Healthcare and economic burden of adverse events among patients with chronic myelogenous leukemia treated with BCR-ABL1 tyrosine kinase inhibitors

Objectives: BCR-ABL1 tyrosine kinase inhibitors (TKIs) are established treatments for chronic myelogenous leukemia (CML); however, they are associated with infrequent, but clinically serious adverse events (AEs). The objective of this analysis was to assess healthcare resource utilization and costs associated with AEs, previously identified using the FDA Adverse Event Reporting System (FAERS) in another study, among TKI-treated patients.

Methods: Adult patients with ≥1 inpatient or ≥2 outpatient ICD-9-CM diagnosis codes for CML and ≥1 claim for a TKI treatment between January 1, 2006 and September 30, 2012 were identified from the Commercial and Medicare MarketScan databases. The first claim for a TKI was designated as the index event. Patients were required to have no TKI treatment during a 12-month baseline period. Healthcare resource utilization and costs associated with select AEs having the strongest association with TKI treatment (femoral arterial stenosis [FAS], peripheral arterial occlusive disease [PAOD], intermittent claudication, coronary artery stenosis [CAS], pericardial effusion, pleural effusion, malignant pleural effusion, conjunctival hemorrhage) were evaluated during a 12-month follow-up period.

Results: The study sample included 2,005 CML patients receiving TKI therapy (mean age?=?56 years; 56% male). Among all evaluated AEs, the highest mean inpatient healthcare costs were observed for FAS ($16,800 per patient) and PAOD ($14,263 per patient), which had total mean medical costs (inpatient?+?outpatient) of $17,015 and $15,154 per patient, respectively. Mean outpatient healthcare costs were highest for CAS ($1,861 per patient), followed by intermittent claudication ($947 per patient), PAOD ($891 per patient), and pleural effusion ($890 per patient). Total mean medical costs for fluid retention-related AEs, including pericardial effusion and pleural effusion, were $2,797 and $1,908 per patient, respectively.

Conclusions: The healthcare costs of AEs identified in the FAERS as having the strongest association with TKI treatment are substantial. Vascular stenosis-related AEs, including FAS and PAOD, have the highest cost burden.     

Economic benefits of adequate molecular monitoring in patients with chronic myelogenous leukemia

Objective:

Molecular monitoring of chronic myeloid leukemia (CML) has been associated with improved clinical outcomes during tyrosine kinase inhibitor therapy (TKI), yet recent studies have demonstrated its use is far below published guidelines. This study sought to determine frequencies of molecular monitoring and its impact on resource utilization and medical costs.

Methods:

A retrospective US claims administrative database (IMS LifeLink Health Plan Claims and Truven Health Analytics MarketScan databases, 11/2007–06/2012) was used to analyze the economic impact of qPCR testing in CML patients on first-line TKIs during the initial 12-months of treatment.

Results:

One thousand two hundred and five adult CML patients met the sample selection criteria. Among these, 41.0% had no qPCR tests, 31.9% had 1–2 tests, and 27.1% had 3–4 tests; 88.9% were initiated on imatinib; 47.7% were female. Patients in the 3–4 tests cohort incurred 44% (p?p?=?0.005) lower for the 3–4 tests cohort than the 0-tests cohort. Adjusted progression-related IP cost was $4132 (p?=?0.013) lower for the 3–4 tests cohort than the 0-tests cohort. Adjusted medical service cost was $5997 (p?=?0.049) lower for the 3–4 tests cohort than the 0-tests cohort.

Limitations:

Claims databases did not include information on the primary cause of hospitalizations.

Conclusions:

Among CML patients in two large claims databases, nearly three-quarters did not receive adequate molecular monitoring per published guidelines. Those who were more frequently monitored incurred lower medical service costs, with the majority of the difference in costs being related to disease progression. These findings underscore the clinical and economic values of molecular monitoring in CML.     

Cost-effectiveness analysis of ferric carboxymaltose in iron-deficient patients with chronic heart failure in Sweden

Abstract

Objective:

Iron deficiency is a common but treatable comorbidity in chronic heart failure (CHF) that is associated with impaired health-related quality-of-life (HRQoL). This study evaluates the cost-effectiveness of the intravenous iron preparation ferric carboxymaltose (FCM) for the treatment of iron deficiency in CHF from a Swedish healthcare perspective.     

