Bayesian cost-effectiveness analysis for censored data: an application to antiplatelet therapy

Abstract

Objective:

Cost-effectiveness analysis (CEA) on trial-based data has played an important role in pharmacoeconomics. A regression model can be used to account for patient-level heterogeneity throughout covariates adjustment in CEA. However, the estimates from CEA could be biased if ignoring the censoring issue on effectiveness and costs. This study is to propose a regression model to account for both time-to-event effectiveness and cost.

Methods:

A bivariate regression model was proposed to analyze both effectiveness and cost simultaneously, while censored observations were also taken into account. The regression coefficients were estimated using a Bayesian approach by drawing a random sample from their posterior distribution derived from the Markov chain Monte Carlo (MCMC) method. The proposed method was illustrated using empirical data of anti-platelet therapies to the management of cardiovascular diseases for those patients with high risk of gastrointestinal (GI) bleeding, where cost-effectiveness between different therapies was analyzed under both censored and non-censored circumstances, where the effectiveness was defined as the time to re-hospitalization due to GI complications, and the cost was measured by the total drug expenditure.

Results:

Under censored circumstances, aspirin plus proton-pump inhibitors (PPIs) was considered more cost-effective than clopidogrel with/without PPIs, as shown in the cost-effectiveness acceptability curve, and clopidogrel was preferred to aspirin for a willingness-to-pay of 89 NTD for delaying 1 day to hospitalization due to GI complications.

Conclusions:

Ignoring censoring problems could possibly bias the results in CEA. This study has provided an appropriate method to conduct regression-based CEA to improve the estimation which serves its purpose for CEA concerns.

Limitations:

The normality assumption for the cost and effectiveness in the bivariate normal regression needs to be examined, and the conclusions may be biased if this assumption is violated. However, when sample size is sufficiently large, a slight deviation from normality would not be a serious problem.     

Modelling the cost-effectiveness of nevirapine triple combination therapy and dual combination therapy for the treatment of HIV disease in the United Kingdom

Summary

Recent advances in HIV antiretroviral therapy together with limited budgets have forced payers to look for evidence that new combinations provide good value for money. Using a public financing perspective, two Markov models are employed to evaluate the first-year outcomes and costs and the long-term cost-effectiveness of adding nevirapine (NVP) to dual combination therapy with zidovudine (ZDV) and didanosine (ddI) in the United Kingdom.

First-year medical care savings are estimated to be £2,122 (103.8% of NVP cost). In the longer term, NVP/ZDV/ddI therapy yields £6,186 per life year saved (costs discounted at 6%). The model is moderately sensitive only to duration of therapy effects and the therapy initiation time. These model estimates suggest that policy makers may expect to observe superior initial health outcomes and substantial medical cost savings during the first year of therapy, as well as acceptable long-term cost-effectiveness, when NVP/ZDV/ddI is used in place of dual therapy.     

Individualized cost-effectiveness analysis of patient-centered care: a case series of hospitalized patient preferences departing from practice-based guidelines

Objective: To develop cases of preference-sensitive care and analyze the individualized cost-effectiveness of respecting patient preference compared to guidelines.

Methods: Four cases were analyzed comparing patient preference to guidelines: (a) high-risk cancer patient preferring to forgo colonoscopy; (b) decubitus patient preferring to forgo air-fluidized bed use; (c) anemic patient preferring to forgo transfusion; (d) end-of-life patient requesting all resuscitative measures. Decision trees were modeled to analyze cost-effectiveness of alternative treatments that respect preference compared to guidelines in USD per quality-adjusted life year (QALY) at a $100,000/QALY willingness-to-pay threshold from patient, provider and societal perspectives.

Results: Forgoing colonoscopy dominates colonoscopy from patient, provider, and societal perspectives. Forgoing transfusion and air-fluidized bed are cost-effective from all three perspectives. Palliative care is cost-effective from provider and societal perspectives, but not from the patient perspective.

Conclusion: Prioritizing incorporation of patient preferences within guidelines holds good value and should be prioritized when developing new guidelines.     

Incorporating adherence in cost-effectiveness analyses of asthma: a systematic review

Abstract

Aims: Non-adherence is associated with poor clinical outcomes among patients with asthma. While cost-effectiveness analysis (CEA) is increasingly used to inform value assessment of the interventions, most do not take into account adherence in the analyses. This study aims to: (1) Understand the extent of studies considering adherence as part of the economic analyses, and (2) summarize the methods of incorporating adherence in the economic models.

