A cost-effectiveness modeling evaluation comparing a biosimilar follitropin alfa preparation with its reference product for live birth outcome in Germany,Italy and Spain

Abstract

Background/objective: Although biosimilar drugs may be cheaper to purchase than reference biological products, they may not be the most cost-effective treatment to achieve a desired outcome. The analysis reported here compared the overall costs to achieve live birth using the reference follitropin alfa (GONAL-f) or a biosimilar (Ovaleap) in Spain, Italy and Germany.

Methods: Patient and treatment data was obtained from published sources; assisted-reproductive technology, gonadotropin, follow-up and adverse-event-related costs were calculated from tariffs and reimbursement frameworks for each country. Incremental cost-effectiveness ratios (ICERs) were calculated from the difference in costs between reference and biosimilar in each country, divided by the difference in live-birth rates. Mean cost per live birth was calculated as total costs divided by the live-birth rate.

Results: The published live birth rates were 32.2% (reference) and 26.8% (biosimilar). Drug costs per patient were higher for the reference recombinant human follicle-stimulating hormone in all three countries, with larger cost differences in Germany (€157.38) and Italy (€141.50) than in Spain (€22.41). The ICER for the reference product compared with the biosimilar was €2917.47 in Germany, €415.43 in Spain and €2623.09 in Italy. However, the overall cost per live birth was higher for the biosimilar in all three countries (Germany €8135.04 vs. €9185.34; Italy €8545.22 vs. €9733.37; Spain €14,859.53 vs. €17,767.19). Uncertainty in efficacy, mean gonadotropin dose and costs did not have a strong effect on the ICERs.

Conclusions: When considering live birth outcomes, treatment with the reference follitropin alfa was more cost effective than treatment with the biosimilar follitropin alfa.     

A cost-effectiveness analysis comparing the originator follitropin alfa to its biosimilars in patients undergoing a medically assisted reproduction program from a French perspective

Objective: To assess the cost-effectiveness (CE) of the originator follitropin-α (Gonal-F) in patients undergoing a medically assisted reproduction (MAR) program in comparison to its biosimilars Bemfola and Ovaleap in a French context.

Methods: A CE model was developed for France with a National Health Service (NHS) perspective. Clinical, safety, and dosage data were derived from pivotal clinical trials that compared Gonal-F to Ovaleap and Bemfola. Costs pertaining to drugs, hospitalizations, specialist visits, and examinations were retrieved from the French Programme de Médicalisation des Systèmes d'Information (PMSI) hospital database, literature review, and French clinical experts using 2017?Euro tariffs. In order to test the robustness of results, deterministic one-way sensitivity analyses were carried out on the main variables to assess the impact of treatment cost, probability of birth, ovarian hyperstimulation syndrome (OHSS) rates, and dosage.

Results: The average incremental cost per live birth with OHSS and without OHSS was €259.56 and €278.39, respectively, for Gonal-F compared to the pooled biosimilars (i.e. Ovaleap and Bemfola). GONAL-F had an incremental efficacy of 0.06 over the pooled biosimilars. The incremental cost-effectiveness ratio for Gonal-F with OHSS ranged from €3,274.80 to €4,877.76 compared to the pooled biosimilars, owing to the additional live births reported with Gonal-F. Sensitivity analyses also supported results from the base case analyses, with Gonal-F being cost-effective or the dominant strategy in most cases.

Conclusion: Gonal-F seems to be a cost-effective strategy compared to its biosimilars Ovaleap and Bemfola, irrespective of the incidence of OHSS events, but further data are needed to confirm these results.     

Real-world healthcare resource utilization related to migraine treatment failure: a panel-based chart review in France,Germany, Italy,and Spain

Abstract

Aims: This retrospective chart review examined the six-month migraine-related healthcare resource use (HRU) among European patients who had ≥4 migraine days per month and previously failed at least two prophylactic migraine treatments.

Methods: Neurologists, headache specialists, and pain specialists in France, Germany, Italy, and Spain who treated ≥10 patients with migraine in 2017 were recruited (April–June 2018) to extract anonymized patient-level data. Eligible physicians randomly selected charts of up to five adult patients with clinically-confirmed migraine, ≥4 migraine days in the month prior to the index date, and had previously failed at least two prophylactic migraine treatments. Treatment failure was defined as discontinuation due to lack of efficacy and/or tolerability. Demographic and disease characteristics as of the index date, and migraine-related HRU incurred during the 6-month study period, were recorded.

