Ex-factory Prices Research Articles

Spatio-temporal differentiation characteristics of coal mine safety levels in China based on spatial spillover effects

In order to solve the problem of "potpourri" of safety risk prevention and control measures, which is caused by the unclear mechanism of the spatial effect of coal mine safety level heterogeneity and its influencing factors. This paper discriminates the dominant factors of spatio-temporal heterogeneity of coal mine safety production level in China and their spatial effect types by means of GeoDetector and the Spatial Dubin Model (SDM), specifies the categories and degrees of acts on local and surrounding areas by changes in indicators, and provides further visualization of the detection outcomes with the assistance of the Neo4j graph database, and the findings indicate that:(1) All 15 indicators selected in the study have a certain influence on the generation of spatial heterogeneity in China's coal mine safety production level, and all of them show an enhancement relationship after the interaction of indicators. Especially, the combination of excavated environment and other indicators basically has a non-linear enhancement relationship. (2) In terms of spatial effects, the influence of the 5 effects on the spatio-temporal heterogeneity of coal mine safety level is, in descending order, industrial development effect > capital allocation effect > production environment effect > government supervision effect > enterprise management effect, which indicates that macroeconomic and market conditions have a much stronger influence on the generation of spatio-temporal heterogeneity in coal mine production safety status. (3) From the single indicator perspective, the average annual temperature, average annual wind speed, coal consumption and monitoring efficiency primarily affect the dependent variable through direct effects; GDP per capita, average labor compensation as well as railroad operating mileage have positive spatial spillover on the changes of coal mine safety production level in surrounding areas; the evaluation of the spatial effect for average labor compensation exhibits a positive indirect effect with low influence; for the two indicators of production efficiency and ex-factory price, not only do they have negative effects on the local coal mine safety level, but also have significant spillover effects on surrounding areas.

An assessment of the implications of distribution remuneration and taxation policies on the final prices of prescription medicines: evidence from 35 countries

AbstractThis paper analyses the structure of and variability in taxation and prescription drug distribution policies and quantifies the impact of such policies on the cost of prescription drugs to health systems in 35 countries. Taxes on prescription drugs remain highly prevalent (83% of the sample) although 63% of the sample countries implement a lower than standard VAT rate. Three remuneration types of the wholesale and retail distribution chain have been identified. Wholesale and retail distributors are remunerated on a regressive mark-up basis, which is price-dependent, although fixed fees and fixed percentages, which are non-price dependent, are also highly prevalent. Price component analysis for three groups of products classed as high-, medium- and low-priced suggests that mark-ups plus taxes varied significantly across countries and products, and ranged from 5% to 187% of ex-factory prices. Average margins also vary significantly by countries and products ranging 5–65% of retail prices. The cost of distribution and taxation contributes significantly to prescription drug costs for health systems. Although distribution chain remuneration raises efficiency and overall affordability questions, these need to be considered together with the regulatory framework shaping market structure of the distribution chain, as well as any prevailing horizontal and vertical integration policies. The overall cost of prescription drugs could be reduced immediately by eliminating taxation; this could go some way to alleviate fiscal pressures on health budgets, whilst avoiding resource re-allocation from health to other sectors.

Cost per responder analysis of abrocitinib versus dupilumab in moderate to severe atopic dermatitis.

