# Reference materials and open proficiency testing for residual disease tests

Source: https://onco.cc/ideas/idea-bio2-mrd-reference-standards/  
OnCo record `idea-bio2-mrd-reference-standards` (Idea). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

## Fields

- Kind: Idea
- Last checked: 2026-09-08
- 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.
- Proposed 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

## Sources

- Bottleneck evidence (Dormant cells and minimal residual disease): Tie et al., ctDNA analysis guiding adjuvant therapy in stage II colon cancer (NEJM 2022): https://doi.org/10.1056/NEJMoa2200075

## Connected records

- technologies: [Liquid biopsy (ctDNA)](https://onco.cc/technologies/liquid-biopsy/), [MRD / molecular residual disease testing](https://onco.cc/technologies/mrd-testing/), [NGS-based MRD (clonoSEQ and molecular MRD)](https://onco.cc/technologies/ngs-mrd-clonoseq/)
- companies: [Adaptive Biotechnologies](https://onco.cc/companies/adaptive-biotechnologies/), [Foresight Diagnostics](https://onco.cc/companies/foresight-diagnostics/), [Guardant Health](https://onco.cc/companies/guardant-health/), [Natera](https://onco.cc/companies/natera/)
- terms: [Minimal / molecular residual disease (MRD)](https://onco.cc/terms/mrd/), [Variant allele frequency (VAF)](https://onco.cc/terms/vaf/)
- bottlenecks: [Biomarkers are not validated or standardised](https://onco.cc/bottlenecks/b-biomarker-validation/), [Dormant cells and minimal residual disease](https://onco.cc/bottlenecks/b-dormancy-mrd/)
- roadmaps: [ctDNA tests roadmap: from a curiosity in plasma to blood tests that decide treatment](https://onco.cc/roadmaps/ctdna-tests/)

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