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AMP, CAP Publish Validation Guidelines for NGS-Based Oncology Panels

NEW YORK (GenomeWeb) – The Association for Molecular Pathology and the College of American Pathologists today published a set of guidelines for the validation of next-generation sequencing-based oncology panels, with the aim of improving the quality of sequencing results in the lab and providing better care for cancer patients in the clinic.

Published today in The Journal of Molecular Diagnostics, the guidelines include overviews of targeted NGS methods and data analysis, considerations for new test development, and recommendations for test validations and implementation of quality control metrics.

"In this era of precision medicine, NGS has quickly become the method of choice for detecting multiple somatic variants, diagnosing disease, and predicting response to targeted therapies. However, the required analytical validation process remains challenging," Lawrence Jennings, chairman of the working group that developed the guidelines, and attending pathologist at Ann and Robert H. Lurie Children's Hospital of Chicago, said in a statement. "AMP convened and led a multidisciplinary subject matter expert working group with liaison representation from CAP to summarize current knowledge, expose challenges, and provide guidance on how to best validate these tests to ultimately improve patient care."

The recommendations particularly emphasize the role molecular labs play in establishing best practices for NGS-based assays, and AMP noted the high likelihood of future updates to the guidelines as the field continues to change.

"These joint consensus recommendations address NGS test development, optimization, and validation, including recommendations on panel content selection and rationale for optimization and familiarization phase conducted before test validation; utilization of reference cell lines and reference materials for evaluation of assay performance; determining of positive percentage agreement and positive predictive value for each variant type; and requirements for minimal depth of coverage and minimum number of samples that should be used to establish test performance characteristics," the working groups wrote.

Among its recommendations, the group said it is important to establish a protocol for test validation before accumulating validation data, and that assay validation should be performed using samples of the type intended for the assay. The guidelines also cautioned that test performance could vary depending on the genomic region being tested, and that variation in results can occur despite the use of best instruments or most-qualified personnel.

Further, the authors wrote, "The quantitative analytical performance of a laboratory test, in this case an NGS test, does not necessarily predict performance at a clinical level. The intrinsic biological variability of disease has the greatest impact on the clinical sensitivity and specificity of NGS testing." They recommended that clinical validity and clinical utility of each assay be defined during the design process and evaluated during validation.  

NGS-based tests are advantageous for detecting multiple somatic alterations, but are challenging to use and require thorough analytical validation to ensure high-quality results, the authors concluded, adding, "This document summarizes a current knowledge about targeted NGS in the field of molecular diagnostics, exposes challenges of this technology, and provides guidance on how to ensure high-quality sequencing when it is used for patient care."