The JADE COMPARE was a multicenter, phase 3 randomized, double-blind, placebo-controlled trial with the objective of comparing the 16-week efficacy and safety of oral abrocitinib 100 or 200 mg once daily, dupilumab 300 mg subcutaneous injection every 2 weeks, or placebo in adults with moderate-to-severe atopic dermatitis (AD). Pharmacoeconomic evaluation of these new drugs for AD is lacking. The objective of our study was to compare the cost per responder of abrocitinib versus dupilumab in patients with AD using the data from the JADE COMPARE trial. The cost per responder was calculated by multiplying the cost of treatment by the number needed to treat for each therapy, as obtained from the JADE COMPARE trial. The 12-week primary endpoint was the Investigator global assessment (IGA) 0/1 and eczema area and severity index improvement of at least 75% (EASI75) response rate. The key secondary end points were itch response (defined as an improvement of ≥4 points in the score on the Peak Pruritus Numerical Rating Scale [PP-NRS; scores range from 0 to 10]) at week 2 and IGA and EASI-75 responses at week 16. The cost per responder model was based on the perspective of the Italian National Health System. Regarding the costs of drugs, ex-factory wholesale purchase prices were used, including the mandatory discounts according to the national legislation (5% discount, plus a further 5% reduction on the discount result). Abrocitinib 100 mg and 200 mg have flat price in Italy. The 12-week IGA 0/1 cost per responder was € 3955.77 and € 2984.94 for abrocitinib 100 mg and 200 mg, respectively, versus € 7467.96 for dupilumab; as for 12-week EASI75 the cost were € 2463.30 and € 2057.58 vs. € 4705.09, respectively. As far as the secondary end points, the costs per responder were always lower for abrocitinib 100 and 200 mg compared to dupilumab, including the PP-NRS (€ 3791.55 and € 2451.22, vs. € 6462.65), the IGA 0/1 at week 16 (€ 6931.05 and € 4854.15 vs. € 8787.85) and the EASI75 at week 16 (€ 3984.75 and € 3381.00 vs. € 5197.45). According to JADE COMPARE trial data, the costs per responder of abrocitinib were considerably lower than dupilumab. The results of the study are limited to the short time frame of JADE COMPARE trial.

Budget impact analysis of natalizumab biosimilar on pharmaceutical expenditure for the treatment of relapsing-remitting multiple sclerosis in Italy

Background: The availability of high-efficacy disease-modifying therapy (DMT), including natalizumab, improved treatment efficacy in adults with highly-active relapsing-remitting multiple sclerosis (RRMS). Natalizumab patent protection has expired, and the natalizumab biosimilar (Tyruko®) has been recently reimbursed by AIFA. As the price of natalizumab biosimilar is expected to be lower as compared with natalizumab originator’s price, a budget impact analysis was conducted to assess the economic impact associated to the introduction of natalizumab biosimilar for patients with highly-active RRMS. Methods: A budget impact model was developed, considering the INHS perspective and a 5-years time horizon. The number of patients treated with natalizumab was estimated based on historical natalizumab consumption data, disease prevalence rates and natalizumab market share. The budget impact population was divided into prevalent and incident patients. The model assumes that some patients in treatment with natalizumab originator will switch to natalizumab biosimilar and that some naïve patients will directly start treatment with natalizumab biosimilar. The ex-factory price of natalizumab originator (intravenous and subcutaneous) and biosimilar (intravenous) and the corresponding administration costs were included. All assumptions were validated by expert opinion. Results: Eligible population was estimated at 7,552, 7,779, 8,090, 8,494 and 8,834 in years 1, 2, 3, 4 and 5 respectively. The introduction of natalizumab biosimilar, considering a progressive increase in market share from 9.6% (year 1) to 40.5% (year 5), would provide an overall savings (5-years time horizon) over € 47 million to the INHS. The scenario analysis highlights that the lower treatment cost of biosimilar natalizumab compared to originator natalizumab would offset the higher cost associated with intravenous versus subcutaneous administration. Conclusion: Considering the results of this budget impact analysis, it is realistic to expect that the presence of biosimilar natalizumab will contribute to the sustainability of public pharmaceutical expenditure.

Examining confidential wholesale margin estimates in European countries for the price negotiation of patented drugs in Germany: a statistical model

BackgroundBased on the legal framework laid down in section 130b (9) of Book V of the German Social Code, various criteria are relevant for the negotiated price for new patented drugs in Germany. European reference prices (ERPs) are one criterion. The ERP is based on the ex-factory prices (EFPs) of the countries included in the European country basket. However, in some of these countries, the EFP is not published due to confidential wholesale margins. Wholesale margins must therefore be estimated and deducted from purchase prices. In this context literature-based estimates to date do not assume regressive margins with higher pharmaceutical prices. This assumption is questionable and can lead to systematically underestimated country prices, especially for high-priced drugs. Percentage wholesale margins in the majority of European countries develop to a comparable extent regressively with increasing prices. It should therefore be examined (1) whether statistical models can predict the margins of individual countries, in principle and especially for countries where margins are unknown and regressive trends are likely, and (2) to what extent the estimation of margins improves when regressive statistical models are used to estimate margins instead of cross-price averages published in the literature.MethodsQualitative preliminary research explores the basic wholesale pricing mechanisms in countries with confidential wholesale margins. Wholesale margins for reimbursable drugs were then modeled for regulated European countries. Estimation quality and impact of the model was compared to estimations based on average margins.ResultsIn both regulated countries and in countries with confidential wholesale margins, percentage margins of wholesalers develop regressively as drug prices rise. Regressive courses of margins can be resiliently modeled for the regulated countries using a power distribution with significantly lower mean squared errors in a linear mixed model in comparison to literature-based estimations with country-specific cross-price averages.ConclusionIf there is reason to believe that margins are regressive, confidential wholesale margins are expected to be better estimated by the power function based on margins of regulated countries than by the published country-specific average margins, reducing significantly inaccurate effects on margin estimations of high-price drugs.

