Comparative Analysis of External Quality Assessment Schemes for Next-Generation Sequencing–Based Germline Variant Testing

Background: Proficiency testing (PT), also known as external quality assessment (EQA), provides external evaluation of clinical laboratory test performance.Because the types of diseases and genes targeted by nextgeneration sequencing (NGS) tests vary widely, evaluating these tests using accuracy-based PT is challenging; therefore, the evaluations should be based on method-specific criteria.We investigated existing PT schemes of germline NGS testing.Methods: This study was a qualitative comparative study of domestic and international PT programs for germline NGS testing.Multiple databases were searched using terms such as "EQA" and "PT" in October 2022.We included reports from individual PT providers (the College of American Pathologists [CAP] and the Korean Association of External Quality Assessment Service [KEQAS] and the Korean Institute of Genetic Testing Evaluation [KIGTE]), as well as peer-reviewed literature describing programmatic structures and evaluation criteria.Results: Among the PT schemes offered by the CAP, KEQAS, and KIGTE, no substantial differences were observed in the materials provided or the required response items.Regarding variant types, all three organizations provided single nucleotide variants, insertion/deletion variants, or samples with no variant.Conclusions: In this study, we compared various PT schemes for germline NGS testing.Because each scheme has its own advantages, clinical laboratories can select the scheme that is most appropriate for their NGS testing workflow and participate accordingly.The continuous development and global harmonization of PT schemes are necessary to improve the quality of NGS testing in clinical laboratories.