Cost-effectiveness of sofosbuvir plus ribavirin with or without pegylated interferon for the treatment of chronic hepatitis C in Italy

Abstract

Objective:

Across Italy up to 7.3% of the population is infected with hepatitis C virus (HCV), with long-term complications resulting in high medical costs and significant morbidity and mortality. Current treatment options have limitations due to side effects, interferon intolerability and ineligibility, long treatment durations and low sustained virological response (SVR) rates, especially for the most severe patients). Sofosbuvir is the first nucleotide polymerase inhibitor with pan-genotypic activity. Sofosbuvir, administered with ribavirin (RBV) and with or without pegylated interferon (PEG-INF), resulted in >90% SVR across treatment-naïve (TN) genotype (GT) 1–6 patients. It is also the first treatment option for patients that are unsuitable for interferon (UI). This analysis evaluates the cost – effectiveness of sofosbuvir for GTs 1–6 in Italy.     

Cost-effectiveness of natalizumab versus fingolimod for the treatment of relapsing multiple sclerosis

Abstract

Background:

With the addition of new agents for the treatment of multiple sclerosis (MS) (e.g., fingolimod), there is a need to evaluate the relative value of newer therapies in terms of cost and effectiveness, given healthcare resource constraints in the United States.

Objective:

To assess the cost-effectiveness of natalizumab vs fingolimod in patients with relapsing MS.

Methods:

A decision analytic model was developed to estimate the incremental cost per relapse avoided of natalizumab and fingolimod from a US managed care payer perspective. Two-year costs of treating patients with MS included drug acquisition costs, administration and monitoring costs, and costs of treating MS relapses. Effectiveness was measured in terms of MS relapses avoided (data from AFFIRM and FREEDOMS trials). One-way and probabilistic sensitivity analyses were conducted to assess uncertainty.

Results:

Mean 2-year estimated treatment costs were $86,461 (natalizumab) and $98,748 (fingolimod). Patients receiving natalizumab had a mean of 0.74 relapses avoided per 2 years vs 0.59 for fingolimod. Natalizumab dominated fingolimod in the incremental cost-effectiveness analysis, as it was less costly and more effective in reducing relapses. One-way sensitivity analysis showed the results of the model were robust to changes in drug acquisition costs, administration costs, and costs of treating MS relapses. Probabilistic sensitivity analysis showed natalizumab was cost-effective 95.1% of the time, at a willingness-to-pay (WTP) threshold of $0 per relapse avoided, increasing to 96.3% of the time at a WTP threshold of $50,000 per relapse avoided.

Limitations:

Absence of data from direct head-to-head studies comparing natalizumab and fingolimod, use of relapse rate reduction rather than sustained disability progression as primary model outcome, assumption of 100% adherence to MS treatment, and not capturing adverse event costs in the model.

Conclusions:

Natalizumab dominates fingolimod in terms of incremental cost per relapse avoided, as it is less costly and more effective.     

Nilotinib versus dasatinib as second-line therapy in patients with Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase who are resistant or intolerant to imatinib: a cost-effectiveness analysis based on real-world data

Objective: To evaluate the cost-effectiveness of second-line nilotinib vs dasatinib among patients with Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase (Ph+?CML-CP) who are resistant or intolerant to imatinib, from a US third-party perspective.

Methods: A lifetime partitioned survival model was developed to compare the costs and effectiveness of nilotinib vs dasatinib, which included four health states: CP on treatment, CP post-discontinuation, progressive disease (accelerated phase [AP] or blast crisis [BC]), and death. Time on treatment, progression-free survival, and overall survival of nilotinib and dasatinib were estimated using real-world comparative effectiveness data. Parametric survival models were used to extrapolate outcomes beyond the study period. Drug treatment costs, medical costs, and adverse event costs were obtained from the literature and publicly available databases. Utilities of health states were derived from the literature. Incremental cost-effectiveness ratios, including incremental cost per life-year (LY) gained and incremental cost per quality-adjusted life-year (QALY) gained, were estimated comparing nilotinib and dasatinib. Deterministic sensitivity analyses were performed by varying patient characteristics, cost, and utility inputs.