Cost per Number Needed to Treat (NNT) for upadacitinib in the treatment of bio-exposed patients with moderately-severely active ulcerative rectocolitis

Background: Only limited information is available on cost efficacy of the advanced therapies for the treatment of ulcerative rectocolitis. We evaluated the efficacy and the treatment costs of these advanced therapies in the treatment of bio-exposed (primary failure to a biological agent) patients with moderately to severely active ulcerative rectocolitis. Methods: Data from a previous network meta-analysis (NMA) in the treatment of bio-exposed patients with moderately to severely active ulcerative rectocolitis was used. The analysis involved three therapies approved in Italy for the treatment of moderately to severely active ulcerative rectocolitis: upadacitinib (UPA), ustekinumab (UST) and vedolizumab (VDZ). According to the NMA results, the analysis was conducted considering two different timepoints: induction and maintenance. The pharmacoeconomic comparison between advanced therapies was carried out to estimate the respective cost for the NNT (Number Needed to Treat) compared to placebo using the clinical response (CRes) for the induction and clinical remission (CRem) and endoscopic improvement (EI) for the maintenance. Only the ex-factory price of each advanced therapy was considered. The cost per NNT was adopted as a cost-effectiveness indicator. Results: Independently of the timepoint considered (induction or maintenance) and the clinical (CRem and CRes) or endoscopic endpoint (EI) evaluated, UPA had always the lower cost per NNT than UST and VDZ. For example, considering the induction and the CRes, the cost per NNT for upadacitinib (45 mg) was € 7,862.07 compared to € 30,459.38 for ustekinumab (6 mg/kg) and to € 67,868.00 for vedolizumab. Conclusion: Upadacitinib is a cost-effective therapeutic option compared to ustekinumab and vedolizumab in the treatment of bio-exposed patients with moderately to severely active ulcerative rectocolitis.

Cost per NNT for upadacitinib in the treatment of patients with moderate-severe atopic dermatitis in Italy

Background: Targeted systemic therapies, including abrocitinib, baricitinib, dupilumab, tralokinumab and upadacitinib, are new treatments for moderate to severe atopic dermatitis (AD). We evaluated the efficacy and the costs of these targeted systemic therapies in the treatment of adult patients with moderate to severe AD. Methods: The clinical efficacy was assessed considering the results of a previous network meta-analysis (NMA). The analysis involved five therapies approved in Italy for the treatment of moderate to severe AD: abrocitinib (ABR), baricitinib (BAR), dupilumab (DUP), tralokinumab (TRA) and upadacitinib (UPA). According to the NMA, the cost of the treatment was based on the number of administrations dispensed at 16 weeks and the clinical efficacy was measured by the number needed to treat (NNT) compared to placebo using the improvement ≥ 75% (EASI-75) or ≥ 90 (EASI-90) from baseline of the eczema area and severity index (EASI). Only the ex-factory price of the targeted systemic therapies was considered. The cost per NNT was adopted as a cost-effectiveness indicator. Results: At 16 weeks, the cost per NNT based on EASI-75 was lower for UPA 15 mg (€ 6,384.00) compared to BAR 4 mg (€ 11,619.73) and 2 mg (€ 14,524.66), ABR 100 mg (€ 16,265.22), DUP 300 mg (€ 16,115.04) and TRA 300 mg (€ 31,710.24). UPA 15 (€ 8,512.00) also showed the lower cost per NNT based on EASI-90 at 16 weeks compared to BAR 4 mg (€ 14,788.75) and 2 mg (€ 20,862.70), ABR 100 mg (€ 25,922.69), DUP 300 mg (€ 25,992.00) and TRA 300 mg (€ 41,067.36). Conclusions: The findings show that upadacitinib is the most cost-effective option (cost per NNT) for the treatment of moderate to severe atopic dermatitis.

