A Committee-Based Diagnostic Stewardship Model for Pathogen Metagenomic Sequencing in Children

Abstract Background Metagenomic next-generation sequencing (mNGS) for pathogen detection offers the potential for broad pathogen detection directly from clinical specimens. However, the yield and impact of testing is variable, financial cost is high, and questions surrounding its optimal use remain. Our pediatric institution used a clinical committee-based approach to discuss and approve or deny mNGS test requests. In this study, we evaluate the patient characteristics for which mNGS testing was considered, test yield, and clinical impact of mNGS results when employing this model of diagnostic stewardship. Methods Patients for which plasma cell-free DNA mNGS testing was requested and assessed by the clinical committee between August 1, 2018, and April 30, 2021, were included. The committee discussion emails were used to evaluate reasons for making the test request and treatment plans. Patient characteristics and additional clinical information were gathered by chart review. For approved cases, the clinical impact of the mNGS results were retrospectively adjudicated by infectious disease and clinical microbiology experts. Results Twelve requests for plasma cell-free DNA mNGS were evaluated and 9 were approved. mNGS results led to a positive clinical management change in 55% of approved requests. Negative clinical impact of mNGS testing did not occur during the study. The patients for which testing requests were denied had resolution of symptoms without further intervention. Conclusions This committee-based test request approval diagnostic stewardship model has the potential to support high-yield mNGS testing while using healthcare resources responsibly.