Results: Over a lifetime horizon, nilotinib-treated patients were associated with 11.7 LYs, 9.1 QALYs, and a total cost of $1,409,466, while dasatinib-treated patients were associated with 9.5 LYs, 7.3 QALYs, and a total cost of $1,422,122. In comparison with dasatinib, nilotinib was associated with better health outcomes (by 2.2 LYs and 1.9 QALYs) and lower total costs (by $12,655). Deterministic sensitivity analysis results showed consistent findings in most scenarios.

Limitations: In the absence of long-term real-world data, the lifetime projection could not be validated.

Conclusions: Compared with dasatinib, second-line nilotinib was associated with better life expectancy, better quality-of-life, and lower costs among patients with Ph+?CML-CP who were resistant or intolerant to imatinib.     

Cost-effectiveness analysis of roflumilast/tiotropium therapy versus tiotropium monotherapy for treating severe-to-very severe COPD

Abstract

Objective:

To conduct a cost-effectiveness analysis comparing roflumilast/tiotropium therapy vs tiotropium monotherapy in patients with severe-to-very severe COPD.

Methods:

The economic evaluation applied a disease-based Markov cohort model with five health states: (1) severe COPD, (2) severe COPD with a history of severe exacerbation, (3) very severe COPD, (4) very severe COPD with a history of severe exacerbation, and (5) death. Within a given health state, a patient may have a mild/moderate or severe exacerbation or die. Data from roflumilast clinical trials and published literature were used to populate model parameters. The model calculated health outcomes and costs for roflumilast/tiotropium therapy vs tiotropium monotherapy over a 5-year horizon. Incremental cost and benefits were then calculated as cost-effectiveness ratios, including cost per exacerbation avoided and cost per quality adjusted life year ($/QALY).

Results:

Over a 5-year horizon, the estimated incremental costs per exacerbation and per severe exacerbation avoided were $589 and $5869, respectively, and the incremental cost per QALY was $15,815. One-way sensitivity analyses varying key parameters produced an incremental cost per QALY ranging from $1963–$32,773.

Limitations:

A number of key parameters used in the model were obtained from studies in the literature that were conducted under different contexts. Specifically, the relative risk estimate for severe COPD patients originates from a small trial not designed to demonstrate the impact of roflumilast on frequency of exacerbations. In addition, the model extrapolates the relative risk estimates over periods of 5–30 years, even though the estimates were only observed in trials that spanned less than a year.

Conclusions:

The addition of roflumilast to tiotropium is cost-effective for the treatment of severe to very severe COPD patients.     

Cost-effectiveness of combination daclatasvir-sofosbuvir for treatment of genotype 3 chronic hepatitis C infection in the United States

Background: A phase III trial evaluated the efficacy and safety of Daklinza (daclatasvir or DCV) in combination with sofosbuvir (SOF) for treatment of genotype (GT) 3 hepatitis C virus (HCV) patients.

Aim: This study evaluated the cost-effectiveness of DCV?+?SOF vs SOF in combination with ribavirin (RBV) over a 20-year time horizon from the perspective of a United States (US) payer.

Methods: A published Markov model was adapted to reflect US demographic characteristics, treatment patterns, costs of drug acquisition, monitoring, disease and adverse event management, and mortality risks. Clinical inputs came from the ALLY-3 and VALENCE trials. The primary outcome was the incremental cost-utility ratio. Life-years, incidence of complications, number of patients achieving sustained virological response (SVR), and the total cost per SVR were secondary outcomes. Costs (2014 USD) and quality-adjusted life years (QALYs) were discounted at 3% per year. Deterministic, probabilistic, and scenario sensitivity analyses were conducted.

Results: DCV?+?SOF was associated with lower costs and better effectiveness than SOF?+?RBV in the base case and in almost all scenarios (i.e. treatment-experienced, non-cirrhotic, time horizons of 5, 10, and 80 years). DCV?+?SOF was less costly, but also slightly less effective than SOF?+?RBV in the cirrhotic and treatment-naïve population scenarios. Results were sensitive to variations in the probability of achieving SVR for both treatment arms. DCV?+?SOF costs less than $50,000 per QALY gained in 79% of all probabilistic iterations compared with SOF?+?RBV.

Conclusion: DCV?+?SOF is a dominant option compared with SOF?+?RBV in the US for the overall GT 3 HCV patient population.     

