Bendamustine-rituximab: a cost-utility analysis in first-line treatment of indolent non-Hodgkin’s lymphoma in England and Wales

Objective:

To evaluate the cost-effectiveness of bendamustine-rituximab (B-R) compared with CHOP-R (cyclophosphamide, doxorubicin, vincristine, prednisone, rituximab) and CVP-R (cyclophosphamide, vincristine, prednisone, rituximab) as first-line treatment for patients with advanced indolent non-Hodgkin’s lymphoma (NHL).

Methods:

A patient-level simulation was adapted from the model used by the University of Sheffield School of Health and Related Research (ScHARR) in a health technology appraisal of rituximab for first-line treatment of follicular lymphoma. This approach allowed modelling of the complex treatment pathways in indolent NHL. Data from a Phase 3 randomized, open-label trial were used to compare B-R with CHOP-R. The relative efficacy of CHOP-R and CVP-R was estimated using an indirect treatment comparison similar to the original ScHARR approach. The analysis was conducted from the perspective of the National Health Service in England and Wales, using a lifetime time horizon. A number of one-way sensitivity and scenario analyses were conducted, including one using recently published data comparing CVP-R with CHOP-R.

Results:

The deterministic incremental cost-effectiveness ratio (ICER) was £5249 per quality adjusted life year (QALY) for B-R vs CHOP-R, and £8092 per QALY for B-R vs CVP-R. The alternative scenario using direct data comparing CVP-R with CHOP-R approximately halved the ICER for B-R vs CVP-R to £4733. Owing to its better toxicity profile, B-R reduced the cost of treating adverse events by over £1000 per patient vs CHOP-R.

Limitations:

The main limitations were: immaturity of overall survival data from the Phase 3 trial; reliance on quality-of-life data from previous health technology appraisals (as this was not collected in the trial); and a lack of direct evidence or a network of connected evidence comparing B-R with CVP-R.

Conclusions:

The ICERs for B-R vs CHOP-R and CVP-R were considerably below the thresholds normally regarded as cost-effective in England and Wales (£20,000–30,000 per QALY).     

Cost-effectiveness of pembrolizumab versus brentuximab vedotin for patients with relapsed or refractory classical Hodgkin’s lymphoma: a United States payer perspective

Aims: Patients with classical Hodgkin’s lymphoma (cHL) who have relapsed after or are ineligible for autologous stem cell transplantation (ASCT) have limited treatment options and generally a poor prognosis. Pembrolizumab was recently approved in the US for the treatment of such patients having demonstrated clinical benefit and tolerability in relapsed/refractory cHL; however, the cost-effectiveness of pembrolizumab in this population is currently unknown.

Materials and methods: A three-state Markov model (progression-free [PF], progressed disease, and death) was developed to assess the cost-effectiveness of pembrolizumab (200?mg) vs brentuximab vedotin (BV; 1.8?mg/kg) in patients with relapsed/refractory cHL after ASCT who have not received BV post-ASCT over a 20-year time horizon from a US payer perspective. PF survival was modeled using a naïve indirect treatment comparison of data from KEYNOTE-087 and the SG035-003 trial. Post-progression survival was modeled using data from published literature. Costs (drug acquisition and administration, disease management, subsequent treatment, and adverse events) and outcomes were discounted at an annual rate of 3.0%. Uncertainty surrounding cost-effectiveness was assessed via probabilistic, deterministic, and scenario analyses.

Results: In the base case, pembrolizumab was predicted to yield an additional 0.574 life-years (LYs) and 0.500 quality-adjusted life-years (QALYs) vs BV and cost savings of $63,278. Drug acquisition costs were the biggest driver of incremental costs between strategies. Pembrolizumab had a 99.6% probability of being cost-effective compared with BV at a willingness-to-pay threshold of $20,000/QALY and dominated BV in all scenarios tested.

Limitations: The analysis was subject to potential bias due to the use of a naïve indirect treatment comparison and, given the current immaturity of OS in KEYNOTE-087, PPS was assumed equivalent across both treatments.

Conclusion: Pembrolizumab is a cost-effective alternative to BV for patients with relapsed/refractory cHL after ASCT.     

Healthcare costs for Crohn’s disease patients treated with infliximab: a propensity weighted comparison of the effects of treatment adherence

Objective:

The objective for the research was to evaluate the direct healthcare costs for Crohn’s disease (CD) patients categorized by adherence status.

Methods:

Adult patients with ≥1 claim for infliximab and ≥2 claims for CD who were continuously insured for 12 months before and after their first infliximab infusion (index date) were identified in a 2006–2009 US managed care database. Patients were excluded if they had rheumatoid arthritis claims, received infliximab billed as a pharmacy benefit, or received another biologic drug. Patients were categorized as being either adherent or intermittently adherent to infliximab using a pre-defined algorithm. Total and component direct costs, CD-related costs, rates of surgery, and days of hospitalization were estimated for the 360-day post-index period. Propensity weighted generalized linear models were used to adjust the cost estimates for potential confounding variables.