544 - Cost-per-responder analysis of tralokinumab versus dupilumab in patients with moderate-to-severe atopic dermatitis in the US and Canada

Abstract Introduction/Background Biologic treatments such as tralokinumab and dupilumab are therapeutic options for adult patients with moderate-to-­severe atopic dermatitis (AD) who do not achieve adequate control with topical treatments or phototherapy. To date, no trials have been conducted to directly evaluate the relative efficacy of these biologic treatments. Objectives Applying indirect comparison of efficacy, we examined the cost-per-responder of tralokinumab compared to dupilumab in combination with topical corticosteroids (TCS) for the treatment of moderate-to-serve AD in the United States (US) and Canada. Methods A cost-per-responder analysis was undertaken considering the Eczema Area and Severity Index 75 (EASI-75) and Investigator’s Global Assessment (IGA-0/1) response criteria over a 32-week period. For each treatment, the cost-per-­responder was computed by multiplying the treatment cost by the number needed to treat (NNT). Efficacy data were derived from an unanchored matching-adjusted indirect comparison (MAIC) utilizing patient-level data from ECZTRA-3 (tralokinumab) and aggregate data from LIBERTY AD CHRONOS (dupilumab). Treatment cost was defined as the drug cost of the biologic treatment with a duration corresponding to 32 weeks. TCS cost was not considered. Treatments were assumed to be administered every 2 weeks (Q2W). The costs were estimated based on Wholesale Acquisition Costs (WAC) from the US and ex-factory prices via the McKesson price list for Canada. All prices were converted to US dollars ($). Sensitivity analyses (SA) were conducted with every 4 week (Q4W) dosing beginning at week 16 for 10% and 20% of patients treated with tralokinumab. Results For the US, the average cost-per-responder was $62,714 (Q4W SA: 10%: $61,239; 20%: $59,763) for tralokinumab versus $63,993 for dupilumab considering the EASI-75 response criteria, while the average cost-per-responder was $82,419 (Q4W SA: 10%: $80,480; 20%: $78,450) for tralokinumab versus $118,835 for dupilumab considering the IGA 0/1 response criteria. For Canada, the average cost-per-responder was $22,846 (Q4W SA: 10%: $22,308; 20%: $21,771) for tralokinumab versus $26,475 for dupilumab considering the EASI-75 response criteria, while the average cost-per-responder was $30,024 (Q4W SA: 10%: $29,317; 20%: $28,611) for tralokinumab versus $49,165 for dupilumab considering the IGA 0/1 response criteria. Conclusions Assessing EASI-75 and IGA-0/1 response criteria at 32 weeks, this analysis indicates that tralokinumab in combination with TCS is associated with lower costs-per-responder compared with dupilumab in combination with TCS in the treatment of moderate-to-severe AD in the US and Canada.

Cost-per-Responder Analysis of Tralokinumab versus Dupilumab in Patients with Moderate-to-Severe Atopic Dermatitis in the US and Canada

