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Review
. 2023 Nov;50(11):9587-9599.
doi: 10.1007/s11033-023-08748-z. Epub 2023 Oct 3.

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

Tatjana Huebner  1 , Michael Steffens  2 , Catharina Scholl  2
Affiliations
Review

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

Tatjana Huebner et al. Mol Biol Rep. 2023 Nov.

Abstract

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.

Keywords: Analytical validation; NGS; Next generation sequencing; PGx; Performance; Pharmacogenomics; Profiling; Third generation sequencing; WES; WGS; Whole exome sequencing; Whole genome sequencing.

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Conflict of interest statement

Tatjana Huebner, Michael Steffens and Catharina Scholl declare that they have no conflicts of interest that might be relevant to the contents of this manuscript.

Figures

Fig. 1
Fig. 1
PRISMA 2020 scheme of the literature search for analytical performance studies of NGS-applications with FDA cleared or approved orthogonal tests in Pubmed and Pubmed Central
Fig. 2
Fig. 2
Scheme of the literature search for analytical performance evaluations of NGS-applications in Pubmed and Pubmed Central
See this image and copyright information in PMC

References

    1. Ritzhaupt A, Hayes I, Ehmann F. Implementing the EU in vitro diagnostic regulation – a european regulatory perspective on companion diagnostics. Expert Rev Mol Diagn. 2020;20(6):565–567. doi: 10.1080/14737159.2020.1720653. - DOI - PubMed
    1. Luh F, Yen Y. FDA guidance for next generation sequencing-based testing: balancing regulation and innovation in precision medicine. NPJ Genom Med. 2018;3:28. doi: 10.1038/s41525-018-0067-2. - DOI - PMC - PubMed
    1. COUNCIL EPA REGULATION (EU) 2017/746 OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL of 5 April 2017 on in vitro diagnostic medical devices and repealing Directive 98/79/EC and Commission Decision 2010/227/EU in Official Journal of the European Union
    1. Administration USFD (2021) Overview of IVD Regulation. [cited 2023 10.02.2023]; Available from: https://www.fda.gov/medical-devices/ivd-regulatory-assistance/overview-i...
    1. Linderman MD, et al. Analytical validation of whole exome and whole genome sequencing for clinical applications. BMC Med Genom. 2014;7(1):20. doi: 10.1186/1755-8794-7-20. - DOI - PMC - PubMed

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