The Role of a Research Administration Program in Adverse Event Reporting

Article excerpt

Introduction

Clinical research has endured remarkable and beneficial expansion in the past 25 years, although this growth has resulted in an unprecedented increase in workload for the human research protection system. Most of the expansion in clinical research has been in the form of multicenter trials, which present significant challenges for a local institutional review board (IRB). The dramatic increase in the number of multicenter clinical trials over the past two decades coincides with a tremendous influx of clinical trial funding from industry, which has resulted in the exposure of inadequacies in human subject protection programs developed to manage clinical trials on a smaller scale, usually at single sites (Morse, Califf, & Sugarman, 2001).

One of the leading challenges facing Human Research Protection Programs (HRPPs) is the volume of AE reports that sponsors and clinical investigators file with IRBs. The current process is burdensome, inefficient, and fails to provide IRBs with meaningful information needed to fully ensure the safety of human research participants. The federal Office for Human Research Protections (OHRP) has estimated that approximately 5% of all AEs reported to IRBs actually warrant some level of review; 70% have little or no impact or concern resulting in meaningful action(s) taken by an IRB, and only 25% require resources for assessment or further consideration by an IRB (Weschler, 2004). The current challenge is how to triage the 70% efficiently and address the remaining 30%, while dedicating resources toward action on the small percent of that latter group where an impact can be made. IRBs have a greater responsibility and ability to evaluate AEs at the sites over which they have purview.

As noted by Burman, Reves, Cohn, & Schooley (2001), additional trends include a recent major change in federal oversight that resulted in a three-fold increase in regulatory actions against local IRBs, with a marked increase in regulatory actions against the IRBs of academic medical centers (l in 1997 compared with 14 in 1999). Inadequate review of safety reports was among the list of reasons for regulatory actions by both OHRP and the U.S. Food and Drug Administration (FDA). Recent reviews by the Office of the Inspector General (OIG) of the Department of Health and Human Services (DHHS) and the National Institutes of Health (NIH) concluded that the continuing review process should be reevaluated and that local IRBs should not be required to review off-site (external) safety reports (OIG, 1998; NIH, 1999). On the basis of a series of reports, the OIG concluded that IRBs are now forced to "review too much, too quickly, with too little expertise," and with inadequate resources (OIG, 1998). A major contributing factor to this dismal outlook for HRPPs is the volume of AEs submitted to IRBs for review.

Background

A key factor in the current crisis in the function of local IRBs is the escalation of multicenter clinical trials as the consistent method for the performance of clinical research. Though Data and Safety Monitoring Boards (DSMBs) have become commonplace in multicenter trials, federal rules and regulations concerning human subject protections require that local IRBs bear the fundamental responsibility of research oversight (Morse et al., 2001). Current rules encourage researchers and sponsors to report all unexpected, serious, or related AEs to a number of parties, including IRBs, FDA, and other regulatory and research agencies in the United States.

One AE alone can result in a multitude of reports to various organizations, which in turn must be assessed by the IRB (Weschler, 2005). For multicenter clinical trials, an IRB receives individual external AE reports. The receipt of reports that are not aggregated and that come from disparate sources contributes to confusion and an added workload for the IRB. More importantly, the format of the reports jeopardizes the IRB's ability to make an informed judgment on the appropriate action, if any, to be taken. …