From: Rik Schoemaker <*rik.schoemaker*>

Date: Thu, 28 Jul 2016 06:57:16 +0000

Dear Manu,

NONMEM doesn't care about negative values when analysing data in the log do=

main. The sure-fire test is to do the analysis both after log-transforming =

in the original units, and after multiplying by 1000 as Dennis suggests, an=

d the results should be identical (if you adjust your afflicted starting va=

lues accordingly of course).

Kind regards,

Rik

Rik Schoemaker, PhD

Occams

Malandolaan 10

1187 HE Amstelveen

The Netherlands

www.occams.eu<http://www.occams.eu/>

+31 20 441 6410

rik.schoemaker

[cid:image003.png

From: owner-nmusers

Behalf Of Dennis Fisher

Sent: 27 July 2016 23:26

To: Bharadwaj, Manushree <manushb

Cc: nmusers

Subject: Re: [NMusers] Log transformation of imputed BQL

one thing that you could do is multiply all the values by 1000 (i.e., chang=

e the units)

Dennis Fisher MD

P < (The "P Less Than" Company)

Phone / Fax: 1-866-PLessThan (1-866-753-7784)

www.PLessThan.com<http://www.plessthan.com/>

On Jul 27, 2016, at 11:11 AM, Bharadwaj, Manushree <manushb

ate.edu<mailto:manushb

Dear friends,

I log transformed the plasma concentrations in my data and I am using this =

log transformed data as my dependent variable (DV). I imputed the BQLs to L=

LOQ/2, which is my case is (1/2=0.5). The natural log of 0.5 is negative =

which mean that I have negative values in my DV column.

While the parameter estimates look somewhat reliable, I have negative point=

s plotted in the diagnostic plots such as DV vs PRED, DV and PRED vs TIME, =

etc.

My questions are-

1. What is the best way of dealing with <1 DV/plasma concentration values w=

hile transforming into natural logarithm?

2. In my situation discussed above, where I have negative DV values in my d=

ata, has the NONMEM ignored or considered the negative numbers when estimat=

ing the parameter values?

Thank you,

Manu

--

With regards-

Manushree Bharadwaj, BVSc, PhD Candidate

Graduate Teaching Associate

Department of Physiological Sciences

Center for Veterinary Health Sciences

Oklahoma State University

Stillwater, OK-74074

Received on Thu Jul 28 2016 - 02:57:16 EDT

Date: Thu, 28 Jul 2016 06:57:16 +0000

Dear Manu,

NONMEM doesn't care about negative values when analysing data in the log do=

main. The sure-fire test is to do the analysis both after log-transforming =

in the original units, and after multiplying by 1000 as Dennis suggests, an=

d the results should be identical (if you adjust your afflicted starting va=

lues accordingly of course).

Kind regards,

Rik

Rik Schoemaker, PhD

Occams

Malandolaan 10

1187 HE Amstelveen

The Netherlands

www.occams.eu<http://www.occams.eu/>

+31 20 441 6410

rik.schoemaker

[cid:image003.png

From: owner-nmusers

Behalf Of Dennis Fisher

Sent: 27 July 2016 23:26

To: Bharadwaj, Manushree <manushb

Cc: nmusers

Subject: Re: [NMusers] Log transformation of imputed BQL

one thing that you could do is multiply all the values by 1000 (i.e., chang=

e the units)

Dennis Fisher MD

P < (The "P Less Than" Company)

Phone / Fax: 1-866-PLessThan (1-866-753-7784)

www.PLessThan.com<http://www.plessthan.com/>

On Jul 27, 2016, at 11:11 AM, Bharadwaj, Manushree <manushb

ate.edu<mailto:manushb

Dear friends,

I log transformed the plasma concentrations in my data and I am using this =

log transformed data as my dependent variable (DV). I imputed the BQLs to L=

LOQ/2, which is my case is (1/2=0.5). The natural log of 0.5 is negative =

which mean that I have negative values in my DV column.

While the parameter estimates look somewhat reliable, I have negative point=

s plotted in the diagnostic plots such as DV vs PRED, DV and PRED vs TIME, =

etc.

My questions are-

1. What is the best way of dealing with <1 DV/plasma concentration values w=

hile transforming into natural logarithm?

2. In my situation discussed above, where I have negative DV values in my d=

ata, has the NONMEM ignored or considered the negative numbers when estimat=

ing the parameter values?

Thank you,

Manu

--

With regards-

Manushree Bharadwaj, BVSc, PhD Candidate

Graduate Teaching Associate

Department of Physiological Sciences

Center for Veterinary Health Sciences

Oklahoma State University

Stillwater, OK-74074

(image/png attachment: image003.png)