Treatment experience,burden and unmet needs (TRIBUNE) in MS study: results from Turkey

Abstract

Objective:

To estimate the economic burden of multiple sclerosis (MS) in Turkey, including the relapses and disease severity, and to evaluate the quality-of-life of MS patients.

Methods:

The Treatment Experience, Burden and Unmet Needs (TRIBUNE) study was a multi-national, cross-sectional, retrospective, burden-of-illness survey. Total costs were calculated using unit costs derived from price lists or published literature, where relevant, and inflated to 2011 TL prices.

Results:

A total of 295 MS patients (74% females) were included in the analysis. The population had a mean age of 36 years; 73% had the relapsing–remitting form. Mean Expanded Disability Status Scale (EDSS) score was 2.2. Twenty-two per cent of the MS patients required hospitalization in the past year and spent an average of 29.2 days/year in hospital. These values were 43% and 5.6 days for the outpatients, respectively. Total cost per patient/year was 18,700 TL (Turkish Lira). Total costs for patients with mild, moderate, and severe disability were 15,418 TL, 26,002 TL, and 44,208 TL per patient/year, respectively. The mean EuroQol 5D scores in the same groups were 0.73, 0.52, and 0.05, respectively.

Conclusions:

Multiple sclerosis imposes a significant economic burden on patients and society in Turkey.     

The impact of increasing neurological disability of multiple sclerosis on health utilities: a systematic review of the literature

Abstract

Background: Multiple sclerosis (MS) is a debilitating disease, accompanied by neurological symptoms of varying severity. Utilities are a key summary index measure used in assessing health-related quality of life in individuals with MS.

Objectives: To provide a systematic review of the literature on utilities of relapsing-remitting MS (RRMS) and secondary progressive MS (SPMS) patients and to review changes in utilities associated with the increasing neurological disability of different stages of MS, as measured by the Expanded Disability Status Scale (EDSS).

Methods: Employing pre-defined search terms and inclusion/exclusion criteria, systematic searches of the literature were conducted in EMBASE, MEDLINE, PsycINFO, the Health Economic Evaluation Database (HEED), and the NHS Economic Evaluations Database (NHS/EED). Proceedings for the International Society for Pharmacoeconomics and Outcomes Research (ISPOR), the European Society for Treatment and Research in MS (ECTRIMS), the American Society for Treatment and Research in MS (ACTRIMS), and the Latin American Society for Treatment and Research in MS (LACTRIMS) were reviewed in addition to the UK National Institute for Health and Clinical Excellence website and the table of contents of PharmacoEconomics and Value in Health.

Results: This review identified 18 studies reporting utilities associated with health states of MS. Utilities ranged from 0.80 to 0.92 for patients with an EDSS score of 1, from 0.49 to 0.71 for patients with an EDSS score of 3, from 0.39 to 0.54 for patients with an EDSS score of 6.5, and from –0.19 to 0.1 for patients with an EDSS score of 9.

Limitations: Several of the studies reviewed relied on data from patient organizations, which may not be fully representative of the general patient populations. Additionally, the majority of the studies relied on retrospective data collection.

Conclusions: Utilities decrease substantially with increasing neurological disability. Cross-country differences are minimal with utility scores following a similar pattern across countries for patients at similar disease severity levels. This consistency in findings is noteworthy, as there is a reliable evidence base for selecting utility values for economic evaluation analyses. However, more research is needed to explore potential differences in utilities between RRMS and SPMS patients.     

Cost-utility analysis of alemtuzumab in comparison with interferon beta,fingolimod, and natalizumab treatment for relapsing-remitting multiple sclerosis in Austria

Background: Multiple sclerosis (MS), a chronic progressive, demyelinating, inflammatory disease, affects 2.5 million people worldwide. Approximately 63% of cases are classified as relapsing–remitting MS (RRMS) at the time of diagnosis. The aim of this cost-utility analysis is to evaluate alemtuzumab vs interferon beta (intramuscular [IM] interferon beta-1a, subcutaneous [SC] interferon beta-1a, SC interferon beta-1b, and SC pegylated interferon beta-1a) in previously treated, and vs SC interferon beta-1a, fingolimod, and natalizumab in untreated RRMS patients to determine the incremental cost-effectiveness ratio among the treatment alternatives as prices, the route, and the frequency of administration of considered products vary significantly.

