title: College of American Pathologists' laboratory standards for next-generation sequencing clinical tests.
abstract: BACKGROUND
  The higher throughput and lower per-base cost of next-generation sequencing (NGS) as compared to Sanger sequencing has led to its rapid adoption in clinical testing. The number of laboratories offering NGS-based tests has also grown considerably in the past few years, despite the fact that specific Clinical Laboratory Improvement Amendments of 1988/College of American Pathologists (CAP) laboratory standards had not yet been developed to regulate this technology.
  
  
  OBJECTIVE
  To develop a checklist for clinical testing using NGS technology that sets standards for the analytic wet bench process and for bioinformatics or "dry bench" analyses. As NGS-based clinical tests are new to diagnostic testing and are of much greater complexity than traditional Sanger sequencing-based tests, there is an urgent need to develop new regulatory standards for laboratories offering these tests.
  
  
  METHODS
  To develop the necessary regulatory framework for NGS and to facilitate appropriate adoption of this technology for clinical testing, CAP formed a committee in 2011, the NGS Work Group, to deliberate upon the contents to be included in the checklist. Results . -A total of 18 laboratory accreditation checklist requirements for the analytic wet bench process and bioinformatics analysis processes have been included within CAP's molecular pathology checklist (MOL).
  
  
  CONCLUSIONS
  This report describes the important issues considered by the CAP committee during the development of the new checklist requirements, which address documentation, validation, quality assurance, confirmatory testing, exception logs, monitoring of upgrades, variant interpretation and reporting, incidental findings, data storage, version traceability, and data transfer confidentiality.
authors.affiliation: From Molecular Medicine (Dr Aziz), Laboratory Improvement Programs (Dr Zhao and Ms Palicki), and Laboratory Accreditation and Regulatory Affairs (Ms Driscoll), College of American Pathologists, Northfield, Illinois; the Department of Pathology, Brigham & Women's Hospital, Harvard Medical School, Boston, Massachusetts (Dr Bry); the Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts (Dr Funke); the Department of Clinical Sciences, University of Central Florida College of Medicine, Orlando (Dr Gibson); the Divisions of Medical Genetics and Molecular Diagnostics, Department of Pathology & Laboratory Medicine, Pediatrics, and Human Genetics, UCLA School of Medicine, UCLA Institute for Society and Genetics, Molecular Diagnostic Laboratories and Clinical Genomics Center, UCLA Medical Center, Los Angeles, California (Dr Grody); the Department of Human Genetics, Emory University School of Medicine, Decatur, Georgia (Dr Hegde); Robert J. Tomsich Pathology & Laboratory Medicine Institute, Cleveland Clinic, Cleveland, Ohio (Dr Hoeltge); the Department of Pathology, University of Vermont College of Medicine, Burlington (Dr Leonard); the Departments of Pathology (Drs Merker and Schrijver) and Pediatrics (Dr Schrijver), Stanford University School of Medicine, Stanford, California; the Department of Pathology & Immunology, Washington University School of Medicine, St Louis, Missouri (Dr Nagarajan); the Department of Laboratory Medicine & Pathology, Mayo Clinic in Arizona, Phoenix (Dr Robetorye); the Departments of Pathology & Laboratory Medicine and Genetics, University of North Carolina at Chapel Hill, Chapel Hill (Dr Weck); and ARUP Laboratories Institute for Clinical and Experimental Pathology, and Department of Pathology, University of Utah School of Medicine, Salt Lake City (Dr Voelkerding). Dr Aziz is now with Phoenix Children's Hospital, Phoenix, Arizona.
authors.forename: Nazneen
authors.initials: N
authors.lastname: Aziz
authors.forename: Qin
authors.initials: Q
authors.lastname: Zhao
authors.forename: Lynn
authors.initials: L
authors.lastname: Bry
authors.forename: Denise K
authors.initials: DK
authors.lastname: Driscoll
authors.forename: Birgit
authors.initials: B
authors.lastname: Funke
authors.forename: Jane S
authors.initials: JS
authors.lastname: Gibson
authors.forename: Wayne W
authors.initials: WW
authors.lastname: Grody
authors.forename: Madhuri R
authors.initials: MR
authors.lastname: Hegde
authors.forename: Gerald A
authors.initials: GA
authors.lastname: Hoeltge
authors.forename: Debra G B
authors.initials: DG
authors.lastname: Leonard
authors.forename: Jason D
authors.initials: JD
authors.lastname: Merker
authors.forename: Rakesh
authors.initials: R
authors.lastname: Nagarajan
authors.forename: Linda A
authors.initials: LA
authors.lastname: Palicki
authors.forename: Ryan S
authors.initials: RS
authors.lastname: Robetorye
authors.forename: Iris
authors.initials: I
authors.lastname: Schrijver
authors.forename: Karen E
authors.initials: KE
authors.lastname: Weck
authors.forename: Karl V
authors.initials: KV
authors.lastname: Voelkerding
mesh_terms: D019411:Clinical Laboratory Techniques / Q000379:methods* / Q000592:standards; D019295:Computational Biology / Q000379:methods; D005820:Genetic Testing / Q000379:methods* / Q000592:standards; D017408:Guidelines as Topic / Q000592:standards; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D006801:Humans; D010338:Pathology, Clinical / Q000379:methods*; D012015:Reference Standards; D015203:Reproducibility of Results; D012955:Societies, Medical; D014481:United States