Collider in RCT Subgroup Analysis

Good point but even if pathway operability and pathway intensity form a biological continuum, enrichment remains a distinct causal category because it presupposes an already-established mechanistic pathway. The enrichment marker modifies the expected magnitude of response within a pathway-positive population, whereas the predictive marker establishes that the pathway is available to the intervention in the first place. Thus the distinction is not necessarily biological but causal and hierarchical. Predictive marker ↓ Pathway operative ↓ Enrichment marker ↓ Expected treatment effect size