Clinical and Economic Value of a Biosimilar Portfolio to Stakeholders: An Integrative Literature Review.

Purpose: While the value of individual biosimilars is evident, little is known about the value of a biosimilar portfolio beyond the cost savings between biosimilars and originators. Stakeholders may consider the value of a manufacturer's biosimilar portfolio, especially when negotiating portfolio-based contracts or other rebate programs. However, little is known about what other types of value, in addition to financial benefits, decision-makers perceive regarding a manufacturer with a biosimilar portfolio compared to those without one. The objective of this integrative literature review was to describe a conceptual framework consisting of themes that may help define the value of a biosimilar portfolio. Methods: An integrative literature review was conducted using Excerpta Medica Database (Embase) and Medical Literature Analysis and Retrieval System Online (MEDLINE). Grey literature searches of search engines, journals not indexed in Embase or MEDLINE, healthcare payers, health technology assessment bodies, value frameworks, and non-pharmaceutical industry analogs were also conducted. Eligible studies reported on the value of a biosimilar portfolio in decision-making by stakeholders. Apart from the literature, insights were gained from clinical experience and observation. Results: No studies investigating biosimilar portfolio value were identified; however, several themes were identified that may help define the value of a biosimilar portfolio: Manufacturing; procurement, inventory, and storage; administration; education; and transaction costs. Several non-pharmaceutical industry analogs were identified: Product line length and single-supplier versus multiple-supplier procurement. Several themes were identified through other sources: Science credibility and research. Based on these themes, we developed a conceptual framework for biosimilar portfolio value. Conclusion: To our knowledge, this is the first study to systematically assess and create a framework for biosimilar portfolio value. The conceptual framework described here could be tested to quantify the clinical and economic value associated with a biosimilar portfolio.

Though the value of single biosimilars is evident, little is known about the value of a biosimilar portfolio beyond the cost savings incurred between biosimilars and originators.We identified seven themes that may help to define the value of a biosimilar portfolio: Manufacturing; procurement, inventory, and storage; administration; education; transaction costs; science credibility; and research.These themes may be integrated into a conceptual framework that may form a basis to help quantify the clinical and economic benefit of a biosimilar portfolio to stakeholders.

The Impact of Biosimilar Use on Total Cost of Care and Provider Financial Performance in the Medicare Oncology Care Model: A Population-Based Simulation Study.

INTRODUCTION: Payment for oncology care is increasingly moving from fee-for-service to value-based payment (VBP). VBPs are agreements in which providers are held accountable for total cost of care (TCOC) through risk-sharing arrangements with payers that tie reimbursement levels to TCOC benchmarks. Oncology biosimilars may play an important role in managing financial risk in the VBPs like Medicare's Oncology Care Model (OCM), but there has been limited research in this area. The objective of this study is to estimate the impact of biosimilar adoption on TCOC and oncology provider financial performance under the terms of the Medicare OCM. METHODS: We conducted a population-based simulation study using the Medicare Limited Data Set (LDS) and the methodology of Medicare's OCM. The primary outcome was the simulated average change in TCOC per 6-month episode of care attributable to use of biosimilars as an alternative to reference products. The study population consisted of episodes of care in 2020 and using the reference product or corresponding biosimilar for bevacizumab, rituximab, trastuzumab, epoetin alfa, filgrastim, or pegfilgrastim. TCOC was calculated for each episode of care with use of reference products only and compared with TCOC with corresponding biosimilars. The simulation calculated TCOC outcomes in cohorts of 100 episodes sampled from the Medicare LDS study population using a Monte Carlo simulation with 10,000 iterations. RESULTS: Among the total of 8281 6-month oncology care episodes identified in the study period (initiating January 2020 to July 2020) in Medicare claims, 1586 (19.2%) episodes met OCM and study criteria and were included. Applying the simulation methods to these observed episodes, biosimilar substitution reduced mean TCOC per episode by $1193 (95% CI $583-1840). The cost reduction from biosimilars represented 2.4% of the average TCOC benchmark and led to a 15% reduction in the risk of providers needing to pay recoupments to Medicare for exceeding TCOC benchmarks. CONCLUSIONS: On the basis of our simulation study using observed Medicare claims and OCM criteria, we found that biosimilar substitution for reference products can significantly lower episode TCOC and improve provider financial performance under the terms of the largest value-based payment model implemented to date.

Greater uptake, an alternative reimbursement methodology needed to realize cost-saving potential of oncology biosimilars in the United States.

