RE: PD modeling of dataset with opposite values in the measurement effect

From: Scott VanWart Scott.VanWart@cognigencorp.com Subject: RE: [NMusers] PD modeling of dataset with opposite values in the measurement effect Date: Fri, 27 Jan 2006 18:01:56 -0500 Dear Li-Pin, If blood pressure is the PD response you are modeling, there is already a wide body of evidence in the literature that suggests that there is a circadian pattern to this type of process. Therefore, you may need to model your baseline response as a function of clock-time prior to trying to study the pharmocology of your drug. A good example of one approach that has been done to do this has been published by Hempel et al. (1998), Clinical Pharmacology and Therapeutics; 64: 622-635. I would also consider looking at other factors that may confound your ability to detect a concentration-response relationship, such as use of other non-study related medications or increases in the production of other endogenous modulators (if measured). A second point to consider is that there may be patients, who for any number of reasons, simply do not respond regardless of what drug concentration they are exposed to. There are several different approaches that you could consider here as well, one of which is the use of a mixture model within NONMEM to identify "responders" versus "non-responders". Scott Van Wart -- ----------------------------------- Scott Van Wart Assistant Director, Population PK/PD Cognigen Corporation 395 Youngs Road Buffalo, NY 14221-5831 (716) 633-3463 ext 241