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Updated: May 12, 2026
Integration of Wet and Dry Bench Processes Optimizes Targeted Next-generation Sequencing of Low-quality and Low-quantity Tumor Biopsies
Published on: April 11, 2016
Description and pilot results from a novel method for evaluating return of incidental findings from next-generation
Katrina A B Goddard1, Evelyn P Whitlock, Jonathan S Berg
1Center for Health Research, Kaiser Permanente Northwest, Portland, Oregon, USA. Katrina.AB.Goddard@kpchr.org
Purpose:
The aim of this study was to develop, operationalize, and pilot test a transparent, reproducible, and evidence-informed method to determine when to report incidental findings from next-generation sequencing technologies.
Methods:
Using evidence-based principles, we proposed a three-stage process. Stage I "rules out" incidental findings below a minimal threshold of evidence and is evaluated using inter-rater agreement and comparison with an expert-based approach. Stage II documents criteria for clinical actionability using a standardized approach to allow experts to consistently consider and recommend whether results should be routinely reported (stage III). We used expert opinion to determine the face validity of stages II and III using three case studies. We evaluated the time and effort for stages I and II.
Results:
For stage I, we assessed 99 conditions and found high inter-rater agreement (89%), and strong agreement with a separate expert-based method. Case studies for familial adenomatous polyposis, hereditary hemochromatosis, and α1-antitrypsin deficiency were all recommended for routine reporting as incidental findings. The method requires <3 days per topic.
Conclusion:
We establish an operational definition of clinically actionable incidental findings and provide documentation and pilot testing of a feasible method that is scalable to the whole genome.
