James Eaton

Cost-effectiveness of transcatheter aortic valve replacement in patients ineligible for conventional aortic valve replacement

Objective To assess the cost-effectiveness of transcatheter aortic valve implantation (TAVI) compared with medical management in patients with severe aortic stenosis who are ineligible for conventional aortic valve replacement (SAVR) from the perspective of the UK National Health Service. Design Probabilistic decision analytical model. Methods A decision analytical model was developed to assess the costs and benefits associated with both interventions over a 10-year time horizon. A literature review was performed to identify relevant clinical evidence. Health-related quality of life and mortality were included using data from the PARTNER clinical trial (cohort B). Unit costs were taken from national databases. Costs and benefits were discounted at 3.5% per year, and extensive sensitivity analyses (probabilistic and deterministic) were performed to explore the impact of uncertainty on the cost-effectiveness estimates. Main outcome measure Incremental cost-effectiveness ratio (ICER) with benefits expressed as quality-adjusted life years (QALYs). Results The base case ICER was approximately £16 100 per QALY gained. At a cost-effectiveness threshold of £20 000 per QALY gained, the probability that TAVI was cost-effective compared with medical management was 1.00. The results were robust to changes in key clinical parameters as well as choice of baseline survival data. The observed PARTNER survival data only have to be extrapolated for 2 years to generate an ICER below £30 000 per QALY gained, which is the upper value of the threshold range used by the National Institute for Health and Clinical Excellence in the UK. Conclusions TAVI is highly likely to be a cost-effective treatment for patients with severe aortic stenosis who are currently ineligible for SAVR.

Cost-effectiveness of cardiac resynchronization therapy in patients with asymptomatic to mild heart failure: insights from the European cohort of the REVERSE (Resynchronization Reverses remodeling in Systolic Left Ventricular Dysfunction)

AIMS To assess the cost-effectiveness of cardiac resynchronization therapy (CRT) compared with optimal medical therapy in patients with New York Heart Association (NYHA) II heart failure (HF) or NYHA I with previous HF symptoms. METHODS AND RESULTS A proportion in state model with Monte Carlo simulation was developed to assess the costs, life years and quality-adjusted life year (QALYs) associated with CRT-ON and -OFF over a 10 year time period. Data from 262 patients in the European cohort of the REVERSE clinical trial (QRS ≥ 120 ms, left ventricular ejection fraction ≤ 40%, CRT-ON, n = 180, CRT-OFF, n = 82) were used to model all-cause mortality, change in NYHA class and resource use. EQ-5D preference weights were taken from a previous cost-effectiveness model of CRT and unit costs from national UK databases. Costs and benefits were discounted at 3.5% p.a. Extensive deterministic and probabilistic sensitivity analyses were performed. Compared with CRT-OFF, 0.94 life years or 0.80 QALYs were gained in the CRT ON group at an additional cost of €11 455, yielding an incremental cost-effectiveness ratio of €14.278 per quality-adjusted life year (QALY) gained. At a threshold of €33 000 (£30 000) per QALY gained, the probability that CRT is cost-effective is 79.6%. Cardiac resynchronization therapy becomes cost effective after ∼4.5 years. Cardiac resynchronization therapy needs only to demonstrate a modest impact on all cause mortality (hazard ratio = 0.82) in order to demonstrate cost-effectiveness. The results are robust to changes in all other parameters. CONCLUSION Cardiac resynchronization therapy is a cost-effective intervention for patients with mildly symptomatic HF and for asymptomatic patients with left ventricular dysfunction and previous HF symptoms.

EVEREST II high risk study based UK cost-effectiveness analysis of MitraClip® in patients with severe mitral regurgitation ineligible for conventional repair/replacement surgery

Abstract Objectives: To evaluate the cost-effectiveness of MitraClip, an interventional procedure for patients with chronic severe mitral regurgitation. Methods: A decision analytic model with a lifetime horizon was developed to assess the cost-effectiveness of MitraClip vs conventional medical management in patients with severe mitral regurgitation, ineligible for surgery. The analysis was performed from a UK NHS perspective and the estimates for mortality, adverse events, and cross-sectional NYHA class were obtained from the EVEREST II High Risk Study (HRS). Utility decrements were obtained from a heath technology assessment on Cardiac Resynchronization Therapy, while unit costs were obtained from national databases. The concept model was clinically validated. Costs (2011 £UK) and benefits were discounted at an annual rate of 3.5%. Results: Compared to medical management, over 2- and 10-year periods MitraClip had incremental Quality Adjusted Life Year (QALY) gains of 0.48 and 2.04, respectively. The Incremental Cost-Effectiveness Ratios for MitraClip at 2 and 10 years are £52,947 and £14,800 per QALY gained. Overall, the model was most sensitive to the choice of time horizon, the discount rate applied to benefits, the starting age of cohort, the utility decrement associated with NYHA II, and cost of the MitraClip procedure. The model was insensitive to changes in all other parameters. MitraClip was also found to be cost-effective, regardless of the modelling approach, and insensitive to the key assumptions of the procedure cost. Study limitations: The primary limitation of the analysis is the reliance on aggregate data from a modestly sized non-randomized study with a short-term follow-up period. Aligned to this was the need to extrapolate survival well beyond the study period in order to generate meaningful results. The impact of both of these limitations was explored via extensive sensitivity analyses. Conclusion: Compared to medical management, MitraClip is a cost-effective interventional procedure at conventional threshold values.

