RE: How to model delayed count data due to time needed to form an event
Yaning, A trick Nick Holford showed me many years ago that works nicely: Set up two parallel systems. The "real" system has your "real" pk (doses, observations etc). The other system is the delay system. Doses are the same into the two systems. No pk observations in the delay system (probably non-pk observations of AEs in the delay system, dependent on the delay pk). But, key is that the same parameters (estimated from the "real" system) are also applied to the delayed system. So, the delayed system is just like the real system, except delayed. You can then use the concentrations in the delayed system to drive the AE's. I've even done this with two delay systems, works very nicely. So, Data looks like: ID TIME CMT AMT DV 1 0 1 100 . ; CMT 1 is "real" system 1 0 2 100 . ; CMT 2 is delayed system 1 1 1 . 100 ; real observation 1 2 1 . 50 ; real observation 1 3 1 . 25 ; real observation control file is: $MODEL COMP = (REAL) COMP = (DELAY) $PK K10 = THETA(1) K20 = K10 S1 = THETA(2) S2 = S1 ALAG2 = THETA(3) $DES DADT(1) = -K10*A(1) DADT(2) = -K20*A(2) This will give you a concentration in compartment 2 that is identical to compartment 1, except delayed by ALAG2. PK parameters are drive only by observation in compartment 1. Mark Sale MD President, Next Level Solutions, LLC www.NextLevelSolns.com 919-846-9185 A carbon-neutral company See our real time solar energy production at: http://enlighten.enphaseenergy.com/public/systems/aSDz2458
Quoted reply history
-------- Original Message --------
Subject: [NMusers] How to model delayed count data due to time needed
to form an event
From: Yaming Hang < [email protected] >
Date: Mon, June 18, 2012 11:08 am
To: " [email protected] " < [email protected] >
Dear NONMEM Users, I’m dealing with some longitudinal count data (number of AEs observed in fixed time interval over certain time period). One feature with the data is the delay in PK/PD relationship because it takes time to develop the AE (i.e. there is lag time between the start of the AE formation process and the time you can observe the AE). The onset of the process of developing an AE is clearly PK dependent, but the exact time (or PK level) it onsets can never be observed. In addition, the exact time that the AE first appears is also not available, we only know the interval during which it first appears. What is a good approach to handle this kind of delay? Is there any published paper for similar data type? Many thanks in advance for you suggestions! Yaming Hang, Ph.D. Pharmacometrics Biogen Idec 14 Cambridge Center Cambridge, MA 02142 Office: 781-464-1741 Fax: 617-679-2804 Email: [email protected]