Cost-effectiveness of 3-month paliperidone treatment for chronic schizophrenia in Spain

Background: A 3-month long treatment of paliperidone palmitate (PP3M) has been introduced as an option for treating schizophrenia. Its cost-effectiveness in Spain has not been established.

Aims: To compare the costs and effects of PP3M compared with once-monthly paliperidone (PP1M) from the payer perspective in Spain.

Methods: This study used the recently published trial by Savitz et al. as a core model over 1 year. Additional data were derived from the literature. Costs in 2016 Euros were obtained from official lists and utilities from Osborne et al. The authors conducted both cost-utility and cost-effectiveness analyses. For the former, the incremental cost per quality-adjusted life-year (QALY) gained was calculated. For the latter, the outcomes were relapses and hospitalizations avoided. To assure the robustness of the analyses, a series of 1-way and probability sensitivity analyses were conducted.

Results: The expected cost was lower with PP3M (4,780€) compared with PP1M (5,244€). PP3M had the fewest relapses (0.080 vs 0.161), hospitalizations (0.034 v.s 0.065), and emergency room visits (0.045 v.s 0.096) and the most QALYs (0.677 v.s 0.625). In both cost-effectiveness and cost-utility analyses, PP3M dominated PP1M. Sensitivity analyses confirmed base case findings. For the primary analysis (cost-utility), PP3M dominated PP1M in 46.9% of 10,000 simulations and was cost-effective at a threshold of 30,000€/QALY gained.

Conclusions: PP3M dominated PP1M in all analyses and was, therefore, cost-effective for treating chronic relapsing schizophrenia in Spain. For patients who require long-acting therapy, PP3M appears to be a good alternative anti-psychotic treatment.     

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.     

Treatment patterns and healthcare costs among newly-diagnosed patients with chronic myeloid leukemia receiving dasatinib or nilotinib as first-line therapy in the United States

Objective: To compare treatment patterns and economic outcomes of dasatinib and nilotinib as 1st-line therapies for chronic myeloid leukemia (CML).

Methods: Adult CML patients initiated on first-line dasatinib or nilotinib in 2010–2014 were identified from two large US administrative claims databases. Treatment patterns, tyrosine kinase inhibitor (TKI) adherence and healthcare resource utilization (HRU) and costs were measured from the 1st-line TKI initiation (index date) to the end of follow-up.

Results: A total of 604 and 418 patients were included in the dasatinib and nilotinib cohorts (mean ages = 50.9 and 52.5 years, 46.4% and 45.7% female), respectively. Among the dasatinib patients, 91% started with 100?mg/day, 3% with <100?mg/day, and 6% with >100?mg/day. Among the nilotinib patients, 76% started with 600?mg/day, 16% with >600?mg/day, and 8% <600?mg/day. The dasatinib cohort had a higher hazard of dose decrease (hazard ratio [HR]?=?1.66; p?=?.002) and of switching to another TKI (HR =1.62; p?=?.019) compared to the nilotinib cohort. The hazard of dose increase (HR =0.76; p?=?.423) and treatment discontinuation (HR =1.10; p?=?.372) were not significantly different between cohorts. There was also no significant difference in TKI adherence levels (mean proportion of days covered [PDC] difference over first 6 months = ?0.0003, p?=?.981; mean PDC difference over first 12 months = ?0.0022, p?=?.880) and HRU (inpatient day incidence rate ratio [IRR]?=?1.03, p?=?.930; emergency room IRR =1.26, p?=?.197; and days with outpatient services IRR = 1.01, p?=?.842). The dasatinib cohort incurred higher healthcare costs by $749 per patient per month (p?=?.044) compared to the nilotinib cohort.

Limitation: Information on CML phase and Sokal score was not available.

Conclusions: Dasatinib was associated with an increased hazard of dose decrease and switching to another TKI and higher healthcare costs, vs nilotinib.     

Cost-effectiveness of telaprevir in combination with pegylated interferon alpha and ribavirin in treatment-experienced chronic hepatitis C genotype 1 patients

Background:

Telaprevir (TVR,T) and boceprevir (BOC,B) are direct-acting antivirals (DAAs) used for the treatment of chronic genotype 1 hepatitis C virus (HCV) infection. This analysis evaluated the cost-effectiveness of TVR combined with pegylated interferon (Peg-IFN) alfa-2a plus ribavirin (RBV) compared with Peg-IFN alfa-2a and RBV (PR) alone or BOC plus Peg-IFN alfa-2b and RBV in treatment-experienced patients.

