{"entity":{"id":"idea-tr2-ctdna-reference-plasma","kind":"idea","name":"Certified reference samples to benchmark every tumour-DNA blood test","aka":[],"tldr":"Dozens of companies sell blood tests for tumour DNA and they report different results on the same sample. Government-issued reference samples with known amounts of tumour DNA would expose the differences.","summary":"ctDNA assays differ in limit of detection, variant calling and reporting; head-to-head comparisons on clinical samples show discordance, especially at low variant allele fractions where MRD decisions are made. A national metrology institute issuing certified reference plasma (fragmented DNA with defined variants at defined allele fractions, including sub-0.1% levels) and requiring assays to report performance on them in labelling would make claims comparable and detect drift over time.","asOf":"2026-09-08","links":[{"label":"FDA SEQC2 project (page moved; nearest live section)","url":"https://www.fda.gov/science-research/bioinformatics-tools/"}],"tags":[],"related":["guardant-health","natera","idea-tr2-liquid-biopsy-challenge"],"cancers":[],"sections":[],"technologies":["liquid-biopsy","mrd-testing"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["ctdna","vaf","mrd"],"trials":[],"people":[],"bottlenecks":["b-biomarker-validation"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Assays that report performance on certified reference plasma will show a spread of sensitivity at 0.1% allele fraction wide enough to change clinical decisions, and the requirement will drive convergence within three years.","rationale":"Certified reference materials underpin every quantitative clinical assay; ctDNA is being used for treatment decisions without them.","test":"Produce reference plasma at four allele fraction levels; run a blinded round across ten commercial assays; publish results.","maturity":"early-clinical","actor":"regulator","cost":"small","horizonYears":2},"route":"/ideas/idea-tr2-ctdna-reference-plasma/","neighbours":{"company":[{"id":"guardant-health","kind":"company","name":"Guardant Health","route":"/companies/guardant-health/"},{"id":"natera","kind":"company","name":"Natera","route":"/companies/natera/"}],"idea":[{"id":"idea-tr2-liquid-biopsy-challenge","kind":"idea","name":"An annual blinded shoot-out for liquid biopsy tests","route":"/ideas/idea-tr2-liquid-biopsy-challenge/"}],"technology":[{"id":"liquid-biopsy","kind":"technology","name":"Liquid biopsy (ctDNA)","route":"/technologies/liquid-biopsy/"},{"id":"mrd-testing","kind":"technology","name":"MRD / molecular residual disease testing","route":"/technologies/mrd-testing/"}],"term":[{"id":"ctdna","kind":"term","name":"Circulating tumour DNA (ctDNA)","route":"/terms/ctdna/"},{"id":"mrd","kind":"term","name":"Minimal / molecular residual disease (MRD)","route":"/terms/mrd/"},{"id":"vaf","kind":"term","name":"Variant allele frequency (VAF)","route":"/terms/vaf/"}],"bottleneck":[{"id":"b-biomarker-validation","kind":"bottleneck","name":"Biomarkers are not validated or standardised","route":"/bottlenecks/b-biomarker-validation/"}],"roadmap":[{"id":"ctdna-tests","kind":"roadmap","name":"ctDNA tests roadmap: from a curiosity in plasma to blood tests that decide treatment","route":"/roadmaps/ctdna-tests/"}]}}