Drug Acquisition Costs Research Articles

Usefulness of Sodium-Glucose Cotransporter 2 Inhibitors for Primary Prevention of Heart Failure in Patients With Type 2 Diabetes Mellitus

The sodium-glucose cotransporter 2 inhibitors (SGLT2i) empagliflozin, canagliflozin, and dapagliflozin reduce the risk of heart failure (HF) events in patients with diabetes mellitus (DM) at high risk for HF. Differences in HF outcomes between SGLT2i were demonstrated in a recent-published meta-analysis. Nevertheless, comparative cost-effectiveness analyses of SGLT2i provided for this indication have not been published yet. Therefore, we aimed to provide a preceding economic comparison of the costs required for improving HF outcomes by these three SGLT2i. The primary outcome was the cost needed to treat (CNT) to prevent one event of hospitalization for HF or cardiovascular mortality. CNT is calculated by multiplying the annualized number needed to treat to prevent one event by the annual cost of therapy. Clinical outcome data were extracted from pre-specified cohorts of HF-naïve patients in the pivotal randomized controlled trials (RCTs). Costs of interventions were estimated as 75% of the US National Average Drug Acquisition Cost listing. Sensitivity analysis was performed to mitigate differences between the RCT's populations. We figured the CNT for the primary prevention of HF events in DM patients to be $542,328 ($409,044-$905,412) for empagliflozin, $2,347,488 ($1,066,208-∞) for canagliflozin and $2,128,374 ($1,204,740-$48,140,518) for dapagliflozin. Sensitivity analysis confirmed the cost benefit of empagliflozin. Our findings suggest that between the available SGLT2i, the cost of primary prevention of HF in patients with DM at high risk for HF is lowest with empagliflozin. These findings may help choose an SGLT2i until head-to-head RCTs, and comprehensive cost-effective analyses for this indication are available.

Minimization of resource utilization data collected within cost-effectiveness analyses conducted alongside Canadian Cancer Trials Group phase III trials.

BackgroundCost-effectiveness analyses embedded within randomized trials allow for evaluation of value alongside conventional efficacy outcomes; however, collection of resource utilization data can require considerable trial resources.MethodsWe re-analyzed the results from four phase III Canadian Cancer Trials Group trials that embedded cost-effectiveness analyses to determine the impact of minimizing potential cost categories on the incremental cost-effectiveness ratios. For each trial, we disaggregated total costs into component incremental cost categories and recalculated incremental cost-effectiveness ratios using (1) only the top 3 cost categories, (2) the top 5 cost categories, and (3) all cost components. Using individual trial-level data, confidence intervals for each incremental cost-effectiveness ratio simulation were generated by bootstrapping and descriptively presented with the original confidence intervals (and incremental cost-effectiveness ratios) from the publications.ResultsDrug acquisition costs represented the highest incremental cost category in three trials, while hospitalization costs represented the other consistent cost driver and the top incremental cost category in the fourth trial. Recalculated incremental cost-effectiveness ratios based on fewer cost components (top 3 and top 5) did not differ meaningfully from the original published results. Based on conventional willingness-to-pay thresholds (US$50,000–US$100,000 per quality-adjusted life-year), none of the re-analyses would have changed the original perception of whether the experimental therapies were considered cost-effective.ConclusionsThese results suggest that the collection of resource utilization data within cancer trials could be narrowed. Omission of certain cost categories that have minimal impact on incremental cost-effectiveness ratio, such as routine laboratory investigations, could reduce the costs and undue burden associated with the collection of data required for cancer trial cost-effectiveness analyses.

Budget Impact Analysis of Vericiguat for the Treatment of Chronic Heart Failure with Reduced Ejection Fraction Following a Worsening Event.

IntroductionIn the USA, patients with chronic heart failure (HF) with reduced ejection fraction (HFrEF) following a worsening HF event (WHFE) have significantly increased healthcare resource use and medical costs. This analysis aimed to estimate the budget impact of vericiguat as an add-on therapy to guideline-directed medical therapy (GDMT) for the treatment of chronic HFrEF following a WHFE from a US commercial payer perspective.MethodsA model was developed to estimate the budget impact of adding vericiguat to the formulary by comparing a current scenario (GDMT) and a new scenario (vericiguat plus GDMT) to a hypothetical 10-million-member commercial payer over a 3-year time horizon. Epidemiology data was obtained from literature. Treatment utilization rates of GDMT and clinical inputs (HF hospitalization and cardiovascular [CV] morality) were based on the VICTORIA trial in which patients with chronic HFrEF following a WHFE were randomized to GDMT plus placebo or GDMT plus vericiguat. Costs (2020 US$) included drug acquisition, hospitalization, routine care, and mortality.ResultsApproximately 20,510 prevalent cases in year 1 and 3109 annual incident cases in subsequent years were estimated to be eligible for treatment with vericiguat. At a utilization rate of 5%, 10%, and 15% for vericiguat over years 1–3, the per member per month (PMPM) budget impact was estimated to be $0.048, $0.064, and $0.086, respectively, associated with 44, 32, and 30 fewer HF hospitalizations and 7, 12, and 18 fewer CV deaths, respectively. Reduction in HF hospitalizations and CV deaths reduced the budget impact by 14% in total over 3 years.ConclusionAdding vericiguat to commercial plan formulary was associated with limited budget impact, primarily driven by drug acquisition costs but partially offset by reduced cost of HF hospitalizations and CV deaths.Supplementary InformationThe online version contains supplementary material available at 10.1007/s12325-021-01681-2.

