Reference materials and external quality assessment for liquid biopsy assays: Expert opinions from the European...

The European Liquid Biopsy Society (ELBS) ctDNA Workshop in 2023 brought together 44 experts from various disciplines to discuss the current status and future needs for reference materials and external quality assessment (EQA) in cancer liquid biopsy assays. The workshop focused on identifying, through presentations, discussion, and polls, key aspects that participants considered important for the design and use of reference materials and EQA schemes in ctDNA testing, which is increasingly used to guide crucial treatment decisions in cancer patients. The experts emphasized the importance of using well-characterized reference materials that closely mimic patient-derived ctDNA in terms of biochemical properties and assay performance, including plasma-like reference materials, multiple serial dilutions, and various input amounts to assess analytical sensitivity and specificity. The workshop participants also highlighted the importance of EQA schemes that include a broad range of clinically relevant genetic alterations, low variant allele frequencies, and cover different cancer types. Overall, the outputs of the workshop provide a snapshot of expert opinions with the ELBS community and are intended to inform ongoing discussions on reference materials and EQA for ctDNA testing, to eventually standardize EQA schemes, support improved assay validation, and ensure high-quality clinical reporting when liquid biopsy is used in routine clinical practice.