An economic evaluation of ramipril in the treatment of patients at high risk for cardiovascular events due to diabetes mellitus

SUMMARY

Cardiovascular disease (CVD) is a major cause of death and morbidity in the United Kingdom (UK) and carries with it a significant financial cost through health care resource use. More than one in three people die from CVD events, and the cost to the UK National Health Service (NHS) was £1.6 billion in 1996¹. The recently published MICRO-HOPE study evaluated the treatment of 3,577 patients at high risk for cardiovascular events from diabetes mellitus and demonstrated significant survival and morbidity benefits associated with ramipril.

The purpose of this paper is to assess whether the significant clinical benefits offered by ramipril can be translated into economic benefits, and to what extent it can reduce the economic burden of CVD to the UK NHS.

Applying the same analytical framework used in a previous economic analysis of the HOPE study, our base case estimate of cost-effectiveness for ramipril in the MICRO HOPE study is £2,396 per life-year saved (undiscounted) and £2,971 per life-year saved (discounted). A sensitivity analysis was performed which ranged from a best case of £1,954 per life-year saved (undiscounted) to a worst case of £2,964 per life-year saved (undiscounted). Our base case estimate of cost-effectiveness suggests that treating patients at high risk for CVD events with ramipril is likely to be a good investment of NHS resources.     

Burden of illness among patients at high risk versus low risk for major cardiovascular events

Abstract

Objective:

This study was designed to compare the burden of illness (BOI) in patients at high risk versus low risk of developing a major cardiovascular (CV) event.

Methods:

This retrospective claims data analysis included commercial health plan members identified with a primary diagnosis on a medical claim for cardiovascular disease (CVD) from January 1, 2001 through December 31, 2002. Patients were categorized as: low risk (LR), high risk (HR), or high risk aged ≥55 (HR55), based on the ONTARGET clinical trial.

Results:

Most patients (85%) were in the LR category (8% in HR55, 7% in HR). A significantly greater proportion of patients in the HR55 group were hospitalized and experienced a greater number of ambulatory visits compared with LR and HR patients. Controlling for covariates, HR55 patients averaged $22,502 in paid healthcare services over 2 years versus $15,645 for HR patients and $11,423 for LR patients (p?<?0.001). CV-related costs represented about 46% of costs for the HR55 group, versus 41% for the HR group and 31% for the LR group.

Limitations:

Claims data are collected for the purpose of payment and not research and the presence of a diagnosis code is not proof of disease, due to possible coding errors or the use of a rule-out criterion. Also, patients who died in the follow-up were not included in the analyses, resulting in lower BOI estimates. Finally, the results of this study reflect treatment of CVD in managed-care settings, and may not be applicable to a different type of population.

Conclusion:

This study demonstrates the high BOI associated with CVD, especially for patients within the high-risk group aged ≥55 years. Opportunities exist for reducing costs in this population.     

The cost implications of the use of telmisartan or ramipril in patients at high risk for vascular events: the ONTARGET study

Abstract

Background:

The recently published ONTARGET trial found that telmisartan was non-inferior to ramipril in reducing CV death, MI, stroke, or heart failure in patients with vascular disease or high-risk diabetes. The cost implications of ramipril and telmisartan monotherapy use based on the ONTARGET study are reported here.

Methods and Results:

Only healthcare system costs were considered. Healthcare resource utilization was collected for each patient during the trial. The authors obtained country-specific unit costs to the different healthcare care resources consumed (i.e., hospitalizations events, procedures, non-study, and study drugs) for all enrolled patients. Purchasing power parities were used to convert country-specific costs into US dollars (US$ 2008). The total undiscounted costs of the study for the telmisartan group was $12,762 per patient and is higher than the ramipril group at $12,007 per patient, an un-discounted difference of $755 (95% confidence interval [CI], $218–$1292); The discounted costs for the telmisartan group was $11,722 compared with $11,019 for the ramipril group; a difference of $703 (95% CI, $209–$1197). The difference in costs is exclusively related to the acquisition cost of telmisartan over generic ramipril.

Limitations:

This analysis only considered direct healthcare system costs. Costs accrued outside the hospital were not collected. Combination therapy was excluded since it would likely be more expensive than ramipril alone, with no additional benefit and a risk of some harm.