Materials and methods: A literature search was performed from the inception to February 2018 using four databases: PubMed, EMBASE, NHS EED, and the Tufts CEA registry. Decision model-based CEA of asthma were identified. Outcomes of interest were the number of studies incorporating adherence in the economic models, and the incorporating methods. All data were extracted using a standardized data collection form.

Results: From 1,587 articles, 23 studies were decision model-based CEA of asthma, of which four CEA (17.4%) incorporated adherence in the analyses. Only the method of incorporating adherence by adjusting treatment effectiveness according to adherence levels was demonstrated in this review. Two approaches were used to derive the associations between adherence and effectiveness. The first approach was to apply a mathematical formula, developed by an expert panel, and the second was to extrapolate the associations from previous published studies. The adherence-adjusted effectiveness was then incorporated in the economic models.

Conclusions: A very low number of CEA of asthma incorporated adherence in the analyses. All the CEA adjusted treatment effectiveness according to adherence levels, applied to the economic models.     

剖宫产产妇抗菌药物使用疗程的成本-效果分析

目的:寻找广州市妇婴医院剖宫产产妇术后预防性使用抗菌药物的最佳疗程。方法:采用回顾性研究,收集和整理该院2006年6月至2007年5月493例剖宫产产妇相关资料,利用成本-效果分析方法对剖宫产产妇术后预防性使用抗菌药的不同疗程进行分析。结果:剖宫产产妇预防性使用抗菌药的疗程A组((d<3)天)、B组((3≤d<4)天)、C组((4≤d<5)天)、D组((d≥5)天)的有效率分别为:66.67%、85.12%、89.5%、85.19%;以抗菌药费用作为成本计算的成本-效果比分别为:9.21、7.22、8.62、14.32;以西药费作为成本计算的成本-效果比分别为:13.92、15.29、16.89、21.89;以住院费作为成本计算的成本-效果比分别为:61.15、67.09、66.78、79.96。结论:剖宫产产妇术后预防性使用抗菌药物,最经济、有效、合理的使用时间为术后3天(B组),增加用药天数并不能增加治疗效果,而费用却明显增加。     

A cost-effectiveness and budget impact analysis of apremilast in patients with psoriatic arthritis in Italy

Abstract

Aims: The aim of this study was to conduct a cost-effectiveness analysis, as well as a budget impact analysis, on the use of apremilast for the treatment of adult patients with psoriatic arthritis (PsA), within the Italian National Health Service (NHS).

Methods: A Markov state transition cohort model, which was adapted to the Italian context, was used to compare the costs of the currently available treatments and of the patients’ quality of life with two alternative treatment sequences, with or without apremilast as pre-biologic therapy. Moreover, a budget impact model was developed based on the population of patients treated for PsA in Italy, who can be eligible for treatment with apremilast. The eligible population was represented by adult patients with PsA who had an inadequate response to or were intolerant to previous disease-modifying antirheumatic drugs (DMARDs), for the approved indication, and for the treatment studied in the economic analytic model.

Results: This cost-effectiveness analysis estimated that the strategy of using apremilast before biologic therapy is cost-effective, with an incremental cost-effectiveness ratio of €32,263.00 per QALY gained which is slightly over the normal threshold found in other Italian economic studies, which usually considers a 40-year-period. Conversely, the budget impact analysis was conducted over 3?years, and it led to an estimated annual saving of €1.6 million, €4.6 million and €5.5 million in the first, second and third year of apremilast commercialization, respectively, for a total saving of €11.75 million in 3?years.

Limitations: Limitations of this analysis include the absence of head-to-head trials comparing therapies included in the economic model, the lack of comparative long-term data on treatment efficacy, and the assumption of complete independence between the considered response rates to therapy.

Conclusion: The use of apremilast as a first option before the use of biologic agents may represent a cost-effective treatment strategy for patients with PsA who fail to respond to, or are intolerant to, previous DMARD therapy. In addition, based on a budget impact perspective, the use of apremilast may lead to cost savings to the Italian healthcare system.     

A cost-effectiveness and budget impact analysis of apremilast in patients with psoriasis in the Italian setting

Abstract

Aims: The aim of this study was to conduct a cost-effectiveness analysis, as well as a budget impact analysis, on the use of apremilast for the treatment of adult patients with moderate-to-severe plaque psoriasis (defined as a psoriasis area severity index [PASI]?≥?10), who failed to respond to, had a contraindication to, or were intolerant to other systemic therapies, within the Italian National Health Service (NHS).