Results:

The total propensity weighted cost for infliximab adherent patients was $40,425 (95% CI?=?[$38,686, $42,242]), compared to $41,082 (95% CI?=?[$38,163, $44,223]) for the intermittently adherent (p?=?0.71). However, adherent patients had lower total direct medical costs, exclusive of infliximab, that were $13,097 (95% CI?=?[$12,141, $14,127]) compared with $20,068 (95% CI?=?[$17,676, $22,784]) for intermittently adherent patients as a result of substantially lower hospital and outpatient costs (p?Conclusions:

Greater drug-related costs for infliximab adherent patients were offset by lower costs from hospitalization and outpatient visits. These findings indicate that adherent patients have improved clinical outcomes, at a similar aggregate cost, than patients who are only intermittently adherent to therapy.     

Balancing the risk of ‘Lazearian’ interrupters and the benefits of educational and social peers: tracing parental preferences for class-size reduction

Using Danish survey data from a choice experiment, parental preferences for class-size reduction are estimated. While parents with children in large classes are willing to pay for class-size reduction, parents with children in small classes are reluctant and even express negative utility for further class-size reduction. We interpret this as parents balancing the risk of ‘Lazearian’ interrupters and the benefits of educational and social peers when forming their preferences for class size.     

The cost-effectiveness of dulaglutide versus liraglutide for the treatment of type 2 diabetes mellitus in Spain in patients with BMI ≥30 kg/m2

Objective: Dulaglutide 1.5?mg once weekly is a novel glucagon-like peptide 1 (GLP-1) receptor agonist, for the treatment of type two diabetes mellitus (T2DM). The objective was to estimate the cost-effectiveness of dulaglutide once weekly vs liraglutide 1.8?mg once daily for the treatment of T2DM in Spain in patients with a BMI ≥30?kg/m².

Methods: The IMS CORE Diabetes Model (CDM) was used to estimate costs and outcomes from the perspective of Spanish National Health System, capturing relevant direct medical costs over a lifetime time horizon. Comparative safety and efficacy data were derived from direct comparison of dulaglutide 1.5?mg vs liraglutide 1.8?mg from the AWARD-6 trial in patients with a body mass index (BMI) ≥30?kg/m². All patients were assumed to remain on treatment for 2 years before switching treatment to basal insulin at a daily dose of 40?IU. One-way sensitivity analyses (OWSA) and probabilistic sensitivity analyses (PSA) were conducted to explore the sensitivity of the model to plausible variations in key parameters and uncertainty of model inputs.

Results: Under base case assumptions, dulaglutide 1.5?mg was less costly and more effective vs liraglutide 1.8?mg (total lifetime costs €108,489 vs €109,653; total QALYS 10.281 vs 10.259). OWSA demonstrated that dulaglutide 1.5?mg remained dominant given plausible variations in key input parameters. Results of the PSA were consistent with base case results.

Limitations: Primary limitations of the analysis are common to other cost-effectiveness analyses of chronic diseases like T2DM and include the extrapolation of short-term clinical data to the lifetime time horizon and uncertainty around optimum treatment durations.

Conclusion: The model found that dulaglutide 1.5?mg was more effective and less costly than liraglutide 1.8?mg for the treatment of T2DM in Spain. Findings were robust to plausible variations in inputs. Based on these results, dulaglutide may result in cost savings to the Spanish National Health System.     

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.     

On the assessment of the performance in earnings management for the banking industry: the case of China’s banks

Earnings management is popular in the banking industry. Earnings can be manipulated by discretionary loan loss provisions (DLLP). Analysing the trajectories of banks’ DLLP (i.e. their change in DLLP over time) is an effective way to assess the performance in earnings management for the banking industry, but seems not to have been addressed in the earnings management literature. In this study, we analyse the trajectories of DLLP with the yearly data from 2007 through 2012 for four types of banks in China. The results have indicated that state-owned banks, policy banks and city commercial banks seem to manage earnings well. Cautionary notes about bank risks are provided.     

Cost and outcomes associated with rivaroxaban vs enoxaparin for the prevention of postsurgical venous thromboembolism from a US payer’s perspective

Abstract

Objective:

The objective of this analysis was the evaluation of the outcomes and costs associated with rivaroxaban and enoxaparin for the prevention of postsurgical venous thromboembolism (VTE) in patients undergoing total hip replacement (THR) and total knee replacement (TKR) from the US payer perspective.

Methods:

VTE event rates have been reported in three Phase III clinical trials that compared rivaroxaban and enoxaparin for VTE prevention after orthopedic surgery during the prophylaxis (≤35 days for THR patients and 10–14 days for TKR patients) and post-prophylaxis periods (≤90 days following surgery). These data were used in this decision-analytic model to estimate and compare health outcomes and costs associated with rivaroxaban and enoxaparin. The base-case analysis considered the number and costs of symptomatic VTE events during the prophylaxis period only. A 90-day horizon was considered in the sensitivity analysis.