Methods:

A Markov cohort model of chronic genotype 1 HCV disease progression reflected the pathway of experienced patients retreated with DAA therapy. The population was stratified by previous response to treatment (i.e., previous relapsers, partial responders, and null responders). Sustained virologic response (SVR) rates were derived from a mixed-treatment comparison that included results from separate Phase III trials of TVR and BOC. Incremental cost per life year (LY) gained and quality-adjusted-life-year (QALY) gained were computed at lifetime, adopting the NHS perspective. Costs and health outcomes were discounted at 3.5%. Uncertainty was assessed using deterministic and probabilistic sensitivity analyses. Sub-group analyses were carried out by interleukin (IL)-28B genotype.

Results:

Higher costs and improved outcomes were associated with T/PR relative to PR alone for all experienced patients (ICER of £6079). T/PR was cost-effective for each sub-group population with high SVR advantage in relapsers (ICER of £2658 vs £7593 and £20,875 for partial and null responders). T/PR remained cost-effective regardless of IL-28B sub-type. Compared to B/PR, T/PR prolonged QALYs by 0.57 and reduced lifetime costs by £13,960 for relapsers. For partial responders T/PR was less costly but less efficacious than B/PR, equating to an ICER of £128,117 per QALY gained.

Limitations:

No head-to-head trial provides direct evidence of better efficacy of T/PR vs B/PR.

Conclusion:

T/PR is cost-effective compared with PR alone in experienced patients regardless of treatment history and IL-28B genotype. Compared to B/PR, T/PR is always cost-saving but only more effective in relapsers.     

Cost-effectiveness analysis of atypical long-acting antipsychotics for treating chronic schizophrenia in Finland

Abstract

Objective:

In Finland, regional rates of schizophrenia exceed those in most countries, impacting the healthcare burden. This study determined the cost-effectiveness of long-acting antipsychotic (LAI) drugs paliperidone palmitate (PP-LAI), olanzapine pamoate (OLZ-LAI), and risperidone (RIS-LAI) for chronic schizophrenia.

Method:

This study adapted a decision tree analysis from Norway for the Finnish National Health Service. Country-specific data were sought from the literature and public documents, guided by clinical experts. Costs of health services and products were retrieved from literature sources and current price lists. This simulation study estimated average 1-year costs for treating patients with each LAI, average remission days, rates of hospitalization and emergency room visits and quality-adjusted life-years (QALY).

Results:

PP-LAI was dominant. Its estimated annual average cost was €10,380/patient and was associated with 0.817 QALY; OLZ-LAI cost €12,145 with 0.810 QALY; RIS-LAI cost €12,074 with 0.809 QALY. PP-LAI had the lowest rates of hospitalization, emergency room visits, and relapse days. This analysis was robust against most variations in input values except adherence rates. PP-LAI was dominant over OLZ-LAI and RIS-LAI in 77.8% and 85.9% of simulations, respectively. Limitations include the 1-year time horizon (as opposed to lifetime costs), omission of the costs of adverse events, and the assumption of universal accessibility.

Conclusion:

In Finland, PP-LAI dominated the other LAIs as it was associated with a lower cost and better clinical outcomes.     

Cost-effectiveness of partially-hydrolyzed formula for prevention of atopic dermatitis in Australia

Abstract

Objective:

To perform an economic evaluation of a specific brand of partially hydrolyzed infant formula (PHF-W) in the prevention of atopic dermatitis (AD) among Australian infants.

Methods:

A cost-effectiveness analysis was undertaken from the perspectives of the Department of Health and Aging (DHA), of the family of the affected subject and of society as a whole in Australia, based on a decision-analytic model following a hypothetical representative cohort of Australian newborns who are not exclusively breastfed and who have a familial history of allergic disease (i.e., are deemed ‘at risk’). Costs, consequences, and incremental cost-effectiveness ratios (ICER) were calculated for PHF-W vs standard cow’s milk based infant formula (SF), and, in a secondary analysis, vs extensively hydrolyzed infant formula (EHF-Whey), when the latter was used for the prevention of AD.