Budget Impact Analysis of Biosimilar Products in Spain in the Period 2009-2019.

Since the first biosimilar medicine, Omnitrope® (active substance somatropin) was approved in 2006, 53 biosimilars have been authorized in Spain. We estimate the budget impact of biosimilars in Spain from the perspective of the National Health System (NHS) over the period between 2009 and 2019. Drug acquisition costs considering commercial discounts at public procurement procedures (hospital tenders) and uptake data for both originator and biosimilar as actual units consumed by the NHS were the two variables considered. Two scenarios were compared: a scenario where no biosimilars are available and the biosimilar scenario where biosimilars are effectively marketed. All molecules exposed to biosimilar competition during this period were included in the analysis. The robustness of the model was tested by conducting multiple sensitivity analyses. From the payer perspective, it is estimated that the savings produced by the adoption of biosimilars would reach EUR 2306 million over 11 years corresponding to the cumulative savings from all biosimilars. Three molecules (infliximab, somatropin and epoetin) account for 60% of the savings. This study provides the first estimation of the financial impact of biosimilars in Spain, considering both the effect of discounts that manufacturers give to hospitals and the growing market share of biosimilars. We estimate that in our last year of data, 2019, the savings derived from the use of biosimilars relative total pharmaceutical spending in Spain is 3.92%. Although more research is needed, our evidence supports the case that biosimilars represent a great opportunity to the sustainability of the NHS through rationalizing pharmaceutical spending and that the full potential of biosimilar-savings has not been achieved yet, as there is a high variability in biosimilar uptake across autonomous regions.

The Effect of Market Competition on the Price of Topical Eye Drops

ABSTRACT Purpose To describe the relationship between the number of Federal Drug Administration (FDA)-approved manufacturers and the price change of generic and branded topical eye drops. Methods Retrospective analysis of topical eye drop medications with formulations listed in the FDA Orange Book and the National Average Drug Acquisition Cost database from 2013 to 2017. Results The most frequently prescribed generic topical drugs were glaucoma medications (34%), antimicrobials (32%), anti-inflammatories (24%), mydriatics (5%), and anesthetics (5%). The most frequently prescribed branded topical drugs were anti-inflammatories (45%), glaucoma medications (32%), antimicrobials (21%) and dry eye medications (3%). From 2013 to 2017, generic eye drops had a median price decrease of 20% (IQR 32%) while branded eye drops had a median price increase of 44% (IQR 28%) (P < .001). A significant inverse association was identified between the price change of generic eye drops and the total number of all manufacturers (r = −.41, P = .010), generic drug manufacturers (r = −.32, P = .0496), and alternative branded drug manufacturers (r = −.57, P = .002). There was no significant association between the price change of branded eye drops and number of manufacturers. Glaucoma (r = −.58, P = .039) and anti-inflammatory (r = −.69, P = .047) eye drops also had significant inverse associations with the number of generic manufacturers. Conclusion From 2013 to 2017, the price of generic eye drops decreased whereas the price of branded eye drops increased. Market competition was significantly inversely associated with price changes of generic eye drops but not branded eye drops.

Estimating the annual economic burden for the management of patients with transthyretin amyloid polyneuropathy in Spain

ABSTRACT Background: Transthyretin amyloid polyneuropathy (ATTR-PN) is a fatal disease associated with substantial burden of illness. Three therapies are approved by the European Medicines Agency for the management of this rare disease. The aim of this study was to compare the total annual treatment specific cost per-patient associated with ATTR-PN in Spain. Methods: An Excel-based patient burden and cost estimator tool was developed to itemize direct and indirect costs related to treatment with inotersen, patisiran, and tafamidis in the context of ATTR-PN. The product labels and feedback from five Spanish ATTR-PN experts were used to inform resource use and cost inputs. Results: Marked differences in costs were observed between the three therapies. The need for patisiran- and inotersen-treated patients to visit hospitals for pre-treatment, administration, and monitoring was associated with increased patient burden and costs compared to those treated with tafamidis. Drug acquisition costs per-patient per-year were 291,076€ (inotersen), 427,250€ (patisiran) and 129,737€ (tafamidis) and accounted for the majority of total costs. Overall, the total annual per-patient costs were lowest for patients treated with tafamidis (137,954€), followed by inotersen (308,358€), and patisiran (458,771€). Conclusions: Treating patients with tafamidis leads to substantially lower costs and patient burden than with inotersen or patisiran.

