Use of latent growth curve models for assessing the effects of darbepoetin alfa on hemoglobin and fatigue

Background: The relationship between darbepoetin alfa and fatigue in chemotherapy-induced anemia (CIA) patients is complex because of patients receiving transfusions and the mediating effect of hemoglobin. Latent growth models (LGMs) were used to examine simultaneously relationships among drug exposure, fatigue outcomes, covariates, and mediating factors. Methods: Data from four CIA studies (AMG 20010145: small cell lung cancer, n = 547; AMG 980297: lung cancer, n = 288; AMG 20000161: lymphoproliferative malignancies, n = 339; AMG 20030232: non-myeloid malignancies, n = 320) were analyzed separately. Patients reported fatigue using the FACT-Fatigue. The effect of darbepoetin alfa on FACT-F changes mediated through hemoglobin changes was examined with LGMs controlling for transfusions, age, sex, baseline ECOG performance status, and health status (EQ-5D VAS). Model fit was assessed using multiple indices including the comparative fit index (CFI). Results: Darbepoetin alfa increased hemoglobin levels which were associated with decreases in fatigue. Increases in hemoglobin were statistically significantly (p