Conclusions:

Based on these results, it is suggested that for the ONTARGET patients, the use of telmisartan instead of ramipril increases costs by 6.3%. These findings suggest that the choice to put patients on telmisartan should be justified based on the patient’s susceptibility to specific adverse events to minimize the cost implications.     

Economic evaluation of sevelamer for the treatment of hyperphosphatemia in chronic kidney disease patients not on dialysis in the United Kingdom

Abstract

Objectives:

To determine the cost effectiveness of sevelamer vs calcium carbonate in patients with chronic kidney disease and not on dialysis (CKD-ND) from the perspective of the National Health Service (NHS) in the UK.

Methods:

A Markov decision analytic model was developed to estimate (1) total life years (LYs), quality-adjusted life years (QALYs), and costs for patients treated with sevelamer or calcium carbonate; and (2) incremental costs per LY gained (LYG) and per QALY gained for sevelamer vs calcium carbonate. Data informing probability transitions to all-cause death and dialysis inception in CKD-ND patients were taken directly from the INDEPENDENT-CKD study and were extrapolated beyond the 3-year clinical trial using Weibull regression analysis. Estimates of health utility and costs (in £2011) were derived from the published literature.

Results:

Over a lifetime horizon, sevelamer treatment resulted in a gain of 2.05 LYs and 1.56 QALYs per patient, an increase of £37,282 in total costs per patient vs calcium carbonate (3.5% discount), and a per-patient cost of £18,193/LYG and £23,878/QALY gained. Results were robust to alternative assumptions in key parameters; results were most sensitive to alternative assumptions regarding the mean daily dose of sevelamer, impact of sevelamer on dialysis initiation, cost of dialysis, and health utility estimates. The probabilistic sensitivity analysis showed that sevelamer was cost-effective vs calcium carbonate in 93% of simulations at a willingness-to-pay threshold of £30,000/QALY gained.

Limitations:

While the model simulated a real-world clinical setting, this analysis was subject to limitations common to all decision analytic models, in that it used a mix of data sources and relied on several assumptions. Not all variables that impact real-world outcomes and costs were included in this model.

Conclusions:

Sevelamer is a cost-effective option compared to calcium carbonate for the first-line treatment of hyperphosphatemia in CKD-ND patients in the UK.     

Cost effectiveness analysis of a next generation risk assessment score for cardiovascular disease

Objectives:

The goal of this study is to determine the cost-effectiveness of MIRISK VP, a next generation coronary heart disease risk assessment score, in correctly reclassifying and appropriately treating asymptomatic, intermediate risk patients.

Study design:

A Markov model was employed with simulated subjects based on the Multi-Ethnic Study of Atherosclerosis (MESA). This study evaluated three treatment strategies: (i) practice at MESA enrollment, (ii) current guidelines, and (iii) MIRISK VP in MESA.

Methods:

The model assessed patient healthcare costs and outcomes, expressed in terms of life years and quality-adjusted life years (QALYs), over the lifetime of the cohort from the provider and payer perspective. A total of 50,000 hypothetical individuals were used in the model. A sensitivity analysis was conducted (based on the various input parameters) for the entire cohort and also for individuals aged 65 and older.

Results:

Guiding treatment with MIRISK VP leads to the highest net monetary benefits when compared to the ‘Practice at MESA Enrollment’ or to the ‘Current Guidelines’ strategies. MIRISK VP resulted in a lower mortality rate from any CHD event and a modest increase in QALY of 0.12–0.17 years compared to the other two approaches.

Limitations:

This study has limitations of not comparing performance against strategies other than the FRS, the results are simulated as with all models, the model does not incorporate indirect healthcare costs, and the impact of patient or physician behaviors on outcomes were not taken into account.

Conclusions:

MIRISK VP has the potential to improve patient outcomes compared to the alternative strategies. It is marginally more costly than both the ‘Practice at MESA Enrollment’ and the ‘Current Guidelines’ strategies, but it provides increased effectiveness, which leads to positive net monetary benefits over either strategy.     

Economic evaluation of duloxetine as a first-line treatment for painful diabetic peripheral neuropathy in Mexico

Abstract

Objective:

To perform an economic evaluation of duloxetine, pregabalin, and both branded and generic gabapentin for managing pain in patients with painful diabetic peripheral neuropathy (PDPN) in Mexico.