Materials and methods: A Markov state-transition cohort model adapted to the Italian context was used to compare the costs of the currently available treatments and of the patients’ quality of life with two alternative treatment sequences, with or without apremilast as pre-biologic therapy. Moreover, a budget impact model was developed based on the population of patients treated for psoriasis in Italy, who would be eligible for treatment with apremilast.

Results: Over 5?years, the cost-effectiveness analysis showed that the strategy of using apremilast before biologic therapy was dominant compared with the sequence of biologic treatments without apremilast. In addition, it is important to underline that the use of apremilast slightly increases the quality-adjusted life years gained over 5?years. Furthermore, within the budget impact analysis, the strategy including apremilast would lead to a saving of €16 million within 3?years. Savings would mainly be related to a reduction in pharmaceutical spending, hospital admissions and other drug administration-related costs.

Conclusion: These models proved to be robust to variation in parameters and it suggested that the use of apremilast would lead to savings to the Italian healthcare system with potential benefits in terms of patients’ quality of life.     

Prasugrel vs clopidogrel in patients with acute coronary syndrome undergoing percutaneous coronary intervention: a model-based cost-effectiveness analysis for Germany,Sweden, the Netherlands,and Turkey

Abstract

Objective:

To evaluate the long-term cost-effectiveness of 12-months treatment with prasugrel vs clopidogrel from four European healthcare systems’ perspectives (Germany, Sweden, the Netherlands, and Turkey).

Methods:

In the TRITON-TIMI 38 trial, patients with an acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI) were treated with prasugrel or clopidogrel. Prasugrel reduced the composite end-point (cardiovascular death, MI, or stroke), but increased TIMI major bleeding. A Markov model was constructed to facilitate a lifetime horizon for the analysis. A series of risk equations constructed using individual patient data from TRITON-TIMI 38 was used to estimate risks of clinical events. Quality-adjusted life-years (QALYs) were derived by weighting survival time by estimates of health-related quality-of-life. Incremental cost-effectiveness is presented based on differences in treatments’ mean costs and QALYs for the licensed population in TRITON-TIMI 38, and the sub-groups of UA-NSTEMI, STEMI, diabetes, and the ‘core clinical cohort’ (<75 years, ≥60?kg, no history of stroke or TIA).

Results:

Mean cost of study drug was €364 (Turkey) to €818 (Germany) higher for prasugrel vs clopidogrel. Rehospitalization costs at 12 months were lower for prasugrel due to reduced rates of revascularization, although hospitalization costs beyond 12 months were higher due to longer life expectancy associated with lower rates of non-fatal MI in the prasugrel group. The incremental cost per QALY saved with prasugrel in the licensed population ranged from €6520 (for Sweden) to €14,350 for (Germany). Prasugrel’s cost per QALY was more favourable still in the STEMI and diabetes sub-groups of the licensed population.

Limitations:

Probabilistic analyses of the whole trial population is impractical due to the number of individual patient profiles over which population level results are calculated.

Conclusion:

Among patients undergoing PCI for ACS, treatment with prasugrel compared with clopidogrel resulted in favourable cost-effectiveness profiles from these healthcare systems’ perspectives.     

Costs of bleeds relating to acute coronary syndrome therapies

Objective: To estimate the costs to manage selected types of bleeding complications in patients with acute coronary syndrome (ACS) treated with antithrombotics, including antiplatelet, and fibrinolytic therapies: decrease in haemoglobin >3 g/dL, puncture site, and bleeding requiring transfusion of blood products.

Methods: Retrospective chart reviews of ACS patients experiencing decrease in Hb, puncture site, or bleeding requiring transfusion were conducted in hospitals in France, Germany, Italy, Spain and Sweden to determine the total length of stay (LOS), stay post-bleeding, procedures to identify the extent of bleeding, number and types of transfusion products, patient demographics, reason for hospital admission and disposition upon discharge. Country-specific costs were applied to estimate the average cost per patient by type of bleeding event.

