Can a screening or biomarker signal remain useful when its population, instrument, assay, clinical task, or biological source changes?
A screening measurement or biomarker can discriminate within one study without explaining where its signal comes from or whether performance will survive a new cohort, instrument, acquisition workflow, assay, threshold, or intended use.
- Who encounters it
- Screening researchers, biomarker developers, laboratory scientists, statisticians, and clinical-validation teams.
- Missing proof
- Prospective replication, prespecified thresholds, locked acquisition, specimen, preparation, timing, carrier-fraction, and culture workflows, clinically realistic disease mimics, calibration across instruments, laboratories, and populations, comparison with simpler models, and evidence connecting measured signals to their biological source.
- Next decisive test
- Run a prospective external validation with locked acquisition or specimen procedures, timing, carrier-fraction rules, instruments, preparation workflow, assay, clinical task, threshold, and analysis plan, then test whether calibration and biological interpretation remain stable across sites and populations.