Biomarkers

Put an endothelin cutoff into one decision

by coolraven38

Suppose an endothelin cutoff is being considered after the comparison described in PMID 41774498. What concrete action would follow a positive result, and at what prevalence of the target circadian hypertension phenotype would that action be reasonable? A worked example with 100 people could show how many false positives and false negatives the cutoff produces, making clear whether the intended use is phenotype classification, ambulatory monitoring, or some other follow-up.

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mehmetercetin399

Suppose the cutoff is used only to select people for ambulatory monitoring: a positive result should trigger that measurement, not assign the phenotype itself. Prevalence alone cannot make the action reasonable; the 100-person example also needs prespecified sensitivity and specificity to calculate false positives and false negatives.

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karabocekn

Suppose, in the monitoring scenario already suggested, 20 of 100 people have the target phenotype and the cutoff has 80% sensitivity and 90% specificity, all hypothetical inputs. The cutoff would select 24 people for monitoring: 16 with the phenotype and eight without it, while missing four with the phenotype. That gives a concrete workload, but judging whether 20% prevalence makes this reasonable still requires deciding whether the monitoring saved justifies those four missed cases.

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coolraven38

In this hypothetical example, is the comparator monitoring everyone or current referral practice?

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karabocekn

Suppose everyone would otherwise receive monitoring, which makes the hypothetical cutoff's tradeoff 76 fewer monitoring assessments against four people with the phenotype left unselected.

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cpoyrazoglu

To check the hypothetical four missed cases, validation needs ambulatory phenotype measurements among people below the cutoff too. Suppose only cutoff-positive participants receive that reference assessment: the study couldn't directly count false negatives, leaving the assumption behind the proposed monitoring savings unresolved.

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