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.

Clinical, economic, and humanistic burden of community acquired pneumonia in Europe: a systematic literature review.

BACKGROUND: Community-acquired pneumonia (CAP) is an infectious lung inflammation contracted outside the hospital. CAP is a leading cause of death among young children, elderly, and immunocompromised persons. Incidence can reach 14 cases/1,000 adults. Up to 50% of cases require inpatient hospitalization. Mortality is 0.7/1,000 cases or 4 million deaths per year. We sought to summarize multi-dimensional burden of CAP for selected European countries. METHODS: We conducted a systematic literature review of literature published from 2011 to 2021 whereby we sought information pertaining to the epidemiologic, clinical, economic, and humanistic burden of CAP. Findings were summarized descriptively. RESULTS: CAP incidence in Europe is variable, with the highest burden among those of advanced age and with chronic comorbidities. Etiology is primarily bacterial infection with Streptococcus pneumoniae being the most frequently implicated. Direct medical costs are primarily attributable to inpatient stay, which is exacerbated among high-risk populations. Higher mortality rates are associated with increasing age, the need for inpatient hospitalization, and antibiotic resistance. CONCLUSIONS: A better understanding of CAP is needed, specifically the economic and quality of life burden on patients and caregivers. We recommend further assessments using population-level and real-world data employing consistent disease definitions.

Retrospective Database Analysis to Explore Patterns and Economic Burden of Switchback to Brand After Generic or Authorized Generic Utilization.

Background: Despite demonstration of bioequivalence of generics to brands and the potential for reduced costs, some patients switch back from a generic to the brand. A prior retrospective analysis suggested that this switchback rate may be lower among patients that had initially switched to authorized generics (AG), often both produced and marketed by the brand company, compared to those initially switched to another generic. Objective: Explore switching patterns of brands, AGs, and generics, switchback rates, and the potential impact of switchbacks on healthcare costs. Methods: An analysis of the Pharmetrics Plus™ database (2007-2019), a United States (US) payer administrative database, was conducted to examine the use of Upjohn medications available as AGs across multiple therapeutic areas. Patients initiating treatment with brand medication in the 6 months prior to generic market entry were identified and switch rates to generics and AGs, as well as switchback rates, were evaluated. Costs were descriptively compared between patients who switched back to brand and those who remained on any generic. Results: Across 14 brand medications, more than half of the patients initiating treatment with the brand medication were switched to a generic. Generally, switching to AG, which ranged from 0.5 to 39.6%, was lower than switching to non-AG generics (16.7-79.9%). The comparison of switchback rates from AGs to brand and non-AGs to brand showed similar results (AG:1.3-7.5%; non-AG:1.4-12.9%); however, the most substantial differences were observed where non-AG switchbacks were higher. Patients that switched back to brand remained on AG or generic for an average of 1-3 months (32-88 days). The analysis showed a tendency towards increased medical costs in the period immediately preceding switchback for all medications except sildenafil in both indications (erectile dysfunction and pulmonary arterial hypertension). For the remaining medications, medical costs ranged from $63 to $1544 higher for the switchback population. Pharmacy costs similarly tended to be higher for patients who had a switchback, with the exception of sildenafil for pulmonary arterial hypertension and sirolimus. Conclusion: Patients receiving a brand medication are likely to be switched to a generic upon market availability. Some patients switch back to the brand medication, usually within 1-3 months; this may be associated with increased medical costs. Additional research is needed to understand switching, its potential disruption to patients, and the role of brands, generics, and AGs.

Cost impact of hydroxocobalamin in the treatment of patients with known or suspected cyanide poisoning due to smoke inhalation from closed-space fires.

BACKGROUND & OBJECTIVES: Cyanide poisoning can occur due to exposure to smoke in closed-space fires. With no point of care cyanide test at the scene of a fire, first responders and clinicians base decisions to treat with cyanide antidote on patient history, clinical signs, and other indirect data points that have not been proven to correspond with actual systemic levels of cyanide. The aim of this exploratory study was to determine the economic implications of treating patients with known or suspected cyanide poisoning due to smoke inhalation with hydroxocobalamin. METHODS: A decision analysis model was developed from the US hospital perspective. Healthcare resource utilization was estimated from a retrospective evaluation of clinical outcomes in hydroxocobalamin-treated patients and in historical controls without hydroxocobalamin use (Nguyen, et al. 2017). Epidemiologic parameters and costs were estimated from the published literature, and publicly-available hospital charges were identified. Outcomes reported in the analysis included expected healthcare resource utilization in the US population and per-patient costs with and without the use of hydroxocobalamin. A cost-to-charge ratio was applied so that all costs would reflect hospital costs rather than hospital charges. Deterministic sensitivity analysis was performed to identify the most influential model parameters. All costs were reported in 2017 US dollars. RESULTS: Use of hydroxocobalamin reduces healthcare resource utilization and contributes to decreased per-patient hospital costs ($15,381 with hydroxocobalamin treatment versus $22,607 with no cyanide antidote). The most substantive cost-savings resulted from decreased hospital length of stay (i.e., intensive care unit [ICU] and non-ICU). Costs attributed to mechanical ventilation also decreased with use of hydroxocobalamin. A univariate sensitivity analysis demonstrated that the most impactful variables in the cost analysis were related to hospital length of stay (ICU followed by non-ICU stay), followed by the daily cost of ICU stay. CONCLUSIONS: Use of hydroxocobalamin in patients with known or suspected cyanide poisoning from closed-space fire smoke inhalation may decrease hospital costs and contribute to more efficient healthcare resource utilization.

