Re: Plcebo Corrected PK/PD

From: "Nick Holford" n.holford@auckland.ac.nz Subject: Re: [NMusers] Plcebo Corrected PK/PD Date: Fri, March 4, 2005 1:54 pm Joga, I think it is possible to estimate both the disease progress AND the drug effect in an individual in one arm of a parallel group design. Suppose the model is: S(t) = S0 + alpha*t + beta*ce(t) S is disease status ('response'), S0 is the baseline status, alpha is the rate of progression, beta is the slope of a linear PD model, Ce(t) is drug conc at time t. The drug effect (beta*ce(t)) will be superimposed on the disease progress line and with a suitable design and reasonable parameters then the observed status could be used to estimate the parameters of this model with random effects (i.e. BSV) on each parameter. Of course with the over sparse designs that are commonly used in clinical trials or if the time course of disease progression is too closely correlated with the time course of drug effect then there may be an a posteriori identifiability problem but in theory the parameters are a priori identifiable. Nick -- Nick Holford, Dept Pharmacology & Clinical Pharmacology University of Auckland, 85 Park Rd, Private Bag 92019, Auckland, New Zealand email:n.holford@auckland.ac.nz tel:+64(9)373-7599x86730 fax:373-7556 http://www.health.auckland.ac.nz/pharmacology/staff/nholford/