Using provisional diagnoses in monitoring a clinical trial

In clinical trials there is delay between the occurrence of an event and the recording of that event as an end point in the trial data base. Delays are especially likely if events are reviewed carefully to determine whether diagnostic criteria for end points are satisfied. As a result, the value of a statistic used to evaluate efficacy during a trial may differ from the value of that statistic based on the true end point status of all events which have already occurred. Simulating the process causing delays can be useful in evaluating interim efficacy data by providing a quantitative estimate of the uncertainty in a monitoring statistic. These ideas are illustrated using data from the Lipid Research Clinics Coronary Primary Prevention Trial.