System Audit of a Megatrial

Abstract

Audits of megatrials present a major challenge for sponsors as the limited resources make it impossible to audit an adequate sample of sites and patients. This article describes how by using a system-oriented approach, it is still possible to execute an effective audit plan. The trial for which this audit approach was applied had 15000 patients enrolled over 850 sites. The majority of sites were located in Europe (700); sites were spread over 27 countries. General study coordination and data management were handled by a contract research organization (CRO). Monitoring was shared between the sponsor and seven CROs. The enrollment was planned to be completed in less than 12 months.

Systems that were different from normal company practice and systems that were under the responsibility of the coordinating CRO were analyzed and critical systems were identified. The selection of systems to be audited was based on a priority ranking of the various systems. Some systems were evaluated at the coordinating CRO, others through site audits.

By focusing on the underlying systems, results could be extrapolated to all sites. Corrective actions were obtained at a study management level, which ensured that they were widely shared and followed up. This system-oriented approach can also be used for smaller size trials and project audits.