Intravenous Iron Replacement in Patients with Left Ventricular Assist Devices

<h3>Purpose</h3> In patients supported by LVADs, iron deficiency is a common cause of anemia (IDA) and its associated morbidity. The clinical benefits of intravenous (IV) iron replacement in heart failure are well described, but there are fewer data supporting IDA treatment in LVAD patients. This study assessed the clinical and financial impact of IV ferric carboxymaltose (FCM) in an outpatient LVAD population through evaluation of anemia, blood transfusion requirements, readmissions, and insurance reimbursement. <h3>Methods</h3> This was a single-center prospective observational study of LVAD patients with IDA (ferritin <100 ng/mL or 100-300 ng/mL with Tsat <20%). Outpatients received FCM 750 mg x 2 doses given 1 week apart. The primary endpoint was the resolution of anemia at 1, 3, and 6 months. Blood transfusion requirements and readmissions were assessed pre- and post-FCM therapy. Financial analysis included the comparison of drug-specific reimbursement to drug acquisition cost. <h3>Results</h3> Eighty patients received FCM therapy. Baseline data are shown in Table 1. On average, patients were 19 months post-implant, 16% had experienced a gastrointestinal bleed within the last 3 months, and mean baseline Hgb was 9.9 g/dL. At 1 month, mean Hgb significantly improved (12.0±1.9 g/dL vs 9.9±1.4, p<0.0001), and this was maintained at 3 months (12.1±2.0, p<0.0001) and 6 months (12.2±2.1, p<0.0001) (Figure 1). When comparing the 3- and 6-month periods pre- and post-FCM, blood transfusion requirements and hospital admissions were both significantly reduced (Table 3). The majority of patients were covered by Medicare (67.5%) or a commercial payor (18.2%) with drug reimbursement to cost ratios of 0.81 and 1.97, respectively. <h3>Conclusion</h3> This prospective evaluation of IV iron replacement with 2 doses of FCM in a large cohort of LVAD patients demonstrated a resolution of anemia and subsequent reduction in blood transfusion and readmission requirements. In a mixed payor patient population, drug reimbursement supports utilization of FCM for this indication.

Economic impact of improving patient safety using Sugammadex for routine reversal of neuromuscular blockade in Spain

BackgroundNeuromuscular blocking (NMB) agents are often administered to facilitate tracheal intubation and prevent patient movement during surgical procedures requiring the use of general anesthetics. Incomplete reversal of NMB, can lead to residual NMB, which can increase the risk of post-operative pulmonary complications. Sugammadex is indicated to reverse neuromuscular blockade induced by rocuronium or vecuronium in adults. The aim of this study is to estimate the clinical and economic impact of introducing sugammadex to routine reversal of neuromuscular blockade (NMB) with rocuronium in Spain.MethodsA decision analytic model was constructed reflecting a set of procedures using rocuronium that resulted in moderate or deep NMB at the end of the procedure. Two scenarios were considered for 537,931 procedures using NMB agents in Spain in 2015: a scenario without sugammadex versus a scenario with sugammadex. Comparators included neostigmine (plus glycopyrrolate) and no reversal agent. The total costs for the healthcare system were estimated from the net of costs of reversal agents and overall cost offsets via reduction in postoperative pneumonias and atelectasis for which incidence rates were based on a Spanish real-world evidence (RWE) study. The model time horizon was assumed to be one year. Costs were expressed in 2019 euros (€) and estimated from the perspective of a healthcare system. One-way sensitivity analysis was carried out by varying each parameter included in the model within a range of +/− 50%.ResultsThe estimated budget impact of the introduction of sugammadex to the routine reversal of neuromuscular blockade in Spanish hospitals was a net saving of €57.1 million annually. An increase in drug acquisition costs was offset by savings in post-operative pulmonary events, including 4806 post-operative pneumonias and 13,996 cases of atelectasis. The total cost of complications avoided was €70.4 million. All parameters included in the model were tested in sensitivity analysis and were favorable to the scenario with sugammadex.ConclusionsThis economic analysis shows that sugammadex can potentially lead to cost savings for the reversal of rocuronium-induced moderate or profound NMB compared to no reversal and reversal with neostigmine in the Spanish health care setting. The economic model was based on data obtained from Spain and from assumptions from clinical practice and may not be valid for other countries.

Abstract PS9-68: Budget impact of Ontruzant for the treatment of breast cancer and gastric cancer in the United States