Research design and methods:

The analysis was conducted using a 3-month decision model, which compares duloxetine 60?mg once daily (DUL), pregabalin 150?mg twice daily (PGB), and gabapentin 600?mg three-times daily (GBP) for PDPN patients with moderate-to-severe pain. A systematic review was performed and placebo-adjusted risk ratios for achieving good pain relief (GPR), adverse events (AE), and withdrawal owing to intolerable AE were calculated. Direct medical costs included drug acquisition and additional visits due to lack of efficacy (poor pain relief) or intolerable AE. Unit costs were taken from local sources. Adherence rates were used to estimate the expected drug costs. All costs are expressed in 2010 Mexican Pesos (MXN). Utility values drawn from published literature were applied to health states. The proportion of patients with GPR and quality-adjusted life years (QALY) were assessed.

Results:

Branded-GBP was dominated by all the other options. PGB was more costly and less effective than DUL. Compared with branded-GBP and PGB, DUL led to savings of 1.01 and 1.74 million MXN (per 1000 patients). The incremental cost per QALY gained with DUL used instead of generic-GBP was $102 433 MXN. This amount is slightly lower than the estimated gross domestic product per capita in Mexico for 2010. During a second-order Monte Carlo simulation, DUL had the highest probability of being cost-effective (61%), followed by generic-GBP (25%) and PGB (14%).

Limitations:

Study limitations include a short timeframe and using data from different dosage schemes for GBP and PGB.

Conclusions:

This study suggests that DUL provides overall savings and better health outcomes compared with branded-GBP and PGB. Administering DUL rather than generic-GBP is a cost-effective intervention to manage PDPN in Mexico.     

Economic evaluation of human urinary kallindinogenase for patients with acute ischemic stroke in China

Objectives: In China, both human urinary kallindinogenase (HUK) and 3-n-butylphthalide (NBP) are recommended for clinical use to improve cerebral blood circulation during an acute ischemic stroke (AIS). The objective was to evaluate the economic value of HUK vs NBP for patients with AIS from a Chinese payer’s perspective.

Methods: An economic evaluation based on data of patients who have been treated with either HUK (n?=?488) or NBP (n?=?885) from a prospective, phase IV, multi-center, clinical registry study (Chinese Acute Ischemic Stroke Treatment Outcome Registry, CASTOR) was conducted to analyze the cost and effectiveness of HUK vs NBP for AIS in China. Before the analysis, the patients were matched using propensity score. Both a cost-minimization analysis and a cost-effectiveness analysis were conducted to compare the matched pairs. A bootstrapping exercise was conducted for the matched arms to demonstrate the probability of one intervention being cost-effective over another for a given willingness-to-pay for an extra quality-adjusted life-year (QALY).

Results: After propensity score matching, 463 pairs were matched. The overall medical cost in the HUK arm is USD 2,701.20, while the NBP arm is USD 3,436.83, indicating HUK is preferred with cost-minimization analysis. Although the QALY gained in the HUK arm (0.77176) compared with the NBP arm (0.76831) is statistically insignificant (p?=?.4862), the cost-effectiveness analysis as exploratory analysis found that, compared with NBP, HUK is a cost-saving strategy with the lower costs of USD 735.63 and greater QALYs gained of 0.00345. Among the 5,000 bootstrapping replications, 100% indicates that HUK is cost-effective compared with NBP under a 1-time-GDP threshold; and 97.12% indicates the same under a 3-time-GDP threshold.

Conclusion: This economic evaluation study indicates that administrating HUK is a cost-saving therapy compared with NBP for managing blood flow during AIS in the Chinese setting.     

Economic evaluation of inhalers used in the treatment of asthma

Summary

Asthma is an important disease for New Zealand in terms of prevalence and costs, both direct and indirect. The objective of this study was to determine if there were any differences in primary care medical costs between treatment of asthma with four corticosteroid inhaler drug delivery systems (Autohaler? [AUTO], Diskhaler? [DISK], metered dose inhaler [MDI] and Turbuhaler? [TURB]) in a general practice setting.

