Biases in clinical trials performed for regulatory approval

Abstract

Method comparisons are routinely performed in hospital laboratories as part of the regulatory approval process. These trials are often biased in several ways. There is often a conflict of interest bias because the hospital is paid for the trial by the manufacturer of the assay. Moreover, the trial itself is often conducted in a way that is different from routine use. The reagents selected for the trial cannot be randomly selected from all possible reagents since future reagents do not exist. Yet, future reagents often have new lots of raw materials and/or changed manufacturing procedures, which can affect assay trueness. User error is often minimized because the user chosen to perform the study receives more training then would be routinely provided. All of these factors can lead to better performance in the regulatory evaluation then performance seen after release for sale as shown by examples for glucose meters. The above biases are largely unavoidable. Steps are suggested to reduce the above biases.