Cluster-Based Profile Monitoring in Phase I Analysis

An innovative profile monitoring methodology is introduced for Phase I analysis. The proposed technique, which is referred to as the cluster-based profile monitoring method, incorporates a cluster analysis phase to aid in determining if non conforming profiles are present in the historical data set (HDS). To cluster the profiles, the proposed method first replaces the data for each profile with an estimated profile curve, using some appropriate regression method, and clusters the profiles based on their estimated parameter vectors. This cluster phase then yields a main cluster which contains more than half of the profiles. The initial estimated population average (PA) parameters are obtained by fitting a linear mixed model to those profiles in the main cluster. In-control profiles, determined using the Hotelling’s T² statistic, that are not contained in the initial main cluster are iteratively added to the main cluster and the mixed model is used to update the estimated PA parameters. A simulated example and Monte Carlo results demonstrate the performance advantage of this proposed method over a current noncluster based method with respect to more accurate estimates of the PA parameters and better classification performance in determining those profiles from an in-control process from those from an out-of-control process in Phase I.