Publication

Biomarkers and next-generation sequencing (NGS) tests have become pivotal in the diagnosis and treatment of diseases. Recent data shows, for example, increasing use of biomarker testing by oncologists. NGS testing is not only increasingly prevalent but also complex: today, large-scale gene panels can survey hundreds or even thousands of genes to provide critical insights about a patient’s health and inform treatment decisions.

These trends come at a time when the regulatory landscape in the United States for overseeing diagnostic tests remains in flux, with diverse stakeholders opining on the optimal oversight approach for diagnostic tests. In the absence of an updated regulatory framework, some stakeholders believe the community must continue to advance and evolve test development, validation, and quality assurance (QA) performance specifications, guided by current scientific knowledge and diagnostic capabilities to ensure consistent and accurate results for clinicians and patients.

In-silico sequence data sets and reference files (referred to herein as in-silico reference files, or I-SRFs) are one possible avenue of advancement. Various stakeholders have employed I-SRFs to support diagnostic development and validation, harmonization initiatives, and external QA activities, such as the diagnostic quality assurance pilot of the Sustainable Predictive Oncology Therapeutics and Diagnostics (SPOT/Dx) working group. Others have observed that compared with hard-to-obtain patient specimens or engineered wet-lab samples, customized I-SRFs cost less, are more versatile in design, and can assess bioinformatics performance across many types of genetic variants.

In September 2022, a small subset of experts and stakeholders working to advance diagnostic quality convened to launch a working group to pragmatically consider the value of I-SRFs and options for expanding their application in a variety of potential use cases. Launch participants took stock of several in-silico-related initiatives to date and provided insights on the potential scope of the working group, which may add additional participants over time. Key points from these discussions are detailed in the following Summary of Themes.