Results: A total of 104 physicians contributed 168 charts for patients (63% female). On average, patients were 38?years old and failed 2.3 prophylactic treatments as of the index date. During the study period, 83% of patients had ≥1 outpatient visit for migraine in the physician’s office, and 27% went to the ER/A&E. Approximately 5% of patients were hospitalized for migraine, with an average of one hospitalization and an average length of stay of 3 days. Approximately 39% of patients had ≥1 blood test, 22% had ≥1 magnetic resonance imaging, 17% had ≥1 electroencephalogram, and 13% had ≥1 computerized tomography scan. Visits to other healthcare providers were common.

Limitations: This study is subject to the limitations of chart review studies, such as errors in data entry.

Conclusions: Across four European countries, the HRU burden of migraine among patients who previously failed at least two prophylactic treatments was high, indicating a need for more effective prophylactic treatments to appropriately manage migraine and reduce the HRU burden attributable to this common disorder.     

Economic impact of contrast-induced acute kidney injury associated with invasive cardiology: role of iso-osmolar contrast media in Germany,Italy, Poland,and Spain

Objective:

Iso-osmolar Iodixanol is associated with a lower rate of contrast-induced acute kidney injury (CI-AKI) in patients at increased risk compared to low-osmolar contrast media (LOCM). The aim of this study was to assess the financial consequences of CI-AKI risk reduction in patients undergoing coronary angiography (CA) with or without percutaneous coronary intervention (PCI) in German, Italian, Polish and Spanish hospitals.

Methods:

This budget impact analysis (BIA) compared a scenario with iodixanol to a scenario without, where only LOCM were used, in patients at increased risk of CI-AKI over a 3-year horizon. A meta-analysis based on a systematic review observed a lower rate of CI-AKI with iodixanol compared to LOCM (Risk Reduction?=?0.46) in patients with underlying impaired renal function (serum creatinine ≥1.6?mg/dl and estimated glomerular filtration rate ≤50?ml/min/1.73 m²). Contrast media and CI-AKI hospitalization costs were included in the analysis and unit costs were obtained from published literature, official sources or, when available, from hospital data. In the absence of country-specific data, resource utilization for a CI-AKI hospitalization was obtained by interviews with local clinicians in each country. The percentage of patients who received iodixanol was assumed to increase over time.

Results:

Based on a percentage of patients at increased risk of CI-AKI equal to 20% in Germany, 24% in Italy, 23% in Poland and 10% in Spain, results showed that the introduction of iodixanol would bring a 3-years cumulative net percentage saving on the total hospital budget of 29%, 34%, 25%, and 33% in the four countries respectively.

Conclusion:

The results of the analysis for the four countries showed that iodixanol use in patients at increased risk of CI-AKI undergoing CA with or without PCI may bring considerable savings on the hospital’s budget, due to the associated reduction in CI-AKI incidence.     

A cost-effectiveness analysis of denosumab for the prevention of skeletal-related events in patients with multiple myeloma in four European countries: Austria,Belgium, Greece,and Italy

Aim: The approved indication for denosumab (120?mg) was expanded in 2018 to include skeletal-related event (SRE) prevention in patients with multiple myeloma (MM). Therefore, a cost-effectiveness analysis was conducted comparing denosumab with zoledronic acid (ZA) for SRE prevention in patients with MM from the national healthcare system perspective in a representative sample of European countries: Austria, Belgium, Greece, and Italy.

Methods: The XGEVA global economic model for patients with MM was used to calculate incremental cost-effectiveness ratios (ICERs) for denosumab vs ZA over a lifetime horizon. Clinical inputs were derived from the denosumab vs ZA randomized, phase 3 study (“20090482”) in patients newly-diagnosed with MM, and comprised real-world adjusted SRE rates, serious adverse event (SAE) rates, treatment duration, dose intensity, progression-free survival (PFS), and overall survival (OS). Economic inputs comprised country-specific denosumab and ZA acquisition and administration costs, SRE and SAE management costs, and discount rates. Health utility decrements associated with MM disease progression, SRE and SAE occurrence, and route of administration were included.