Results: Records of 158 ACS patients with the bleeding complications were examined (26.9% decrease in Hb, 35.5% puncture site, and 37.8% transfusion). The average LOS was 10.6 days for decreasing Hb, 7.7 days for puncture site bleeding, and 11.3 days for patients receiving transfusions due to these bleeding events. The average costs per patient ranged between €3,986 and €10,252. The LOS ranged widely both within and across countries.

Limitations: The study has a small sample size and costs are confounded by co-morbidities.

Conclusions: The estimated costs for decreasing Hb, puncture site bleeding and bleeding resulting in transfusions provide a tool for researchers to conduct economic analyses of bleeding events associated with therapies for ACS.     

On the long run effect of public capital on aggregate output: Estimation and sensitivity analysis

We undertake a sensitivity analysis of the productivity of public capital under the aggregate production function approach. Several proxies are used for the private inputs and for public capital, several dummy variables are included to adjust for energy price shocks, newly revised data is studied, and Stock and Watson's dynamic OLS estimator is used. Our main results are that the productivity of public capital depends critically on the proxies used, the effects are typically smaller than the early estimates, and omitting the oil price shocks introduces significant upward bias in the measured productivity of public capital. First version received: January 1998/final version received: June 1999     

L-carnitine in the management of patients after acute myocardial infarction: a cost effectiveness analysis in Italy

Summary

The prevalence of acute myocardial infarction (AMI) is estimated at 500,000 individuals in the Italian population; the annual incidence can be crudely estimated at 100,000 events. This represents a major healthcare problem and generates questions about the rational allocation of public resources devoted to healthcare, since in Italy there is a National Health Service. We focused on modelling the possible economic consequences of adding L-carnitine administration to the standard care of AMI patients in Italy, by extrapolating the results obtained in the SAVE trial and matching entry criteria from the CEDIM and SAVE studies. The cost-effectiveness ratios were explored using different assumptions of the effectiveness and cost of the intervention under analysis. In our base case, administering L-carnitine had an Incremental Cost/Effectiveness Ratio of 28.2 and 22.2 million Lira per life year saved (LYS), respectively, depending on whether discounted or non-discounted benefits were used in this model. The results were sensitive to both the cost and effectiveness of L-carnitine.     

Investment cash flow sensitivity and financial constraint: a cluster analysis approach

This article sheds light on the mixed empirical evidence concerning financial constraint and investment sensitivity to cash flow. The literature suggests that measuring financial constraint is far from straightforward, and we therefore propose a cluster analysis procedure to identify unambiguous groups of constrained firms. We found the investment results to be highly sensitive to cash flow for financial constraint firms. Moreover, in line with previous research, our results showed that the traditional criteria used to identify financially constrained firms led to ambiguous interpretations. Overall, our results propose that the cluster analysis can be used to encompass the various single-criterion approaches, thereby providing a finer measurement of the financial constraint construct and deeper insight into the relationship between investment sensitivity to cash flow and financial constraint.     

Cost of care for new versus recurrent acute coronary syndrome patients

Abstract

Introduction: The economic burden of acute coronary syndrome (ACS) continues long after the acute event has resolved. This study compared ACS-related costs between new and recurrent ACS patients using retrospective claims data from a large US health plan.

Methods: Patients with ACS were identified using ICD-9 codes between the 1st January 2001 and the 30th June 2003. The first diagnosis was defined as the index event. Patient claims were examined 1 year before, and up to 1 year after, the index event. Hospitalisations, revascularisations and costs for new and recurrent cohorts were compared. Multivariate regression was used to examine cost predictors.

Results: In total, 15,508 patients were identified, 82% had new ACS. The new ACS cohort was more likely to have myocardial infarction and be hospitalised for the index event, leading to higher index event costs. However, the recurrent ACS cohort had more re-hospitalisations, longer lengths of inpatient stay and a higher probability of revascularisation during follow-up. The index event cost per patient and per patient-month was higher for new ACS patients. After adjusting for confounding factors, multivariate cost models revealed annualised follow-up medical costs were 9.9% higher (p=0.017) and annualised follow-up pharmacy costs were 8.3% higher (p≤0.0001) for the new ACS cohort.

Conclusion: Newly diagnosed ACS patients had significantly higher adjusted costs in the year following the index event, but recurrent ACS patients still experienced high medical costs. More emphasis by providers and patients on adherence to treatment guidelines may be one step to improving patient outcomes.

*This paper was presented in part at the Academy of Managed Care Pharmacy Annual Meeting, 7th April 2006.     

