RE: Using evid 0 before dosing

From: [email protected] <[email protected]> On Behalf Of Dennis Fisher Sent: Thursday, 7 November 2019 5:45 a.m. To: Mark Sale <[email protected]> Cc: [email protected] Subject: Re: [NMusers] Using evid 0 before dosing Mark I disagree (more than a little). If a sample is reported as BQL and the expected value is 0 (i.e., pre-dose, not endogenous), what information is there about assay precision. If the error model is additive (or additive + proportional), the sample will contribute zero to the objective function. If the error model is proportional, NONMEM will report an error (0/0). I agree that pre-dose samples > LOQ provide IMPORTANT information about assay precision. Were you evacuated during the fires? Dennis Dennis Fisher MD P < (The "P Less Than" Company) Phone / Fax: 1-866-PLessThan (1-866-753-7784) www.plessthan.com%2F&data=02%7C01%7Cstephen.duffull%40otago.ac.nz%7Cbacc42042d8942312bc608d762d97d4a%7C0225efc578fe4928b1579ef24809e9ba%7C1%7C0%7C637086558625087255&sdata=7yYTKHuQtvfdvaXYpZZBuRCO%2FaGLgYYmWy3sWhAdXEc%3D&reserved=0">https://apc01.safelinks.protection.outlook.com/?url=http%3A%2F%2Fwww.plessthan.com%2F&data=02%7C01%7Cstephen.duffull%40otago.ac.nz%7Cbacc42042d8942312bc608d762d97d4a%7C0225efc578fe4928b1579ef24809e9ba%7C1%7C0%7C637086558625087255&sdata=7yYTKHuQtvfdvaXYpZZBuRCO%2FaGLgYYmWy3sWhAdXEc%3D&reserved=0 On Nov 6, 2019, at 8:40 AM, Mark Sale <[email protected]<mailto:[email protected]>> wrote: Dennis, I may have to disagree, a little. There is information, a little, in a pre dose BQL, about assay precision. I think you might agree that is a pre dose sample is NOT BQL (which happens), tells you (and NONMEM) something about the assay. Converse, even a BQL predose sample has a small amount of information. That not withstanding, we also remove and pre-dose BQLs from the data set. Mark Sale M.D. Senior Vice President, Pharmacometrics Nuventra Inc. 2525 Meridian Parkway, Suite 200 Durham, NC 27713 Phone (919)-973-0383 [email protected]<x-msg://138/[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: [email protected]<mailto:[email protected]> <[email protected]<mailto:[email protected]>> on behalf of Dennis Fisher <[email protected]<mailto:[email protected]>> Sent: Wednesday, November 6, 2019 7:23 AM To: [email protected]<mailto:[email protected]> <[email protected]<mailto:[email protected]>>; Bill Denney <[email protected]<mailto:[email protected]>> Cc: Carlos ST <[email protected]<mailto:[email protected]>>; Steven Shafer <[email protected]<mailto:[email protected]>> Subject: Re: [NMusers] Using evid 0 before dosing WARNING: This email originated from outside of the company. Do not click links or open attachments unless you recognize the sender and are expecting the message. Bill I think that the issue is more complicated than you acknowledge. Assuming that the drug is not an endogenous substance, the pre-dose concentration is likely to be BQL. However, there are two kinds of BQL values: 1. Samples that are truly zero because they were obtained pre-dose 2. Samples that are > 0 but < LOQ. Yet both are reported as BQL. >From my perspective, a BQL value pre-dose provides no information to NONMEM. >Therefore, one should apply EVID=2 to that sample. This allows a prediction >at that timepoint but the sample does not influence the analysis. Dennis Dennis Fisher MD P < (The "P Less Than" Company) Phone / Fax: 1-866-PLessThan (1-866-753-7784) www.plessthan.com%2F&data=02%7C01%7Cstephen.duffull%40otago.ac.nz%7Cbacc42042d8942312bc608d762d97d4a%7C0225efc578fe4928b1579ef24809e9ba%7C1%7C0%7C637086558625087255&sdata=7yYTKHuQtvfdvaXYpZZBuRCO%2FaGLgYYmWy3sWhAdXEc%3D&reserved=0">https://apc01.safelinks.protection.outlook.com/?url=http%3A%2F%2Fwww.plessthan.com%2F&data=02%7C01%7Cstephen.duffull%40otago.ac.nz%7Cbacc42042d8942312bc608d762d97d4a%7C0225efc578fe4928b1579ef24809e9ba%7C1%7C0%7C637086558625087255&sdata=7yYTKHuQtvfdvaXYpZZBuRCO%2FaGLgYYmWy3sWhAdXEc%3D&reserved=0 On Nov 6, 2019, at 7:12 AM, Bill Denney <[email protected]<mailto:[email protected]>> wrote: Hi Carlos, It is commonly used. For most datasets, there will be at least one observation that occurs before dosing to estimate the baseline value, and in almost every scenario, the modeling dataset should mirror the real world actions. So, there is no issue with it, and usually you will have an EVID=0 before the first dose. Thanks, Bill -----Original Message----- From: [email protected]<mailto:[email protected]> <[email protected]<mailto:[email protected]>> On Behalf Of Carlos ST Sent: Wednesday, November 6, 2019 10:03 AM To: [email protected]<mailto:[email protected]> Subject: [NMusers] Using evid 0 before dosing Dear NMUsers, I would like advice in the best practice to use evid 0 before dosing, which is to say an observation just before a dosing (*to estimate the value in that compartment just before dosing event). Thank you, Carlos,