{"entity":{"id":"idea-bio2-mrd-reference-standards","kind":"idea","name":"Reference materials and open proficiency testing for residual disease tests","aka":[],"tldr":"Different companies' leftover-cancer blood tests disagree, and there is no shared yardstick. Public reference samples would let anyone check which test actually works.","summary":"Tumour-informed and tumour-naive ctDNA assays report different sensitivities at different variant allele fractions, and cross-assay comparisons are almost entirely vendor-run. A public reference material programme (synthetic and patient-derived contrived plasma at defined fractions, blinded rounds, published per-assay results) would do for MRD what proficiency schemes did for HER2 immunohistochemistry.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Dormant cells and minimal residual disease): Tie et al., ctDNA analysis guiding adjuvant therapy in stage II colon cancer (NEJM 2022)","url":"https://doi.org/10.1056/NEJMoa2200075"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["mrd-testing","liquid-biopsy","ngs-mrd-clonoseq"],"targets":[],"drugs":[],"companies":["natera","guardant-health","foresight-diagnostics","adaptive-biotechnologies"],"institutions":[],"pathways":[],"terms":["vaf","mrd"],"trials":[],"people":[],"bottlenecks":["b-dormancy-mrd","b-biomarker-validation"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Blinded proficiency testing reveals at least a threefold spread in limit of detection between commercial MRD assays at 0.01% variant allele fraction, and publishing results narrows that spread within two rounds.","rationale":"Every biomarker that decides treatment eventually needs external quality assessment; HER2 and PD-L1 scoring both improved measurably once schemes existed. MRD is about to gate adjuvant therapy decisions, so the cost of unquantified variability is now clinical.","test":"A metrology institute or reference laboratory network produces contrived plasma panels and runs one blinded round with five commercial and three academic assays, publishing all results with assay names attached.","maturity":"speculative","actor":"regulator","cost":"small","horizonYears":3},"route":"/ideas/idea-bio2-mrd-reference-standards/","neighbours":{"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/"},{"id":"ngs-mrd-clonoseq","kind":"technology","name":"NGS-based MRD (clonoSEQ and molecular MRD)","route":"/technologies/ngs-mrd-clonoseq/"}],"company":[{"id":"adaptive-biotechnologies","kind":"company","name":"Adaptive Biotechnologies","route":"/companies/adaptive-biotechnologies/"},{"id":"foresight-diagnostics","kind":"company","name":"Foresight Diagnostics","route":"/companies/foresight-diagnostics/"},{"id":"guardant-health","kind":"company","name":"Guardant Health","route":"/companies/guardant-health/"},{"id":"natera","kind":"company","name":"Natera","route":"/companies/natera/"}],"term":[{"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/"},{"id":"b-dormancy-mrd","kind":"bottleneck","name":"Dormant cells and minimal residual disease","route":"/bottlenecks/b-dormancy-mrd/"}],"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/"}]}}