ideasIdea
Certified reference samples to benchmark every tumour-DNA blood test
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.
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.
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.
What would test it
Produce reference plasma at four allele fraction levels; run a blinded round across ten commercial assays; publish results.
Maturity
early clinical
Who has to act
regulator
Cost to try
Small (under $1M)
Years to first evidence
2
Bottlenecks it attacks
- Biomarkers are not validated or standardised · Tests that decide who gets a drug are often not validated prospectively and are measured differently in every lab.