Cost-utility of transcatheter aortic valve implantation for inoperable patients with severe aortic stenosis treated by medical management: a UK cost-utility analysis based on patient-level data from the ADVANCE study

Objective To use patient-level data from the ADVANCE study to evaluate the cost-effectiveness of transcatheter aortic valve implantation (TAVI) compared to medical management (MM) in patients with severe aortic stenosis from the perspective of the UK NHS. Methods A published decision-analytic model was adapted to include information on TAVI from the ADVANCE study. Patient-level data informed the choice as well as the form of mathematical functions that were used to model all-cause mortality, health-related quality of life and hospitalisations. TAVI-related resource use protocols were based on the ADVANCE study. MM was modelled on publicly available information from the PARTNER-B study. The outcome measures were incremental cost-effectiveness ratios (ICERs) estimated at a range of time horizons with benefits expressed as quality-adjusted life-years (QALY). Extensive sensitivity/subgroup analyses were undertaken to explore the impact of uncertainty in key clinical areas. Results Using a 5-year time horizon, the ICER for the comparison of all ADVANCE to all PARTNER-B patients was £13 943 per QALY gained. For the subset of ADVANCE patients classified as high risk (Logistic EuroSCORE >20%) the ICER was £17 718 per QALY gained). The ICER was below £30 000 per QALY gained in all sensitivity analyses relating to choice of MM data source and alternative modelling approaches for key parameters. When the time horizon was extended to 10 years, all ICERs generated in all analyses were below £20 000 per QALY gained. Conclusion TAVI is highly likely to be a cost-effective treatment for patients with severe aortic stenosis.

Is transcatheter aortic valve implantation (TAVI) a cost-effective treatment in patients who are ineligible for surgical aortic valve replacement? A systematic review of economic evaluations

Abstract Objectives: Health Technology Assessment (HTA) agencies often undertake a review of economic evaluations of an intervention during an appraisal in order to identify published estimates of cost-effectiveness, to elicit comparisons with the results of their own model, and to support local reimbursement decision-making. The aim of this research is to determine whether Transcatheter Aortic Valve Implantation (TAVI) compared to medical management (MM) is cost-effective in patients ineligible for surgical aortic valve replacement (SAVR), across different jurisdictions and country-specific evaluations. Methods: A systematic review of the literature from 2007–2012 was performed in the MEDLINE, MEDLINE in-process, EMBASE, and UK NHS EED databases according to standard methods, supplemented by a search of published HTA models. All identified publications were reviewed independently by two health economists. The British Medical Journal (BMJ) 35-point checklist for economic evaluations was used to assess study reporting. To compare results, incremental cost effectiveness ratios (ICERs) were converted to 2012 dollars using purchasing power parity (PPP) techniques. Results: Six studies were identified representing five reimbursement jurisdictions (England/Wales, Scotland, the US, Canada, and Belgium) and different modeling techniques. The identified economic evaluations represent different willingness-to-pay thresholds, discount rates, medical costs, and healthcare systems. In addition, the model structures, time horizons, and cycle lengths varied. When adjusting for differences in currencies, the ICERs ranged from

The Authors' reply: Table 1

27K–

Brentuximab vedotin in relapsed/refractory Hodgkin lymphoma post-autologous stem cell transplant: a cost-effectiveness analysis in Scotland

65K per QALY gained. Conclusions: Despite notable differences in modeling approach, under the thresholds defined by using either the local threshold value or that recommended by the World Health Organization (WHO) threshold value, each study showed that TAVI was likely to be a cost-effective intervention for patients ineligible for SAVR.

Brentuximab vedotin in relapsed/refractory Hodgkin lymphoma following autologous stem cell transplant: A cost-effectiveness analysis updated with 5-year follow-up data from the pivotal trial.

