Assessing performance of sequential analysis methods for active drug safety surveillance using observational data

Abstract

ABSTRACTThe routine use of sequential methods is well established in clinical studies. Recently, there has been increasing interest in applying these methods to prospectively monitor the safety of newly approved drugs through accrual of real-world data. However, the application to marketed drugs using real-world data has been limited and work is needed to determine which sequential approaches are most suited to such data. In this study, the conditional sequential sampling procedure (CSSP), a group sequential method, was compared with a log-linear model with Poisson distribution (LLMP) through a SAS procedure (PROC GENMOD) combined with an alpha-spending function on two large longitudinal US administrative health claims databases. Relative performance in identifying known drug–outcome associations was examined using a set of 50 well-studied drug–outcome pairs. The study finds that neither method correctly identified all pairs but that LLMP often provides better ability and shorter time for identifying the known drug–outcome associations with superior computational performance when compared with CSSP, albeit with more false positives. With the features of flexible confounding control and ease of implementation, LLMP may be a good alternative or complement to CSSP.