Abstract OBJECTIVES: Breast cancer is estimated to have the highest incidence among all cancers in the United States (US) in 2020. In turn, the incidence of gastric cancer is ranked fifteenth among all cancers in the US. Targeted therapies, such as trastuzumab, have drastically improved clinical outcomes for patients with over-expressive human epidermal growth factor receptor 2 (HER2+) in early-stage breast cancer (EBC) and metastatic breast cancer (MBC) as well as metastatic gastric cancer (MGC). However, due to the high cost of treatment and eligible patient population size, originator trastuzumab has caused patient affordability challenges and represents a high budget burden on payers. The objective of this study is to assess the potential financial impact associated with the use of intravenous (IV) trastuzumab biosimilar Ontruzant compared to the originator, in patients with HER2+ EBC, MBC and MGC from the US healthcare payer perspective. METHODS: A budget impact model with a 5-year time horizon was developed to compare costs ($; 2020) under scenarios with and without the entry of Ontruzant to a healthcare plan. Only direct costs were considered following a payer perspective. Drug acquisition costs were estimated based on the published wholesale acquisition cost (WAC) price. The target population consisted of incident HER2+ patients eligible to receive trastuzumab IV or subcutaneous. Epidemiological data were obtained from SEER database and Epic Oncology. Predictions on trastuzumab market share and Ontruzant uptake were based on internal market research. The model calculated the budget impact of Ontruzant by indication and across all indications. RESULTS: In a hypothetical healthcare plan with one million members, the number of incident patients treated with the trastuzumab class was estimated to range from 107 in year 1 to 100 in year 5 in HER2+ EBC and 17 to 16 in HER2+ MBC. About ten new patients with HER2+ MGC were estimated to be treated with trastuzumab or biosimilars each year in year 1 to 5. The market uptake of Ontruzant with the trastuzumab class was assumed 50% in year 1 and rising over time to 90% in year 5, which led to a total budget saving of $13,534,498 in EBC and MBC and $459,331 in MGC over the 5-year period for the healthcare plan. The model yielded an average saving of $1,859, $2,073 and $766 per treated member per month in EBC, MBC and MGC, respectively. The cost saving was mainly driven by the lower drug acquisition cost of Ontruzant compared to originator trastuzumab, as well as potential reduction of vial wastage due to the availability of Ontruzant multi-dose vials. CONCLUSIONS: Adding Ontruzant to the formulary for treatment of HER2+ breast cancer and gastric cancer and creating mechanisms to encourage providers to utilize Ontruzant instead of the reference branded agent, could lead to substantial cost-savings for the US healthcare payers; and consequently, improve access to treatments for the patients. Citation Format: Min Huang, Puneet Singhal, Reshma Shinde, Sarah K Wilkes, Nirav Nagda, Yunni Yi, Stefano Lucherini. Budget impact of Ontruzant for the treatment of breast cancer and gastric cancer in the United States [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS9-68.

Abstract PS10-45: Budget impact of introducing neratinib for third-line treatment of HER2+ metastatic breast cancer in the United States

Abstract Background Neratinib, an oral, irreversible tyrosine kinase inhibitor of multiple HER receptors, was recently approved in combination with capecitabine (neratinib doublet regimen) in the United States (US) for adults with HER2+ metastatic breast cancer (mBC) who have received 2 or more anti-HER2 therapies. Clinical trials showed that neratinib plus capecitabine significantly improved progression-free survival versus lapatinib plus capecitabine. There are several existing and potential treatment options for this population with varying efficacies, side effect profiles, and costs. Objective This analysis estimates the budget impact for US health care payers of adding a neratinib doublet regimen to the currently available third-line HER2+ mBC treatments in the US. Methods A budget-impact model was developed to compare health care payer costs associated with third-line treatment of HER2+ mBC over 5 years between a treatment setting with neratinib and a treatment setting without neratinib for a hypothetical 1-million-person commercial plan of adults over age 18. The treatment options considered in the model include neratinib doublet regimen, oral combination therapy with lapatinib and capecitabine (lapatinib doublet regimen), tucatinib plus capecitabine plus trastuzumab (tucatinib triplet regimen), and intravenous fam-trastuzumab deruxtecan-nxki (DS-8201 single agent). The population eligible for treatment was calculated based on prevalence and incidence of HER2+ mBC and progression to third-line HER2-direct treatment; estimates were obtained from the published literature. The impact of including neratinib doublet regimen was assessed under two market share scenarios: one in which all regimens had equal market share and a second in which a clinical expert provided judgement on projected uptake of the regimens over the five-year period. In the treatment setting without the neratinib regimen, market shares for neratinib were distributed equally to the other treatments. Treatment duration, dosing, adverse event incidence, and monitoring requirements were obtained from key clinical trials and prescribing information. Drug acquisition costs, unit monitoring costs, and adverse event costs were obtained from wholesale acquisition costs, fee schedules, and the Healthcare Cost and Utilization Project, respectively. The total incremental costs and per-member-per-month (PMPM) costs were calculated by comparing total health plan costs in the treatment setting with neratinib with costs in the treatment setting without neratinib over a 5-year period. Costs were presented in 2019 US dollars. Results It was estimated that 47 patients would be eligible for third-line HER2 mBC treatment in the first year, with an additional 17 incident patients becoming eligible each subsequent year. Average monthly costs per treated patient were $15,037, $9,283, $27,759, and $14,826 for neratinib doublet regimen, lapatinib doublet regimen, tucatinib triplet regimen, and DS-8201, respectively. When market shares were assumed to be even across regimens, the treatment setting with neratinib doublet regimen reduced total annual health plan costs by $1.4 million ($0.02 PMPM) over 5 years compared with the treatment setting without neratinib doublet regimen. Cost reductions for the treatment setting with neratinib doublet regimen were $575,738 ($0.01 PMPM) over 5 years when market shares were based on clinical expert estimates. Conclusions The introduction of neratinib over the course of 5 years has the potential to reduce US health plan costs for the treatment of patients with HER2+ mBC by reducing the usage of more expensive treatment regimens. Citation Format: Seri AL Anderson, Justin Carrico, Thor-Henrik Brodtkorb, Deepa Lalla, Adam Brufsky. Budget impact of introducing neratinib for third-line treatment of HER2+ metastatic breast cancer in the United States [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS10-45.

