Drug Acquisition Research Articles

Budget impact analysis of subcutaneous infliximab (CT-P13 SC) for treating inflammatory bowel disease in Saudi Arabia: Analysis from payer perspective.

The Saudi Food and Drug Authority (SFDA) has approved the subcutaneous (SC) administration of infliximab, presenting a more convenient alternative with reduced outpatient visits and diminished expenses compared to the intravenous (IV) administration. However, the financial implications of this formulation have not been examined from the perspective of Saudi payers. A prevalence-based budget impact model was developed to evaluate the financial effects of introducing "environment without" versus "with infliximab SC." The model's time horizon spanned over 2 years (2021-2023), aligning with the biennial national pharmaceutical procurement cycle. The comparison focused on infliximab SC versus all available formulations of infliximab IV in the Saudi market for two inflammatory bowel diseases (IBD): Ulcerative Colitis (UC) and Crohn's Disease (CD). Treatment comparators' comparability and dose escalations were substantiated by published studies, utilizing dosing information from the summary of product characteristics. Drug acquisition costs were derived from SFDA registered prices, with IV formulation administration costs included. Scenario analysis assessed the budget impact of infliximab SC introduction at uptake rates ranging from 0% to 100%. Introducing infliximab SC demonstrated cost-saving potential in the treatment of IBD. At 100% uptake with UC patients for 2 years, infliximab SC resulted in savings of -SAR-31.9 million (-SAR29,145 per patient). Similarly, for CD, introducing infliximab SC at 100% uptake over 2 years yielded savings of -SAR106.2 million (-SAR36,585 per patient). This study reveals that infliximab SC is associated with cost-saving potential when compared to infliximab IV formulations available in Saudi Arabia. Future research should address uncertainties related to real-world comparative effectiveness, the convenience of administration, patient tolerability, and physician acceptance of the SC formulation of infliximab, alongside comparisons with other TNF-alpha inhibitors.

The Frequency and Characteristics of Brokered Illegal Drug Sales: Reconceptualizing Illegal Drug Markets and Measuring Local Demand

Background Drug policies and interventions require an ongoing understanding of the local demand for illegal drugs. How illegal drugs are distributed to consumers is critical in the demand process. To overcome barriers to purchasing illegal drugs, people utilize their peers to purchase substances for them. These brokered drug sales allow buyers to leverage their peer networks to make purchases. For brokers, this form of exchange allows them to obtain drugs for free. This drug acquisition strategy is underappreciated in understanding how local drug market's function. Methods This paper presents findings from a brief survey on brokering collected from a random sample (N = 241) of active illegal drug injectors recruited from two syringe services programs in Ohio, USA. Results Findings indicate that 30-day and lifetime brokering behavior is common (71% and 90% respectively). Respondents who brokered in the last 30 days (n = 181) purchased drugs for an average of 7 people and from an average of 4 different sellers. Among this group, over 84% indicated that they used drugs with the person they brokered for, 49% reported often or always inflating the price to the buyer, and 27% indicated they removed some drug before returning to the buyer. Conclusion Measuring brokering offers new insight on the dynamics of drug markets, how they operate, and ways to measure their activity. The demand for illegal drugs incorporates the increased use of a drug, changes in the use of different drugs, and/or a novel drug being used. Accessing drugs via brokering accommodates these dynamics. By including brokering in drug market activity, the concept and scope of illegal drug markets transform into networks and not places.

The administration of immune checkpoint inhibitors via an elastomeric pump versus conventional intravenous infusion: an economic perspective

BackgroundRecent studies have underscored the potential of innovative administration methods to mitigate the capacity burden on healthcare systems, without compromising the quality of care. This study assessed and compared the resource utilization and associated costs of two distinct administration modes of immune checkpoint inhibitors: the innovative elastomeric pump and conventional intravenous infusion. This comparison can inform sustainable healthcare practices and healthcare decision-making to optimize treatment efficiency in an era of escalating healthcare demands.MethodsIn this micro-costing study, data on resource use and time allocation for drug preparation and administration were collected using an observational, non-interventional study design. Data were registered at the oncology daycare unit and hospital pharmacy. Cost categories included drug acquisition, disposable materials, healthcare professional time for drug administration, drug preparation, and patient time spent at the oncology day care unit.ResultsDrug administration through the elastomeric pump resulted in substantially lower healthcare costs when compared to conventional infusion, particularly due to reduced labor and chair time. The elastomeric pump reduced the total chair time by 78% and nurse time by 55%. Total average costs (excluding drug costs) were €103,47 and €77.99 for conventional infusion and the elastomeric pump, respectively, showcasing potential savings of €25.48 (P < 0.001) per administration.ConclusionsThis study demonstrated that the elastomeric pump not only offers substantial cost savings but also enhances the treatment capacity of the oncology day care unit. These findings support the adoption of the elastomeric pump in clinical settings as a cost-saving and efficient alternative to conventional infusion.Trial registrationThis study has been registered in the National Trial Register (NTR), with the reference number NTR NL9473. Registration date: 05-05-2021.