Introduction and objective: Biologic treatments such as tralokinumab and dupilumab are therapeutic options for adult patients with moderate-to-severe atopic dermatitis (AD) who do not achieve adequate control with topical treatments or phototherapy. To date, no trials have been conducted to directly evaluate the relative efficacy of these biologic treatments. Applying indirect comparison of efficacy, we examined the cost-per-responder of tralokinumab compared to dupilumab in combination with topical corticosteroids (TCS) for the treatment of moderate-to-serve AD in the United States (US) and Canada.
 Method: A cost-per-responder analysis was undertaken considering the Eczema Area and Severity Index 75 (EASI-75) and Investigator’s Global Assessment (IGA-0/1) response criteria over a 32-week period. For each treatment, the cost-per-responder was computed by multiplying the treatment cost by the number needed to treat (NNT). Efficacy data were derived from an unanchored matching-adjusted indirect comparison (MAIC) utilizing patient-level data from ECZTRA-3 (tralokinumab) and aggregate data from LIBERTY AD CHRONOS (dupilumab). Treatment cost was defined as the drug cost of the biologic treatment with a duration corresponding to 32 weeks. TCS cost was not considered. Treatments were assumed to be administered every 2 weeks (Q2W). The costs were estimated based on Wholesale Acquisition Costs (WAC) from the US and ex-factory prices via the McKesson price list for Canada. All prices were converted to US dollars ($). Sensitivity analyses (SA) were conducted with every 4 week (Q4W) dosing beginning at week 16 for 10% and 20% of patients treated with tralokinumab.
 Results: For the US, the average cost-per-responder was $62,714 (Q4W SA: 10%: $61,239; 20%: $59,763) for tralokinumab versus $63,993 for dupilumab considering the EASI-75 response criteria, while the average cost-per-responder was $82,419 (Q4W SA: 10%: $80,480; 20%: $78,450) for tralokinumab versus $118,835 for dupilumab considering the IGA 0/1 response criteria. For Canada, the average cost-per-responder was $22,846 (Q4W SA: 10%: $22,308; 20%: $21,771) for tralokinumab versus $26,475 for dupilumab considering the EASI-75 response criteria, while the average cost-per-responder was $30,024 (Q4W SA: 10%: $29,317; 20%: $28,611) for tralokinumab versus $49,165 for dupilumab considering the IGA 0/1 response criteria.
 Conclusion: Assessing EASI-75 and IGA-0/1 response criteria at 32 weeks, this analysis indicates that tralokinumab in combination with TCS is associated with lower costs-per-responder compared with dupilumab in combination with TCS in the treatment of moderate-to-severe AD in the US and Canada.

From Indication-Based Pricing to Blended Approach: Evidence on the Price and Reimbursement Negotiation in Italy.

New indications for existing medicines are increasing over time. In most countries, drug pricing and reimbursement conditions are renegotiated every time a new indication is approved. There is a growing interest in the price negotiation model for new indications, specifically comparing an indication-based versus blended approach. However, little evidence currently exists regarding the complexity of these negotiations and their impact on actual prices. Italy has recently transitioned from an indication-based approach to a blended price model. This study aims to measure the impact of price and reimbursement negotiation of new indications on discounts (i.e. actual prices) and on the negotiation duration, used as a proxy of its complexity. We considered new indications approved through a European centralized procedure from January 2013 to March 2022 for which the price and reimbursement status was approved in Italy between January 2015 and March 2022, amounting to 52 new indications. Data on the timeframe of the Italian price and reimbursement process and its phases were obtained from publicly available sources. Discounts for the first indication and their subsequent increases for new indications were estimated by comparing ex-factory prices and tendered prices. To calculate p-values, we employed the Mann-Whitney test, and multiple regression models were utilized to examine correlations between negotiation time and the characteristics of the medicines. The mean time to reimbursement was 603 days, in contrast to 583 days for the first launch. Price negotiation took longer for rare diseases, cancer drugs, and in case of therapies with minor added therapeutic value. On average, the additional discount (on top of discounts for prior indications) was 13%, significantly lower than the mean discount for the first indications approved (24.9%). The discounts increment was lower, but negotiation took longer if a Managed Entry Agreement accompanied the final agreement. Additionally, discounts have increased over the years. The negotiation for new indications takes longer than the first one, and provides, on average, an additional discount of 13%. While our findings bear the potential for significant policy implications, they necessitate prudent interpretation due to a limited number of observations. The increasing trend in additional discounts over time applied to all indications in recent negotiations, may suggest a descending trend of value for new indications and a shift from an indication-based pricing approach to a blended model. Otherwise, budget impact considerations might have outweighed a value-based approach in the recent negotiations. If so, two potential options for restoring a value-based approach are returning to an indication-based pricing or giving explicit and higher weight to value within a blended model.

Budget impact analysis of dexamethasone intravitreal implant for the treatment of diabetic macular oedema

