Brentuximab Vedotin Plus CHP in Frontline sALCL: Adjusted Estimates of Efficacy and Cost-Effectiveness Removing the Effects of Re-Treatment with Brentuximab Vedotin.

BACKGROUND: In the randomised controlled trial ECHELON-2 (NCT01777152; January 2013), brentuximab vedotin (BV) plus cyclophosphamide, doxorubicin and prednisone (CHP) demonstrated improved efficacy compared with CHOP (CHP and vincristine) in frontline CD30+ peripheral T-cell lymphoma (PTCL), an aggressive cancer with poor survival. In ECHELON-2, 70% of patients had systemic anaplastic large cell lymphoma (sALCL), a subtype of PTCL. Of sALCL patients who progressed from BV+CHP and CHOP, 36% (n = 17) and 56% (n = 36) received subsequent BV-containing therapy, respectively. As BV re-treatment was not funded in England at the time, our objective was to estimate adjusted efficacy and cost-effectiveness by excluding BV re-treatment from BV+CHP. METHODS: To remove the effects of BV re-treatment, the inverse probability of censoring weights (IPCW) and two-stage estimator (TSE) approaches, with and without re-censoring, were applied to overall survival (OS) in the BV+CHP arm of the ECHELON-2 sALCL population. Cost-effectiveness was determined in a three-state partitioned survival (PartSA) model from the perspective of the National Health Service (NHS) in England. RESULTS: The unadjusted hazard ratio (HR) for death in patients with sALCL with BV+CHP versus CHOP was 0.54 (95% CI 0.34, 0.87; p = 0.011). The model base case used TSE analysis without re-censoring, which provided an adjusted HR for death of 0.55 (95% CI 0.33, 0.86; p = 0.014). Incremental cost-effectiveness ratios (ICERs) including and excluding re-treatment with BV were £29,760/QALY and £27,761/QALY, respectively. CONCLUSION: TSE without re-censoring provided the most clinically plausible estimate of survival whilst retaining sufficient information for OS extrapolation. After adjustment for BV re-treatment, BV+CHP remains an efficacious and cost-effective treatment in frontline sALCL compared with CHOP.

Cost Effectiveness of Inclisiran in Atherosclerotic Cardiovascular Patients with Elevated Low-Density Lipoprotein Cholesterol Despite Statin Use: A Threshold Analysis.

BACKGROUND: Inclisiran is a novel, cholesterol-lowering therapy, with a long duration of effect, administered every 6 months (subcutaneously by a healthcare professional). In the ORION-10 trial in US patients with atherosclerotic cardiovascular disease (ASCVD) in addition to maximum tolerated statins, with or without ezetimibe, inclisiran demonstrated statistically significant reductions in low-density lipoprotein cholesterol (LDL-C) of up to 51%. This is the first peer-reviewed publication to investigate the price at which inclisiran is cost effective in the US. OBJECTIVE: The aim of this study was to determine the maximum price at which inclisiran is cost effective in addition to standard of care, in US patients with ASCVD, versus standard of care alone, at different willingness-to-pay thresholds. DESIGN, SETTING AND PARTICIPANTS: A lifetime Markov model from the US health system perspective, including 15 health states, was used to evaluate the cost effectiveness of inclisiran. The following states were separated by time from a previous cardiovascular event (0-1 years, 1-2 years, 2+ years ['stable']): initial, unstable angina, myocardial infarction, and stroke. Additional states included revascularization and death (cardiovascular or non-cardiovascular causes). Baseline risk of cardivoascular events were from US database sources or published literature. Reductions in LDL-C from inclisiran were from the ORION-10 trial. LDL-C reduction was used to adjust baseline risk of cardiovascular events, based on established relationships between 1 mmol/L reduction in LDL-C and decreases in cardiovascular events, from the Cholesterol Treatment Trialists studies. The population included adults with a history of ASCVD, and LDL-C ≥ 70 mg/dL, despite maximum tolerated doses of statin therapy. INTERVENTIONS: Inclisiran as an adjunct to standard of care, compared with standard of care alone. MAIN OUTCOMES AND MEASURES: The threshold price of inclisiran. RESULTS: Inclisiran as an adjunct to standard of care resulted in threshold annual inclisiran prices of $6383, $9973, and $13,563 at willingness-to-pay thresholds of $50,000, $100,000, and $150,000 per quality-adjusted life-year, respectively. Probabilistic sensitivity analysis showed that at a threshold of $100,000 per QALY, inclisiran had a 100% probability of being cost effective, with an annual price below $9000. At the publicly available price of $3250 per dose, inclisiran was found to have an incremental cost-effectiveness ratio just above the $50,000 per QALY threshold, of $51,686. CONCLUSIONS AND RELEVANCE: This study identified the price at which inclisiran is cost effective for the US health system, at generally accepted willingness-to-pay thresholds.