Economic and Humanistic Burden Associated with Depression and Anxiety Among Adults with Non-Communicable Chronic Diseases (NCCDs) in the United States.

INTRODUCTION: Patients with both major depressive disorder (MDD) and generalized anxiety disorder (GAD) in addition to one or multiple comorbid non-communicable chronic diseases (NCCDs) face unique challenges. However, few studies have characterized how the burden of co-occurring MDD and GAD differs from that of only MDD or only GAD among patients with NCCDs. METHODS: In this study, we used Medical Expenditures Panel Survey data from 2010-2017 to understand how the economic and humanistic burden of co-occurring MDD and GAD differs from that of MDD or GAD alone among patients with NCCDs. We used generalized linear models to investigate this relationship and controlled for patient sociodemographics and clinical characteristics. RESULTS: Co-occurring MDD and GAD was associated with increases in mean annual per patient inpatient visits, office visits, emergency department visits, annual drug costs, and total medical costs. Among patients with 3+ NCCDs, MDD or GAD only was associated with lower odds ratios (ORs) of limitations in activities of daily living (ADLs; 0.532 and 0.508, respectively) and social (0.503, 0.526) and physical limitations (0.613, 0.613) compared to co-occurring MDD and GAD. Compared to patients with co-occurring MDD and GAD, having MDD only or GAD only was associated with significantly lower odds of cognitive limitations (0.659 and 0.461, respectively) in patients with 1-2 NCCDs and patients with 3+ NCCDs (0.511, 0.416). DISCUSSION: Comorbid MDD and GAD was associated with higher economic burden, lower quality of life, and greater limitations in daily living compared to MDD or GAD alone. Health-related economic and humanistic burden increased with number of NCCDs.

Evaluating the Cost-Effectiveness of Celecoxib versus Ibuprofen and Naproxen in Patients with Osteoarthritis in United Arab Emirates Based on the PRECISION Trial.

OBJECTIVE: Data on osteoarthritis patients from the PRECISION trial were used to evaluate the cost-effectiveness of celecoxib (100 mg twice daily) versus ibuprofen (600-800 mg three times daily) and naproxen (375-500 mg twice daily). The perspective was that of the United Arab Emirates (UAE) healthcare system. METHODS: Discrete-state Markov model with monthly cycles, 30-month horizon, and 3% discount rate was constructed to assess incremental costs per quality adjusted life year (QALYs) gained from reduced incidence of three safety domains examined in PRECISION: renal, serious gastrointestinal (GI), and major adverse cardiovascular events (MACE). Costs for managing these toxicities were derived from Dubai Administrative Billing Claims (2018). Median monthly drug costs were derived from UAE Ministry of Health and Prevention's published prices ($26.98 celecoxib; $20.25 ibuprofen; $20.50 naproxen). Health utility and excess mortality associated with toxicities were sourced from the literature. The willingness-to-pay thresholds used were 1 and 3 GDP per capita ($40,000-$120,000). RESULTS: The total average cost per patient was $812.88 for celecoxib, $775.26 for ibuprofen, and $731.17 for naproxen while cost components attributed to toxicities were lowest with celecoxib ($360.26, $438.31, and $388.60, respectively). Patients on celecoxib had more QALYs (1.339), compared with ibuprofen (1.335) and naproxen (1.337), resulting in an incremental cost-effectiveness ratio of $11,502/QALY gained for celecoxib versus ibuprofen and $39,779 for celecoxib versus naproxen. Probabilistic sensitivity analyses demonstrated celecoxib to be 81% cost-effective versus ibuprofen and 50% versus naproxen at $40,000/QALY. The most influential model parameters were MACE relative safety and drug costs. CONCLUSION: From UAE third payer perspective, celecoxib is a long-term cost-effective treatment for osteoarthritis patients when compared with ibuprofen, and equally likely as naproxen to be cost-effective. With the expected increasing burden of chronic diseases in the Gulf region, study findings can inform decisions regarding the cost-effective pain management of osteoarthritis in UAE. CLINICALTRIALSGOV REGISTRATION NUMBER: NCT00346216.