The retrospective observational data-based research completed for this study involved a large population and recorded actual general practitioner prescribing practice. The perspective taken was that of the funder of health care. Data were obtained from the computerised clinical records of 28 New Zealand general practices. Cost data were on a per year per patient basis.

The largest single cost item identified in this study was that of corticosteroid inhalers which ranged from 41% of total primary care cost for MDI to 52% for the TURB group. Total drug acquisition cost (inclusive of dispensing costs and wholesale and retail markups) was highest for TURB at $490 and lowest for MDI at $265, a difference of 85%. There was less variation in general practitioner consultations for asthma with total costs ranging from $104 for AUTO to $127 for DISK. Total primary care costs were lowest for MDI at $392 per annum and highest for TURB at $608, a difference of 55%. If the MDI total primary care costs are used as the base for an index (MDI total primary care costs set at 100) then AUTO becomes 116, DISK 134 and TURB 155.

The model was robust with respect to conclusions relating to cost differences between the treatment groups. In all but one instance TURB remains the highest cost group.     

Economic evaluation of tocilizumab combination in the treatment of moderate-to-severe rheumatoid arthritis in Italy

Abstract

Objective:

This study was designed to evaluate the cost utility of tocilizumab in rheumatoid arthritis (RA) patients, with inadequate responses to traditional disease-modifying anti-rheumatic drugs (tDMARDs) from a payer’s perspective in Italy.

Methods:

An individual patient simulation model was used to project lifetime medical costs (payer’s perspective) and quality-adjusted life-years (QALYs). Treatment sequences starting with tocilizumab or the most commonly prescribed biologics (etanercept, adalimumab, or infliximab) were compared. The addition of tocilizumab to standard of care, without the replacement of anti-tumor necrosis factor (TNF)-α treatments, was also evaluated. Patient characteristics, treatment efficacy, and quality-of-life data were based on three phase 3 tocilizumab clinical trials (TOcilizumab Pivotal Trial in Methotrexate Inadequate respONders [OPTION], Tocilizumab in cOmbination With traditional DMARD therapy [TOWARD], and TociLIzumab Safety and THE Prevention of Structural Joint Damage [LITHE]). Mixed-treatment comparison was used to estimate response probabilities. Resource utilization, treatment acquisition, administration, and monitoring costs were estimated using Italian secondary sources. Uncertainty in model parameters was evaluated by probabilistic sensitivity analysis.

Results:

Replacement of anti-TNF-α treatments with tocilizumab reduced total costs over a patient’s lifetime (base-case analysis: tocilizumab sequence, €141,100 vs standard of care sequence, €143,500). Patients receiving tocilizumab realized more QALYs than patients receiving standard of care (9.8881 vs 9.3502 QALYs). Therefore, according to the base-case analysis, the tocilizumab sequence dominated the standard of care. In a sensitivity analysis, the model base-case result was robust to input changes. When tocilizumab was added to standard of care, without replacing anti-TNF-α treatments, the incremental cost-effectiveness ratio was €17,100 per QALY.

Conclusion:

The analysis demonstrates that, in Italy, replacing another biologic DMARD with tocilizumab or adding tocilizumab to the current standard of care is a cost-effective strategy in the treatment of RA patients with inadequate responses to tDMARDs.     

Economic outcomes among Medicare patients receiving bioengineered cellular technologies for treatment of diabetic foot ulcers

Abstract

Objective:

To assess the real-world medical services utilization and associated costs of Medicare patients with diabetic foot ulcers (DFUs) treated with Apligraf (bioengineered living cellular construct (BLCC)) or Dermagraft (human fibroblast-derived dermal substitute (HFDS)) compared with those receiving conventional care (CC).     

Cost-effectiveness of renal denervation therapy for the treatment of resistant hypertension in The Netherlands

Abstract

Objectives:

Safety and efficacy data for catheter-based renal denervation (RDN) in the treatment of resistant hypertension have been used to estimate the cost-effectiveness of this approach. However, there are no Dutch-specific analyses. This study examined the cost-effectiveness of RDN from the perspective of the healthcare payer in The Netherlands.

Methods:

A previously constructed Markov state-transition model was adapted and updated with costs and utilities relevant to the Dutch setting. The cost-effectiveness of RDN was compared with standard of care (SoC) for patients with resistant hypertension. The efficacy of RDN treatment was modeled as a reduction in the risk of cardiovascular events associated with a lower systolic blood pressure (SBP).