Abstract PS9-33: Cost-effectiveness of neratinib for the extended adjuvant treatment of adult patients with early-stage, HR+, HER2-overexpressed/amplified breast cancer who initiated neratinib within 1 year of completing trastuzumab in the US

Abstract Background: Neratinib, an oral, irreversible tyrosine kinase inhibitor of multiple human epidermal growth factor receptors (HERs), is indicated for the extended adjuvant treatment of adult patients with, HER2-positive early-stage breast cancer (eBC) to follow adjuvant trastuzumab-based therapy in the United States (US). However, greater efficacy has been seen in patients with hormone receptor-positive (HR+) breast cancer and who initiated neratinib within 1 year of completing trastuzumab. Objective: This study explores the cost-effectiveness of neratinib versus placebo from a US third-party payer perspective in adult patients with HR+ HER2-overexpressed/amplified eBC and who are less than 1 year from the completion of prior adjuvant trastuzumab-based therapy. Methods: A Markov model was constructed to model costs and health outcomes of neratinib and placebo over a lifetime horizon. The model consisted of five health states representing the primary stages of disease in eBC—disease-free, local recurrence, remission, distant recurrence, and dead—and corresponds to the primary and secondary endpoints in the neratinib ExteNET trial. Overall survival was modeled based on a combination of post-distant recurrence survival and general population mortality, assuming all cancer-related mortality would occur through the distant recurrence health state. Statistical extrapolation of invasive disease-free survival and post-distant recurrence survival were derived from the ExteNET clinical trial data as well as the proportion of local and distant recurrence and number of adverse events. Non-breast cancer-related mortality was derived from US life tables. Costs per treatment arm were calculated based on drug acquisition, administration, and monitoring costs as well as treatment costs for adverse events and health state-related medical resource use. Quality-adjusted life-years (QALYs) were estimated per health state, and disutilities were applied per adverse event independent of treatment. Utility values for the invasive disease-free survival health state and diarrhoea were estimated using the EQ-5D-3L data collected in ExteNET. Additional health state utilities and adverse events disutilities were identified from the literature. Costs were adjusted to 2020 US dollars. One-way (OWSA) and probabilistic sensitivity analyses (PSA) and scenario analyses were performed to investigate the robustness of the results. Further, analyses were performed to investigate the cost-effectiveness for the subgroup of patients who did not achieve a pathologic complete response (pCR) after neoadjuvant therapy. Results: The results of the base case analysis showed that, compared with placebo, neratinib treatment generated an additional 0.88 incremental QALYs, 0.99 incremental life-years, and a resulting cost per QALY gained of $56,367. The results were robust across multiple scenario analyses with incremental cost-effectiveness ratios (ICERs) below $70,000. OWSA showed that the parameters that most influenced the results were variations in treatment-related costs, efficacy, and health state utility values. The PSA indicated that the probability of neratinib being cost-effective at a $100,000 per QALY threshold was above 75%. The analysis for the subgroup of patients who did not achieve a pCR after neoadjuvant therapy resulted in an improved ICER. Conclusions: The current cost-effectiveness analysis shows that neratinib is a cost-effective therapy for treating adult patients with HR+ HER2-overexpressed/amplified eBC and who are less than 1 year from the completion of prior adjuvant trastuzumab-based therapy in the US and in patients who did not achieve a pCR after neoadjuvant treatment. Citation Format: Thor-Henrik Brodtkorb, Cheryl McDade, Deepa Lalla, Frankie Ann Holmes. Cost-effectiveness of neratinib for the extended adjuvant treatment of adult patients with early-stage, HR+, HER2-overexpressed/amplified breast cancer who initiated neratinib within 1 year of completing trastuzumab in the US [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS9-33.

Short- and long-term cost-effectiveness analysis of CYP2C19 genotype-guided therapy, universal clopidogrel, versus universal ticagrelor in post-percutaneous coronary intervention patients in Qatar

BackgroundPatients having CYP2C19 loss-of-function alleles and receiving clopidogrel are at higher risk of adverse cardiovascular outcomes. Ticagrelor is an effective antiplatelet that is unaffected by the CYP2C19 polymorphism. The main aim of the current research is to evaluate the cost-effectiveness among CYP2C19 genotype-guided therapy, universal ticagrelor, and universal clopidogrel after a percutaneous coronary intervention (PCI). MethodsA two-part decision-analytic model, including a one-year model and a 20-year follow-up Markov model, was created to follow the use of (i) universal clopidogrel, (ii) universal ticagrelor, and (iii) genotype-guided antiplatelet therapy. Outcome measures were the incremental cost-effectiveness ratio (ICER, cost/success) and incremental cost-utility ratio (ICUR, cost/quality-adjusted life years [QALY]). Therapy success was defined as survival without myocardial infarction, stroke, cardiovascular death, stent thrombosis, and no therapy discontinuation because of adverse events, i.e. major bleeding and dyspnea. The model was based on a multivariate analysis, and a sensitivity analysis confirmed the robustness of the model outcomes, including against variations in drug acquisition costs. ResultsAgainst universal clopidogrel, genotype-guided therapy was cost-effective over the one-year duration (ICER, USD 6102 /success), and dominant over the long-term. Genotype-guided therapy was dominant against universal ticagrelor over the one-year duration, and cost-effective over the long term (ICUR, USD 1383 /QALY). Universal clopidogrel was dominant over ticagrelor for the short term, and cost-effective over the long-term (ICUR, USD 10,616 /QALY). ConclusionCYP2C19 genotype-guided therapy appears to be the preferred antiplatelet strategy, followed by universal clopidogrel, and then universal ticagrelor for post-PCI patients in Qatar.