Methods: The primary outcome was the modeled incremental cost-effectiveness ratio (ICER; €/quality-adjusted life-year [QALY] gained). Markov modeling with a 10-year time horizon was carried out. During each 3-month cycle, patients maintained the Expanded Disability Status Scale (EDSS) score or experienced progression, developed secondary progressive MS (SPMS), or showed EDSS progression in SPMS; experienced relapses; suffered from an adverse event (AE); changed treatment; or died. A published network meta-analysis (NMA) was used for indirect comparison. The possibility of a therapy switch was considered. Clinical input data and resource utilization data were derived from the literature. Costs were extracted from price lists published in Austria and were calculated from the payer’s perspective.

Results: In treatment naïve patients, alemtuzumab is associated with costs of €132,663 and 5.25 QALYs in a 10-year time horizon. Costs for SC interferon beta amount to €164,159 and generate 4.85 QALYs. Also, in the pre-treated patients, alemtuzumab dominated comparators by accumulating higher total QALYs (4.88) and lower total costs (€137.409) compared to interferon beta-1a (€200.133), fingolimod (€240.903), and natalizumab (€247.758).

Conclusion: The analysis shows that alemtuzumab is a cost-saving alternative to treat RRMS in pre-treated and therapy naïve patients. From the patient perspective, alemtuzumab improves quality-of-life.     

Cost effectiveness of zoledronic acid in the management of skeletal metastases in hormone-refractory prostate cancer patients in France,Germany, Portugal,and the Netherlands

Abstract

Objective:

Zoledronic acid (ZOL) reduces the risk of skeletal related events (SREs) in hormone-refractory prostate cancer (HRPC) patients with bone metastases. This study assessed the cost effectiveness of ZOL for SRE management in French, German, Portuguese, and Dutch HRPC patients.

Methods:

This analysis was based on the results of a randomized phase III clinical trial wherein HRPC patients received up to 15 months of ZOL (n?=?214) or placebo (n?=?208). Clinical inputs were obtained from the trial. Costs were estimated using hospital tariffs, published, and internet sources. Quality adjusted life-years (QALYs) gained were estimated from a separate analysis of EQ-5D scores reported in the trial. Uncertainty surrounding outcomes was addressed via univariate sensitivity analyses.

Results:

ZOL patients experienced an estimated 0.759 fewer SREs and gained an estimated 0.03566 QALYs versus placebo patients. ZOL was associated with reduced SRE-related costs [net costs] (?€2396 [€1284] in France, ?€2606 [€841] in Germany, ?€3326 [€309] in Portugal and ?€3617 [€87] in the Netherlands). Costs per QALY ranged from €2430 (Netherlands) to €36,007 (France).

Conclusions:

This analysis is subject to the limitations of most cost-effectiveness analyses: it combines data from multiple sources. Nevertheless, the results strongly suggest that ZOL is cost effective versus placebo in French, German, Portuguese, and Dutch HRPC patients.     

An economic evaluation of perioperative enteral nutrition in patients undergoing colorectal surgery (SANICS II study)

Aims: The objective of this (trial based) economic evaluation was to assess, from a societal perspective, the cost-effectiveness of perioperative enteral nutrition compared with standard care in patients undergoing colorectal surgery.

Materials and methods: Alongside the SANICS II randomized controlled trial, global quality-of-life, utilities (measured by EQ-5D-5L), healthcare costs, production losses, and patient and family costs were assessed at baseline, 3?months, and 6?months. Incremental cost-effectiveness ratios (ICERs) (i.e. cost per increased global quality-of-life score or quality-adjusted life year [QALY] gained) and cost effectiveness acceptability curves were visualized.

Results: In total, 265 patients were included in the original trial (n?=?132 in the perioperative enteral nutrition group and n?=?133 in the standard care group). At 6?months, global quality-of-life (83 vs 83, p?=?.357) did not differ significantly between the groups. The mean total societal costs for the intervention and standard care groups were €14,673 and €11,974, respectively, but did not reach statistical significance (p?=?.109). The intervention resulted in an ICER of –€6,276 per point increase in the global quality of life score. The gain in QALY was marginal (0.003), with an additional cost of €2,941, and the ICUR (Incremental cost utility ratio) was estimated at €980,333.

Limitations: The cost elements for all the participating centers reflect the reference prices from the Netherlands. Patient-reported questionnaires may have resulted in recall bias. Sample size was limited by exclusion of patients who did not complete questionnaires for at least at two time points. A power analysis based on costs and health-related quality-of-life (HRQoL) was not performed. The economic impact could not be analyzed at 1?month post-operatively where the effects could potentially be higher.

