Implications of performance variation in next-generation sequencing-based laboratory-developed tests for oncology: Stakeholder views

Precision Medicine and DiagnosticsApril 2024

In 2013, the Sustainable Predictive Oncology Therapeutics and Diagnostics (SPOT/Dx) working group committed to developing a new approach to assess laboratory test validation and performance. Participants aimed to ensure that oncologists could confidently select appropriate targeted therapies for treatment, regardless of which molecular diagnostic test was used. Launched in 2016, the Diagnostic Quality Assurance Pilot provided clinical laboratories with digital images of tissue-section slides, engineered wet-lab reference samples (the “wet-lab challenge”), and in-silico sequence data file samples (the “in-silico challenge”) and developed an evaluation methodology to assess the analytical performance of validated laboratory-developed tests (LDTs) relative to a US Food and Drug Administration (FDA)-approved companion diagnostic (CDx) for a targeted cancer therapy. The pilot’s results were published in American Journal of Clinical Pathology on December 2021. The pilot’s steering committee (SC) has released this white paper as a companion document to the technical article to describe the pilot’s impetus, design, and outcomes, as well as the SC members’ and liaisons’ reflections on the pilot’s implications. This summary highlights SC member conclusions and recommended next steps.