Adjusting survival analysis for the presence of unadjudicated study events

In the Coumadin Aspirin Reinfarction Study (CARS), the primary (efficacy) e nd-point was time to the first occurrence of reinfarction, ischemic stroke, or cardiovascular death. Study events likely to be a component of the prim ary endpoint were reviewed by a blinded Events Classification Committee (EC C). To accommodate the inherent delay imposed by the adjudication process, we used the results of prior adjudication to predict classifications for se lected unadjudicated study events in order to conduct "up-to-date" interim analyses for the Data and Safety Monitoring Committee (DSMC). Rates at whic h previously adjudicated study events were confirmed as primary event compo nents were used to adjust the Kaplan-Meier estimates of survival and the lo g-rank statistics. Multiple events for a given subject were weighted accord ing to the probability that prior events would be confirmed. Once all study events were adjudicated, final analyses confirmed the results of the adjus ted interim analysis. For monitoring clinical trials with adjudicated endpo int events, models based on prior adjudication histories can be reliably us ed to predict event classifications for unadjudicated events and support ac curate, contemporary interim analyses. Control Clin: Trials 2000;21:208-222 (C) Elsevier Science Inc. 2000.