Results: Estimated ICERs (cost per quality-adjusted life-year [QALY] gained) for denosumab vs ZA in Austria, Belgium, Greece, and Italy were €26,294, €17,737, €6,982, and €27,228, respectively. Using 1–3 times gross domestic product (GDP) per capita per QALY as willingness to pay thresholds, denosumab was 69–94%, 84–96%, 79–96%, and 50–92% likely to be cost-effective vs ZA, respectively.

Limitations: Economic inputs were derived from various sources, and time to event inputs were extrapolated from 20090482 study data.

Conclusions: Denosumab is cost-effective vs ZA for SRE prevention in patients with MM in Austria, Belgium, Greece, and Italy, based on often-adopted World Health Organization thresholds. This conclusion is robust to changes in model parameters and assumptions. Cost-effectiveness estimates varied across the four countries, reflecting differences in healthcare costs and national economic evaluation guidelines.     

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.     

A systematic review of cost-effectiveness modeling of pharmaceutical therapies in neuropathic pain: variation in practice,key challenges,and recommendations for the future

Objectives: Complexities in the neuropathic-pain care pathway make the condition difficult to manage and difficult to capture in cost-effectiveness models. The aim of this study is to understand, through a systematic review of previous cost-effectiveness studies, some of the key strengths and limitations in data and modeling practices in neuropathic pain. Thus, the aim is to guide future research and practice to improve resource allocation decisions and encourage continued investment to find novel and effective treatments for patients with neuropathic pain.

Methods: The search strategy was designed to identify peer-reviewed cost-effectiveness evaluations of non-surgical, pharmaceutical therapies for neuropathic pain published since January 2000, accessing five key databases. All identified publications were reviewed and screened according to pre-defined eligibility criteria. Data extraction was designed to reflect key data challenges and approaches to modeling in neuropathic pain and based on published guidelines.

Results: The search strategy identified 20 cost-effectiveness analyses meeting the inclusion criteria, of which 14 had original model structures. Cost-effectiveness modeling in neuropathic pain is established and increasing across multiple jurisdictions; however, amongst these studies, there is substantial variation in modeling approach, and there are common limitations. Capturing the effect of treatments upon health outcomes, particularly health-related quality-of-life, is challenging, and the health effects of multiple lines of ineffective treatment, common for patients with neuropathic pain, have not been consistently or robustly modeled.

Conclusions: To improve future economic modeling in neuropathic pain, further research is suggested into the effect of multiple lines of treatment and treatment failure upon patient outcomes and subsequent treatment effectiveness; the impact of treatment-emergent adverse events upon patient outcomes; and consistent and appropriate pain measures to inform models. The authors further encourage transparent reporting of inputs used to inform cost-effectiveness models, with robust, comprehensive and clear uncertainty analysis and, where feasible, open-source modeling is encouraged.     

The unbiasedness hypothesis in the forward foreign exchange market: A specification analysis with application to France,Italy, Japan,the United Kingdom and West Germany

The purpose of this paper is to carry out a specification analysis of a test relation for the unbiasedness hypothesis using thirty-day forward foreign exchange data from France, Italy, Japan, the United Kingdom, and West Germany. The results indicate that econometric problems do exist for each country's test equation over the entire sample. For each country, there is at least one period which admits a statistically adequate regression equation. Results for these periods show that the null hypothesis of the unbiasedness of the forward rate is rejected for some countries but is retained for others.     

Toward a multilateral framework for identifying national security threats posed by foreign acquisitions: with special reference to Chinese acquisitions in the United States,Canada, and Australia

This article presents a framework for differentiating between foreign acquisitions of companies that might plausibly pose a national security threat to the home country of the target acquisition and those that do not. This framework originally derives from the experience of the United States. The framework is then shown to be relevant and useful for foreign acquisitions in Canada and Australia. In each case, Chinese acquisitions of US, Canadian, or Australian firms are highlighted. The article concludes by arguing that this framework can serve as an effective nondiscriminatory basis for separating genuine from implausible national security threats from foreign acquisitions across OECD states, to include all countries around the world.