Evaluating the budget impact of Empagliflozin in managing heart failure with reduced ejection fraction: Proposing strategic policies for Malaysian public healthcare.

Sodium-glucose co-transporter-2 (SGLT2) inhibitors such as Empagliflozin, are increasingly recommended as part of guideline-directed medical therapy (GDMT) for heart failure with reduced ejection fraction (HFrEF) in many developed nations. This recommendation is based on robust clinical evidence showing that adding Empagliflozin to GDMT improves heart failure symptoms, clinical outcomes, functional status, and overall quality of life. In Malaysia, where healthcare is predominantly public and heavily subsidized, the introduction of new treatments can significantly impact costs, requiring detailed economic assessments. This study evaluates the budget impact of incorporating Empagliflozin into GDMT for HFrEF from the perspective of the public healthcare system. A five-year budget impact model was developed, integrating local data such as population, drug use, costs, clinical outcomes, and healthcare expenses. In the current scenario (GDMT alone), the projected five-year expenditure is MYR 6.12 billion (USD 3.92 billion). With Empagliflozin, the total cost rises by 0.71% to MYR 6.16 billion (USD 3.95 billion), driven by drug acquisition costs of MYR 160.12 million (USD 102.64 million) and adverse event costs of MYR 211,543 (USD 135,604). However, these costs are offset by savings from reduced HF hospitalizations, fewer cardiovascular deaths, and improved renal outcomes. Sensitivity analysis identified hospitalization costs, the price of Empagliflozin, and cardiovascular deaths in diabetic patients as key factors influencing the budget impact. Policymakers can improve the affordability of Empagliflozin through strategies like price negotiations, cost-sharing, and focusing on high-risk groups to optimize healthcare expenditure while ensuring effective treatment access.

Economic burden of vulvar, vaginal, anal, penile and head &amp;amp; neck cancers in Bulgaria

A retrospective, cost-of-illness study aimed at identifying direct healthcare costs of vulvar, vaginal, anal, penile, and H&amp;N cancers in Bulgaria from the payer perspective and calculating indirect costs and the associated years of life lost was carried out. Costs’ data were obtained from the National Health Insurance Fund from January 2018 to December 2020. Years of life lost were calculated based on the country and gender-specific life expectancy. The human capital approach was used to evaluate the indirect costs. The total treatment costs for 3623 patients were EUR 10,875,771 (2018), EUR 11,922,521 (2019) and EUR 12,329,463 (2020). The costs associated with radiotherapy and drug acquisition and administration accounted for the majority (75–78%) of total healthcare costs. A cumulative loss of approximately 33,299 life years occurred between 2018 and 2020. The costs of productivity losses were estimated at EUR 14,113,265.

Cost-effectiveness of pembrolizumab as an adjuvant treatment of renal cell carcinoma post-nephrectomy in Switzerland

Aims Pembrolizumab has demonstrated significantly prolonged disease-free survival and overall survival (OS) among adult patients post-nephrectomy who have an intermediate-high risk, high-risk, or M1 stage with no evidence of disease (M1 NED) renal cell carcinoma (RCC) with clear cell component. The aim of this study was to evaluate the cost-effectiveness of pembrolizumab for patients with RCC post-nephrectomy versus observation in Switzerland. Materials and methods A previously published Markov model was adapted for the Swiss setting to estimate the cost-effectiveness of adjuvant pembrolizumab versus observation from the Swiss statutory health insurance perspective. Transition probabilities between model states were estimated using survival curves from KEYNOTE-564 (data cut-off: June 14, 2021). Outcomes included costs (2022 Swiss francs [CHF]), quality-adjusted life-years (QALYs), and life-years (LYs), measured over a lifetime horizon. Costs included drug acquisition and administration for adjuvant and subsequent therapy. Both costs and effectiveness were discounted at 3.0% annually. Cost-effectiveness was evaluated at a hypothetical willingness-to-pay (WTP) threshold of CHF 100,000 Sensitivity was assessed through scenario analyses as well as deterministic and probabilistic sensitivity analyses. Results Over a lifetime horizon, the total incremental cost for pembrolizumab versus observation was CHF 59,089, providing incremental gains of 0.90 QALYs (1.07 LYs); the incremental cost-effectiveness ratio was CHF 65,299/QALY. Pembrolizumab was deemed cost-effective versus observation, with a 69.9% probability of cost-effectiveness. Limitations A more recent interim analysis data cut from KEYNOTE-564 with median follow up of 57.2 months has since been published; however, these were not available at the time of analysis. It would likely have minimal impact on transition probabilities from disease-free, and the current approach remains conservative for predicting OS for pembrolizumab. Conclusions As an adjuvant treatment of RCC post-nephrectomy, pembrolizumab was found to be cost-effective versus observation in Switzerland at a WTP threshold of CHF 100,000/QALY. Policy makers should consider pembrolizumab as an adjuvant treatment for patients with RCC post-nephrectomy when making decisions regarding resource allocation.

