When does economic model type become a decisive factor in health technology appraisals? Learning from the expanding treatment options for relapsing–remitting multiple sclerosis

Objectives: Specific economic model types often become de facto standard for health technology appraisal over time. Markov and discrete event simulation (DES) models were compared to investigate the impact of innovative modeling on the cost-effectiveness of disease-modifying therapies (DMTs) in relapsing–remitting multiple sclerosis (RRMS). Fingolimod was compared to dimethyl fumarate (DMF; in highly active [HA] RRMS), alemtuzumab (in HA RRMS) and natalizumab (in rapidly evolving severe RRMS). Comparator DMTs were chosen to reflect different dosing regimens.

Materials and methods: Markov and DES models used have been published previously. Inputs were aligned in all relevant respects, with differences in the modeling of event-triggered attributes, such as relapse-related retreatment, which is inherently difficult with a memoryless Markov approach. Outcomes were compared, with and without different attributes.

Results: All results used list prices. For fingolimod and DMF, incremental cost-effectiveness ratios (ICERs) were comparable (Markov: £4206/quality-adjusted life year [QALY] gained versus DES: £3910/QALY gained). Deviations were observed when long-term adverse events (AEs) were incorporated in the DES (Markov: £25,412 saved/QALY lost, versus DES: £34,209 saved/QALY lost, fingolimod versus natalizumab; higher ICERs indicate greater cost-effectiveness). For fingolimod versus alemtuzumab, when relapse-triggered retreatment was included in the DES, large cost differences were observed (difference between incremental cost is £35,410 and QALY is 0.10).

Limitations: UK payer perspective, therefore societal approach was not considered. Resource utilization and utilities for both models were not derived from the subpopulations; as the focus is on model type, input limitations that apply to both models are less relevant.

Conclusions: Whilst no model can fully represent a disease, a DES allows an opportunity to include features excluded in a Markov structure. A DES may be more suitable for modeling in RRMS for health technology assessment purposes given the complexity of some DMTs. This analysis highlights the capabilities of different model structures to model event-triggered attributes.     

Cost-effectiveness of rivaroxaban compared with enoxaparin plus a vitamin K antagonist for the treatment of venous thromboembolism

Background:

Venous thromboembolism (VTE), comprised of deep vein thrombosis (DVT) and pulmonary embolism (PE), is commonly treated with a low-molecular-weight heparin such as enoxaparin plus a vitamin K antagonist (VKA) to prevent recurrence. Administration of enoxaparin?+?VKA is hampered by complexities of laboratory monitoring and frequent dose adjustments. Rivaroxaban, an orally administered anticoagulant, has been compared with enoxaparin?+?VKA in the EINSTEIN trials. The objective was to evaluate the cost-effectiveness of rivaroxaban compared with enoxaparin?+?VKA as anticoagulation treatment for acute, symptomatic, objectively-confirmed DVT or PE.

Methods:

A Markov model was built to evaluate the costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios associated with rivaroxaban compared to enoxaparin?+?VKA in adult patients treated for acute DVT or PE. All patients entered the model in the ‘on-treatment’ state upon commencement of oral rivaroxaban or enoxaparin?+?VKA for 3, 6, or 12 months. Transition probabilities were obtained from the EINSTEIN trials during treatment and published literature after treatment. A 3-month cycle length, US payer perspective ($2012), 5-year time horizon and a 3% annual discount rate were used.

Results:

Treatment with rivaroxaban cost $2,448 per-patient less and was associated with 0.0058 more QALYs compared with enoxaparin?+?VKA, making it a dominant economic strategy. Upon one-way sensitivity analysis, the model’s results were sensitive to the reduction in index VTE hospitalization length-of-stay associated with rivaroxaban compared with enoxaparin?+?VKA. At a willingness-to-pay threshold of $50,000/QALY, probabilistic sensitivity analysis showed rivaroxaban to be cost-effective compared with enoxaparin?+?VKA approximately 76% of the time.

Limitations:

The model did not account for the benefits associated with an oral and minimally invasive administration of rivaroxaban. ‘Real-world’ applicability is limited because data from the EINSTEIN trials were used in the model. Also, resource utilization and costs were based on the US healthcare system.

Conclusion:

Rivaroxaban is a cost-effective option for anticoagulation treatment of acute VTE patients.     