Results:

Treatment with RDN compared to SoC gave an incremental quality-adjusted life year (QALY) gain of 0.89 at an additional cost of €1315 over a patient’s lifetime, resulting in a base case incremental cost-effectiveness ratio (ICER) of €1474. Deterministic and probabilistic sensitivity analyses (PSA) showed that treatment with RDN therapy was cost-effective at conventional willingness-to-pay thresholds (€10,000–80,000/QALY).

Conclusion:

RDN is a cost-effective intervention for patients with resistant hypertension in The Netherlands.     

A Canadian cost-effectiveness analysis of transcatheter mitral valve repair with the MitraClip system in high surgical risk patients with significant mitral regurgitation

Objective:

In patients with significant mitral regurgitation (MR) at high risk of mortality and morbidity from mitral valve surgery, transcatheter mitral valve repair with the MitraClip System is associated with a reduction in MR and improved quality-of-life and functional status compared with baseline. The objective was to evaluate the cost-effectiveness of MitraClip therapy compared with standard of care in patients with significant MR at high risk for mitral valve surgery from a Canadian payer perspective.

Methods:

A decision analytic model was developed to estimate the lifetime costs, life years, quality-adjusted life years (QALYs), and incremental cost per life year and QALY gained for patients receiving MitraClip therapy compared with standard of care. Treatment-specific overall survival, risk of clinical events, quality-of-life, and resource utilization were obtained from the Endovascular Valve Edge-to-Edge REpair High Risk Study (EVEREST II HRS). Health utility and unit costs (CAD $2013) were taken from the published literature. Sensitivity analyses were conducted to explore the impact of alternative assumptions and parameter uncertainty on results.

Results:

The base case incremental cost per QALY gained was $23,433. Results were most sensitive to alternative assumptions regarding overall survival, time horizon, and risk of hospitalization for congestive heart failure (CHF). Probabilistic sensitivity analysis showed MitraClip therapy to have a 92% chance of being cost-effective compared with standard of care at a willingness-to-pay threshold of $50,000 per QALY gained.

Study limitations:

Key limitations include the small number of patients included in the EVEREST II HRS which informed the analysis, the limited data available to inform clinical events and disease progression in the concurrent comparator group, and the lack of a comparator group from a randomized control trial.

Conclusion:

MitraClip therapy is likely a cost-effective option for the treatment of patients at high risk for mitral valve surgery with significant MR.     

Cost effectiveness of rosuvastatin in patients at risk of cardiovascular disease based on findings from the JUPITER trial

Abstract

Objective:

This study assessed the long-term cost effectiveness of rosuvastatin therapy compared with placebo in reducing the incidence of major cardiovascular (CVD) events and mortality.

Methods:

A probabilistic Monte Carlo simulation model estimated long-term cost effectiveness of rosuvastatin therapy (20?mg daily) for the prevention of CVD mortality and morbidity. The model included three stages: (1) CVD prevention simulating the 4 years of the JUPITER trial, (2) initial CVD prevention beyond the trial, and (3) subsequent CVD event prevention. A US payer perspective was assessed reflecting direct medical costs, and up to a lifetime horizon. Sensitivity analyses tested the robustness of the model estimates.

Results:

For a hypothetical cohort of 100,000 patients at moderate and high risk of CVD events based on Framingham risk of ≥10%, estimated quality-adjusted life-years (QALYs) gained with rosuvastatin therapy compared with placebo was 33,480 over a lifetime horizon, and 25,380 and 9916 over 20-year and 10-year horizons, respectively. Approximately 12,073 events were avoided over the lifetime; 6,146 non-fatal MIs, 2905 non-fatal strokes, and 4030 CVD deaths avoided. Estimated incremental cost-effectiveness ratio (ICER) for cost per QALY was $7062 (lifetime), $10,743 (20-year horizon), and $44,466 (10-year horizon). For a hypothetical cohort similar to the overall JUPITER population, the cost per QALY ICER was $11,025 for the lifetime and $60,112 for a 10-year horizon.