Results:

From a representative starting cohort of 87,724 ‘at risk’ newborns in Australia in 2009, the expected ICERs for PHF-W vs SF were AU$496 from the perspective of the DHA and savings of AUD1739 and AU$1243 from the family and societal perspectives, respectively. When compared to EHF-Whey, PHF-W was associated with savings for the cohort of AU$5,183,474 and AU$6,736,513 from the DHA and societal perspectives.

Limitations:

The generalizability and transferability of results to other settings, populations, or brands of infant formula should be made with caution. Whenever possible, a conservative approach directing bias against PHF-W rather than its comparators was applied in the base case analysis. Assumptions were verified in one-way and probabilistic sensitivity analyses, which confirmed the robustness of the model.

Conclusions:

PHF-W appears to be cost-effective when compared to SF from the DHA perspective, dominant over SF from the other perspectives, and dominant over EHF-Whey from all perspectives, in the prevention of AD in ‘at risk’ infants not exclusively breastfed, in Australia.     

Cost-effectiveness of telaprevir in combination with pegylated interferon alpha and ribavirin in previously untreated chronic hepatitis C genotype 1 patients

Background:

Telaprevir (T, TVR) is a direct-acting antiviral (DAA) used for the treatment of genotype 1 chronic hepatitis C virus (HCV) infection. The sustained virological response (SVR) rates, i.e., undetectable HCV RNA levels 24 weeks after the end of treatment, is what differentiate treatments. This analysis evaluated the cost-effectiveness of TVR combined with pegylated interferon (Peg-IFN) alfa-2a plus ribavirin (RBV), with Peg-IFN and RBV (PR) alone or with boceprevir (B, BOC) plus Peg-IFN alfa-2b and RBV, in naïve patients.

Methods:

A Markov cohort model of chronic HCV disease progression reflected the pathway of naïve patients initiating anti-HCV therapy. SVR rates were derived from a mixed-treatment comparison including results from Phase II and III trials of TVR and BOC, and trials comparing both PR regimens. SVR has significant impact on survival, quality-of-life, and costs. Incremental cost per life year (LY) gained and quality-adjusted-life-year (QALY) gained were computed at lifetime, adopting the (National Health Service) NHS perspective. Cost and health outcomes were discounted at 3.5%. Uncertainty was assessed using deterministic and probabilistic sensitivity analyses. Sub-group analyses were also performed by interleukin (IL)-28B genotype and fibrosis stage.

Results:

Higher costs and improved outcomes were associated with T/PR relative to PR alone, resulting in an ICER of £12,733 per QALY gained. T/PR retained a significant SVR advantage over PR alone and was cost-effective regardless of IL-28B genotype and fibrosis stages. T/PR regimen ‘dominated’ B/PR, generating 0.2 additional QALYs and reducing lifetime cost by £2758. Sensitivity analyses consistently resulted in ICERs less than £30,000/QALY for the T/PR regimen over PR alone.

Limitations:

No head-to-head trial provides direct evidence of better efficacy of T/PR vs B/PR.

Conclusion:

The introduction of TVR-based therapy for genotype 1 HCV patients is cost-effective for naïve patients at the £30,000 willingness-to-pay threshold, regardless of IL-28B genotype or fibrosis stage.     

Cost-effectiveness analysis of first-line pembrolizumab treatment for PD-L1 positive,non-small cell lung cancer in China

Purpose: Pembrolizumab was recently approved in several countries as a first-line treatment for patients with PD-L1 positive, non-small cell lung cancer (NSCLC). However, it is expensive. This study aimed to assess the cost-effectiveness of pembrolizumab in treating advanced NSCLC patients with PD-L1 positive cancer in China.

Methods: A Markov model was developed to compare the cost-effectiveness of pembrolizumab with chemotherapy for patients with PD-L1 expression on at least 50% of NSCLC tumor cells. Model inputs for transition probabilities and toxicity were derived from published clinical trial data, while health utilities were estimated from a literature review. Costs for drugs were updated to standard fee data from West China Hospital in 2017. Health outcomes were measured in quality-adjusted life years (QALYs), and cost-effectiveness was measured as the incremental cost-effectiveness ratio (ICER). Sensitivity analyses were conducted to test the robustness of the model.