Cost-effectiveness analysis of ramucirumab treatment for patients with hepatocellular carcinoma who progressed on sorafenib with α-fetoprotein concentrations of at least 400 ng/ml

Abstract

Objective: This study aimed to compare the cost-effectiveness of ramucirumab versus placebo for patients with hepatocellular carcinoma who progressed on sorafenib with α-fetoprotein concentrations (AFP) of at least 400?ng/ml in the United States.

Methods: A Markov model was constructed to assess the cost-effectiveness of ramucirumab. Health outcomes were measured as quality-adjusted life years (QALYs). With TreeAge software, the disease process was modeled as three health states: progression-free survival (PFS), progressive disease (PD), and death. Costs were extracted from the REACH-2 trial, and utility was derived from published literature. Incremental cost-effectiveness ratios (ICERs) were calculated to compare ramucirumab with placebo. Probabilistic sensitivity analyses were developed to examine the robustness of the results.

Results: In the base case analysis, ramucirumab therapy had a cost of $55,508.41 and generated 0.54 QALYs, while placebo therapy had a cost of $761.09 and generated 0.47 QALYs, leading to an additional $54,747.32 in costs and 0.07 QALYs. The ICER was $782,104.57 per QALY, which was much higher than the willingness-to-pay threshold of $100,000 per QALY. According to sensitivity analyses, the utility of PD in the two groups was the dominant parameter influencing the ICER.

Conclusion: Although ramucirumab was associated with prolonged survival for patients with advanced hepatocellular carcinoma who progressed on sorafenib treatment with an AFP of at least 400?ng/ml, it is not a cost-effective treatment from a United States payer perspective.     

The cost-effectiveness of alectinib in anaplastic lymphoma kinase-positive (ALK+) advanced NSCLC previously treated with crizotinib

Introduction Anaplastic lymphoma kinase (ALK) targeting drugs provide an important option for advanced non-small cell lung cancer patients with this distinct tumor type; however, there is considerable uncertainty as to which drug provides the optimal value after crizotinib treatment. This study estimated the cost-utility of alectinib vs ceritinib from a US payer perspective.

Methods A cost-utility model was developed using partition survival methods and three health states: progression-free (PF), post-progression (PP), and death. Survival data were derived from the key clinical trials (alectinib: NP28761 &; NP28673, ceritinib: ASCEND I and II). Costs included drugs, adverse events, and supportive care. Utilities were based on trial data and the literature. One-way and probabilistic sensitivity analyses (PSA) were performed to assess parameter uncertainty.

Results Treatment with alectinib vs ceritinib resulted in increases of 2.55 months in the PF state, 0.44 quality adjusted life-years (QALYs), and $13,868, yielding a mean cost/QALY of $31,180. In the PSA, alectinib had a 96% probability of being cost-effective at a willingness-to-pay of $100,000/QALY. Drivers of model results were drug costs and utilities in the PF health state. The ICER ranged from $10,600–$65,000 per QALY in scenario analyses, including a sub-group analysis limited to patients with prior chemotherapy and crizotinib treatment.

Conclusions Treatment with alectinib in ALK?+?crizotinib-treated patients increased time progression-free and QALYs vs ceritinib. The marginal cost increase was driven by longer treatment durations with alectinib. This model demonstrates that alectinib may be considered a cost-effective treatment after progression on crizotinib.     

Cost-effectiveness of dedicated dietitians for hyperphosphatemia management among hemodialysis patients in Lebanon: results from the Nutrition Education for Management of Osteodystrophy trial

Aim: To assess the cost-effectiveness of nutrition education by dedicated dietitians (DD) for hyperphosphatemia management among hemodialysis patients.

Materials and methods: This was a trial-based economic evaluation in 12 Lebanese hospital-based units. In total, 545 prevalent patients were cluster randomized to DD, trained hospital dietitian (THD), and existing practice (EP) groups. During Phase I (6 months), DD (n?=?116) received intensive education by DD trained on renal nutrition, THD (n?=?299) received care from trained hospital dietitians, and EP (n?=?130) received usual care from untrained hospital dietitians. Patients were followed-up during Phase II (6 months).

