PHARMACODYNAMIC ANALYSIS OF ANALGESIC CLINICAL-TRIALS USING EMPIRICAL-METHODS

Data from analgesic clinical trials have characteristics such as order ed categorical longitudinal responses with repeated measures, delay of effect with respect to analgesic plasma concentration. and right-hand censoring of response due to remedication. In order to determine the concentration-effect relationship of such data, we propose convolving an empirical function for plasma concentration, in the form of broken lines which connect each pair of neighboring observations, with a mono exponential function, to generate ''effect site concentration.'' Effec t site concentration and time are used, simultaneously, as independent variables in the fit of the model for the legit of the probability of having a specific pain relief(PR) score at each time point pre-remedi cation, via maximum likelihood. Using corresponding effect site concen tration, the probabilities of having specific PR scores post-remedicat ion are predicted via the concentration-response relationship establis hed. The overall (pre- and post-remedication) predictions and correspo nding standard errors for the responses are then estimated. Inference of the PR scoring, using a posterior method, is proposed. An illustrat ion using real data is used to demonstrate these methods.