Results: Pembrolizumab gained 0.45 QALYs at an incremental cost of $46,362 compared to chemotherapy for an ICER of $103,128 per QALY gained. In most scenarios, the ICER exceeded three times the Chinese Gross Domestic Product per capita. Two-way sensitivity analysis showed that, when the utility of the progression-free status increased to the maximal value of 0.845 and the 1?mg dose price decreased to $10.50, the ICER reduced to $25,216/QALY.

Conclusions: Pembrolizumab is not likely to be cost-effective in the treatment of PD-L1 positive, NSCLC for Chinese patients. Less aggressive pricing may increase accessibility for patients in China.     

Cost-effectiveness of tapentadol prolonged release compared with oxycodone controlled release in the UK in patients with severe non-malignant chronic pain who failed 1st line treatment with morphine

Abstract

Objectives:

The aim of this analysis was to assess the cost-effectiveness of tapentadol PR (prolonged release) compared with oxycodone CR (controlled release) in severe non-malignant chronic pain patients in whom controlled release morphine was ineffective or not tolerated.

Methods:

A Markov model was developed to assess costs and benefits over a 1-year time horizon from the National Health Service perspective in the UK. Patients could either continue on 2nd line therapy or switch to 3rd line opioid due to lack of efficacy or poor tolerability. Patients failing also 3rd line therapy entered the final absorbing health state (4th line). Data on tolerability, efficacy, and utilities for tapentadol and oxycodone were obtained from the three comparative phase III clinical trials. Costs of resource consumption associated with opioid treatment were derived from a retrospective database analysis of anonymized patient records.

Results:

The model results predicted that initiating 2nd line therapy with tapentadol leads to higher effectiveness and lower costs vs oxycodone. For the overall population included in the clinical trials, mean annual costs per patient when treated with tapentadol and oxycodone were £3543 and £3656, respectively. Treatment with tapentadol, while cheaper than oxycodone, was more effective (0.6371 vs 0.6237 quality-adjusted life years (QALYs) for tapentadol and oxycodone, respectively), meaning that tapentadol dominated oxycodone. For the sub-group of opioid-experienced patients with severe pain at baseline the ranking in terms of costs and QALYs remained unchanged. Extensive sensitivity analyses showed that conclusions about the cost-effectiveness are consistent.

Conclusions:

The cost-effectiveness study suggested that initiating 2nd line treatment in patients with severe non-malignant chronic pain in the UK with tapentadol instead of oxycodone improves patients’ quality-of-life and is less costly. Key limitations when interpreting the results are the use of different sources to populate the model and restricted generalizability due to data extrapolation.     

Cost-effectiveness of daclatasvir plus sofosbuvir-based regimen for treatment of hepatitis C virus genotype 3 infection in Canada

Objective:

New regimens for the treatment of chronic hepatitis C virus (HCV) genotype 3 have demonstrated substantial improvement in sustained virologic response (SVR) compared with existing therapies, but are considerably more expensive. The objective of this study was to evaluate the cost-effectiveness of two novel all-oral, interferon-free regimens for the treatment of patients with HCV genotype 3: daclatasvir plus sofosbuvir (DCV?+?SOF) and sofosbuvir plus ribavirin (SOF?+?RBV), from a Canadian health-system perspective.

Methods:

A decision analytic Markov model was developed to compare the effect of various treatment strategies on the natural history of the disease and their associated costs in treatment-naïve and treatment-experienced patients. Patients were initially distributed across fibrosis stages F0–F4, and may incur disease progression through fibrosis stages and on to end-stage liver disease complications and death; or may achieve SVR. Clinical efficacy, health-related quality-of-life, costs, and transition probabilities were based on published literature. Probabilistic sensitivity analysis was performed to assess parameter uncertainty associated with the analysis.

Results:

In treatment-naive patients, the expected quality-adjusted life years (QALYs) for interferon-free regimens were higher for DCV?+?SOF (12.37) and SOF?+?RBV (12.48) compared to that of pINF?+?RBV (11.71) over a lifetime horizon, applying their clinical trial treatment durations. The expected costs were higher for DCV?+?SOF ($170,371) and SOF?+?RBV ($194,776) vs pINF?+?RBV regimen ($90,905). Compared to pINF?+?RBV, the incremental cost-effectiveness ratios (ICER) were $120,671 and $135,398 per QALYs for DCV?+?SOF and SOF?+?RBV, respectively. In treatment-experienced patients, DCV?+?SOF regimen dominated the SOF?+?RBV regimen. Probabilistic sensitivity analysis indicated a 100% probability that a DCV?+?SOF regimen was cost saving in treatment-experienced patients.

