Automated method for detecting increases in frequency of spontaneous adverse event reports over time.

A statistical methodology--focused on temporal change detection--was developed to highlight excursions from baseline spontaneous adverse event (AE) reporting. We used regression (both smooth trend and seasonal components) to model the time course of a drug's reports containing an AE, and then compared the sum of counts in the past 2 months with the fitted trend. The signaling threshold was tuned, using retrospective analysis, to yield acceptable sensitivity and specificity.

Developing tools for the safety specification in risk management plans: lessons learned from a pilot project.

Purpose: Following the adoption of the ICH E2E guideline, risk management plans (RMP) defining the cumulative safety experience and identifying limitations in safety information are now required for marketing authorisation applications (MAA). A collaborative research project was conducted to gain experience with tools for presenting and evaluating data in the safety specification. This paper presents those tools found to be useful and the lessons learned from their use.