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

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.

TERT Mutations in Non–Small Cell Lung Cancer: Clinicopathologic Features and Prognostic Implications

“…19 NGS can effectively identify the status of various important lung cancer-related gene changes. 20 TERT mutations are considered a low mutation type in NSCLC. 21 In a cohort study of 103 patients with NSCLC, using DNA gene sequencing, Yuan et al 22 suggested that the mutation rate of the TERT region was approximately 5.8%.…”

“… 19 NGS can effectively identify the status of various important lung cancer-related gene changes. 20 …”

Clinical Quality in Cancer Research: Strategy to Assess Data Integrity of Germline Variants Inferred from Tumor-Only Testing Sequencing Data

“…Furthermore, should the decision be made to use PGPV data inferred from tumor-only testing for a regulatory ling, having assessed the method and applied quality checks could avoid having to implement quality assurance measures retrospectively, and therefore save signi cant resources. Of note, if PGPV data are intended to be used for ling, all regulatory and quality requirements pertaining to process, systems and computer system validation must be met [21].…”

Potential Intersections between lncRNA, Vascular Cognitive Impairment, and Immunization Strategies: Insights and Future Directions

“…NGS allows for the cost-effective comprehensive analysis of genetic sequences at an unprecedented scale, facilitating a deeper understanding of the genetic variations of complex genetic diseases and molecular mechanisms underlying various biological processes. NGS is extensively utilized across various areas within biomedical science, encompassing areas such as genetics [ 9 ], infectious diseases [ 10 ], oncology [ 11 ], personalized medicine [ 12 ], drug development [ 13 ], and preventive medicine [ 14 ]. By enabling the detailed study of genomes and gene expression, NGS is revolutionizing our approach to diagnosing and treating diseases, understanding genetic disorders, and exploring the complexities of the human genome.…”