Clinical and pharmacoeconomic evaluation of antifungal prophylaxis with continuous micafungin in patients undergoing allogeneic stem cell transplantation: A six‐year cohort analysis

Patients undergoing allogeneic stem cell transplantation (aSCT) are at high risk to develop an invasive fungal disease (IFD). Optimisation of antifungal prophylaxis strategies may improve patient outcomes and reduce treatment costs. To analyse the clinical and economical impact of using continuous micafungin as antifungal prophylaxis. We performed a single-centre evaluation comparing patients who received either oral posaconazole with micafungin as intravenous bridging as required (POS-MIC) to patients who received only micafungin (MIC) as antifungal prophylaxis after aSCT. Epidemiological, clinical and direct treatment cost data extracted from the Cologne Cohort of Neutropenic Patients (CoCoNut) were analysed. Three hundred and thirteen patients (97 and 216 patients in the POS-MIC and MIC groups, respectively) were included into the analysis. In the POS-MIC and MIC groups, median overall length of stay was 42 days (IQR: 35-52 days) vs 40 days (IQR: 35-49 days; p =.296), resulting in median overall costs of €42,964 (IQR: €35,040-€56,348) vs €43,291 (IQR: €37,281 vs €51,848; p = .993), respectively. Probable/proven IFD in the POS-MIC and MIC groups occurred in 5 patients (5%) vs 3 patients (1%; p = .051), respectively. The Kaplan-Meier analysis showed improved outcome of patients in the MIC group at day 100 (p = .037) and day 365 (p < .001) following aSCT. Our study results demonstrate improved outcomes in the MIC group compared with the POS-MIC group, which can in part be explained by a tendency towards less probable/proven IFD. Higher drug acquisition costs of micafungin did not translate into higher overall costs.

Cost-effectiveness of nivolumab monotherapy in the third-line treatment of small cell lung cancer

Aims Present cost-effectiveness analysis of nivolumab monotherapy vs. commonly prescribed third-line (3 L+) treatment in small cell lung cancer (SCLC). Materials and methods A three health states partitioned survival model (progression-free, progressed disease, and death; US payer perspective) was developed. The systematic literature review identified no randomized controlled or single-arm trials with separate outcomes for 3 L + SCLC patients. Topotecan was chosen as a comparator because it is frequently prescribed in real-world practice for 3 L SCLC. Clinical inputs for topotecan were derived from the Flatiron database with inclusion/exclusion criteria matched to patients treated with 3 L + nivolumab in CheckMate 032. Intravenous (IV) and oral topotecan clinical efficacy were assumed equivalent. Base-case analysis used a 20-year lifetime horizon. An annual discount rate of 3.0% for costs and outcomes was applied. Uncertainty was assessed using sensitivity analyses adjusted for key parameters. Results Incremental cost per quality-adjusted life-year (QALY) gained with nivolumab was US$153,312 vs. IV topotecan and US$123,003 vs. oral topotecan, respectively. When results were disaggregated, nivolumab-related costs were mainly driven by drug acquisition costs, and topotecan-related costs were primarily due to adverse event treatment. Mean overall survival (OS) was 21.69 months with nivolumab and 5.80 months with IV or oral topotecan. More favorable outcomes were found by the landmark response analyses. Deterministic sensitivity analyses showed that changes to the discount rate for costs and outcomes and body weight had the greatest impacts on results. Limitations Included use of real-world data for OS outcomes associated with 3 L topotecan, use of second-line topotecan data for progression-free survival, and no indirect costs. Conclusions Based on the literature on willingness-to-pay for a QALY in metastatic cancer, nivolumab monotherapy might represent a cost-effective option for 3 L + treatment of SCLC compared with IV and oral topotecan. Sensitivity analysis using response-based methods yielded further favorable cost-effectiveness estimates.

Cost-effectiveness of pembrolizumab + chemotherapy versus chemotherapy and pembrolizumab monotherapy in first line treatment of NSCLC in the US – updated analyses with additional trial follow-up