Limitations:

The cost-effectiveness comparison of rosuvastatin 20?mg was against no active treatment (as opposed to an alternative statin) due to lack of comparative cardiovascular morbidity and mortality risk reduction data for other statins in a population similar to the JUPITER trial population. The analysis was conducted from the payer perspective and lack of inclusion of indirect costs limit interpretability of results from a societal perspective.

Conclusions:

Treatment with rosuvastatin 20?mg daily, is a cost-effective treatment alternative to no treatment in patients at a higher risk (Framingham risk ≥10%) of CVD.     

Cost-effectiveness of 3-year vs 1-year adjuvant therapy with imatinib in patients with high risk of gastrointestinal stromal tumour recurrence in the Netherlands; a modelling study alongside the SSGXVIII/AIO trial

Abstract

Background:

Surgical resection of gastrointestinal stromal tumour (GIST) is rarely curative in patients at high risk of tumour recurrence and therefore 1 year of post-surgery adjuvant imatinib therapy has been recommended in this sub-group. Recently, adjuvant imatinib therapy administered for 3 years has been demonstrated to further increase recurrence-free survival and overall survival. The goal of this study was to assess the economic value of extending the duration of adjuvant imatinib therapy in high-risk patients in the Netherlands.

Methods:

A multistate Markov model was developed to simulate how patients’ clinical status after GIST excision evolves over time until death. The model structure encompassed four primary health states: free of recurrence, first GIST recurrence, second GIST recurrence, and death. Transition probabilities between the health states, data on medical care costs, and quality-of-life were obtained from published sources and from expert opinion.

Results:

The expected number of life years (or quality-adjusted life years, QALYs) was higher in the 3-year group than in the 1-year group, 8.91 (6.55) and 7.04 (5.18) years, respectively. In the 3-year and 1-year group, the expected total costs amounted to €120,195 and €79,361, of which, €74,631 (62%) and €27,619 (35%) were adjuvant therapy drug costs, respectively. The difference in health benefits, that is 1.87 life years or 1.37 QALYs, and costs, €40,835, resulted in incremental cost-effectiveness ratios (ICER) of €21,865 per life year gained, and €29,872 per QALY gained.

Limitations:

A limitation of the study was inherently related to the uncertainty around the predictions of RFS. Scenario analyses were conducted to test the sensitivity of different RFS predictions on the results.

Conclusions:

Delayed recurrence due to treatment with longer-term adjuvant imatinib therapy represents a cost-effective treatment option with an ICER below the generally accepted threshold in the Netherlands.     

Economic and clinical comparison of atypical depot antipsychotic drugs for treatment of chronic schizophrenia in the Czech Republic

Abstract

Purpose:

The Czech Republic is faced with making choices between pharmaceutical products, including depot injectable antipsychotics. A pharmacoeconomic analysis was conducted to determine the cost-effectiveness of atypical depots.

Methods:

An existing 1-year decision-analytic framework was adapted to model drug use in this healthcare system. The average direct costs to the General Insurance Company of the Czech Republic of using paliperidone palmitate (Xeplion®), risperidone (Risperdal Consta®), and olanzapine pamoate (Zypadhera®) were determined. Literature-derived clinical rates populated the model, with costs adjusted to 2012 Euros using the consumer price index. Outcomes included quality-adjusted life-years (QALYs), days in remission, and proportions hospitalized or visiting emergency rooms. One-way sensitivity analyses were calculated for all important inputs. A multivariate probability analysis was used to examine the stability of results using 10,000 iterations of simulated input over reasonable ranges of all included variables.

Results:

Expected average costs/per patient treated were €5377 for PP-LAI, €6118 for RIS-LAI, and €6537 for OLZ-LAI. Respective QALYs were 0.817, 0.809, and 0.811; ER visits were 0.127, 0.134, and 0.141; hospitalizations were 0.252, 0.298, and 0.289. Results were generally robust in sensitivity analyses. PP-LAI dominated RIS-LAI and OLZ-LAI in 90.2% and 92.1% of simulations, respectively. Results were insensitive to drug prices but sensitive to adherence and hospitalization rates.

Conclusions:

PP-LAI dominated the other two drugs, as it had a lower overall cost and superior clinical outcomes, making it the preferred choice. Using PP-LAI in place of RIS-LAI for chronic relapsing schizophrenia would reduce the overall costs of care for the healthcare system.     