Mapping the EORTC-QLQ-C30 to the EQ-5D-3L: An Assessment of Existing and Newly Developed Algorithms.

OBJECTIVES: To assess the external validity of mapping algorithms for predicting EQ-5D-3L utility values from EORTC QLQ-C30 responses not previously validated and to assess whether statistical models not previously applied are better suited for mapping the EORTC QLQ-C30 to the EQ-5D-3L. METHODS: In total, 3866 observations for 1719 patients from a longitudinal study (Cancer 2015) were used to validate existing algorithms. Predictive accuracy was compared to previously validated algorithms using root mean squared error, mean absolute error across the EQ-5D-3L range, and for 10 tumor-type specific samples as well as using differences between estimated quality-adjusted life years. Thirteen new algorithms were estimated using a subset of the Cancer 2015 data (3203 observations for 1419 patients) applying various linear, response mapping, beta, and mixture models. Validation was performed using 2 data sets composed of patients with varying disease severity not used in the estimation and all available algorithms ranked on their performance. RESULTS: None of the 5 existing algorithms offer an improvement in predictive accuracy over preferred algorithms from previous validation studies. Of the newly estimated algorithms, a 2-part beta model performed the best across the validation criteria and in data sets composed of patients with different levels of disease severity. Validation results did, however, vary widely between the 2 data sets, and the most accurate algorithm appears to depend on health state severity as the distribution of observed EQ-5D-3L values varies. Linear models performed better for patients in relatively good health, whereas beta, mixture, and response mapping models performed better for patients in worse health. CONCLUSION: The most appropriate mapping algorithm to apply in practice may depend on the disease severity of the patient sample whose utility values are being predicted.

Cost-effectiveness of sacubitril/valsartan in the treatment of heart failure with reduced ejection fraction.

OBJECTIVE: Chronic heart failure with reduced ejection fraction (HF-REF) represents a major public health issue and is associated with considerable morbidity and mortality. We evaluated the cost-effectiveness of sacubitril/valsartan (formerly LCZ696) compared with an ACE inhibitor (ACEI) (enalapril) in the treatment of HF-REF from the perspective of healthcare providers in the UK, Denmark and Colombia. METHODS: A cost-utility analysis was performed based on data from a multinational, Phase III randomised controlled trial. A decision-analytic model was developed based on a series of regression models, which extrapolated health-related quality of life, hospitalisation rates and survival over a lifetime horizon. The primary outcome was the incremental cost-effectiveness ratio (ICER). RESULTS: In the UK, the cost per quality-adjusted life-year (QALY) gained for sacubitril/valsartan (using cardiovascular mortality) was £17 100 (€20 400) versus enalapril. In Denmark, the ICER for sacubitril/valsartan was Kr 174 000 (€22 600). In Colombia, the ICER was COP$39.5 million (€11 200) per QALY gained. Deterministic sensitivity analysis showed that results were most sensitive to the extrapolation of mortality, duration of treatment effect and time horizon, but were robust to other structural changes, with most scenarios associated with ICERs below the willingness-to-pay threshold for all three country settings. Probabilistic sensitivity analysis suggested the probability that sacubitril/valsartan was cost-effective at conventional willingness-to-pay thresholds was 68%-94% in the UK, 84% in Denmark and 95% in Colombia. CONCLUSIONS: Our analysis suggests that, in all three countries, sacubitril/valsartan is likely to be cost-effective compared with an ACEI (the current standard of care) in patients with HF-REF.