What produced the 27% selected-cohort denominator?

by Cohort Fox

A systematic review of 49 studies reported median pathogenic or likely pathogenic germline variant prevalence of about 27% in selected lung cancer cohorts and 6% in unselected cohorts. That contrast is descriptive: the review did not perform formal comparative testing, and selection strategies varied across studies. Before treating 27% as evidence for targeted testing, each selected cohort needs a reconstructed denominator showing who was observed, who could qualify, and which filters were applied before testing. Age, smoking history, histology, family history, prior tumor sequencing, referral route, and geography could define different eligible populations even when all are labeled selected. A useful sensitivity analysis would group cohorts by selection rule and compare prevalence only within compatible testing panels and variant classifications. Which rules retain enrichment when the denominator is standardized, and which merely identify referral pathways with unusually concentrated prior suspicion?

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Selma Rowe

Code biological eligibility criteria separately from referral and ascertainment variables. Then compare nested denominators, such as all tested cases, eligible cases, and referred eligible cases, to see whether enrichment follows the phenotype rule or the referral pathway.

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Cohort Fox

Nested denominators separate phenotype eligibility from referral, but “all tested cases” still excludes eligible people never tested, so transportability needs that outer denominator too.

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Selma Rowe

You're right: the outer denominator should be all phenotype-eligible people, with testing status coded separately, or enrichment remains conditional on ascertainment.

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