Results: At baseline, EP had the lowest weekly hemodialysis time, and DD had the highest serum phosphorus and malnutrition-inflammation score. The additional costs of the intervention were low compared with the societal costs (DD: $76.7, $21,007.7; EP: $4.6, $18,675.4; THD: $17.4, $20,078.6, respectively). Between Phases I and II, DD showed the greatest decline in services use and societal costs (DD: –$2,364.0; EP: –$1,727.7; THD: –$1,105.7). At endline, DD experienced the highest decrease in adjusted serum phosphorus (DD: –0.32; EP: +0.16; THD: +0.04?mg/dL), no difference in quality-adjusted life-years (QALY), and the highest societal costs. DD had a cost-effectiveness ratio of $7,853.6 per 1?mg decrease in phosphorus, compared with EP; and was dominated by THD. Regarding QALY, DD was dominated by EP and THD. The results were sensitive to changes in key parameters.

Limitations: The analysis depended on numerous assumptions. Interpreting the results is limited by the significant baseline differences in key parameters, suggestive of higher baseline societal costs in DD.

Conclusions: DD yielded the greatest effectiveness and decrease in societal costs, but did not affect QALY. Regarding serum phosphorus, DD was likely to be cost-effective compared with EP, but had a low cost-effectiveness probability compared with THD. Regarding QALY, DD was not likely to be cost-effective. Assessing the long-term cost-effectiveness of DD, on similar groups, is recommended.     

The evolution of the disability-adjusted life year (DALY)

The disability-adjusted life year (DALY) is a summary health measure that combines mortality and morbidity into a single measure as a way to estimate global disease burden and the effectiveness of health interventions. We review the methodological progression of the DALY, focusing on how the use of life expectancy estimates, disability weights, age weighting, and discounting has evolved since the first DALY reports were published in 1993. These changes have generally improved the metric but have made it difficult for researchers to interpret, compare, and conduct DALY studies.     

The estimation of agricultural policy effects on soil erosion—An application for the bio-economic model MODAM

As agricultural policies affect land use, they have effects on the amount of soil erosion in agricultural regions through changes of the economic conditions of agricultural production. Prices of inputs and outputs, regulations and incentives can change, forcing or encouraging farmers to adopt new crop rotations. This paper shows how a bio-economic model can be used to describe and estimate the effects of policies on agricultural production and the risk of soil erosion at the example of a region in North-Eastern Germany. The model uses both an assessment tool that is based on a fuzzy-logic approach for the estimation of soil erosion risk of cropping practices, and a linear programming model, that simulates farmers’ economic behaviour under the assumption of gross margin maximisation being the main goal of farmers’ actions.The analysed policy options were both a targeted and an untargeted incentive programme for reduced tillage, and a restriction option where high erosive crops are not allowed on high erodible field types. The results show that policy changes can have an impact on soil erosion. Furthermore, soil conservation policies are shown to have different levels of efficiency in terms of reduced soil erosion related to the costs of the policy. In the case of this study, a restriction option was more efficient than the incentive options. The results of such simulations can serve as a decision support for the development of soil conservation policies and help to foresee the effects of general changes of agricultural policies.     

Health economic evaluation of a vaccine for the prevention of herpes zoster (shingles) and post-herpetic neuralgia in adults in Belgium

Abstract

Objective:

To determine the cost-effectiveness of vaccination against herpes zoster (HZ) and post-herpetic neuralgia (PHN) in individuals aged 60 years and older in Belgium.

Methods:

A Markov model was developed to compare the cost-effectiveness of vaccination with that of a policy of no vaccination. The model estimated the lifetime incidence and consequences of HZ and PHN using inputs derived from Belgian data, literature sources, and expert opinion. Cost-effectiveness was measured by the incremental cost-effectiveness ratio (ICER), expressed as cost per quality-adjusted life-year (QALY) gained.

Results:

Vaccination in individuals aged 60 years and older resulted in ICERs of €6,799 (third party payer perspective), €7,168 (healthcare perspective), and €7,137 (societal perspective). The number needed to vaccinate to prevent one case was 12 for HZ, and 35 or 36 for PHN depending on the definition used. Univariate sensitivity analyses produced ICERs of €4,959–19,052/QALY; duration of vaccine efficacy had the greatest impact on cost-effectiveness. Probabilistic sensitivity analysis showed at least a 94% probability of ICERs remaining below the unofficial €30,000 threshold.

Discussion:

Key strengths of the model are the combination of efficacy data from a pivotal clinical trial with country-specific epidemiological data and complete sensitivity analysis performed. Main limitations are the use of non country-specific PHN proportion and non Belgian disease-specific utilities. Results are comparable with those recently published.

Conclusions:

HZ vaccination in individuals aged 60 years and older would represent a cost-effective strategy in Belgium.