BACKGROUND: Biologics are an important treatment option for solid tumors and hematological malignancies but are a primary driver of health care spending growth. The United States has yet to realize the promise of reduced costs via biosimilars because of slow uptake, partially resulting from commercial payer reimbursement models that create economic incentives favoring the prescribing of reference biologics. OBJECTIVE: To examine the economic feasibility of an alternative reimbursement methodology that prospectively shares savings across commercial payers and providers to shift economic incentives in favor of lower-cost oncology biosimilars. METHODS: Using 3 oncology monoclonal antibody drugs (trastuzumab, bevacizumab, and rituximab) as examples, we developed an alternative reimbursement model that would offer an additional per unit payment (or "extra consideration") such that providers' net income per unit for biosimilars and reference biologics become equal. Provider-negotiated rates (or payer-allowable amounts) and average sales prices were obtained from claims data and projected to develop prices/costs from 2021 through 2025. Scenario analyses by varying key model assumptions were performed. RESULTS: The alternative reimbursement model achieved 1-year and 5-year payer savings in the commercial market for all 3 drugs in the sites of service analyzed. The base analysis showed first-year cost savings to payers, net of cost sharing, of up to 9% in physician offices (POs) and up to 1% in non-340B hospital outpatient departments (HOPDs) for patients using the drugs analyzed. Five-year cumulative savings per patient ranged from about $12,600-$16,100 in PO and $2,200-$4,100 in HOPD. Payer savings varied depending on the characteristics of the provider with which the payer was negotiating (eg, lower- vs highermarkup providers, POs vs HOPDs). CONCLUSIONS: Positive payer savings shown in our modeling suggest that an alternative reimbursement arrangement could facilitate an economic compromise wherein commercial payers can save on biosimilars while providers' incomes are preserved. DISCLOSURES: Research funding was provided by Pfizer Inc. Yang and Shelbaya are employees of Pfizer Inc. and own Pfizer stock. Carioto, Pyenson, Smith, Jacobson, and Pittinger are employees of Milliman Inc., which received research funding from Pfizer Inc., for work on this study. Milliman, Inc., provides actuarial and other professional services to organizations throughout the healthcare industry. None of these are contingent, equity or investment relationships.

Does Biosimilar Bevacizumab Offer Affordable Treatment Options for Cancer Patients in the USA? A Budget Impact Analysis from US Commercial and Medicare Payer Perspectives.

BACKGROUND: Bevacizumab remains the most widely used and most thoroughly characterized angiogenesis inhibitor for a range of advanced cancers. Bevacizumab-bvzr (Zirabev®), a biosimilar of bevacizumab, was recently approved by the US Food and Drug Administration (FDA), which provides a less costly option. This study aimed to evaluate the financial impact of introducing bevacizumab-bvzr from US commercial and Medicare payer perspectives. METHODS: A Microsoft Excel-based budget impact model was developed over a 5-year time horizon. Target population was patients to be treated with bevacizumab for FDA-approved indications. Drug costs (2020 US$) were based on average sales price and wholesale acquisition cost, accounting for payer-specific reimbursement models and provider settings. Drug dosing and duration were based on prescribing information and pivotal trial publications. RESULTS: In a hypothetical 10-million-member health plan, 503 and 723 patients were estimated to be treated with bevacizumab in year 1 and year 5, respectively. Assuming an annual market shift of 1.7%, 3.6%, 6.7%, 9.4%, and 11.9% to bevacizumab-bvzr, an annual cost saving of $313,363 ($0.003 per member per month [PMPM]) was estimated for a commercial payer and $92,880 ($0.001 PMPM) for Medicare in year 1. Cumulative 5-year cost savings were $7,030,924 ($0.012 PMPM) for a commercial payer and $4,059,257 ($0.007 PMPM) for Medicare. More than half of the cost savings was attributed to patients with metastatic colorectal cancer. CONCLUSIONS: The introduction of biosimilar bevacizumab-bvzr was estimated to provide substantial cost savings for US payers, which would allow additional patients access to bevacizumab treatment.

Economic Outcomes Related to Persistence and Dosing of Celecoxib in Patients with Osteoarthritis (OA) Using a Retrospective Claims Database Analysis.