ObjectiveTo assess the economic impact following the inclusion of an intravitreal implant of dexamethasone for the treatment of diabetic macular oedema in a healthcare area in Spain. MethodA 3-year budget impact model was designed to estimate healthcare direct costs for adult patients with diabetic macular oedema from the National Health System perspective. The approved therapies in use (aflibercept/ranibizumab/dexamethasone) were considered. The target population was estimated from published diabetic macular oedema prevalence (6.41%) and incidence (0.82%) for a population of 25,000 adults. Dexamethasone was assumed to be used annually in 20%, 30% and 40% of patients, respectively. Annual total costs included: drug acquisition (based on frequency of injections per every year, considering ex-factory prices with mandatory deduction and split of vials), intravitreal administration, patient monitoring, management of cardiovascular and ocular adverse events (cataracts, increased intraocular pressure, endophthalmitis, vitreous haemorrhage and retinal detachment). Detailed resource consumption reflecting clinical practice was provided from local experts in retina and vitreous. Unitary costs (€, 2016) were obtained from national databases and literature. Sensitivity analyses were performed to assess model robustness. ResultsThe inclusion of intravitreal dexamethasone implant would lead to annual cost savings of €35,030 (–4.2%), €10,743 (–1.8%) and €5,051 (–0.9%), years 1-3 respectively. Total costs were reduced mainly by the fewer annual injections required by dexamethasone. The average annual incremental costs were –€350, –€96 and –€41 per patient. ConclusionsThe inclusion of an intravitreal dexamethasone implant for the treatment of diabetic macular oedema would lead to cost-savings for the considered health area, mainly by reducing the administration costs.

Cost-Effectiveness of Nivolumab Plus Ipilimumab for the First-Line Treatment of Intermediate/Poor-Risk Advanced and/or Metastatic Renal Cell Carcinoma in Switzerland.

This study assessed the cost-effectiveness of nivolumab plus ipilimumab versus both sunitinib and pazopanib for the treatment of first-line unresectable advanced renal cell carcinoma (aRCC) from a healthcare system perspective in Switzerland. A three-state partitioned survival model, consisting of progression-free, progressed disease, and death, was constructed. Efficacy estimates were based on data from the CheckMate 214 trial (NCT02231749) with a minimum follow-up of 42 months. Two Swiss oncologists were consulted to determine disease management resource use. Costs were derived from the Swiss tariff lists for outpatient (TARMED Online Browser 1.09) and inpatient (2020 data from Swiss diagnosis-related groups) treatments. Drug acquisition costs (ex-factory prices) were obtained from the March 2020 price list published by the Swiss Federal Office of Public Health. Treatment-specific EQ-5D-3L-based utilities were derived from CheckMate 214 using a French value set as a proxy for Switzerland. The model utilized a 1-week cycle length and a 40-year time horizon, with costs and effects discounted by 3.0% per annum. One-way sensitivity analyses, probabilistic analysis, and scenario analyses assessed the robustness of the results. Nivolumab plus ipilimumab yielded incremental 1.43 life-years and 1.36 lifetime discounted quality-adjusted life-years (QALYs) relative to sunitinib and pazopanib at an additional cost of 147,453 Swiss Francs (CHF) and CHF145,643, respectively. With an incremental cost-utility ratio of CHF108,326 per QALY gained versus sunitinib, and CHF106,996 per QALY gained versus pazopanib, the nivolumab plus ipilimumab combination can be considered a cost-effective option for the treatment of patients with aRCC in Switzerland, with a willingness-to-pay threshold of CHF200,000. Sensitivity and scenario analyses confirmed the robustness of the deterministic results. This study showed that nivolumab plus ipilimumab, which represents one of the standard-of-care first-line treatments for intermediate- or poor-risk aRCC patients, is a life-extending and cost-effective treatment option for patients in Switzerland.

Budget impact analysis of anakinra in the treatment of familial Mediterranean fever in Italy

ABSTRACT Introduction: Familial Mediterranean Fever (FMF) is a hereditary autoinflammatory disease that significantly reduces occupational productivity and quality-of-life in affected patients. Italy has an estimated FMF prevalence of 1 in 60,000 people. While colchicine is the primary treatment for FMF, biologics are administered to intolerant and non-responder patients. Anakinra and canakinumab are the only biologics approved and reimbursed for FMF in Italy. Both medicines have demonstrated efficacy in FMF patients yet differ in treatment costs. This study aimed to perform a budget impact analysis (BIA) following anakinra’s reimbursement for FMF treatment, considering pharmaceutical costs from the Italian National Healthcare Service (NHS) perspective. Methods: A ‘Reference scenario’ (all patients treated with canakinumab) was compared to an ‘Alternative scenario’, with increased anakinra market shares. The target population was estimated based on the Italian population, epidemiological and market research data. Drugs costs were estimated based on Summary of Product Characteristics and net ex-factory prices. Sensitivity analyses were implemented to test results’ robustness. Results:The base case analysis showed an overall cumulative expenditure of €30,586,628 for ‘Reference scenario’ and € 16,465,548 for ‘Alternative scenario’. A cumulative savings of €14,121,080 (46.2%) was calculated over 3 years as a result of the reimbursement and increasing uptake of anakinra. The sensitivity analyses, even considering a discount of 50% for canakinumab, confirmed the base case results. Conclusions: Anakinra’s introduction, in FMF treatment, provides a financially sustainable option for Italian patients, with savings increasing according to greater use of anakinra.

