What does analytical validity mean for genomic assays and how should a lab evalu

Analytical validity is the ability of a test to accurately and reliably measure the genomic features it claims to detect. For NGS assays, this includes accuracy (agreement with truth), precision/reproducibility, sensitivity/specificity across variant types (SNVs, indels, CNVs), limit of detection (e.g., variant allele fraction), reportable range, and robustness to sample and process variability. Evaluation should be end-to-end, covering pre-analytical inputs (e.g., DNA quality), wet-lab steps, and the bioinformatics pipeline. Use well-characterized reference materials and “truth sets” (e.g., NIST Genome in a Bottle) to estimate performance by variant class and genomic context (GC-rich, homopolymers, repeats). Conduct multi-operator, multi-day studies; include contrived positives/negatives; and assess batch effects. Document acceptance criteria, version-locked pipeline parameters, and residual risks. For clinical intended uses, align with FDA guidance for analytical validation of NGS IVDs, and leverage curated variant databases appropriately. Maintain continuous monitoring with control charts and re-verification after any significant process or software change. Key Takeaway: Validate end-to-end performance by variant class using truth sets, define acceptance criteria, and monitor continuously for changes.