Rivaroxaban for non-valvular atrial fibrillation and venous thromboembolism in the Netherlands: a real-world data based cost-effectiveness analysis

Background: Non-vitamin K antagonist oral anticoagulants (NOACs) have been included in international guidelines as important alternatives to vitamin K antagonists (VKAs) for the treatment of venous thromboembolism (VTE) and stroke prevention in non-valvular atrial fibrillation (NVAF). Meanwhile, in the Netherlands, NOACs are widely used next to VKAs. The objective of this study is to estimate the cost-effectiveness of treatment with rivaroxaban compared to VKAs in NVAF and VTE patients in the Netherlands, using data from international prospective observational phase IV studies.

Methods: Two models were developed to represent NVAF and VTE patients, populated with patients from the XANTUS (NCT01606995) and XALIA (NCT01619007) international prospective observational studies. The 1-year cost-effectiveness of rivaroxaban use, compared to VKAs, was explored in a population consisting of NVAF and VTE patients (base case) as well as for four scenarios with sub-populations: NVAF patients only, VTE patients only, NVAF patients with unstable international normalized ratio (INR), and NVAF patients using an INR self-measuring device.

Results: In the base case, rivaroxaban saved €72,350 and gained 21 quality-adjusted life-years (QALYs) in a simulation of 2,000 patients over the use of VKAs. Ergo, rivaroxaban was dominant over VKAs. The probabilistic sensitivity analysis showed a probability of 85% for rivaroxaban being dominant and 100% at a willingness-to-pay threshold of €20,000/QALY. Rivaroxaban appeared to be dominant in all scenarios as well, except for the NVAF-patients-only scenario where the incremental cost-effectiveness ratio (ICER) was €157/QALY.

Conclusions: In patients with NVAF or VTE, rivaroxaban treatment is likely to be cost-effective and a potentially cost-saving alternative to VKA in the Netherlands.     

Comparison of costs and outcomes of dapagliflozin with other glucose-lowering therapy classes added to metformin using a short-term cost-effectiveness model in the US setting

Objective: To compare 1-year costs and benefits of dapagliflozin (DAPA), a sodium-glucose cotransporter-2 (SGLT-2) inhibitor, with those of other treatments for type 2 diabetes (T2D), such as glucagon-like peptide-1 receptor agonists (GLP-1RAs), sulfonylureas (SUs), thiazolidinediones (TZDs), and dipeptidyl peptidase-4 inhibitors (DPP-4i), all combined with metformin.

Methods: A short-term decision-analytic model with a 1-year time horizon was developed from a payer’s perspective in the United States setting. Costs and benefits associated with four clinical end-points (glycated hemoglobin [A1C], body weight, systolic blood pressure [SBP], and risk of hypoglycemia) were evaluated in the analysis. The impact of DAPA and other glucose-lowering therapy classes on these clinical end-points was estimated from a network meta-analysis (NMA). Data for costs and quality-adjusted life-years (QALYs) associated with a per-unit change in these clinical end-points were taken from published literature. Drug prices were taken from an annual wholesale price list. All costs were inflation-adjusted to December 2016 costs using the medical care component of the consumer price index. Total costs (both medical and drug costs), total QALYs, and incremental cost-effectiveness ratios (ICERs) were estimated. Sensitivity analyses (SA) were performed to explore uncertainty in the inputs. To assess face validity, results from the short-term model were compared with long-term models published for these drugs.

Results: The total annual medical cost for DAPA was less than that for GLP-1RA ($186 less), DPP-4i ($1,142 less), SU ($2,474 less), and TZD ($1,640 less). Treatment with DAPA resulted in an average QALY gain of 0.0107, 0.0587, 0.1137, and 0.0715 per treated patient when compared with GLP-1RA, DPP-4i, SU, and TZD, respectively. ICERs for DAPA vs SU and TZD were $19,005 and $25,835, respectively. DAPA was a cost-saving option when compared with GLP-1RAs and DPP-4is. Among all four clinical end-points, change in weight had the greatest impact on total annual costs and ICERS. Sensitivity analysis showed that results were robust, and results from the short-term model were found to be similar to those of published long-term models.

Conclusion: This analysis showed that DAPA was cost-saving compared with GLP-1RA and DPP-4i, and cost-effective compared with SU and TZD in the US setting over 1 year. Furthermore, the results suggest that, among the four composite clinical end-points, change in weight and SBP had an impact on cost-effectiveness results.     