Economic evaluation of linaclotide for the treatment of adult patients with irritable bowel syndrome with constipation in the United States

Abstract

Objectives:

To use techniques of decision-analytic modeling to evaluate the effectiveness and costs of linaclotide vs lubiprostone in the treatment of adult patients with irritable bowel syndrome with constipation (IBS-C).

Methods:

Using model inputs derived from published literature, linaclotide Phase III trial data and a physician survey, a decision-tree model was constructed. Response to therapy was defined as (1) a ≥14-point increase from baseline in IBS-Quality-of-Life (IBS-QoL) questionnaire overall score at week 12 or (2) one of the top two responses (moderately/significantly relieved) on a 7-point IBS symptom relief question in ≥2 of 3 months. Patients who do not respond to therapy are assumed to fail therapy and accrue costs associated with a treatment failure. Model time horizon is aligned with clinical trial duration of 12 weeks. Model outputs include number of responders, quality-adjusted life-years (QALYs), and total costs (including direct and indirect). Both one-way and probabilistic sensitivity analyses were conducted.

Results:

Treatment for IBS-C with linaclotide produced more responders than lubiprostone for both response definitions (19.3% vs 13.0% and 61.8% vs 57.2% for IBS-QoL and symptom relief, respectively), lower per-patient costs ($803 vs $911 and $977 vs $1056), and higher QALYs (0.1921 vs 0.1917 and 0.1909 vs 0.1894) over the 12-week time horizon. Results were similar for most one-way sensitivity analyses. In probabilistic sensitivity analyses, the majority of simulations resulted in linaclotide having higher treatment response rates and lower per-patient costs.

Limitations:

There are no available head-to-head trials that compare linaclotide with lubiprostone; therefore, placebo-adjusted estimates of relative efficacy were derived for model inputs. The time horizon for this model is relatively short, as it was limited to the duration of available clinical trial data.

Conclusions:

Linaclotide was found to be a less costly option vs lubiprostone for the treatment of adult patients with IBS-C.     

Economic evaluation of ombitasvir/paritaprevir/ritonavir and dasabuvir for the treatment of chronic genotype 1 hepatitis c virus infection

Objectives: To estimate clinical outcomes and cost-effectiveness of ombitasvir/paritaprevir/ritonavir and dasabuvir?±?ribavirin (OMB/PTV/r?+?DSV?±?RBV) compared with treatment regimens including pegylated interferon (PegIFN) for patients with chronic genotype 1 hepatitis C virus (HCV) infection.

Methods: An Excel spreadsheet Markov model tracking progression through stages of liver disease was developed. Costs and patient utilities for liver disease stages were taken from published studies. Rates of disease progression were based on studies of untreated HCV infection and long-term follow-up of those achieving sustained virologic response (SVR) after drug treatment. Impact of OMB/PTV/r?+?DSV?±?RBV and other drug regimens on progression was estimated through SVR rates from clinical trials. Analyses were performed for treatment-naive and treatment-experienced patients. Impact of alternative scenarios and input parameter uncertainty on the results were tested.

Results: For genotype 1 treatment-naive HCV patients, for OMB/PTV/r?+?DSV?±?RBV, PegIFN?+?ribavirin (PegIFN/RBV), sofosbuvir?+?PegIFN/RBV, telaprevir?+?PegIFN/RBV, boceprevir?+?PegIFN/RBV, lifetime risk of decompensated liver disease was 5.6%, 18.9%, 7.4%, 11.7%, and 14.9%; hepatocellular carcinoma was 5.4%, 9.2%, 5.7%, 7.0%, and 7.4%; and death from liver disease was 8.7%, 22.2%, 10.4%, 14.8%, and 17.6%, respectively. Estimates of the cost-effectiveness of OMB/PTV/r?+?DSV?±?RBV for treatment-naive and treatment-experienced patients indicated that it dominated all other regimens except PegIFN/RBV. Compared with PegIFN/RBV, the incremental cost-effectiveness ratios were £13,864 and £10,258 per quality-adjusted life-year (QALY) for treatment-naive and treatment-experienced patients, respectively. The results were similar for alternative scenarios and uncertainty analyses.

