ideas? Mark Sale M.D. Vice President, Modeling and Simulation Nuventra Pharma Sciences, Inc. 2525 Meridian Parkway, Suite 280 Durham, NC 27713 Phone (919)-973-0383 [email protected]<[email protected]> CONFIDENTIALITY NOTICE The information in this transmittal (including attachments, if any) may be privileged and confidential and is intended only for the recipient(s) listed above. Any review, use, disclosure, distribution or copying of this transmittal, in any form, is prohibited except by or on behalf of the intended recipient(s). If you have received this transmittal in error, please notify me immediately by reply email and destroy all copies of the transmittal. ________________________________ https://protect-eu.mimecast.com/s/E52oBu0A5VWC1[Image removed by sender. Human Predictions https://protect-eu.mimecast.com/s/E52oBu0A5VWC1 https://protect-eu.mimecast.com/s/E52oBu0A5VWC1William S. Denney, PhD Chief Scientist, Human Predictions LLC +1-617-899-8123 [email protected]<mailto:[email protected]>

From: [email protected] [mailto:[email protected]] On Behalf Of Mark Sale Sent: Sunday, July 17, 2016 2:00 PM To: Bill Denney; [email protected] Subject: Re: [NMusers] Laplacian, BQL and initial estimates pretty standard $EST I think $ESTIMATION METH=1 NUMERICAL SLOW LAPLACIAN INTER NOTHETABOUNDTEST NOOMEGABOUNDTEST MAXEVAL=9999 PRINT=1 NOABORT MSFO=MSF1 and just 1. Mark Sale M.D. Vice President, Modeling and Simulation Nuventra Pharma Sciences, Inc. 2525 Meridian Parkway, Suite 280 Durham, NC 27713 Phone (919)-973-0383 [email protected]<[email protected]> CONFIDENTIALITY NOTICE The information in this transmittal (including attachments, if any) may be privileged and confidential and is intended only for the recipient(s) listed above. Any review, use, disclosure, distribution or copying of this transmittal, in any form, is prohibited except by or on behalf of the intended recipient(s). If you have received this transmittal in error, please notify me immediately by reply email and destroy all copies of the transmittal. ________________________________ From: Bill Denney <[email protected]> Sent: Sunday, July 17, 2016 4:54:05 PM To: Mark Sale; [email protected] Subject: Re: [NMusers] Laplacian, BQL and initial estimates Hi Mark, Might you have more than one $EST step where Laplacian is not used in one of them? And, can you share your $EST step options? Thanks, Bill On 7/17/2016 4:28 PM, Mark Sale wrote: Question: NONMEM has a function to run a grid search to obtain initial estimates for THETA. But, when I try to do this with BQL data/Laplacian I get this run time error message: 0PROGRAM TERMINATED BY OBJ WITH INDIVIDUAL 1 ID= 1.00000000000000E+00 DATA REC. 13 WITH NMPR17, LAPLACIAN ESTIMATION METHOD MUST BE USED It seems the Laplacian isn't used for the grid search for initial estimates (even though specified in $EST). any ideas? Mark Sale M.D. Vice President, Modeling and Simulation Nuventra Pharma Sciences, Inc. 2525 Meridian Parkway, Suite 280 Durham, NC 27713 Phone (919)-973-0383 [email protected]<[email protected]> CONFIDENTIALITY NOTICE The information in this transmittal (including attachments, if any) may be privileged and confidential and is intended only for the recipient(s) listed above. Any review, use, disclosure, distribution or copying of this transmittal, in any form, is prohibited except by or on behalf of the intended recipient(s). If you have received this transmittal in error, please notify me immediately by reply email and destroy all copies of the transmittal. ________________________________ http://www.humanpredictions.com[Image removed by sender. Human Predictions http://www.humanpredictions.com http://www.humanpredictions.comWilliam S. Denney, PhD Chief Scientist, Human Predictions LLC +1-617-899-8123 [email protected]<mailto:[email protected]>