Complete and accurate reporting of adverse events (AEs) is a fundamental obligation of clinical investigators, with implications both for the safety of research participants and for the validity of the data derived from clinical research. The integrity of the AE reporting process hinges on self-regulation and professionalism among investigators, reinforced by audits by sponsors, regulatory agencies and research institutions. Yet virtually no data are available that might permit assessment of the quality of the AE reporting process. The present proposal is a preliminary study of the AE reporting process in cancer clinical trials. The proposal focuses on reporting to the institutional review board (IRB) of AEs that occur in adult phase II trials, which account for the largest proportion of trial participants at National Cancer Institute-designated Comprehensive Cancer Centers. Because methods for estimating the true incidence of AEs in clinical trials have not been developed, the proposal adapts chart review-based methods developed for identifying AEs in the routine clinical (non-research) setting to the clinical trial context.
Specific Aims of the proposal include: 1) to estimate the incidence of reportable IRBs in phase II cancer trials; 2) to estimate the proportion of AEs that meet reporting criteria but are not reported to the IRB as required; and 3) to estimate the interrater reliability of reviewers' judgments concerning critical elements of AE determination, including severity, attribution to study interventions, and expectedness. The results of the study will provide initial data that will permit planning of definitive multicenter studies, and establishes a model and methodology for subsequent research on AEs and AE reporting both within and beyond cancer-related clinical research The project described here has important implications for public health. Each year, tens of thousands of patients take part in cancer trials, with many more participating in trials in other areas of medicine. The safety of these volunteers hinges critically on the integrity of the process by which investigators identify and report AEs to appropriate oversight bodies. In addition, accurate AE reporting affects the welfare of future patients whose treatment might be influenced by the outcomes of trials. Finally, public trust in and support for the research enterprise itself requires rigorous attention to the identification and management of adverse events. ? ? ?