Conclusion:

Daclatasvir plus sofosbuvir is a safe and effective option for the treatment of chronic HCV genotype 3 patients. This regimen could be considered a cost-effective option following a first-line treatment of peg-interferon/ribavirin treatment experienced patients with HCV genotype-3 infection.     

Cost-effectiveness analysis of dapagliflozin treatment versus metformin treatment in Chinese population with type 2 diabetes

Background and objective: Dapagliflozin is the first SGLT2 inhibitor available in China, where the disease burden of diabetes and its complications is very heavy. Because a new diabetes treatment strategy for diabetes should consider its cost-effectiveness, compared with an existing treatment, this study aimed to examine the cost-effectiveness between dapagliflozin and metformin treatment in China.

Methods: The Cardiff Diabetes Model (CDM) was used to estimate cost effectiveness and macro- and micro-vascular outcomes of dapagliflozin vs metformin. The CDM effectiveness inputs were derived from indirect comparative efficacy data from meta-analysis of 71 studies comparing monotherapy and add-on therapy of dapagliflozin vs metformin: dapagliflozin or metformin monotherapy, add-on therapy with other oral hypoglycemic agents, and add-on therapy with insulin. Direct medication costs and medical costs on treating diabetes were calculated based on published and local sources. A discount rate of 3% was applied to both costs and health effects. Univariate and probabilistic sensitivity analyses (PSA) were performed to assess uncertainties.

Results: The total healthcare costs accumulated over the lifetime on dapagliflozin treatment arm was 8,626 Chinese yuan higher than the metformin treatment arm for an individual patient, and the quality adjusted life years (QALYs) gained with dapagliflozin treatment was 0.8 more than metformin treatment. Therefore, an incremental cost-effectiveness ratio was 10,729 yuan per QALY gained for dapagliflozin treatment arm vs metformin treatment arm. The cost-effectiveness results were robust to various sensitivity analyses.

Conclusion: Dapagliflozin treatment was more cost-effective compared with metformin treatment for Chinese type 2 diabetes patients. However, the findings of favorable cost-effectiveness results for dapagliflozin are largely driven by the effects of favorable weight profile on clinical, utility, and costs in the Cardiff model.     

Cost-effectiveness of ranibizumab in the treatment of visual impairment due to diabetic macular edema

Objective Ranibizumab, an anti-vascular endothelial growth factor designed for ocular use, has been deemed cost-effective in multiple indications by several Health Technology Assessment bodies. This study assessed the cost-effectiveness of ranibizumab monotherapy or combination therapy (ranibizumab plus laser photocoagulation) compared with laser monotherapy for the treatment of visual impairment due to diabetic macular edema (DME).

Methods A Markov model was developed in which patients moved between health states defined by best-corrected visual acuity (BCVA) intervals and an absorbing ‘death’ state. The population of interest was patients with DME due to type 1 or type 2 diabetes mellitus. Baseline characteristics were based on those of participants in the RESTORE study. Main outputs were costs (in 2013 CA$) and health outcomes (in quality-adjusted life-years [QALYs]) and the incremental cost-effectiveness ratio (ICER) was calculated. This cost-utility analysis was conducted from healthcare system and societal perspectives in Quebec.

Results From a healthcare system perspective, the ICERs for ranibizumab monotherapy and combination therapy vs laser monotherapy were CA$24 494 and CA$36 414 per QALY gained, respectively. The incremental costs per year without legal blindness for ranibizumab monotherapy and combination therapy vs laser monotherapy were CA$15 822 and CA$20 616, respectively. Based on the generally accepted Canadian ICER threshold of CA$50 000 per QALY gained, ranibizumab monotherapy and combination therapy were found to be cost-effective compared with laser monotherapy. From a societal perspective, ranibizumab monotherapy and combination therapy provided greater benefits at lower costs than laser monotherapy (ranibizumab therapy dominated laser therapy).

Conclusions Ranibizumab monotherapy and combination therapy resulted in increased quality-adjusted survival and time without legal blindness and lower costs from a societal perspective compared with laser monotherapy.