Collider in RCT Subgroup Analysis

llynn:

I wonder whether there is value in distinguishing a third category: an “enrichment biomarker.” This would be a marker that neither establishes the pathway nor serves as a purely orthogonal prognostic marker, but instead quantifies pathway intensity within a biologically defined population.

I am not sure enrichment can be classified as prognostic because you might agree that both predictive markers and enrichment markers are entangled with the treatment mechanism (M). The distinction rests on whether the marker establishes pathway operability or merely quantifies intensity within an already-operative pathway. Biologically, that line may be continuous (a dose-response relationship with treatment effect conditional on biomarker-positive status) rather than discrete. Pathway operability may itself be a matter of degree, in which case predictive and enrichment collapse back into a single continuous construct and the distinction dissolves.