Stuart Mealing

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.

Individual patient data network meta-analysis of mortality effects of implantable cardiac devices

Objective Implantable cardioverter defibrillators (ICD), cardiac resynchronisation therapy pacemakers (CRT-P) and the combination therapy (CRT-D) have been shown to reduce all-cause mortality compared with medical therapy alone in patients with heart failure and reduced EF. Our aim was to synthesise data from major randomised controlled trials to estimate the comparative mortality effects of these devices and how these vary according to patients’ characteristics. Methods Data from 13 randomised trials (12 638 patients) were provided by medical technology companies. Individual patient data were synthesised using network meta-analysis. Results Unadjusted analyses found CRT-D to be the most effective treatment (reduction in rate of death vs medical therapy: 42% (95% credible interval: 32–50%), followed by ICD (29% (20–37%)) and CRT-P (28% (15–40%)). CRT-D reduced mortality compared with CRT-P (19% (1–33%)) and ICD (18% (7–28%)). QRS duration, left bundle branch block (LBBB) morphology, age and gender were included as predictors of benefit in the final adjusted model. In this model, CRT-D reduced mortality in all subgroups (range: 53% (34–66%) to 28% (−1% to 49%)). Patients with QRS duration ≥150 ms, LBBB morphology and female gender benefited more from CRT-P and CRT-D. Men and those <60 years benefited more from ICD. Conclusions These data provide estimates for the mortality benefits of device therapy conditional upon multiple patient characteristics. They can be used to estimate an individual patients expected relative benefit and thus inform shared decision making. Clinical guidelines should discuss age and gender as predictors of device benefits.

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.

The relative efficacy of imatinib, dasatinib and nilotinib for newly diagnosed chronic myeloid leukemia: a systematic review and network meta-analysis

ObjectivesDasatinib 100 mg daily and nilotinib 600/800 mg daily have been compared to imatinib as first line treatments for CML in two recent randomised studies. However, no head to head evidence exists of the relative efficacy of dasatinib and nilotinib.MethodsWe conducted a systematic literature review and used the data extracted to perform an indirect comparison meta-analysis of the three interventions.ResultsData from eight clinical studies (3,520 individuals) were included, all of which were of good quality (low risk of bias). At six months, the odds of complete cytogenetic response (CCyR) for dasatinib and nilotinib were approximately three times those for imatinib (range 2.77 to 3.06, all values not significant). At twelve months datatinib and nilotinib were significantly better than imatinib for both CCyR and major molecular response (MMR) (CCyR odds range 2.06 to 2.41, MMR odds range 2.09 to 2.87). At eighteen months dasatinib and nilotinib were again significantly better in terms of CCyR than imatinib (response odds 1.55 to 2.01). When dasatinib and nilotinib were compared to each other, for both clinical endpoints at all time points the response odds were not significantly different.ConclusionsOn the basis of a systematic review of the current literature base, dasatinib 100 mg, nilotinib 600 mg and nilotinib 800 mg should be viewed as equivalent in terms of complete cytogenetic and major molecular response.

Comparative efficacy of tyrosine kinase inhibitor treatments in the third-line setting, for chronic-phase chronic myelogenous leukemia after failure of second-generation tyrosine kinase inhibitors

We compared the efficacy of ponatinib and second-generation tyrosine kinase inhibitors (2G-TKIs: bosutinib, dasatinib, and nilotinib) in chronic phase CML resistant/intolerant to ≥1 prior 2G-TKI. Estimated probabilities of CCyR with 2G-TKI ranged from 22% to 26%, compared with 60% (95% CrI 52-68%) with ponatinib. The estimated probability of ponatinib providing higher response rate than all other included treatments was 99% (CCyR) and 97% (MCyR). Use of further 2G-TKI may provide limited benefit in CP-CML patients resistant/intolerant to prior 2G-TKI treatment. Compared with 2G-TKIs, ponatinib is estimated to provide substantially higher probability of achieving CCyR and MCyR; safety was not compared.

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

Long-Term Extrapolation of Clinical Benefits Among Patients With Mild Heart Failure Receiving Cardiac Resynchronization Therapy: Analysis of the 5-Year Follow-Up From the REVERSE Study

27K–

Cost-effectiveness of implantable cardiac devices in patients with systolic heart failure

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.