Objective Pembrolizumab + chemotherapy substantially extends life expectancy for metastatic non-small cell lung cancer (NSCLC) patients. Its cost-effectiveness (CE) was previously evaluated based on interim trial analyses (follow-up ∼1 year). The present analysis describes CE incorporating additional follow-up based on protocol-specified final trial analyses (1–1.5 years additional follow-up), from a US healthcare payer perspective. Methods A partitioned survival model is used to compare pembrolizumab + chemotherapy vs chemotherapy using data from the KN189 (non-squamous patients) and KN407 (squamous patients) clinical trials. An indirect treatment comparison vs pembrolizumab monotherapy is made for patient subgroups with PD-L1 TPS ≥50% and 1–49% based on data from the KN024 and KN042 trials. Efficacy, treatment utilization, health utility, and safety data are derived from trials and projected over 20 years. Costs for drugs, non-drug disease management, and adverse events are also incorporated. Results Overall, versus chemotherapy alone, pembrolizumab + chemotherapy is projected to increase life expectancy by 1.12 years (3.35 vs 2.23) and 0.67 years (3.17 vs 2.50) in non-squamous and squamous patients, respectively. Resultant ICERs ($158,030/QALY and $178,387/QALY) are below a US 3-times GDP per capita threshold ($195,000/QALY). ICERs vs chemotherapy also generally fall below the threshold within PD-L1 sub-groups (except in squamous PD-L1 < 1%, which may have differed due to small sample size) while ICERs vs pembrolizumab monotherapy in PD-L1 ≥ 50% and 1–49% sub-groups generally exceed it (except in squamous PD-L1 1–49%); largely a result of the higher drug acquisition cost of pembrolizumab + chemotherapy relative to differences in life expectancy. Conclusions Taken together, with longer-term trial follow-up and in the context of prior literature, in the US, one of the two options for pembrolizumab use (either pembrolizumab + chemotherapy or pembrolizumab monotherapy), represents a cost-effective treatment in virtually all non-squamous and squamous metastatic NSCLC patient populations and PD-L1 sub-groups evaluated.

Cost-minimization analysis of biweekly dosing of cetuximab and FOLFIRI compared with panitumumab and FOLFOX for first-line treatment of patients with KRAS wild-type metastatic colorectal cancer in the United States

Aim To compare the cost of biweekly regimens of first-line (1L) treatments of cetuximab-folinic acid, fluorouracil, and irinotecan (FOLFIRI) versus panitumumab-folinic acid, fluorouracil, and oxaliplatin (FOLFOX) in patients with Kirsten’s rat sarcoma wild type (KRAS WT) metastatic colorectal cancer (mCRC) in the United States, across varying weights and body surface areas (BSAs). Materials and methods Cost-minimization analysis (CMA) was performed to estimate per-patient cost differences of cetuximab-FOLFIRI versus panitumumab-FOLFOX. The CMA estimated the costs of RAS testing, premedication, drug acquisition, treating infusion reactions (IRs), supportive therapy, and biweekly administration of chemotherapy, cetuximab (500 mg/m2), and panitumumab (6 mg/kg) over 43 weeks (median progression-free survival). To calculate dose and cost, weight and height data were gathered from an electronic health record-derived de-identified database (n = 7,669; January 2013–October 2020). Base case analysis utilized mean weight/BSA of the overall cohort (82.04 kg/1.92 m2), and alternate scenarios were based on 88.18 kg/2.03 m2 (men, n = 4,477) and 73.43 kg/1.76 m2 (women, n = 3,192). Results For the base case, total treatment costs were $167,853 for cetuximab-FOLFIRI and $168,254 for panitumumab-FOLFOX; cost savings per patient receiving cetuximab-FOLFIRI was $400. Cost savings in alternate scenarios (men, $15,138; women, $15,004) resulted from lower drug acquisition costs for cetuximab (men, $14,833; women $14,854) and administration cost ($440) versus panitumumab. Cost savings of cetuximab-FOLFIRI in treating IR ($353) were similar across all scenarios. Limitations With no head-to-head clinical trial data in the 1L setting, assumptions of similarity in efficacy and safety of cetuximab versus panitumumab were based on published network meta-analysis and the ASPECCT trial. This model did not consider a lifetime horizon. Costs of managing all adverse events (except IR) were not included. Conclusions Biweekly cetuximab-FOLFIRI offers cost savings compared with panitumumab-FOLFOX for 1L therapy of patients with KRAS WT mCRC in the United States. These cost differences were observed for the overall population and across different BSA and weights for men and women.

Budget impact analysis of subcutaneous trastuzumab compared to intravenous trastuzumab in Saudi HER2-positive breast cancer patients

ABSTRACT Background: This study was aimed to assess the budget impact of SC trastuzumab compared to IV trastuzumab in patients with HER2-positive breast cancer (BC) from the perspective of the governmental health sector in Saudi Arabia, over a 3-year time horizon. Methods: A model was developed to calculate the direct medical and indirect costs for 394 incidents HER2-positive BC patients per year who would receive SC trastuzumab compared to IV formulation. We calculated drug acquisition costs for fixed, loading, and subsequent doses of trastuzumab. One-way sensitivity analysis was conducted. Results: Two scenarios were modeled: the first scenario evaluated the impact of gradual replacement of IV formulation by SC, the second scenario, evaluated impact of totally replacing IV formulation. The total annual costs in the first scenario were estimated to be SAR 177 million (USD 98 million) for IV trastuzumab compared to SAR 143 million (USD 79 million) for SC formulation, leading to a total budget saving of SAR 34,527,346 (USD 19,181,858). In the second scenario, the total annual costs were estimated to be SAR 108 million (USD 60 million) for SC trastuzumab compared to SAR 177 million (USD 98 million) for IV formulation, leading to budget savings of SAR 69,054,692 (USD 36,363,717). Conclusion: Benefits of the SC formulation over IV infusions are being converted to realistic monetary benefits for all providers and payers.

Dapagliflozin vs. sacubitril-valsartan for prevention of heart failure events in non-diabetic patients with reduced ejection fraction: a cost per outcome analysis.