OBJECTIVE: This study describes treatment patterns, healthcare resource utilization (HCRU), and costs associated with persistence, switching, and dosing of branded celecoxib in osteoarthritis (OA) patients. METHODS: This retrospective claims database analysis used MarketScan® Commercial Claims and Encounters (MarketScan) data from 2009 to 2013. Included patients were adult (≥ 18 years), incident celecoxib users with ≥ 1 OA claim. The treatment switch analysis analyzed outcomes in patients persistent on celecoxib versus switched to a generic nonsteroidal anti-inflammatory drug (NSAID). The dosing analysis stratified patients as under-dose (<200 mg per day) and standard dose (≥200 mg per day). HCRU, costs, and treatment duration were compared in persistent versus switched and standard dose versus under-dose patients using descriptive, multivariate logistic regression, and Kaplan-Meier analysis. RESULTS: A total of 65,530 patients met the inclusion criteria. During follow-up, 83% discontinued celecoxib without switching, 10% were persistent, and 5% switched to a generic NSAID. Ninety percent received a standard dose of celecoxib. Switched (versus persistent) patients had significantly higher all-cause hospital admissions, length of stay, emergency room (ER) visits, and office visits per person year (PPY), all P <0.001; and under-dosed (versus standard dose) patients had significantly higher hospital admissions (P<0.001), length of stay (P<0.001), and ER visits (P= 0.021) PPY. Persistent versus switched patients had lower mean total all-cause costs PPY ($20,378 vs $23,949, P<0.001). Standard dose versus under-dose patients had lower mean total all-cause costs ($23,680 vs $26,955 PPY, P<0.001), and not statistically significant higher mean total OA-related costs ($5698 vs $5524 PPY, P=0.441). CONCLUSION: Patients that switched from branded celecoxib to a generic NSAID or received an under-dose of branded celecoxib had higher average overall HCRU and costs. OA-related inpatient and outpatient cost savings may offset the higher drug cost of celecoxib for persistent patients.

Economic burden associated with inadequate antidepressant medication management among patients with depression and known cardiovascular diseases: insights from a United States-based retrospective claims database analysis.

Aims: The current study examined the association between insufficient major depressive disorder (MDD) care and healthcare resource use (HCRU) and costs among patients with prior myocardial infarction (MI) or stroke.Methods: This was a retrospective study conducted using the MarketScan Claims Database (2010-2015). The date of the first MI/stroke diagnosis was defined as the cardiovascular disease (CVD) index date and the first date of a subsequent MDD diagnosis was the index MDD date. Adequacy of MDD care was assessed during the 90 days following the index MDD date (profiling period) using 2 measures: dosage adequacy (average fluoxetine equivalent dose of ≥20 mg/day for nonelderly and ≥10 mg/day for elderly patients) and duration adequacy (measured as the proportion of days covered of 80% or higher for all MDD drugs). Study outcomes included all-cause and CVD-related HCRU and costs which were determined from the end of the profiling period until the end of study follow-up. Propensity-score adjusted generalized linear models (GLMs) were used to compare patients receiving adequate versus inadequate MDD care in terms of study outcomes.Results: Of 1,568 CVD patients who were treated for MDD, 937 (59.8%) were categorized as receiving inadequate MDD care. Results from the GLMs suggested that patients receiving inadequate MDD care had 14% more all-cause hospitalizations, 4% more all-cause outpatient visits, 17% more CVD-related outpatient visits, 13% more CVD-related emergency room (ER) visits, higher per patient per year CVD-related hospitalization costs ($21,485 vs. $17,756), higher all-cause outpatient costs ($2,820 vs. $2,055), and higher CVD-related outpatient costs ($520 vs. $434) compared to patients receiving adequate MDD care.Limitations: Clinical information such as depression severity and frailty, which are potential predictors of adverse CVD outcomes, could not be ascertained using administrative claims data.Conclusions: Among post-MI and post-stroke patients, inadequate MDD care was associated with a significantly higher economic burden.

Healthcare resource use and cost associated with timing of pharmacological treatment for major depressive disorder in the United States: a real-world study.

Background: Guidelines recommend selective serotonin reuptake inhibitors (SSRI) and serotonin norepinephrine reuptake inhibitors (SNRI) as first-line treatments for major depressive disorder (MDD) and emphasize the importance of early pharmacological treatment as key factors to treatment success.Objectives: To compare the MDD-related healthcare resource utilization (HCRU) and cost among patients (1) with early vs late pharmacological treatment initiation and (2) achieving minimum therapeutic dose (MTD) early vs late.Methods: The MarketScan database (2010-2015) was used. Adults who were newly-treated with SSRI/SNRI within 12 months after the initial MDD diagnosis (index) were included. Patients who initiated SSRI/SNRI within 2 weeks of the index date were defined as early initiators; those who reached MTD within 4 weeks of index date were defined as early MTD achievers. MDD-related HCRU and costs per year after the index date were compared between early and late initiators and between early and late achievers using propensity score matching and generalized linear models.Results: Of the 55,539 patients, 60% were early initiators and 61% were early MTD achievers. The mean number of MDD-related outpatient visits per year were significantly higher for late initiator (6.7 vs 4.2, p < .001) and late MTD achievers (6.5 vs 4.5, p < .001) vs their early counterparts. Mean annual MDD-related outpatient, drug, and total cost were significantly higher for late initiators and MTD achievers vs the early groups.Conclusions: There is an opportunity to improve outcomes by treating MDD patients with SSRI/SNRI within 2 weeks and at or above the MTD within 4 weeks of diagnosis or less.

