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: [email protected] [mailto:[email protected]] On Behalf Of Garmann, Dirk Sent: 13 January 2010 12:41 To: [email protected] 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 ________________________________ Die vorgenannten Angaben der E-Mail haben grundsätzlich nur informativen Charakter. Dies ist kein Anerkenntnis, dass es sich beim Inhalt dieser E-Mail um eine rechtsverbindliche Erklärung der entsprechenden Gesellschaft der Merz Gruppe handelt, es sei denn dies ist ausdrücklich als solches formuliert. Erklärungen, die eine Gesellschaft der Merz Gruppe verpflichten sollen, bedürfen jeweils der Unterschrift durch zwei zeichnungsberechtigte Personen dieser Gesellschaft. Diese E-Mail enthält vertrauliche und/oder rechtlich geschützte Informationen. Wenn Sie nicht der richtige Adressat sind oder diese E-Mail irrtümlich erhalten haben, informieren Sie bitte sofort den Absender und vernichten Sie diese E-Mail. Das unerlaubte Kopieren sowie die unbefugte Weitergabe dieser E-Mail ist nicht gestattet. This e-mail may contain confidential and/or privileged information. If you are not the intended recipient (or have received this e-mail in error) please notify the sender immediately and destroy this email. Any unauthorised copying, disclosure or distribution of the material in this e-mail is strictly forbidden. (MRZ/2010)