Escalating costs of innovative medicines: perspective and proposals.

Public healthcare systems are challenged by the soaring costs of medications that require increasing resources, often at the expense of other investments. The increasing pharmaceutical budget poses a threat to the allocation of funds for essential preventive and primary healthcare services while also raising concerns about equitable access, particularly in models where patients bear part of the costs out of their own pockets. Proposals on how to ensure ongoing and long-term accessibility, efficiency, and financial stability are required. The escalating costs of medicines may be explained in part by the mismatch between the traditional value-based pricing and reimbursement frameworks and the type of clinical development of targeted therapies and precision medicine in clinical practice. New appraisal methods and managed access strategies should be adapted to therapies targeting small populations and addressing increased uncertainty. Fair pricing strategies, transparent healthcare investments based on problems and outcomes, regulatory reforms, international cooperation, and critically examining the drug acquisition model are potential solutions. Transitioning from an industry-driven pricing approach to a health-driven payment model can help align the cost of treatments with actual health outcomes, establishing a foundation for a healthcare system that addresses immediate challenges and fosters long-term well-being. Acknowledging the lack of a universally applicable solution, the practical implementation of interventions requires a reframing of the pricing and access system and adaption to the targeted therapeutic approaches. Balancing innovation with financial sustainability necessitates a collaborative, adaptive, and transparent approach, as well as transitioning toward health-driven payment models, moving the focus from the cost of medications to the well-being of populations worldwide.

Pricing dynamics of anti-seizure medications in the U.S.

BackgroundThe median cost of anti-seizure medications (ASM) in the United States (U.S.) nearly doubled per person between 2006 and 2021. This increase, combined with shifts in ASM usage and the impact of the COVID-19 pandemic on drug supply chains amid rising inflation, underscored the urgent need to scrutinize ASM pricing dynamics. This study aimed to analyze the complex dynamics of ASM pricing in the U.S. over the past decade (2013–2023); this included how the entry of generic ASMs influenced the pricing of brand-name counterparts and what impacted price variations across different ASM formulations (e.g., significant inflation, the COVID-19 pandemic). MethodsThis study utilized National Average Drug Acquisition Cost (NADAC) data from November 2013 to July 2023. We adjusted ASM prices for inflation using the Consumer Price Index for Medicinal Drugs - Seasonally Adjusted (CPI-MDS). Statistical analyses included fixed effects regressions and multivariable regression analysis to evaluate the impact of inflation, the number of medication labelers, and the COVID-19 pandemic on ASM prices. ResultsOur study analyzed 23 ASMs approved by the U.S. Food and Drug Administration (FDA), which encompassed 223 oral formulations:112 brand-name and 111 generics. From 2013–2016 to 2020–2023, accounting for standard deviations (SD), the average price of brand-name ASMs increased from $8.71 (SD 5.9) to $15.43 (SD 10.7), while generic ASMs saw a slight decrease from $1.39 (SD 1.8) to $1.26 (SD 1.6). Consequently, the price gap between brand-name and generic ASMs surged from 1452.39 % to 3399.26 %. The proportion of matched brand-name and generic ASMs with a price difference of 1000 %–9999 % increased from 32.88 % (2013–2016) to 41.43 % (2020–2023), while those exceeding 10,000 % rose from 16.44 % to 20 % in the same period. Generic immediate-release (IR) formulations were significantly less expensive than extended-release (ER) or delayed-release (DR) counterparts, with cost differences reaching up to 7751.20 %. The number of medication labelers was inversely related to generic ASM prices, which decreased by 5.45 % (p = 0.001) with each additional generic labeler, while brand-name ASM prices increased by 2.46 % (p < 0.001) with each additional generic labeler. The COVID-19 pandemic led to a 24.4 % increase in brand-name ASM prices and a 23.1 % decrease in generic ASM prices. ConclusionsThe findings reveal an expanding price disparity between brand-name and generic oral ASMs. An inverse relationship was observed between the number of medication labelers and generic ASM prices, with additional labelers driving down generic prices. However, introducing more generic labelers led to a significant increase in brand-name ASM prices. Furthermore, following patent expirations, brand-name ASM prices rose—a trend explained by the "generics paradox," where, contrary to expectations, brand prices do not decrease and may even increase when generics enter the market. These findings underscore the need for targeted interventions in drug pricing policies to manage the rising costs associated with epilepsy treatment. To ensure equitable access to ASMs, stakeholders must understand and address the factors driving these pricing dynamics.