Conclusions: This study suggests that perioperative nutrition is not beneficial for the patients in terms of quality-of-life and is not cost-effective.

Trial registration: ClinicalTrials.gov identifier: NCT02175979.

Trial registration: Netherlands National Trial Register identifier: NTR4670.     

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

Abstract

Objective:

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

Methods:

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

Results:

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

Limitations:

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

Conclusion:

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

Cost-effectiveness of glatiramer acetate and interferon beta-1a for relapsing-remitting multiple sclerosis,based on the CombiRx study

Background:

To assess the cost-effectiveness of the Disease Modifying Treatments (DMT), Glatiramer Acetate (GA) and Interferon beta-1a (IFN) in monotherapy alone and in combination for the prevention of relapses among Spanish patients aged between 18–60 years old with established Relapsing–Remitting Multiple Sclerosis (RRMS).

Methods:

A Markov model was developed to represent the transition of a cohort of patients over a 10 year period using the perspective of the Spanish National Health Service (NHS). The model considered five different health states with 1-year cycles including without relapse, patients with suspect, non-protocol defined and protocol defined exacerbations, as well as a category information lost. Efficacy data was obtained from the 3-year CombiRx Study. Costs were reported in 2013 Euros and a 3% discount rate was applied for health and benefits. Deterministic results were presented as the annual treatment cost for the number of relapses. A probabilistic sensitivity analysis was performed to test the robustness of the model.

Results:

Deterministic results showed that the expected annual cost per patient was lower when treated with GA (€13,843) compared with IFN (€15,589) and the combined treatment with IFN?+?GA (€21,539). The annual number of relapses were lower in the GA cohort with 3.81 vs 4.18 in the IFN cohort and 4.08 in the cohort treated with IFN?+?GA. Results from probabilistic sensitivity analysis showed that GA has a higher probability of being cost-effective than treatment with IFN or IFN?+?GA for threshold values from €28,000 onwards, independent of the maximum that the Spanish NHS is willing to pay for avoiding relapses.

Conclusion:

GA was shown to be a cost-effective treatment option for the prevention of relapses in Spanish patients diagnosed with RRMS. When GA in monotherapy is compared with INF in monotherapy and IFN?+?GA combined, it may be concluded that the first is the dominant strategy.     

The cost-effectiveness of solifenacin vs. trospium in the treatment of patients with overactive bladder in the German National Health Service

Objective:

To carry out a cost–utility analysis comparing initial treatment of patients with overactive bladder (OAB) with solifenacin 5?mg/day versus either trospium 20?mg twice a day or trospium 60?mg/day from the perspective of the German National Health Service.

Methods:

A decision analytic model with a 3 month cycle was developed to follow a cohort of OAB patients treated with either solifenacin or trospium during a 1 year period. Costs and utilities were accumulated as patients transitioned through the four cycles in the model. Some of the solifenacin patients were titrated from 5?mg to 10?mg/day at 3 months. Utility values were obtained from the published literature and pad use was based on a US resource utilization study. Adherence rates for individual treatments were derived from a United Kingdom general practitioner database review. The change in the mean number of urgency urinary incontinence episodes/day from after 12 weeks was the main outcome measure. Baseline effectiveness values for solifenacin and trospium were calculated using the Poisson distribution. Patients who failed second-line therapy were referred to a specialist visit. Results were expressed in terms of incremental cost–utility ratios.

Results:

Total annual costs for solifenacin, trospium 20?mg and trospium 60?mg were €970.01, €860.05 and €875.05 respectively. Drug use represented 43%, 28% and 29% of total costs and pad use varied between 45% and 57%. Differences between cumulative utilities were small but favored solifenacin (0.6857 vs. 0.6802 to 0.6800). The baseline incremental cost–effectiveness ratio ranged from €16,657 to €19,893 per QALY.

Limitations:

The difference in cumulative utility favoring solifenacin was small (0.0055–0.0057 QALYs). A small absolute change in the cumulative utilities can have a marked impact on the overall incremental cost-effectiveness ratios (ICERs) and care should be taken when interpreting the results.

Conclusion:

Solifenacin would appear to be cost-effective with an ICER of no more than €20,000/QALY. However, small differences in utility between the alternatives means that the results are sensitive to adjustments in the values of the assigned utilities, effectiveness and discontinuation rates.     