PP13 Development Of Recommendations And Proposal For A Value-Based Managed Entry Agreement For Italian Setting

IntroductionThe continuous and pressing challenge that the drug regulatory authorities in Italy and in Europe are facing is that of guaranteeing patients’ quick access to new drugs, ensuring the economic sustainability of the system at the same time. In recent years, flexible and diversified approaches have been developed known as Managed Entry Agreements (MEA).MethodsWe performed an analysis of the Italian legislative and regulatory aspects in reference to a new Value-based Managed Entry Agreement (VBMEA) pathway. Thus, we tried to investigate the rationale for a new pathway analyzing three main dimensions related to the new medical product (MP): value; time to entry access; and, data quality and registry design. Moreover, we shared the discussion of the proposal with an international experts’ panel.ResultsThe proposal for a new pathway of VBMEA from a procedural point of view shows the novelty related to the possibility to organize joint CTS (Technical Scientific Committee) and CPR (Price and Reimbursement Committee) assessment. A 24-month contract with an ex-factory price (PP) equal to X EUR per dose and a transfer price to the National Public Health System (NPHS), following application of a confidential discount for public structures (-X%), of X EUR per dose. After 24-months, an analysis of VBMEA is carried out. The price of the MP is therefore established based on AIFA registries and VBMEA results. The cost value incurred by the NPHS, intended as the difference between the price in market (entry) access phase and the price negotiated (PVB) in the light of the VBMEA results, shall be returned by the pharmaceutical company in the form of a payback.ConclusionsCurrently, MEAs represent one of the main topics of discussion between the European National Payers Authorities. There is very little information on product performance that results from MEAs. This research project could provide advice to policy makers to decrease negotiation time by ensuring earlier access to innovation for patients.

Savings associated with therapeutic appropriateness for patients with relapsed refractory multiple myeloma and high cytogenetic risk diagnosed by FISH test

Background: Approximately 23% of myeloma patients have cytogenetic abnormalities which confer a significantly poorer prognosis, and therefore they are defined as “high-risk myeloma” (HRC+) patients. Objective: To estimate the economic impact of a large-scale use of the fluorescence in situ hybridization (FISH) test for the identification of HRC+ patients. Methods: The comparison between the total costs of two scenarios, the first one where patients are not tested for cytogenetic abnormalities, the second one where FISH test is used to identify HRC+ patients and to treat them with the most appropriate therapies, was conducted. The Italian National Healthcare Service (NHS) perspective was adopted. The cost of each treatment was estimated by multiplying Italian unit ex-factory prices by median progression-free survival (PFS). For each scenario, the cost per month of PFS gained was calculated. Sensitivity analysis was conducted to evaluate the impact on the results. Results: N = 777 patients are expected to be HRC+ in Italy. If they were all identified through FISH test and treated with the most appropriate therapies, this would result into savings of € 552,000 and a PFS gain of 419 months, compared with a scenario with no identification. The cost per patient per month of PFS gained is lower in the scenario where FISH test was available (€ 9,921 vs € 10,229 in the scenario without testing). Sensitivity analyses confirmed the robustness of the base case results. Conclusions: A larger adoption of FISH test to identify HRC+ patients is expected to improve clinical outcomes in relapsed refractory multiple myeloma.

