Current status of the analytical validation of next generation sequencing applications for pharmacogenetic profiling.

BACKGROUND: Analytical validity is a prerequisite to use a next generation sequencing (NGS)-based application as an in vitro diagnostic test or a companion diagnostic in clinical practice. Currently, in the United States and the European Union, the intended use of such NGS-based tests does not refer to guided drug therapy on the basis of pharmacogenetic profiling of drug metabolizing enzymes, although the value of pharmacogenetic testing has been reported. However, in research, a large variety of NGS-based tests are used and have been confirmed to be at least comparable to array-based testing. METHODS AND RESULTS: A systematic evaluation was performed screening and assessing published literature on analytical validation of NGS applications for pharmacogenetic profiling of CYP2C9, CYP2C19, CYP2D6, VKORC1 and/or UGT1A1. Although NGS applications are also increasingly used for implementation assessments in clinical practice, we show in the present systematic literature evaluation that published information on the current status of analytical validation of NGS applications targeting drug metabolizing enzymes is scarce. Furthermore, a comprehensive performance evaluation of whole exome and whole genome sequencing with the intended use for pharmacogenetic profiling has not been published so far. CONCLUSIONS: A standard in reporting on analytical validation of NGS-based tests is not in place yet. Therefore, many relevant performance criteria are not addressed in published literature. For an appropriate analytical validation of an NGS-based qualitative test for pharmacogenetic profiling at least accuracy, precision, limit of detection and specificity should be addressed to facilitate the implementation of such tests in clinical use.