Assessing the burden of illness from cervical dystonia using the Toronto Western Spasmodic Torticollis Rating Scale scores and health utility: a meta-analysis of baseline patient-level clinical trial data

Purpose:

This study aimed to explore the burden of illness associated with cervical dystonia (CD), including possible demographic and humanistic correlates of baseline disease severity.

Methods:

The analysis involved the five multinational randomized, placebo-controlled clinical trials that had evaluated the efficacy and safety of Dysport® in patients with CD, including assessment using the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS). Patient-level TWSTRS scores from the individual studies were meta-analysed to estimate disease severity at baseline. One of the studies had reported Short Form-36 (SF-36) Health Survey quality-of-life measures, and these data were used to investigate whether the severity of CD was associated with humanistic outcomes, as measured by health utility. A generalized regression model was then applied to explore potential correlation between TWSTRS scores and utilities.

Results:

The estimated pooled mean baseline severity of CD in clinical trial entrants, as measured by TWSTRS score, was 43.23 (95% CI?=?39.31–47.15). In general, disease severity was significantly greater in patients aged over 40 years (compared to the reference group aged 18–30 years). However, there was no correlation between disease severity and other demographic characteristics (e.g., weight, height, gender). Higher TWSTRS scores correlated with worse health-related quality of life as perceived by patients and was reflected in health utility (R^2?=?0.133).

Conclusions:

This study was able to define TWSTRS scores in patients with CD in terms of associated utility. This approach could help in capturing the disease’s burden through measures that are more tangible than TWSTRS scores to patients, carers, clinicians, and healthcare payers.     

Economic burden associated with the management of cervical cancer,cervical dysplasia and genital warts in Belgium

Abstract

Objective: Human papillomavirus (HPV) infections can lead to cervical intraepithelial neoplasia (CIN) lesions, cervical cancer (CC) and genital warts (GWs). This study intended to assess the annual cost of CC, CIN and GW management in Belgium.

Method: A retrospective study using a Belgian Hospital Disease Database (for yearly hospital cost of CC and GW patients) and a clinical expert survey were performed to assess the medical management of CC, CIN and GW patients. Belgian official sources were used to estimate the annual costs of management of CC, CIN and GW patients both from a healthcare payer perspectives (HCPP) and a societal perspective.

Results: Based on the 667 patients diagnosed annually in Belgium with CC and an annual cost per patient of €9,716, the total annual cost of CC is €6.5 million (HCPP). The 10,495 estimated CIN 1, 2 and 3 patients led to an annual cost of €1.97 million (HCPP). The 7,989 estimated annual number of diagnosed GW patients led to an estimated annual cost of €2.53 million (HCPP).

Conclusion: HPV-related diseases represent an important burden on Belgian society, especially when considering that the estimates in this study are probably underestimations, as the management costs of other HPV-related diseases (vulvar, vaginal, penile, oropharyngeal (pre-) cancers, recurrent respiratory papillomatosis etc.) are not included in this analysis.     

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.     

Fingolimod reduces direct medical costs compared to natalizumab in patients with relapsing–remitting multiple sclerosis in The Netherlands

Abstract

Objective:

To assess the costs of oral treatment with Gilenya® (fingolimod) compared to intravenous infusion of Tysabri® (natalizumab) in patients with relapsing–remitting multiple sclerosis (RRMS) in The Netherlands.

Methods:

A cost-minimization analysis was used to compare both treatments. The following cost categories were distinguished: drug acquisition costs, administration costs, and monitoring costs. Costs were discounted at 4%, and incremental model results were presented over a 1, 2, 5, and 10 year time horizon. The robustness of the results was determined by means of a number of deterministic univariate sensitivity analyses. Additionally, a break-even analysis was carried out to determine at which natalizumab infusion costs a cost-neutral outcome would be obtained.

Results:

Comparing fingolimod to natalizumab, the model predicted discounted incremental costs of ?€2966 (95% CI: ?€4209; ?€1801), ?€6240 (95% CI: ?€8800; ?€3879), ?€15,328 (95% CI: ?€21,539; ?€9692), and ?€28,287 (95% CI: ?€39,661; ?€17,955) over a 1, 2, 5, and 10-year time horizon, respectively. These predictions were most sensitive to changes in the costs of natalizumab infusion. Changing these costs of €255 within a range from €165–364 per infusion resulted in cost savings varying from €4031 to €8923 after 2 years. The additional break-even analysis showed that infusion costs—including aseptic preparation of the natalizumab solution—needed to be as low as the respective costs of €94 and €80 to obtain a cost neutral result after 2 and 10 years.