Results:

Following THR, when extended durations of prophylaxis (35 days) were compared, rivaroxaban was associated with lower costs than enoxaparin, with total saving costs of $695/patient. When an extended duration of rivaroxaban prophylaxis (35 days) was compared with a short duration (10–14 days) of enoxaparin prophylaxis, rivaroxaban was estimated to prevent 9.9 additional symptomatic VTE events per 1000 patients, while saving $244/patient (rate/1000 patients). In the TKR population, short duration of rivaroxaban prophylaxis was estimated to prevent 13.1 additional symptomatic VTE events per 1000 patients. It was also less costly than short duration enoxaparin prophylaxis, with a saving of $411/patient (rate/1000 patients).

Limitations:

Only statistically significant differences were captured in the base-case economic analysis, and, therefore, differences in pulmonary embolism (PE) and bleeding events were not captured.

Conclusions:

In this model, rivaroxaban reduced total treatment payer costs vs enoxaparin for the prevention of VTE in THR or TKR patients.     

The macroeconomics of the quiet revolution: Understanding the implications of the rise in women’s participation for economic growth and inequality

We study the impact of the rise in female labor supply on the economic performance of the United States over the period 1967–2002 through the lens of a calibrated structural model. The model features all the key forces behind the increase in female participation (the “Quiet Revolution”): (1) the decline in marriage rates, (2) the narrowing gender wage gap, (3) the preference (or cultural) shift towards market work, and (4) the change in women’s bargaining power within the household. We find that preference shifts and the rise in relative wages of women were the most important driving forces behind rising women’s participation, while changes in marriage patterns have also had a sizeable effect. We conclude that half of the growth in US earnings per capita over this period can be traced to growth in female labor supply. We also find that the rise in female labor supply has had offsetting effects on income inequality and, therefore, its overall role has been negligible relative to skill-biased demand shifts and rising residual wage volatility.     

Specific investment,relational governance and cooperation risk: from the perspective of farmers in China’s “Company+Farmers” alliance

The ‘Company+ Farmers’ alliance is the main organization for China’s agricultural industrialization management. Based on the survey data of farmers cooperating with companies in Guangdong and Jiangxi Provinces, this article explores the relationship among farmers’ specific investment, the relational governance of the alliance and farmers’ cooperation risk. The results show that the relational governance of the alliance can be divided into cognitive relational governance and coordinated relational governance. Among these types, cognitive relational governance can significantly promote farmers’ specific investment. However, with the increase in farmers’ specific investment, farmers’ cooperation risk is significantly improved, and the coordinated relational governance can significantly enhance the role of farmers’ material-specific investment in promoting cooperation risk. Therefore, agricultural enterprises can use cognitive relational governance to encourage farmers’ specific investment, and the specific investment of farmers must rely on a contract governance mechanism.     

Healthcare resource utilization in patients receiving idarucizumab for reversal of dabigatran anticoagulation due to major bleeding,urgent surgery,or procedural interventions: interim results from the RE-VERSE AD™ study

Aims: Patients treated with anticoagulants may experience serious bleeding or require urgent surgery or intervention, and may benefit from rapid anticoagulant reversal. This exploratory analysis assessed healthcare resource utilization (HCRU) in patients treated with idarucizumab, a specific reversal agent for dabigatran etexilate.

Materials and methods: RE-VERSE AD? (NCT02104947), a prospective, multi-center open-label study, is evaluating idarucizumab for dabigatran reversal in patients with serious bleeding (Group A) or undergoing emergency surgery/procedures (Group B). HCRU outcome measures evaluated in the first 90 patients enrolled were use of blood products and pro-hemostatic agents, length of stay (LOS) in hospital, and LOS in intensive care unit (ICU).

Results: Blood products or pro-hemostatic agents were given to 63% (32/51) of patients in Group A and 23% (9/39) of patients in Group B on the day of/day after surgery. An overnight hospital stay was reported for 82% (42/51) of patients in Group A with median LOS?=?7 (range?=?1–71) bed-days. For Group B, 92% (36/39) had an overnight hospital stay with a median LOS?=?9 (range?=?1–92) bed-days. In Group A, 17 patients were admitted to the ICU for at least 1?day with median LOS?=?4 (range?=?1–44) days; in Group B the number was 15 with median LOS?=?2 (range?=?1–92) days.

Limitations: The lack of a control group and the small patient numbers limit the strength of the conclusions.

Conclusions: The use of idarucizumab may simplify emergency management of dabigatran-treated patients with life-threatening bleeds and reduce perioperative complications in patients undergoing emergency surgery.     

Is it the economy,stupid? The role of social versus economic factors in people’s support for hosting the Olympic Games: evidence from 12 democratic countries

Public referenda have gained momentum as a democratic tool to legitimize public mega projects such as hosting the Olympic Games. Interest groups in favour of hosting the Olympics therefore try to influence voters through public campaigns that primarily focus on economic benefits. However, recent studies find no or hardly any economic impact of hosting the Olympics, instead providing evidence for a positive social impact. This raises the question whether citizens consider economic or social factors when deciding on hosting the Olympics. Based on representative survey data from 12 countries, our results suggest that economic factors can influence voting behaviour, although the influence of social factors is stronger.