Impact of 5-HT3 receptor antagonists on chemotherapy-induced nausea and vomiting: a retrospective cohort study

BACKGROUND: 1(st) generation 5-hydroxytryptamine receptor antagonists (5-HT(3) RAs), and palonosetron, a 2(nd) generation 5-HT(3) RA, are indicated for the prevention of chemotherapy (CT)-induced nausea and vomiting (CINV) associated with moderately (MEC) and highly emetogenic CT agents (HEC). This study explores the impact of step therapy policies requiring use of an older 5-HT(3) RA before palonosetron on risk of CINV associated with hospital or emergency department (ED) admissions. METHODS: Patients who received cyclophosphamide post breast cancer (BC) surgery or who were diagnosed with lung cancer on carboplatin (LC-carboplatin) or cisplatin (LC-cisplatin) were selected from PharMetrics’ (IMS LifeLink) claims dataset (2005-2008). Patients were followed for 6 months from initial CT administration for CINV events identified through ICD-9-CM codes. Patients were grouped into those initiated with older, generic 5-HT(3) RAs (ondansetron, granisetron, and dolasetron) and those initiated and maintained on palonosetron throughout study follow-up. CINV events and CINV days were analyzed using multivariate regressions controlling for demographic and clinical variables. RESULTS: Eligible patients numbered 3,606 in BC, 4,497 in LC-carboplatin and 1,154 in LC-cisplatin cohorts, with 52%, 40%, and 34% in the palonosetron group, respectively. There was no significant difference between the two 5-HT(3) RA groups in age or Charlson Comorbidity Index among the two MEC cohorts (BC and LC-carboplatin). Among the LC-cisplatin cohort, palonosetron users were older with more males than the older 5-HT(3) RA group (age: 60.1 vs. 61.3; males, 66.9% vs. 56.9%). Compared to the older 5-HT(3) RAs, the palonosetron groups incurred 22%-51% fewer 5-HT(3) RA pharmacy claims, had fewer patients with CINV events (3.5% vs. 5.5% in BC, 9.5% vs. 12.8% in LC-carboplatin, 16.4% vs. 21.7% in LC-cisplatin), and had lower risk for CINV events (odds ratios 0.62, 0.71, or 0.71, respectively; p < 0.05). The BC and LC-carboplatin palonosetron groups experienced 50% and 30% fewer CINV days than the generic 5-HT(3) RA group (p < 0.05). CONCLUSIONS: Patients with breast or lung cancer initiated and maintained on palonosetron were at significantly lower risk for potentially costly CINV versus those on older 5-HT(3) RAs. Further studies on impact of step therapy policy are warranted in order to minimize the clinical and economic burden of CINV

Comparison of the HUI3 with the SF-36 Preference Based SF-6D in a Clinical Trial Setting

AbstractObjectiveTo test the hypothesis that the Health Utilities Index Mark III (HUI3) and the SF-6D, based on the SF-36, generate similar health state values, and to test and compare their discriminant validity and responsiveness.MethodsThe HUI3 and SF-36 were administered to 331 patients enrolled in a double-blind, multinational phase III clinical trial in patients undergoing percutaneous coronary intervention before hospital discharge and 6 months thereafter.ResultsThe mean SF-6D baseline health state score was 0.67 compared to the HUI3 of 0.63 with r of 0.616 and intraclass correlation coefficient of 0.40. The relationship was nonlinear with greatest divergence found at the lower levels of health. Both measures were found to agree with known differences in health and to be responsive to changes over time. Nevertheless, disagreement resulted in different estimates of change from baseline (0.08 vs. 0.154).ConclusionBoth measures deployed in the present study were found to have discriminant validity, and to be responsive to changes over time in coronary artery disease conditions. Nevertheless, the measures generated different estimates of health state values for this patient population. These differences might in part be the consequence of the health status descriptive system for the HUI that may have been more in line with the hospitalized state than that for the SF-6D. These findings seemed to indicate that measures deployed are not interchangeable for use in cost-utility analysis. More head-to-head comparisons between these two measures are needed to further define and compare relationships in different patient populations