Limitations:

Neither treatment discontinuation and subsequent re-initiation nor patient compliance were taken into account. As a consequence of the applied cost-minimization technique, only direct medical costs were included.

Conclusion:

The present analysis showed that treatment with fingolimod resulted in considerable cost savings compared to natalizumab: starting at €2966 in the first year, increasing to a total of €28,287 after 10 years per RRMS patient in the Netherlands.     

Societal costs of multiple sclerosis in Ireland

Aims: This paper evaluates the impact of multiple sclerosis (MS) in Ireland, and estimates the associated direct, indirect, and intangible costs to society based on a large nationally representative sample.

Materials and methods: A questionnaire was developed to capture the demographics, disease characteristics, healthcare use, informal care, employment, and wellbeing. Referencing international studies, standardized survey instruments were included (e.g. CSRI, MFIS-5, EQ-5D) or adapted (EDSS) for inclusion in an online survey platform. Recruitment was directed at people with MS via the MS Society mailing list and social media platforms, as well as in traditional media. The economic costing was primarily conducted using a ‘bottom-up’ methodology, and national estimates were achieved using ‘prevalence-based’ extrapolation.

Results: A total of 594 people completed the survey in full. The sample had geographic, disease, and demographic characteristics indicating good representativeness. At an individual level, average societal cost was estimated at €47,683; the average annual costs for those with mild, moderate, and severe MS were calculated as €34,942, €57,857, and €100,554, respectively. For a total Irish MS population of 9,000, the total societal costs of MS amounted to €429m. Direct costs accounted for just 30% of the total societal costs, indirect costs amounted to 50% of the total, and intangible or QoL costs represented 20%. The societal cost associated with a relapse in the sample is estimated as €2,438.

Limitations and conclusions: The findings highlight that up to 70% of the total costs associated with MS are not routinely counted. These “hidden” costs are higher in Ireland than the rest of Europe, due in part to significantly lower levels of workforce participation, a higher likelihood of permanent workforce withdrawal, and higher levels of informal care needs. The relationship between disease progression and costs emphasize the societal importance of managing and slowing the progression of the illness.     

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.     

Cost effectiveness of palivizumab for RSV prevention in high-risk children in the Netherlands

Abstract

Background: Respiratory syncytial virus (RSV) is a common pathogen that is the leading cause of lower respiratory tract infections in young children. High-risk children are at risk of severe infection, which may require hospitalisation. RSV is also associated with a high risk for respiratory morbidity and mortality, which may have long-term clinical and economic consequences.

Objective: To assess the cost effectiveness of palivizumab, a humanised monoclonal antibody, used as prevention against severe respiratory syncytial virus (RSV) infection requiring hospitalisation, in the indication of preterm infants and infants with preterm/bronchopulmonary dysplasia and in the second indication of children with congenital heart disease in the Dutch healthcare setting.

Methods: A decision-tree model was used to estimate the cost effectiveness of palivizumab, used as a preventative treatment against severe respiratory syncytial virus (RSV) infection, in high-risk groups of children in the Netherlands. The analysis was based on a lifetime follow-up period in order to capture the impact of palivizumab on long-term morbidity and mortality resulting from an RSV infection. Data sources included published literature, the palivizumab pivotal trials, official price/tariff lists and national population statistics. The study was conducted from the perspective of society in the Netherlands.

Results: The use of palivizumab results in undiscounted incremental cost-effectiveness ratios of €12,728/QALY and €4,256/QALY in the in preterm/bronchopulmonary dysplasia and congenital heart disease indications, respectively. Inclusion of indirect costs leads to even more favourable cost-effectiveness outcomes. The study is limited by a number of conservative assumptions. It was assumed that palivizumab only affects the occurrence of RSV hospitalisation and does not influence the severity of the RSV infection. Another assumption was that international clinical trial data and data on utilities could be applied to the Dutch healthcare setting.

Conclusion: Palivizumab provides cost-effective prophylaxis against RSV in high-risk infants. The use of palivizumab in these children results in positive short- and long-term health-economic benefits.     