Cost-Effectiveness of Early Treatment with Originator Biologics or Their Biosimilars After Methotrexate Failure in Patients with Established Rheumatoid Arthritis.

INTRODUCTION: Evidence supports the clinical benefits of early aggressive biologic treatment in patients with rheumatoid arthritis (RA) who have an inadequate response to conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), but the cost-effectiveness of early intervention with originator biologics such as tumor necrosis factor inhibitors (TNFis) or their biosimilars has not been well studied. METHODS: We developed a Markov model to estimate lifetime costs and utilities for patients with established RA who do not respond to methotrexate (MTX) therapy. A cost-effectiveness analysis was conducted comparing a standard intervention pathway (addition of originator biologic TNFis to MTX monotherapy at 12 months) and two early intervention pathways (either addition of originator biologic TNFis or addition of biosimilar TNFis to MTX monotherapy at 6 months). RESULTS: Early intervention with an originator biologic TNFi at 6 months was associated with increases in total lifetime costs of £1692 and utilities of 0.10 quality-adjusted life-years (QALYs) per patient compared with standard intervention at 12 months, resulting in an incremental cost-effectiveness ratio (ICER) of £17,335/QALY. Early intervention with a biosimilar TNFi increased costs by £70 and utilities by 0.10 QALYs per patient and was associated with an ICER of £713/QALY. CONCLUSION: Switching from MTX monotherapy to combination therapy with either an originator biologic or biosimilar TNFis at 6 months after csDMARD failure in patients with RA was cost-effective at a threshold of £30,000/QALY. FUNDING: Pfizer Inc.

The economic and clinical burden of early versus late initiation of celecoxib among patients with osteoarthritis.

OBJECTIVE: This study aimed to evaluate the characteristics associated with early versus late initiation of celecoxib treatment after osteoarthritis (OA) diagnosis and whether economic and safety outcomes differ between patients with early versus late initiation of celecoxib. METHODS: Adults (≥18 years) with a confirmed OA diagnosis (International Classification of Diseases, 9th Edition, Clinical Modifications code: 715.XX), ≥12 months of continuous pre- and post-index enrollment, and ≥1 post-index claim for celecoxib were included from the MarketScan® Commercial Claims and Encounter Database (2009-2013). Index date was defined as initial OA diagnosis. Patients were categorized as initiating celecoxib early (within 6 months of index date) or late (≥6 months after index date). Logistic regressions were used to assess characteristics associated with early versus late celecoxib initiation. Key outcomes included health care resource utilization (HCRU) and costs post-index, and adverse event incidence post-celecoxib initiation. Unadjusted and adjusted comparisons (using generalized linear models with a gamma distribution for costs and Poisson distribution for event and resource utilization) were made between early and late celecoxib initiators. RESULTS: Of the 62,434 OA patients identified, 27,402 were early and 35,032 were late initiators. Post-index hospital admissions and length of stay did not differ statistically between early versus late initiators after controlling for pre-index event rates and covariates, but early patients had significantly fewer outpatient (incidence rate ratio [IRR]: 0.96; 95% confidence interval [CI]: 0.95, 0.97) and emergency room visits (IRR: 0.89; 95% CI: 0.84, 0.95). After adjustment for key covariates, early initiators (versus late initiators) had lower all-cause (US$12,909 versus US$13,781, P<0.001) and OA-related (US$4,988 versus US$5,178, P=0.015) costs per person-year. Early initiators had no statistically significant difference in the incidence of post-celecoxib cardiovascular (IRR: 0.92; 95% CI: 0.73, 1.14), gastrointestinal (IRR: 1.25; 95% CI: 0.81, 1.92), or renal (IRR: 1.19; 95% CI: 0.65, 2.18) events, controlling for pre-index event rates and covariates when compared to late initiators. CONCLUSION: In this real-world cohort, patients initiated on celecoxib early (versus late) had significantly lower costs and HCRU; this may warrant consideration when making treatment decisions for OA patients.