Mirabegron for the treatment of overactive bladder: cost-effectiveness from US commercial health-plan and Medicare Advantage perspectives

Background and objective: The first class of oral pharmacologic treatments for overactive bladder (OAB) are antimuscarinics that are associated with poor persistence, anticholinergic adverse events, and increased anticholinergic burden (ACB) with risk of cognitive impairment. Mirabegron, a β3-adrenoceptor agonist, is an oral treatment that does not contribute to ACB and has early evidence of improved persistence. The objective of the analysis was to assess the cost-effectiveness of mirabegron for OAB vs six antimuscarinics in the US.

Methods: A Markov state-transition model assessed US commercial health-plan and Medicare Advantage perspectives over a 3-year time horizon in an OAB patient population. Transition probabilities between five micturition and five incontinence severity states were derived from a network meta-analysis of 44 trials of oral OAB treatments. Therapy beginning with an oral OAB agent could discontinue or switch to another oral agent and could be followed by tibial nerve stimulation, sacral neuromodulation, or onabotulinumtoxinA. The primary outcome was cost per quality-adjusted life year (QALY). Utilities were mapped from incontinence and micturition frequencies as well as demographics. Based on analysis of data from a large healthcare system, elevated ACB was associated with increased healthcare utilization and probability of cognitive impairment.

Results: From both commercial and Medicare Advantage perspectives, mirabegron was the most clinically effective treatment, while oxybutynin was the least expensive. Tolterodine immediate release (IR) was also on the cost-effectiveness frontier. The analysis estimated costs per QALY of $59,690 and $66,347 for mirabegron from commercial health plan and Medicare Advantage perspectives, respectively, compared to tolterodine IR. Other antimuscarinics were dominated.

Conclusions: This analysis estimated that mirabegron is a cost-effective treatment for OAB from US commercial health plan and Medicare Advantage perspectives, due to fewer projected adverse events and comorbidities, and data suggesting better persistence.     

Cost effectiveness of benralizumab for severe,uncontrolled oral corticosteroid–dependent asthma in Sweden

Abstract

Aim: We investigated cost effectiveness of benralizumab vs. standard of care (SOC) plus oral corticosteroids (OCS) for patients with severe, eosinophilic OCS-dependent asthma in Sweden.

Materials and methods: A three-state, cohort-based Markov model of data from three Phase III benralizumab clinical trials (ZONDA [NCT02075255], SIROCCO [NCT01928771], and CALIMA [NCT01914757]) was used to assess the incremental cost-effectiveness ratio of benralizumab vs. SOC plus OCS. Health outcomes were estimated in terms of quality-adjusted life-years (QALYs). The model included costs and disutilities associated with extrapolated OCS-related adverse events. Patients with severe asthma were defined as those receiving OCS ≥5?mg/day.

Results: Benralizumab demonstrated a cost-effectiveness ratio vs. SOC plus OCS of 2018 Swedish Kronor (SEK) 366,855 (€34,127) per QALY gained, based on increases of 1.33 QALYs and SEK 488,742 (€45,344) per patient. Benralizumab treatment costs contributed most to incremental costs. The probability of benralizumab’s being cost-effective with willingness-to-pay (WTP) thresholds between SEK 429,972 (€40,000) and SEK 752,452 (€70,000) ranged from 75% to 99%.

Limitations: Potential limitations of these analyses include the use of combined data from three different clinical trials, a one-way sensitivity analysis that did not include mortality and transition estimates, and Observational & Pragmatic Research Institute (OPRI) data from the UK as a proxy of the Swedish health care system.

Conclusions: The results of these analyses demonstrate that benralizumab has a high probability of being cost-effective compared with SOC plus OCS for a subgroup of patients with severe, eosinophilic asthma receiving regular OCS treatment and may support clinicians, payers and patients in making treatment decisions.     