Budget impact analysis on the Italian healthcare system of roxadustat for the treatment of anemia due to chronic kidney disease

Objective: The aim of this study was to evaluate the economic consequences of the introduction of roxadustat on the market as treatment for chronic kidney disease (CKD)-related anaemia in Italy. Method: A budget impact model was developed to assess the economic impact of the introduction of roxadustat for the management of patient with CKD-related anaemia. The analysis was conducted considering National Health Service (NHS) perspective and three years’ time horizon. Eligible population for the treatment with roxadustat was estimated through published literature and clinicians’ support. Direct healthcare costs included drug acquisition (list prices for base case) and administration costs, monitoring costs, cost per blood transfusion, costs related to the management of adverse events and dialysis costs. Results: The model estimated a three years expenditure associated with the management of patients with CKD-related incident anaemia in Italy of about € 260 and € 44.6 million for non-dialysis dependent (NDD) and dialysis-dependent (DD) patients respectively. The introduction of roxadustat on the market could generate a reduction in the expenditure related to the iron supplementation both for NDD and for DD patients (−€ 397,305 and −€ 50,135 over three years of the analysis, respectively) and a reduction in the pharmaceutical expenditure for NDD patients (−€ 2.3 million, −€ 7.5 million and −€ 13 million at first, second and third year of the analysis). Overall, the introduction of roxadustat could generate a saving for NHS approximately equal to € 2.3, € 7.5 and € 13 million at first, second and third year of the analysis. Conclusion: The introduction of roxadustat could generate a reduction in the expenditure for the management of patients with CKD anaemia. A scenario analysis which used tender prices for ESAs and hypothesis of confidential discount for roxadustat showed that the saving for NHS will be kept if roxadustat’s discount is greater than 60.3%.

US cost-utility model of lenacapavir plus optimized background regimen (OBR) vs fostemsavir plus OBR and ibalizumab plus OBR for people with HIV with multidrug resistance.

Heavily treatment-experienced (HTE) people with HIV (PWH) have limited treatment options owing to multidrug resistance (MDR). Lenacapavir (LEN) is indicated, in combination with other antiretrovirals, for the treatment of adults with MDR HIV-1 experiencing failure of their current antiretroviral regimen because of resistance, intolerance, or safety considerations. To evaluate the cost-utility of LEN in combination with an optimized background regimen (OBR) vs alternative recently approved treatments for HTE PWH, fostemsavir (FTR)+OBR and ibalizumab (IBA)+OBR, for the treatment of PWH with MDR, from a mixed US health care payer perspective. A Markov state-transition model with a lifetime time horizon was developed. Transition probabilities between viral load categories were based on individual participant data from the CAPELLA trial for LEN+OBR and on relative efficacy parameters obtained from indirect treatment comparisons for comparators. Health state utilities were sourced from the literature. Costs included drug acquisition costs, drug administration costs, disease management costs, adverse event costs, AIDS-related event costs, and treatment switching costs and were sourced from red book costs, Medicare and Medicaid fees, and the literature. Costs and outcomes were discounted at 3% annually. The model was used to estimate total and incremental costs, life-years (LYs), quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios. A deterministic and a probabilistic sensitivity analysis, as well as scenario analyses, were performed to address elements of uncertainty in the model and to explore the robustness of the results. Over a lifetime time horizon, LEN+OBR was associated with the highest absolute QALYs (9.41) and the greatest number of LYs (12.09) compared with FTR+OBR (QALYs: 8.75; LYs: 11.26) and IBA+OBR (QALYs: 8.36; LYs: 10.78). LEN+OBR was also associated with the lowest total lifetime costs of the 3 interventions (LEN+OBR: $1,441,122 [US dollars]; FTR+OBR: $1,504,986; IBA+OBR: $1,524,396) and therefore was dominant over both comparators in the base case. LEN+OBR remained dominant vs FTR+OBR and IBA+OBR across the range of scenarios tested and LEN+OBR had a 99% probability of being cost-effective compared with FTR+OBR and IBA+OBR in the probabilistic sensitivity analysis at a willingness-to-pay threshold of $50,000/QALY. This economic evaluation demonstrated that LEN+OBR provides meaningful increases in QALYs and LYs, and is dominant over a lifetime time horizon, compared with FTR+OBR and IBA+OBR for the treatment of PWH with MDR in the United States.