Publication of all relevant data is a prerequisite to calculate more balanced incremental cost-effectiveness ratios of TAVI. The study sponsor should be more willing to share complete information on mortality, adverse events and QoL (including EQ-5D results), for both the pivotal and Continued Access trial. It is also desirable that full study results for the relevant subgroup analysis of anatomically inoperable versus medically inoperable patients are made public. As yet, after several attempts, the study sponsor has failed to provide us with this information.

Cost-Effectiveness of Ikervis® In Severe Dry Eye Disease In The Uk [Update].

Abstract Objective: To evaluate cost-effectiveness of brentuximab vedotin in patients with relapsed/refractory Hodgkin lymphoma who have received autologous stem cell transplantation, from a Scottish healthcare payer perspective. Methods: A Microsoft Excel-based partitioned survival model comprising three health states (progression-free survival [PFS], post-progression survival, and death) was developed. Relevant comparators were chemotherapy with or without radiotherapy (C/R) and C/R with intent to allogeneic hematopoietic stem cell transplantation (alloSCT). Data were obtained from the pivotal phase II single-arm trial in 102 patients (SG035-0003; NCT00848926), a systematic literature review and clinical expert opinions (where empirical evidence was unavailable). PFS and overall survival for brentuximab vedotin were estimated using 5-year follow-up data from SG035-0003, and extrapolated using event rates observed for comparator treatments from published survival data. Resource use included drug acquisition and administration; alloSCT; treatment of adverse events; and long-term follow-up. Deterministic and probabilistic sensitivity analyses were conducted to evaluate the impact of uncertainty. Results: In the base case, the incremental cost-effectiveness ratio (ICER) for brentuximab vedotin was £38,769 per quality-adjusted life year (QALY) vs C/R, whereas C/R with intent to alloSCT was dominated by brentuximab vedotin. ICERs for brentuximab vedotin generated by the deterministic sensitivity analysis ranged between £32,000–£54,000 per QALY. Including productivity benefits reduced the ICER to £28,881 per QALY. Limitations: Limitations include lack of comparative data from this single arm study and the heterogeneous population. Inconsistent baseline characteristic reporting across studies prevented complete assessment of heterogeneity and the extent of potential bias in clinical and cost-effectiveness estimates. Conclusions: Although the base case ICER is above the threshold usually applied in Scotland, it is relatively low compared with other orphan drugs, and lower than the ICER generated using a previous data cut of SG035-0003 that informed a positive recommendation from the Scottish Medicines Consortium, under its decision-making framework for assessment of ultra-orphan medicines.

Assessing Consistency in a Network Meta-Analysis to Compare Once Weekly Dulaglutide Versus Other Glp-1 Receptor Agonists in Patients with Type 2 Diabetes

19 Background: In 2015, the Scottish Medicines Consortium (SMC) made a positive recommandation for brentuximab vedotin (BV) in patients with relapsed or refractory (R/R) Hodgkin lymphoma (HL) who have received autologous stem cell transplantation (ASCT) based on 3-year follow-up data from the pivotal phase 2 single-arm trial (SG035-0003; NCT00848926). At 3-years, the incremental cost-effectiveness ratio (ICER) for brentuximab vedotin compared with chemotherapy +/- radiotherapy (C/R) was £43,731 per quality-adjusted life year (QALY). This study re-evaluated the cost-effectiveness analysis with 5-year follow-up data from the pivotal trial. METHODS A partitioned survival model was developed using a Scottish health system perspective over a lifetime time-horizon. Three health states were evaluated: progression-free survival (PFS), post-progression survival, and death. The relevant comparators were C/R, or C/R with intent to allogeneic stem cell transplantation. Clinical outcomes (PFS and overall survival [OS]) for BV were estimated based on data from the pivotal trial in 102 patients. A naïve comparison with the specified comparators was conducted using published survival data. ICERs were calculated with measures of the clinical outcomes, direct costs and QALYs. Deterministic and probabilistic sensitivity analyses were conducted to evaluate the robustness of the model. RESULTS The 5-year follow-up data reduced the base case ICER for BV from £43,731 to £38,769 per QALY versus C/R and increased the probability of cost-effectiveness. The variation in ICER for BV generated by the deterministic sensitivity analyses was also reduced resulting from reduced uncertainty in the estimation of long term clinical outcomes. CONCLUSIONS This update has strengthened the cost-effectiveness evidence for BV in patients with R/R HL post-ASCT. The 5-year follow-up has reduced the uncertainty in the long term outcomes and reduced the ICER, which is low in comparison to other treatments for orphan diseases approved by UK agencies. BV may therefore represent a cost-effective treatment option for this patient group.