Economic burden of inpatient and outpatient antibiotic treatment for methicillin-resistant Staphylococcus aureus complicated skin and soft-tissue infections: a comparison of linezolid, vancomycin, and daptomycin.

BACKGROUND: Previous economic analyses evaluating treatment of methicillin-resistant Staphylococcus aureus (MRSA) complicated skin and soft-tissue infections (cSSTI) failed to include all direct treatment costs such as outpatient parenteral antibiotic therapy (OPAT). Our objective was to develop an economic model from a US payer perspective that includes all direct inpatient and outpatient costs incurred by patients with MRSA cSSTI receiving linezolid, vancomycin, or daptomycin. METHODS: A 4-week decision model was developed for this economic analysis. Published literature and database analyses with validation by experts provided clinical, resource use, and cost inputs on data such as efficacy rate, length of stay, adverse events, and OPAT services. Base-case analysis assumed equal efficacy and equal length of stay for treatments. We conducted several sensitivity analyses where assumptions on resource use or efficacy were varied. Costs were reported in year-end 2011 US dollars. RESULTS: Total treatment costs in the base-case were lower for linezolid ($10,571) than vancomycin ($11,096), and daptomycin ($13,612). Inpatient treatment costs were $740 more, but outpatient costs, $1,266 less with linezolid than vancomycin therapy due to a switch to oral linezolid when the patient was discharged. Compared with daptomycin, both inpatient and outpatient treatment costs were lower with linezolid by $87 and $2,954 respectively. In sensitivity analyses, linezolid had lower costs compared with vancomycin and daptomycin when using differential length of stay data from a clinical trial, and using success rates from a meta-analysis. In a scenario without peripherally inserted central catheter line costs, linezolid became slightly more expensive than vancomycin (by $285), but remained less costly than daptomycin (by $2,316). CONCLUSION: Outpatient costs of managing MRSA cSSTI may be reduced by 30%-50% with oral linezolid compared with vancomycin or daptomycin. Results from this analysis support potential economic benefit and cost savings of using linezolid versus traditional OPAT when total inpatient and outpatient medical costs are evaluated.

Nonadherence to oral linezolid after hospitalization: a retrospective claims analysis of the incidence and consequence of claim reversals.

BACKGROUND: Linezolid is available in an oral as well as an intravenous formulation. It is an oxazolidinone antibiotic and is effective in treating resistant gram-positive organisms such as methicillin-resistant Staphylococcus aureus and multidrug-resistant Streptococcus pneumoniae. OBJECTIVES: The goals of this study were to identify the incidence of claim reversals for oral linezolid in members who were recently discharged from a hospital and to study the subsequent pattern of health care utilization to quantify the consequences for members who have a reversed linezolid claim. METHODS: This study was a retrospective claims analysis of Humana Medicare Advantage Prescription Drug patients who had a claim for oral linezolid after an inpatient discharge between April 1, 2006, and June 30, 2008. The incidence of reversed claims among those with a linezolid prescription was measured as a proxy for medication adherence. Propensity scores were calculated to account for differences in patients' propensity to have a reversed claim. The association of the claim reversal with subsequent expenditures was assessed through 3 multivariate regression models wherein the dependent variables were drug, medical, and total costs for the 60-day period after discharge. The key independent variable was the occurrence of a reversed linezolid claim, and control variables included the propensity score quartiles and other clinical and demographic characteristics. All costs were provided in US dollars and from the year in which they occurred. RESULTS: Of 1046 patients identified (mean [SD] age, 69 [12] years; 51% male), 252 patients (24.1%) had a claim reversal for linezolid. Among these, 125 patients (49.6%) received linezolid within 10 days of the initial reversal, 39 patients (15.5%) received other antibiotics, and 88 patients (34.9%) did not receive any antibiotics. The unadjusted, mean outpatient drug costs were $696 and $2265 for patients with and without a reversal, respectively, whereas mean medical costs were $13,567 and $9355. Multivariable analyses revealed that members who did not receive linezolid after the claim reversal had significantly higher medical expenditures (Wald χ(2), 8.370; P = 0.004) and lower drug expenditures (Wald χ(2), 122.630; P < 0.01). The total costs did not differ significantly between the 2 groups (Wald χ(2), 1.540; P = 0.215), however, as the medical savings were partially negated by the higher drug costs. CONCLUSION: These patients with a reversed outpatient claim for linezolid had lower outpatient drug costs and higher medical costs in the 60-day period after the reversal.