Commercial markups on pediatric oncology drugs at 340B pediatric hospitals.

Eligible pediatric hospitals can purchase clinician-administered drugs at discounted rates through the 340B Drug Pricing Program and charge payers prices exceeding drug acquisition costs, but the magnitude of these markups is not known. In a study of newly approved oncology drugs at pediatric 340B hospitals, median negotiated prices ranged from 102% (interquartile range [IQR]: 91%-156%) of average sales price (ASP) at Phoenix Children's Hospital to 630% (IQR: 526%-630%) at Driscoll Children's Hospital. Pediatric hospitals participating in the federal 340B Drug Pricing Program can extract steep payments on new drugs from commercial insurers, though with wide variation between and within hospitals.

Cost-utility analysis of romiplostim for the treatment of chronic primary immune thrombocytopenia in China.

This study aimed to assess the cost-utility of romiplostim (ROMI) compared to eltrombopag (EPAG) as a second-line treatment for chronic primary immune thrombocytopenia (cITP) in Chinese adults. A decision tree-embedded Markov model with a lifetime horizon was used to estimate the quality-adjusted life years (QALYs) and costs for ROMI versus EPAG from the perspective of the Chinese health care system. The model was driven by platelet response with a 4-week cycle. Both QALYs and costs were discounted 5% per year. Clinical data comparing ROMI and EPAG were obtained by matching-adjusted indirect comparison (MAIC), utilizing individual patient data on ROMI and published Chinese Phase III trial data on EPAG. Costs were reported in 2022 US dollars and included drug acquisition costs, monitoring costs, bleeding-related costs, and costs associated with adverse events. Deterministic and probabilistic sensitivity analyses were performed. The CEA model indicated that treatment with ROMI resulted in an average of $4,344.4 higher costs for 0.004 QALYs. One-way sensitivity analysis (OSA) indicated that the model was most sensitive to the high bleeding rate in response (Markov stage) for EPAG and ROMI. Probabilistic sensitivity analysis (PSA) indicated that ROMI was likely to be cost effective in 0.16% cases at a willingness-to-pay threshold of $12039.1 (China per capita GDP in 2022) per QALY. If the price of ROMI is either lower than or equal to that of EPAG, ROMI could likely be considered cost-effective as a second-line treatment for Chinese adults with cITP.

Budget impact of resmetirom for the treatment of adults with non-cirrhotic non-alcoholic steatohepatitis (NASH) with moderate to advanced liver fibrosis (consistent with stages F2 to F3 fibrosis)

Aims This study assessed the budget impact of resmetirom as a treatment for adults with non-cirrhotic non-alcoholic steatohepatitis (NASH) with moderate-to-advanced liver fibrosis and estimated total costs for a hypothetical private payer in the United States. Materials and methods A three-year budget impact analysis based on an open cohort state transition model was developed for a hypothetical one-million-member private health plan. The comparator was Standard of Care (SOC), defined as routine care for non-cirrhotic NASH patients with moderate-to-advanced liver fibrosis. Each year, the number of resmetirom treatment-eligible patients was estimated through prevalent, incident, and diagnostic rate estimates. Costs included resources incurred by the medical and pharmacy benefits of private payers, including resmetirom drug acquisition costs, diagnosis and monitoring, other medical and other prescription costs stratified by disease progression status (i.e. non-cirrhotic vs. cirrhotic/advanced liver diseases). Resmetirom adverse event management costs were included in sensitivity analysis. Drug costs were estimated based on the average wholesale acquisition cost as of March 2024. Other costs were based on published sources and inflated to 2023 US dollars. Budget impact outcomes were presented in aggregate, net, and on a per-member per-month (PMPM) basis. Results Compared with a scenario without resmetirom, the introduction of resmetirom yielded results ranging from 50 to 238 treated patients, net budget impact of $2.2 to $9.5 million, and PMPM from $0.19 to $0.80 over years one and three. Net costs excluding resmetirom declined over time. In sensitivity analyses, results were most sensitive to diagnostic and epidemiologic inputs. Limitations Market shares are based on internal forecasts, a short time horizon, average treatment effects, and other limitations common to BIMs. Conclusion The adoption of resmetirom on the formulary for the treatment of non-cirrhotic NASH with moderate-to-advanced liver fibrosis resulted in a moderate increase in budget impact with declining costs related to NASH progression.

Clinical Considerations for HealthcareProvider-Administered Lipid-Lowering Medications.

