RE: [NMusers] lab values

Dirk,

 

I think the approach is influenced by what this lab value represents. If =
it is a biomarker/endpoint that is influenced by drug treatment then the =
best approach is to include this in your PK-PD model as a dependent =
variable. If you treat this as a traditional covariate it should not be =
influenced by treatment. Assuming your drug improves disease symptom or =
progression (as measured by this biomarker) it would not be ideal to use =
either LOCF or LOCB. The baseline for this biomarker (DAY -1 in your =
case) can be used as a covariate in your PK model, as it is not =
influenced by drug treatment.

 

If you can not spend the time to build a proper PK-PD model but still =
believe this covariate is important for your PK model then maybe you can =
do something simple, like assuming a linear slope in this biomarker =
between the two measurements and use the two observed values for =
interpolation?

 

Best regards

 

Jakob

 

________________________________

From: owner-nmusers_at_globomaxnm.com [mailto:owner-nmusers_at_globomaxnm.com] =
On Behalf Of Garmann, Dirk
Sent: 13 January 2010 12:41
To: nmusers_at_globomaxnm.com
Subject: [NMusers] lab values

 

Dear NMUSERS,#

 

I would like to ask for some opinions regarding the handling of missing =
lab values in a NONMEM Dataset;

 

Our normal procedure:

Parameter values will be carried backward to the first visit if the =
first visit value is missing, it will be carry forward to the last visit =
if no value is available at the last visit and will be set at the median =
value of two adjacent visits in other cases.

 

Now we have a phase III study (multiple doses), one safety lab at day -1 =
and one safety lab at final examination only, no lab in between (>6 =
month)

 

Two main strategies are possible

 

1.) Different from our standard procedure:

Carry the lab value at final examination backward to day -1.

 

2.) According to our standard: Use the median (or perhaps a =
regression between the first and final examination)

:

My assumptions:

The first strategy might be useful to reflect the influence of the drug =
on lab values and will reflect the steady state situation.

 

The second strategy might be better to characterize the influence of the =
lab values on the PK of the drug, e.g if a disease worsens during the =
study.

 

As our main focus will be the last one, I would use the standard =
approach.

 

I know that this is quite basic, however as this was discussed during a =
meeting I would appreciate to have your opinion.

 

Many thanks in advance

 

Dirk

 

Dirk Garmann, PhD

Clinical Scientific Expert /Pharmacokineticist

Merz Pharmaceuticals

Eckenheimer Landstrasse 100

60318 Frankfurt

Phone +49 (69) 1503 720

 

________________________________

Merz Pharmaceuticals GmbH, Frankfurt am Main

Amtsgericht Frankfurt am Main, HRB 53808

Geschäftsführung: Dr. Martin Zügel (Vors.), Dr. Alexander Gebauer, =


Dr. Karsten Schlemm, Dr. Eugen Wilbert

________________________________

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Received on Wed Jan 13 2010 - 08:34:01 EST