The cost-effectiveness and monetary benefits of dabigatran in the prevention of arterial thromboembolism for patients with non-valvular atrial fibrillation in the Netherlands

Background: Atrial fibrillation (AF) causes a significant health and economic burden to the Dutch society. Dabigatran was proven to have at least similar efficacy and a similar or better safety profile when compared to vitamin K antagonists (VKAs) in preventing arterial thromboembolism in patients with AF.

Objective: To evaluate the cost-effectiveness and monetary benefit of dabigatran vs VKAs in Dutch patients with non-valvular AF. Value-based pricing considerations and corresponding negotiations on dabigatran will be explicitly considered.

Methods: The base case economic analysis was conducted from the societal perspective. Health effects and costs were analysed using a Markov model. The main model inputs were derived from the RE-LY trial and Dutch observational data. Univariate, probabilistic sensitivity, and various scenario analyses were performed.

Results: Dabigatran was cost saving compared to VKAs. A total of 4,552 QALYs were gained, and €13,892,288 was saved in a cohort of 10,000?AF patients. The economic value of dabigatran was strongly related to the costs of VKA control that are averted. Notably, dabigatran was cost saving compared to VKAs if annual costs of VKA control exceeded €159 per person, or dabigatran costs were below €2.81 per day.

Conclusion: Dabigatran was cost saving compared to VKAs for the prevention of atrial thromboembolism in patients with non-valvular AF in the Netherlands. This result appeared robust in the sensitivity analysis. Furthermore, volume based reduction of the price in the Netherlands will further increase the monetary benefits of dabigatran.     

Cost-effectiveness analysis of disease modifiying drugs (interferons and glatiramer acetate) as first line treatments in remitting-relapsing multiple sclerosis patients

Abstract

Objective:

The aim of this study was to assess cost-effectiveness of the different Disease Modifying Drugs (DMD) used as first-line treatments (interferons IM IFNβ-1a, SC IFNβ-1a, SC IFNβ-1b, and glatiramer acetate, GA) in Remitting-Relapsing Multiple Sclerosis (RRMS) in Spain.

Methods:

A Markov model was developed to simulate the progression of a cohort of patients with RRMS, during a period of 10 years. Seven health states, defined by the Expanded Disability Status Scale (EDSS), were considered in the model. Patients with an EDSS score less than 6.0 were assumed to be treated with one of the DMD. In addition, all patients were assumed to receive symptomatic treatment. The monthly transition probabilities of the model were obtained from the literature. The analysis was performed from the societal perspective, in which both direct and indirect (losses in productivity) healthcare costs (€, 2010) were included. A discount rate of 3% was applied to both costs and efficacy results.

Results:

GA was the less costly strategy (€322,510), followed by IM IFNβ-1a (€329,595), SC IFNβ-1b (€ 333,925), and SC IFNβ-1a (€348,208). IM IFNβ-1a has shown the best efficacy results, with 4.176 quality-adjusted life years (QALY), followed by SC IFNβ-1a (4.158 QALY), SC IFNβ-1b (4.157 QALY), and GA (4.117 QALY). Incremental costs per QALY gained with IM IFNβ-1a were €?1,005,194/QALY, €?223,397/QALY, and €117,914/QALY in comparison to SC IFNβ-1a, SC IFNβ-1b, and GA, respectively.

Conclusions:

First-line treatment with GA is the less costly strategy for the treatment of patients with RRMS. Treatment with IM IFNβ-1a is a dominant strategy (lower cost and higher QALY) compared with SC IFNβ-1a and SC IFNβ-1b. However, IM IFNβ-1a is not a cost-effective strategy vs GA, because incremental cost per QALY gained with IM IFNβ-1a exceeds the €30,000 per QALY threshold commonly used in Spain.

Limitations:

The highly-restrictive inclusion criteria of clinical trials limits generalization of the results on efficacy to all patients with multiple sclerosis. Availability of data for head-to-head comparisons is associated with the use of information from clinical trials.     

Costs of haematological adverse events in chronic myeloid leukaemia patients: a retrospective cost analysis of the treatment of anaemia,neutropenia and thrombocytopenia in patients with chronic myeloid leukaemia

Abstract

Objective: The study aim was to assess costs of haematological adverse events (AE) related to pharmacologic treatment of chronic myeloid leukaemia (CML) patients.

Methods: This was a retrospective cohort study using patient records of adults (n=91) with chronic-phase CML treated at a single university medical centre in the Netherlands. Occurrence of grade III/IV haematological AEs, defined according to CTC-NCI guidelines criteria, was derived from the laboratory registration. Mean age at time of diagnosis was 48 years; 56% male. A healthcare perspective was adopted. Cost estimates are presented in 2006 euros.