Atherosclerotic cardiovascular disease (ASCVD), a leading cause of mortality and morbidity, is associated with a substantial healthcare and economic burden. Reduction of low-density lipoprotein cholesterol (LDL-C) to guideline-recommended goals is crucial in the prevention or management of ASCVD, particularly in those at high risk. Despite the availability of several effective lipid-lowering therapies (LLTs), up to 80% of patients with ASCVD do not reach evidence-based LDL-C goals. This nonattainment may be due to poor adherence to, and lack oftimely utilization of, LLTs driven by a range of variables, including polypharmacy, side effects, clinical inertia, costs, and access issues. Inclisiran was approved by the US Food and Drug Administration in 2021 as a novel, twice-yearly, healthcare provider (HCP)-administered LLT. In-office administration allows HCPs more control of drug acquisition, administration, and reimbursement, and may allow for more timely care and increased patient monitoring. In the USA, in-office administered drugs are considered a Medical Benefit and can be acquired and reimbursed using the "buy-and-bill" process. Buy-and-bill is a standard system for medication administration already established in multiple therapeutic areas, including oncology, vaccines, and allergy/immunology. Initiating in-office administration will involve new considerations for clinicians in the cardiovascular specialty, such as the implementation of new infrastructure and processes; however, it could ultimately increase treatment adherence and improve cardiovascular outcomes for patients with ASCVD. This article discusses the potential implications of buy-and-bill for the cardiology specialty and provides a practical guide to implementing HCP-administered specialty drugs in US clinical practice.

Budget Impact of Disease-Modifying Treatments and a CRISPR Gene-Edited Therapy for Sickle Cell Disease.

Treatment of sickle cell disease (SCD) has traditionally focused on symptomatic and preventative care. Recent advances in novel therapeutic developments, likely to be orphan-designated, are anticipated to carry a substantial price tag. This study assesses the potential budget impact of adopting disease-modifying treatments, crizanlizumab and voxelotor, and pioneering CRISPRgene-edited therapy, CTX001, in the Belgian healthcare system. The perspective of the Belgian healthcare payer (RIZIV-INAMI including patient copayments), a 5-year horizon with a 2-10% uptake of disease-modifying interventions, and a 2% uptake of CTX001 were considered. Data, encompassing target population, current (chronic and acute management, curative hematopoietic stem cell transplantation) and new (crizanlizumab, voxelotor, and CTX001) interventions, clinical effectiveness, adverse events, healthcare resource utilization, and associated costs, were gathered through a comprehensive literature review (first phase) and two Delphi panels involving hematologists (second phase). The cost difference between a "world with and without crizanlizumab, voxelotor, and CTX001" was calculated to obtain the budget impact.Three scenario analyses were conducted: a 5-13% and 4% uptake analysis, a 10-18% and 8% uptake analysis, respectively for disease-modifying treatments (crizanlizumab and voxelotor) and CTX001, and a 0% crizanlizumab uptake and managed entry agreements analysis .A ± 20% univariate sensitivity analysis was performed to test the robustness of the analysis. The total five-year cumulative budget impact was estimated at €30,024,968, with 91% attributed to drug acquisition costs. The largest budget impact share was for CTX001 (€25,575,150), while crizanlizumab (€2,301,095) and voxelotor (€2,148,723) was relatively small. In scenarios one and three, a two-fold increase of the cumulative budget impact to €60,731,772 and a four-fold increase to €120,846,256 from the base case was observed. In scenario three, this budget impact decreased by 63% to €11,212,766. Patient population size, number of treated patients, and drug costs influenced the analysis the most, while discontinuation, acute crisis, and adverse event rates had comparatively minimal impact. Belgian decision-makers may consider alternative financing models, such as outcome-based risk-sharing agreements or annuities, to ensure sustainable coverage of these treatments. This study adheres to recommended practices for assessing budget impact of orphan drugs, distinguishing it from earlier studies with potentially weaker methodologies.

37 Cost-effectiveness of treatment sequences with front-line nivolumab+ipilimumab therapy vs immuno-oncology+tyrosine kinase inhibitor therapies in intermediate/poor-risk metastatic renal cell carcinoma

