Estimating Treatment Effect of High Hemoglobin Using the Principal Stratification Approach

Abstract

Anemia is a common complication of chronic kidney disease (CKD) and end-stage renal disease. A high hemoglobin level targeted in the treatment of anemia has been controversial because recent overseas studies have reported that it did not affect renal survival or increased the risk of cardiovascular events. In the motivation study, patients with CKD were randomly assigned to high or low hemoglobin target group (11.0–13.0 or 9.0–11.0 g/dL). The comparison of groups for the composite of renal events as the primary endpoint revealed no significant differences (p = 0.111). In these studies, ad hoc analyses suggested that a high hemoglobin level may potentially reduce cardiovascular events. However, those results could not precisely estimate the effect of treatment with high hemoglobin because of post-treatment selection bias. To address this problem, we used the method based on principal stratification approach to estimate the causal effect of Partial Responders by which the treatment effect of high hemoglobin can be evaluated. The results suggested that not only Partial but also Always Responders may benefit more from high hemoglobin treatment than Never Responders. These data suggest that patients with CKD can receive benefit from high hemoglobin treatment, who can respond to that treatment.