Limitations: A mixed-treatment comparison for SVR rates for the different treatment regimens was not feasible, because many regimens did not have comparator arms; instead SVR rates were based on those from recent trials.

Conclusions: OMB/PTV/r?+?DSV?±?RBV is a cost-effective oral treatment regimen for chronic genotype 1 HCV infection compared with standard treatment regimens and is estimated to reduce the lifetime risks of advanced liver disease.     

A cost-effectiveness analysis of denosumab for the prevention of skeletal-related events in patients with multiple myeloma in the United States of America

Objective: A large, pivotal, phase 3 trial in patients with newly diagnosed multiple myeloma (MM) demonstrated that denosumab, compared with zoledronic acid, was non-inferior for the prevention of skeletal-related events (SREs), extended the observed median progression-free survival (PFS) by 10.7 months, and showed significantly less renal toxicity. The cost-effectiveness of denosumab vs zoledronic acid in MM in the US was assessed from societal and payer perspectives.

Methods: The XGEVA Global Economic Model was developed by integrating data from the phase 3 trial comparing the efficacy of denosumab with zoledronic acid for the prevention of SREs in MM. SRE rates were adjusted to reflect the real-world incidence. The model included utility decrements for SREs, administration, serious adverse events (SAEs), and disease progression. Drug, administration, SRE management, SAEs, and anti-MM treatment costs were based on data from published studies. For the societal perspective, the model additionally included SRE-related direct non-medical costs and indirect costs. The net monetary benefit (NMB) was calculated using a willingness-to-pay threshold of US$150,000. One-way deterministic and probabilistic sensitivity analyses were conducted.

Results: From a societal perspective, compared with zoledronic acid, the use of denosumab resulted in an incremental cost of US$26,329 and an incremental quality-adjusted life-year (QALY) of 0.2439, translating into a cost per QALY gained of US$107,939 and a NMB of US$10,259 in favor of denosumab. Results were sensitive to SRE rates and PFS parameters.

Limitations: Costs were estimated from multiple sources, which varied by tumor type, patient population, country, and other parameters. PFS and overall survival were extrapolated beyond the follow-up of the primary analysis using fitted parametric curves.

Conclusion: Denosumab’s efficacy in delaying or preventing SREs, potential to improve PFS, and lack of renal toxicity make it a cost-effective option for the prevention of SREs in MM compared with zoledronic acid.     

Cost effectiveness of paliperidone palmitate versus risperidone long-acting injectable and olanzapine pamoate for the treatment of patients with schizophrenia in Sweden

Abstract

Objective:

To model the cost effectiveness of paliperidone palmitate (paliperidone long-acting injectable; PLAI), a new once-monthly long-acting antipsychotic therapy, compared with risperidone long-acting injectable (RLAI) and olanzapine pamoate (OLAI), in multi-episode patients (two or more relapses) with schizophrenia in Sweden.

Methods:

A Markov decision analytic model was developed to simulate the history of a cohort of multi-episode patients transitioning through different health states on a monthly basis over a 5-year time horizon from the perspective of the Swedish healthcare system. Therapeutic strategies consisted of starting treatment with RLAI (mean dose 37.5?mg every 2 weeks), PLAI (mean dose 75?mg equivalent (eq.) every month) or OLAI (150?mg every 2 weeks or 300?mg every 4 weeks). Probability of relapse, level of adherence, side-effects (extrapyramidal symptoms, tardive dyskinesia, weight gain and diabetes) and treatment discontinuation (switch) were derived from long-term observational data when feasible. Incremental cost-effectiveness outcomes, discounted at 3% annually, included cost per quality-adjusted life-year (QALY) and cost per relapse avoided (expressed in 2009 Swedish Krona SEK).

Results:

Relative to RLAI and OLAI, PLAI is economically dominant: more effective (additional QALYs, less relapses) and less costly treatment option over a 5-year time horizon. The results were robust when tested in sensitivity analysis.

Limitations:

The impact of once-monthly treatment on adherence levels is not yet known, and not all variables that could impact on real-world outcomes and costs were included in this model.

Conclusion:

PLAI was cost saving from a Swedish payer perspective compared with RLAI and OLAI in the long-term treatment of multi-episode (two or more relapses) schizophrenia patients.