Abstract Background Immuno-oncology (IO) and vascular endothelial growth factor (VEGF) targeted tyrosine kinase inhibitor (TKI) combinations have transformed the treatment of metastatic renal cell carcinoma (mRCC). However, there is a lack of evidence regarding the most cost-effective sequencing of these systemic therapies. This study aimed to assess the expected health and economic outcomes of various treatment sequences for newly diagnosed patients with intermediate/poor-risk RCC from a US payer perspective. Methods We developed a model using a continuous time micro-simulation framework. First-line treatment options included: nivolumab+ipilimumab, nivolumab+cabozantinib, pembrolizumab+lenvatinib, and pembrolizumab+axitinib. Second-line treatment options included: cabozantinib and everolimus+lenvatinib. In both lines, the source data for the overall survival (OS) and progression-free survival (PFS) distributions were obtained from the registrational randomized controlled trials (RCTs) of each therapy. The analysis included costs associated with drug acquisition in the US wholesale setting, drug administration and monitoring, management of treatment-related adverse events, disease management, and terminal care. Treatment duration for all first-line IO and TKI therapies was capped at 2 years. Quality-adjusted life-years (QALYs) were estimated by multiplying time in each phase of the disease by phase-specific utility values estimated from the CheckMate 214 trial data using US tariffs. The analysis was run 1000 times for cohorts of 100 patients over a 20-year time horizon. All costs and health outcomes were discounted annually at a 3% rate. Results Average per-patient QALYs were estimated for each sequence of interest: nivolumab+ipilimumab followed by cabozantinib (3.59), nivolumab+ipilimumab followed by lenvatinib+everolimus (3.26), pembrolizumab+axitinib followed by cabozantinib (3.14), pembrolizumab+axitinib followed by lenvatinib+everolimus (2.97), pembrolizumab+lenvatinib followed by cabozantinib (3.51), and nivolumab+cabozantinib followed by lenvatinib+everolimus (2.99). Average per-patient costs were estimated for each sequence of interest: nivolumab+ipilimumab followed by cabozantinib ($468,856), nivolumab+ipilimumab followed by lenvatinib+everolimus ($491,259), pembrolizumab+axitinib followed by cabozantinib ($675,714), pembrolizumab+axitinib followed by lenvatinib+everolimus ($700,411), pembrolizumab+lenvatinib followed by cabozantinib ($837,888), nivolumab+cabozantinib followed by lenvatinib+everolimus ($873,377). First-line drug acquisition costs accounted for the majority of costs for all sequences. Conclusions Based upon our model using data from registrational RCTs, first-line nivolumab+ipilimumab followed by cabozantinib represents the dominant treatment strategy for intermediate/poor-risk mRCC patients in the US, offering estimated cost savings of up to 45% when compared to IO+TKI options. Additional studies are needed to elucidate whether these cost savings translate to the real-world setting.

Health and Economic Outcomes of Pembrolizumab in the Treatment of Metastatic Non-small Cell Lung Cancer (mNSCLC) and Melanoma in Italy.

In Italy, the management of metastatic non-small cell lung cancer and melanoma leads to significant healthcare challenges, necessitating cost-effective treatment strategies and offering valuable insights for healthcare policymakers and stakeholders. This study was designed to assess the costs, quality-adjusted life-years (QALYs) and disability-adjusted life-years (DALYs) associated with the health and economic outcomes of (1) pembrolizumab-combined chemotherapy administered as a first-line treatment for metastatic non-squamous and squamous non-small cell lung cancer (NSCLC) where the tumour presents with a programmed death-ligand 1 expression level <50% and of (2) adjuvant pembrolizumab treatment for stage III melanoma. Three cost-effectiveness models developed by MSD were investigated for each treatment indication. A unique model was built to assess the overall effect of pembrolizumab versus chemotherapy or watchful waiting in patients with lung cancer or melanoma, respectively. Theoretical cohorts of patients with metastatic squamous and non-squamous NSCLC were followed over time using a partitioned survival model with weekly cycles. A weekly cycle Markov model was employed for melanoma. The analysis was conducted from the Italian National Health Service perspective, considering a time horizon of 40 years (lifetime). A single closed cohort of treatable patients was followed over time for each indication (4000, 7000 and 900 for NSCLC squamous, non-squamous and melanoma, respectively). The costs evaluated included those for adverse drug events, non-drug disease management, subsequent treatment and terminal care. Drug acquisition and administration costs were excluded. For each treatment indication assessed, pembrolizumab produced downstream direct cost offsets (- €122,498,568, -€133,369,076 and -€32,993,242 for NSCLC squamous, non-squamous and melanoma indications, respectively), increased quality of life (+2088, +5317 and +2307 QALYs for NSCLC squamous, non-squamous and melanoma indications, respectively) and reduced disability (-2658, -7202 and -3029 DALYs for NSCLC squamous, non-squamous and melanoma indications, respectively). Across indications, the total cost offsets of pembrolizumab were -€288,860,885, with 9712 QALYs gained and 12,889 DALYs avoided. The analysis demonstrated that, compared with chemotherapy, pembrolizumab is more cost effective in Italy as a first-line treatment in patients with metastatic squamous or non-squamous NSCLC and, if compared with watchful waiting, as adjuvant treatment in patients with stage III melanoma. The present analysis suggested that pembrolizumab use could lead to important health benefits for patients while offsetting a portion of cancer care costs.