Economic analysis of the use of contrast media during percutaneous coronary interventions in France and Spain

Summary

The iso-osmolar contrast medium iodixanol (Visipaque?; GE Healthcare, UK) has been reported to reduce the risk of major adverse cardiac events and to have a higher success rate when used during percutaneous coronary intervention (PCI) compared with the ionic low-osmolar contrast medium ioxaglate (Hexabrix; Guerbet, France) for patients at risk of complications. This study assessed to what extent these clinical benefits translate into economic benefits for patients undergoing PCI in France and Spain using a decision tree model. Clinical data were derived from the COURT and VIP trials. Medical resource use data were obtained from panels of French and Spanish interventional cardiologists. Resource use was converted to costs using country-specific tariffs. The study results suggest that using iodixanol rather than ioxaglate confers an economic benefit in addition to the reported clinical benefit in high-risk patients undergoing PCI in both countries. For low-risk patients, iodixanol may be regarded as cost-effective when relating the extra cost to the small reported increase in angiographic success.     

Economic evaluation of rituximab in addition to standard of care chemotherapy for adult patients with acute lymphoblastic leukemia

Aims: Acute lymphoblastic leukemia (ALL) is an aggressive form of leukemia with a poor prognosis in adult patients. The addition of the monoclonal antibody rituximab to standard chemotherapy has been shown to improve survival in adults with ALL. However, it is unknown whether the addition of rituximab is cost-effective. The objective was to determine the economic impact of rituximab in addition to standard of care (SOC) chemotherapy vs SOC alone in newly-diagnosed Philadelphia chromosome-negative, CD20-positive, B-cell precursor ALL.

Methods: A decision analytic model was constructed, based upon the Canadian healthcare system. It included the following health states over a lifetime horizon (max ≈60 years): event-free survival (EFS), relapsed/resistant disease, cure, and death. SOC was either hyper-CVAD or the Dana Farber Cancer Institute (DFCI) ALL consortium. EFS, overall survival, and serious adverse event (SAE) rates were derived from a large randomized controlled trial. Costs of the model included: first-line treatment and administration, disease management, second-line and third-line treatment and administration, palliative care, and SAE-related treatments. Inputs were sourced from provincial and national public data, the literature, and cancer agency input.

Results: Quality-adjusted life-years (QALYs) increased by 2.20 QALYs with rituximab in addition to SOC. The resulting mean Incremental Cost-Effectiveness Ratio (ICER) was C$21,828/QALY. At a willingness-to-pay threshold of C$100,000/QALY, the probability of being cost-effective was 98%. Decision outcomes were robust to the probabilistic and deterministic sensitivity analyses, including the SOC backbone as either hyper-CVAD or DFCI.

Limitations: The results of this analysis are limited by generalizability of the chemotherapy backbone to Canadian practice.

Conclusions: For adults with ALL, rituximab in addition to SOC was found to be a cost-effective intervention, compared to SOC alone. The addition of rituximab is associated with increased life years and increased QALYs at a reasonable incremental cost.     

Cost-effectiveness analysis of bariatric surgery for morbid obesity in Belgium

Aims: This study presents the cost-effectiveness analysis of bariatric surgery in Belgium from a third-party payer perspective for a lifetime and 10-year horizon.

Materials and methods: A decision analytic model incorporating Markov process was developed to compare the cost-effectiveness of gastric bypass, sleeve gastrectomy, and adjustable gastric banding against conventional medical management (CMM). In the model, patients could undergo surgery, or experience post-surgery complications, type 2 diabetes, cardiovascular diseases, or die. Transition probabilities, costs, and utilities were derived from the literature. The impact of different surgical methods on body mass index (BMI) level in the base-case analysis was informed by the Scandinavian Obesity Surgery Registry and the Swedish Obese Subject (SOS) study. Healthcare resource use and costs were obtained from Belgian sources. A base-case analysis was performed for the population, the characteristics of which were obtained from surgery candidates in Belgium.

Results: In the base-case analysis over a 10-year time horizon, the increment in quality-adjusted life-years (QALYs) gained from bariatric surgery vs CMM was 1.4 per patient, whereas the incremental cost was €3,788, leading to an incremental cost-effectiveness ratio (ICER) of €2,809 per QALY. Over a lifetime, bariatric surgery produced savings of €9,332, an additional 1.1 life years and 5.0 QALYs. Bariatric surgery was cost-effective at 10 years post-surgery and dominant over conventional management over a lifetime horizon.

Limitations: The model did not include the whole scope of obesity-related complications, and also did not account for variation in surgery outcomes for different populations of diabetic patients. Also, the data about management of patients after surgery was based on assumptions and the opinion of a clinical expert.

Conclusions: It was demonstrated that a current mix of bariatric surgery methods was cost-effective at 10 years post-surgery and cost-saving over the lifetime of the Belgian patient cohort considered in this analysis.