# Certified reference samples to benchmark every tumour-DNA blood test

Source: https://onco.cc/ideas/idea-tr2-ctdna-reference-plasma/  
OnCo record `idea-tr2-ctdna-reference-plasma` (Idea). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

## Fields

- Kind: Idea
- Last checked: 2026-09-08
- 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.
- Proposed test: Produce reference plasma at four allele fraction levels; run a blinded round across ten commercial assays; publish results.
- Maturity: early-clinical
- Actor: regulator

## Sources

- FDA SEQC2 project (page moved; nearest live section): https://www.fda.gov/science-research/bioinformatics-tools/

## Connected records

- companies: [Guardant Health](https://onco.cc/companies/guardant-health/), [Natera](https://onco.cc/companies/natera/)
- ideas: [An annual blinded shoot-out for liquid biopsy tests](https://onco.cc/ideas/idea-tr2-liquid-biopsy-challenge/)
- technologies: [Liquid biopsy (ctDNA)](https://onco.cc/technologies/liquid-biopsy/), [MRD / molecular residual disease testing](https://onco.cc/technologies/mrd-testing/)
- terms: [Circulating tumour DNA (ctDNA)](https://onco.cc/terms/ctdna/), [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/)
- 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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