Table 2.

The ladder of causation [40]. Y is the outcome, DFS time; X is treatment, with X = 1 for adjuvant pembrolizumab and X = 0 for placebo; Z is the baseline prognostic risk, with Z = 1 for high risk of recurrence. ccRCC = clear cell renal carcinoma.

Layer	Activity	Analysis Unit	Mathematical Expression	Example Query
One	Observation	Population	P(Y | Z)	What is the DFS time distribution in patients at high risk for ccRCC recurrence?
Two	Intervention	Population	P(Y | do(X = 1))	What is the DFS time distribution in patients with ccRCC treated with adjuvant pembrolizumab?
Three	Potential outcomes	Individual Patient	E(YX = 1 | Z = 1) − E(YX = 0 | Z = 1)	What would the expected DFS time be if I treat a patient with high-risk ccRCC with adjuvant pembrolizumab compared to placebo?