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Review
. 2021 Sep;55(5):1066-1074.
doi: 10.1007/s43441-021-00308-6. Epub 2021 May 27.

Clinical Quality Considerations when Using Next-Generation Sequencing (NGS) in Clinical Drug Development

Timothé Ménard  1 , Alaina Barros  2 , Christopher Ganter  2
Affiliations
Review

Clinical Quality Considerations when Using Next-Generation Sequencing (NGS) in Clinical Drug Development

Timothé Ménard et al. Ther Innov Regul Sci. 2021 Sep.

Abstract

Next-generation sequencing (NGS) and decreased costs of genomic testing are changing the paradigm in precision medicine and continue to fuel innovation. Integration of NGS into clinical drug development has the potential to accelerate clinical trial conduct and ultimately will shape the landscape of clinical care by making it easier to identify patients who would benefit from particular therapy(ies) and to monitor treatment outcomes with less invasive tests. This has led to an increased use of NGS service providers by pharmaceutical sponsors: to screen patients for clinical trials eligibility and for patient stratification, expanded Companion Diagnostic (CDx) development for treatment recommendations and Comprehensive Genomic profiling (CGP). These changes are reshaping the face of clinical quality considerations for precision medicine. Although some clinical quality considerations do exist in Health Authorities (HA) guidances and regulations (e.g., International Conference of Harmonization Good Clinical Practices-GCP), there is currently no holistic GxP-like detailed framework for pharmaceutical sponsors using NGS service providers in clinical trials, or for the development of CDx and CGP. In this research, we identified existing and applicable regulations, guidelines and recommendations that could be translated into clinical quality considerations related to technology, data quality, patients and oversight. We propose these considerations as a basis for pharmaceutical sponsors using NGS service providers in clinical drug development to develop a set of guidelines for NGS clinical quality.

Keywords: Clinical quality; Clinical trials; Genetics; Genomics; Next-generation sequencing; Quality assurance.

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Conflict of interest statement

Timothé Ménard, Alaina Barros and Christopher Ganter were employees of Roche/Genentech at the time this research was completed.

Figures

Fig. 1
Fig. 1
Key clinical quality considerations
Fig. 2
Fig. 2
Data quality considerations
See this image and copyright information in PMC

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