The Angiotensin Receptor-Neprilysin Inhibitor sacubitril-valsartan (ARNI) and dapagliflozin, a sodium-glucose transport protein 2 inhibitor, reduce the risk of heart failure hospitalization (hHF) and cardiovascular (CV) mortality in patients with reduced ejection fraction (HFrEF). Their comparative value for money is undetermined. Therefore, our aim was to compare the cost per outcome implications of utilizing dapagliflozin vs. ARNI for preventing heart failure (HF) events of non-diabetic patients with HFrEF. We calculated the cost needed to treat (CNT) to prevent one HF event. The cost needed to treat was estimated by multiplying the annualized number needed to treat (NNT) to prevent one event by each therapy's annual cost. Efficacy estimates were extracted from published secondary analyses of non-diabetic patients in DAPA-HF and PARADIGM-HF trials. Drug costs were estimated as 75% of the 2020 US National Average Drug Acquisition Cost listing. Sensitivity analysis was performed to mitigate differences between the trial's populations and drug costs in various countries.The annualized NNT to prevent one HF event for dapagliflozin was 31 (95% CI 21-71) vs. 33 (95% CI 24-62) for ARNI. The CNT of dapagliflozin in the US is $141 112 (95% CI $95 592-$323 192) compared to $158 169 (95% CI $115 032-$297 166) for sacubitril-valsartan. The CNT results were sensitive to drug costs in various countries. Dapagliflozin and ARNI provide comparable value for money for preventing HF events in non-diabetic patients with HFrEF. In healthcare settings where dapagliflozin's price is significantly lower than ARNI, it provides superior value for money.

PCN203 Estimating the Budget and Health Impact of the PD-1/PD-L1 Inhibitor Class in Switzerland

Immunotherapy has transformed cancer care, offering improved outcomes in a range of indications, greater quality of life, survival benefits, and regimen tolerability. However, the rapid expansion of immuno-oncology (IO) treatment options and their use has led to concerns about potentially putting healthcare budgets under strain. The objective of this study was to estimate the potential public health and budget impact of PD-1/PD-L1 inhibitors in Switzerland. Budget impact analysis and partitioned survival modelling were used to estimate key clinical and economic outcomes in a world with and without PD-1/PD-L1 inhibitors in nine high-incidence cancer types: adjuvant and metastatic melanoma, first- and second-line non-small cell lung cancer, gastric cancer, head and neck cancer, urothelial carcinoma, renal cell carcinoma, and small cell lung cancer. Outcomes were estimated over a five-year time horizon (2019-2023). Drug acquisition costs were based on publicly available information. Market share assumptions rely on internal available model estimate. Efficacy and adverse events data were taken from clinical trials. Additional 7,770 life years, 6,485 progression-free life years and 6,366 quality-adjusted life years are projected to be gained by using PD-1/PD-L1 inhibitors over a five-year period. We also expect a reduction in the number of high-grade adverse events by 9,641. In 2020, it is estimated that 22.5% of Swiss cancer medicines expenditure (CHF 220 M) will be attributable to PD-1/PD-L1 inhibitors. This accounts for an estimated 0.25% of total health care spending. The average annual budget impact of PD-1/PD-L1 inhibitors over five years is estimated to be CHF 150 million. PD-1/PD-L1 inhibitors can deliver significant survival benefits in cancer patients, with less severe side effects. The budget impact of PD-1/PD-L1 inhibitors in Switzerland is manageable but increasing usage of these treatments will require alternative measures for securing funds, such as reallocation of funds from the treatments losing exclusivity.

PCN62 Budget IMPACT Analysis of Trastuzumab Emtansine for Residual Invasive HER2-Positive Breast Cancer in Argentina

To assess the 10 years-evolution of the annual budget impact of trastuzumab emtansine (T-DM1) compared with trastuzumab to the treatment of patients with HER2-positive early breast cancer and residual invasive disease at surgery, after completion of neoadjuvant chemotherapy plus HER2-targeted therapy from the whole health system perspective in Argentina. A budget impact model was first developed. Age-specific Her2-positive incidence rates published by GLOBOCAN were applied to Argentinian population estimates to determine its annual potential patients. Extrapolation of Kaplan-Meier curves, assuming a lognormal distribution, was used to project the number of relapses avoided by the adoption of T-DM1, and the treatment durations in both adjuvant and metastatic settings. Incremental benefit of T-DM1 was based on the Katherine study. Drug acquisition costs were calculated using publicly available prices and resource usage rates were estimated by conducting a Delphi Panel. Unitary costs were extracted out of the Unit Costs Database. Total Budget Impact is shown in US Dollars using the official exchange rate. The annual Budget Impact from the T-DM1 arm increased from $9,05 MM to $41,58 MM in 10 years compared with an increase from $4,1 MM to $40,51 MM in the Trastuzumab arm. The proportion of the metastatic setting direct costs, presented as percentages of the total variation, ranged from 2% to 44% in the T-DM1 arm and from 9% to 76% in the comparator arm. This analysis shows that purchase and monitoring costs of T-DM1 compared with trastuzumab tend to equate at a 10- year time horizon. This may be related to a lower relapse rate in the T-DM1 group. Although the driver of costs at the beginning of the analysis is related to the acquisition costs, relapse- related costs in the trastuzumab group represent a higher proportion of the total costs of care at the end of the analysis.