A Review of Foreign Pharmaceutical Pricing Structure: Focusing on a Drug Price Formula Based on Ex-factory Prices

A Review of Foreign Pharmaceutical Pricing Structure: Focusing on a Drug Price Formula Based on Ex-factory Prices

Economic Feasibility of Dimethyl Ether from Oil Palm Empty Fruit Bunch as a Substitute for LPG in Indonesia

Oil palm empty fruit bunch (OPEFB) can be utilized as a feedstock for dimethyl ether (DME) production through the gasification route. DME has similar characteristics to liquefied petroleum gas (LPG). Therefore, it can be used as a substitute for LPG. Some research has been conducted on DME as a substitute for LPG from various aspects. However, little research was focused on the economic study of OPEFB-based DME as an LPG substitute and its contribution towards saving the LPG import budget. This study aims to find DME plant feasibility, and to assess its contribution to the LPG import budget reduction, especially in the Kalimantan region. The DME price at the depot is calculated based on the ex-factory price of DME, transportation cost, and depot fee. The OPEFB-based DME plant capacity is 994 t day-1 OPEFB, which produces 192 t day-1 DME. From an economic perspective, the net present value (NPV), internal rate of return (IRR), and payback period (PP) are USD 93.1 million, 17%, and 10 years, respectively, based on 30 years of plant life and USD 185.4 million investment. Only 57% of the DME-LPG mix can be distributed to fulfill Kalimantan region demand per year, while the savings on the import budget is USD 5.81 million y-1. The OPEFB-based DME plant capacity and capital expenditure (CAPEX) are the most sensitive to perturbance, whereas OPEFB feed price is the least sensitive.

Pricing and coordination of automotive supply chain for incorporating efficient charging facilities

This paper constructs a new energy vehicle and traditional vehicle supply chain model composed of a vehicle manufacturer and an automobile retailer, compares the pricing, demand and supply chain profit of the two types of vehicles under decentralized decision-making and centralized decision-making, and then designs a revenue sharing + ex-factory price negotiation contract mechanism to coordinate the supply chain under certain conditions. The results show that: when the contract parameters meet certain conditions, the combination contract can achieve supply chain coordination and improve the profit of each member. In addition, we further study the impact of the perfection of charging facilities on the pricing, demand and supply chain profit of the two types of vehicles.

Cost-effectiveness of benralizumab versus mepolizumab and dupilumab in patients with severe uncontrolled eosinophilic asthma in Spain

Objective To assess the cost-effectiveness of benralizumab (benra) vs. mepolizumab (mepo) and dupilumab (dupi) for the treatment of patients with severe uncontrolled asthma from the Spanish Health System perspective. Methods Exacerbations avoided, quality-adjusted life years (QALYs) gained and costs in a 5-year period were estimated with a Markov model for a cohort of 1,000 patients in which, based on published evidence, 31% of the patients received biologics + oral corticosteroids (OCS) and 69% received only biologics. Efficacy data (exacerbation reduction and OCS elimination) were derived from a matching-adjusted indirect comparison. Published EQ-5D utilities per health state (biologic alone, biologic + OCS, standard of care + OCS, exacerbations, and post-exacerbations) were used for QALY estimation. Utility decrements associated with exacerbation management [-0.1 (OCS or emergency visits), −0.2 (hospitalization)] derived from the literature were applied. Costs (€, 2022) included drug acquisition (ex-factory price), administration and disease management. An expert panel (2 pneumologists and 1 pharmacist) validated all inputs. Results Benra was more effective (52.21 QALYs) than mepo (51.39 QALYs) and dupi (51.30 QALYs). Benra avoided more exacerbations (2.87 exacerbations) compared to mepo (4.70 exacerbations) and dupi (5.11 exacerbations) for the 5-year horizon. Total costs/patient were €56,093.77 (benra), €59,280.45 (mepo) and €62,991.76 (dupi), resulting in benra dominating (more QALYs with lower costs) vs. mepo and dupi. Conclusions Benralizumab can be considered as a dominant treatment alternative vs. other biologic drugs for the treatment of uncontrolled severe eosinophilic asthma patients in Spain.

Pharmaceutical Supply Chain in China: Pricing and Production Decisions with Price-Sensitive and Uncertain Demand

In this paper, we apply game theory to study the price competition between drugstores and hospitals in China’s pharmaceutical supply chain. Motivated by drug shortages and price disparity problems, we build a simplified model with one supplier, one hospital, and one drugstore in which the sellers sell one kind of drug and compete on price. The hospital receives a discount from the government when ordering the drug and both sellers face a price-sensitive and uncertain demand. The existence and uniqueness of a Nash equilibrium are proved and closed-form solutions are found for linear demand cases. We characterize the pricing and ordering decisions of the hospital and drugstore. The analysis shows that high ex-factory price, high price sensitivity, and a small discount are three factors contributing to drug shortages. We consider two special kinds of linear demand to obtain insights into the drug price disparity problem.