Prospective multicenter study of the epidemiological features of emergency patients with overdose of over-the-counter drugs in Japan.

To investigate the epidemiological characteristics of patients presenting to the emergency department with an overdose of over-the-counter (OTC) drugs. A questionnaire survey was conducted to examine the sociodemographic characteristics of patients with OTC drugs overdoses visiting emergency departments at eight sites across the country. The patients were divided into "habitual" and "nonhabitual" groups according to their history of OTC drugs overdose. Student's t-test or Welch's t-test was performed for numerical variables, and Pearson's χ 2 test was performed for dichotomous and nominal variables between the two groups. Of the 124 patients included in this study, 79% were women. The habitual (26.6%) and the nonhabitual (73.4%) groups showed no differences in sex, occupation, cohabitants, history of mental illness, or history of alcohol consumption or smoking; however, those in the habitual group were significantly younger. The proportion of OTC drugs obtained from physical stores was higher in the habitual group, whereas the nonhabitual group used more household medicines. Suicide and self-harm were more common reasons for overdose in the nonhabitual group. Antipyretic analgesics were significantly more common in the nonhabitual group, whereas antitussive expectorants and antihistamines were significantly more common in the habitual group. This is the first multicenter study to determine the status of OTC drugs overdose patients treated at emergency departments of medical facilities in Japan. To prevent new overdoses of OTC drugs, continued detailed epidemiologic studies of patient backgrounds and drug acquisition routes, and investigation of the components of OTC drugs that cause dependency are necessary.

Modelling the opportunity for cost-savings or patient access with biosimilar adalimumab and tocilizumab: a European perspective

Objectives Biosimilars improve patient access by providing cost-effective treatment options. This study assessed the potential for savings and expanded patient access with increased use of two biosimilar disease modifying anti-rheumatic drugs (DMARDs): (a) approved adalimumab biosimilars and (b) the first tocilizumab biosimilar, representing an established biosimilar field and a recent biosimilar entrant in France, Germany, Italy, Spain, and the United Kingdom (UK). Methods Separate ex-ante analyses were conducted for each country, parameterized using country-specific list prices, unit volumes annually, and market shares for each therapy. Discounting scenarios of 10%, 20%, and 30% were tested for tocilizumab. Outputs included direct cost-savings associated with drug acquisition or the incremental number of patients that could be treated if savings were redirected. Two biosimilar conversion scenarios were tested. Results Savings associated with a 100% conversion to adalimumab biosimilar ranged from €10.5 to €187 million (UK and Germany, respectively), or an additional 1,096 to 19,454 patients that could be treated using the cost-savings. Introduction of a tocilizumab biosimilar provided savings up to €29.3 million in the most conservative scenario. Exclusive use of tocilizumab biosimilars (at a 30% discount) could increase savings to €28.8 to €113 million or expand access to an additional 43% of existing tocilizumab users across countries. Conclusion This study demonstrates the benefits that can be realized through increased biosimilar adoption, not only in an untapped tocilizumab market, but also through incremental increases in well-established markets such as adalimumab. As healthcare budgets continue to face downwards pressure globally, strategies to increase biosimilar market share could prove useful to help manage financial constraints.

Budget impact analysis of biosimilar natalizumab in the US.

Biosimilars provide an opportunity for a more sustainable and cost-effective treatment for multiple sclerosis (MS). This study evaluated the potential financial impact of implementing a formulary change from reference to biosimilar natalizumab (NTZ) from the US commercial payer perspective. The budget impact of transitioning to biosimilar NTZ for the treatment of relapsing-remitting MS (RRMS) was estimated over a 3-year time horizon based on real-world dosing. Additional scenario analyses were conducted by varying the price differential of biosimilar NTZ. The target population was estimated from a 1-million-member hypothetical commercial health plan. Model inputs were drug acquisition costs and treatment-related and patient coinsurance costs. Budget impact and cost savings per member per year were calculated by assuming a biosimilar uptake of 10% in year 1 to 20% in year 3. Over 3 years, 255 patients were estimated to be treated with high-efficacy disease-modifying therapies for RRMS. The inclusion of biosimilar NTZ onto a formulary would result in cumulative cost savings to payers of $452,611 over 3 years, with mean savings per treated member per year of $1179, $1769, and $2359 in years 1, 2, and 3, respectively. One-way sensitivity analyses indicated that budget impact results were most sensitive to drug acquisition costs of both reference and biosimilar NTZ. Adoption of biosimilar NTZ can yield considerable cost savings to US health plans that could result in increased treatment access for patients with RRMS.