Results: Average cost of an episode of anaemia was €1,572, of thrombocytopenia €2,955, and of neutropenia €1,152. The mean cost of febrile neutropenia amounted to €2,462.

Conclusions: Treatment costs of AEs varied considerably. However, apart from the cost of anaemia, the results presented seem to be in line with information from the international literature. The key limitations of the study concern the relatively small cohort of patients at a single centre, the retrospective design and the various treatment regimens of CML during the follow-up.     

The cost effectiveness of zoledronic acid 5 mg for the management of postmenopausal osteoporosis in women with prior fractures: evidence from Finland,Norway and the Netherlands

Abstract

Objective:

This study was conducted to assess the cost effectiveness of zoledronic acid 5?mg as a first-line treatment for the secondary prevention of fragility fractures in women with postmenopausal osteoporosis in Finland, Norway and the Netherlands.

Methods:

A discrete-event, individual-patient computer-simulation model was used to compare the cost effectiveness of zoledronic acid with that of basic treatment (calcium and vitamin D) and commonly prescribed bisphosphonates in postmenopausal women aged 50–80 years who have experienced one previous fracture and have a bone mineral density T-score of ?2.5.

Results:

The cost per quality-adjusted life-year (QALY) gained with zoledronic acid compared with basic treatment ranged from being cost saving in all age groups in Norway, to costing approximately €19,000 in Finland and €22,300 in the Netherlands. Compared with the other branded bisphosphonates, zoledronic acid was cost saving in many scenarios, including all age groups in Finland. In Norway, zoledronic acid dominated branded risedronate and ibandronate in all age groups and dominated or had incremental cost-effectiveness ratios (ICERs) of up to NOK83,954 per QALY gained compared with branded alendronate. In the Netherlands, zoledronic acid dominated branded intravenous ibandronate in all age groups; compared with branded risedronate and oral ibandronate, zoledronic acid dominated or had ICERs of up to €4832 per QALY gained; compared with branded alendronate, it had ICERs of up to €48,383 per QALY gained. In all three countries, zoledronic acid may be cost effective compared with generic alendronate when patient compliance with drug therapy is taken into account. Sensitivity analyses showed that the model was robust to changes in key values. The main model limitations were the lack of real-life compliance and persistence data, and lack of country-specific data for some parameters.

Conclusions:

Using local or commonly used thresholds, this analysis suggests that zoledronic acid would be a cost-effective first-line option compared with other branded bisphosphonates and, in some scenarios, compared with generic alendronate, for the secondary prevention of fractures in women with postmenopausal osteoporosis in Finland, Norway and the Netherlands.     

Cost effectiveness of palivizumab in children with congenital heart disease in Germany

Abstract

Objectives: To assess the cost effectiveness of palivizumab, a humanised monoclonal antibody, used as prevention against severe respiratory syncytial virus (RSV) infection requiring hospitalisation, in infants with haemodynamically significant congenital heart disease (CHD) in the German healthcare setting.

Study design: A decision-tree model was used to estimate the cost effectiveness of palivizumab for a hypothetical cohort of patients. The analysis was based on a lifetime follow-up period in order to capture the impact of palivizumab on long-term morbidity and mortality resulting from an RSV infection. Data sources included published literature, the palivizumab pivotal trials, official price/tariff lists and national population statistics. The study was conducted from the perspective of society (primary analysis) and the healthcare purchaser (secondary analysis).

Results: From the societal perspective, use of palivizumab results in an incremental cost-effectiveness ratio (ICER) of €2,615 per quality-adjusted life-year (QALY) without discounting, which increases to €9,529/QALY after discounting. From the perspective of the German healthcare purchaser, use of palivizumab results in an ICER of €4,576/QALY without discounting, which increases to €16,673/QALY after discounting. Probabilistic sensitivity analyses confirmed the robustness of the model. The study is limited by a number of conservative assumptions. It was assumed that palivizumab only affects the occurrence of RSV hospitalisation and does not influence the severity of the RSV infection. Another assumption was that international clinical trial data and data on utilities could be applied to the German healthcare setting.

Conclusion: This analysis showed that palivizumab represents a cost-effective means of prophylaxis against severe RSV infection requiring hospitalisation in infants with haemodynamically significant CHD.