A note on post-marketing safety study design to characterise time-dependent adverse events

Purpose To investigate a suitable post-marketing safety study design, that is number of patients and duration of exposure, to well characterise adverse events (AEs) profiles under limited resources, fixed patient-months. Methods A simulation study is conducted to investigate a suitable study design that can appropriately characterise the shape of the hazard function of AEs using the Weibull model. The reliability of the estimates is evaluated by referring their bias and mean squared error (MSE). Results In general, patients should be followed for a longer period even if the number of patients is relatively small for characterising delayed AEs. Patients' drop-out affects the estimation and deteriorates its reliability. For AEs that are likely to occur soon after the exposure, a study with relatively shorter duration and large number of patients is preferable. Conclusions It is important to evaluate statistically the appropriate study design in planning a safety study so that a good estimate of the hazard function would be obtained. Copyright (C) 2007 John Wiley & Sons, Ltd.