To address the need for more detailed guidance for designing, developing and administering clinical NGS tests, the College of American Pathologists (CAP) with representation from the Association for Molecular Pathologists (AMP) has initiated an effort to create structured documents, or worksheets, that translate regulatory specifications into concrete instructions that guide the user through the entire life cycle of an NGS test.
The initial set of five worksheets focus on variant detection in the setting of inherited disease and each contain background, instructions, and step-by-step guidance with examples for the different phases of NGS test development and implementation. These documents are intended to undergo regular review and updating and will be expanded to cover additional NGS applications over time.
The five worksheets are:
Test Content Design
Focuses on strategic consideration prior to test development in a clinical laboratory.
Translates test design requirements into an initial assay design including defining the coverage over the target regions, capture and sequencing methodologies, as well as any supplementary assays as needed.
Describes analytical performance metrics in addition to associated formulas, suggested reference materials and calculators. Also included are example worksheets on validation study design and subsequent data analysis.
Provides an overview of the procedure monitors for the pre-analytical, analytical and post-analytical phases of NGS based testing.
Bioinformatics and IT
Provides an overview on the critical considerations for the compute infrastructure as well as selection and validation of informatics approaches for tertiary processing of samples (the initial aspects of bioinformatics are covered in previous sections).
Working Group Members:
- Avni Santani, PhD, Children’s Hospital of Philadelphia/ Perelman School of Medicine, University of Pennsylvania
- Birgitte B. Simen, PhD, Veritas Genetics
- Marian Briggs, College of American Pathologists
- Matthew Lebo, PhD, Harvard Medical School/Brigham and Women’s Hospital
- Jason D. Merker, MD, PhD, University of North Carolina at Chapel Hill School of Medicine
- Marina Nikiforova, MD, University of Pittsburgh Medical Center*
- Patricia Vasalos, College of American Pathologists
- Karl Voelkerding, MD, University of Utah School of Medicine/ARUP Institute for Clinical and Experimental Pathology
- John Pfeifer, MD, PhD, Washington University School of Medicine
- Birgit Funke, PhD, Harvard Medical School/Massachusetts General Hospital
*Association for Molecular Pathology (AMP) Representative