Safety Profiling and Benefit-Risk Assessment

Adequate safety management requires a profound knowledge of actual and potential safety concerns of the candidate drug. Focused safety monitoring at PRA is based on AE terms frequently associated with adverse drug effects (e.g. Stevens-Johnson Syndrome, drug-induced hepatitis, etc.). These targeted surveillance terms are generally defined and therapeutic area specific terms may be defined. Based on the selected terms, a Standardized MedDRA Query (SMQ) tool can be implemented for the safety and clinical databases. Searches can be supplemented by individual patient profiles using J-Review^® software, a web-enabled version of Integrated Review™ (iReview). This software supports ongoing monitoring of patient safety and explores data visually to identify trends using aggregated views and individual patient profiles.

The involvement of a Data Monitoring Committee (DMC) allows for an independent evaluation of potential signals. PRA regularly:

• supports the selection of DMC members and chairpersons
• is involved in DMC set-up and charter generation
• provides unblinded tables and listings for interim data reviews
• organizes DMC meetings

PRA's experts serve as unblinded reporting statisticians or as voting members. Endpoint outcome focused studies are often challenging because of size, duration or complexity of the outcomes. PRA also provides services for Event/Endpoint Adjudication Committees. To ensure an ongoing and timely adjudication, PRA offers:

• expertise in selecting committee members
• charter generation to ensure consistent working practices
• coordination and logistical support
• centralized quality control of endpoint/event dossiers
• management of the Adjudication Committee

PRA's web-based tracking system supports all of these activities.