Cost-effectiveness analysis of voriconazole, fluconazole, and amphotericin B for invasive fungal infections following allogeneic hematopoietic stem cell transplantation in Mexico.

BACKGROUND: Patients receiving allogeneic hematopoietic stem cell transplantation (alloHSCT) are at high risk of invasive fungal infections (IFIs), which are associated with high mortality and economic burden. The cost-effectiveness of prophylaxis for the prevention of IFIs in alloHSCT recipients in Mexico has not yet been assessed. METHODS: This analysis modeled a hypothetical cohort of 1,000 patients to estimate costs and outcomes for patients receiving prophylaxis for IFIs following alloHSCT, from the perspective of institutional payers in Mexico. The main prophylaxis agents currently used in Mexican clinical practice are voriconazole, fluconazole, and amphotericin B (AmB). The model accounted for event rates of IFIs during each treatment, assuming IFI causality due to invasive aspergillosis, invasive candidiasis, or other IFIs, and that the outcome for patients during follow-up was IFI-related death, death from other causes, or survival. Clinical efficacies were obtained from published literature; costs were based on local sources. Cost-effectiveness was assessed using incremental cost-effectiveness ratios (ICERs). Univariate (assessing the impact of varying each model parameter) and probabilistic sensitivity analyses were performed. RESULTS: Voriconazole was associated with the lowest number of breakthrough IFIs, IFI-related deaths, and total number of deaths. Total costs were lower for fluconazole (Mexican pesos [MXN] 72,944; US $4,079) than voriconazole (MXN 101,413; US $5,671) or AmB (MXN 110,529; US $6,180). Voriconazole had better clinical outcomes and lower costs than AmB and could be considered cost-effective compared with fluconazole in line with the local ICER threshold. Drug costs, monitoring costs, and duration of prophylaxis were most sensitive to variation from univariate sensitivity analysis. Findings from the probabilistic sensitivity analysis were consistent with the base-case results. CONCLUSION: Voriconazole had the most favorable clinical outcomes, but overall prophylaxis costs were higher than with fluconazole. Overall, based on local ICER thresholds (MXN 184,665; US $10,326), voriconazole was considered a cost-effective option for prophylaxis of IFI in Mexico.

Clinical, economic, and humanistic burden of needlestick injuries in healthcare workers.

INTRODUCTION: Needlestick injuries (NSIs) from a contaminated needle put healthcare workers (HCWs) at risk of becoming infected with a blood-borne virus and suffering serious short- and long-term medical consequences. Hypodermic injections using disposable syringes and needles are the most frequent cause of NSIs. OBJECTIVE: To perform a systematic literature review on NSI and active safety-engineered devices for hypodermic injection. METHODS: MEDLINE, EMBASE, and COCHRANE databases were searched for studies that evaluated the clinical, economic, or humanistic outcomes of NSI or active safety-engineered devices. RESULTS: NSIs have been reported by 14.9%-69.4% of HCWs with the wide range due to differences in countries, settings, and methodologies used to determine rates. Exposure to contaminated sharps is responsible for 37%-39% of the worldwide cases of hepatitis B and C infections in HCWs. HCWs may experience serious emotional effects and mental health disorders after a NSI, resulting in work loss and post-traumatic stress disorder. In 2015 International US$ (IntUS$), the average cost of a NSI was IntUS$747 (range IntUS$199-1,691). Hypodermic injections, the most frequent cause of NSI, are responsible for 32%-36% of NSIs. The use of safety devices that cover the needle-tip after hypodermic injection lowers the risk of NSI per HCW by 43.4%-100% compared to conventional devices. The economic value of converting to safety injective devices shows net savings, favorable budget impact, and overall cost-effectiveness. CONCLUSION: The clinical, economic, and humanistic burden is substantial for HCWs who experience a NSI. Safety-engineered devices for hypodermic injection demonstrate value by reducing NSI risk, and the associated direct and indirect costs, psychological stress on HCWs, and occupational blood-borne viral infection risk.

Rising United States Hospital Admissions for Acute Bacterial Skin and Skin Structure Infections: Recent Trends and Economic Impact.

BACKGROUND: The number of ambulatory patients seeking treatment for skin and skin structure infections (SSSI) are increasing. The objective of this study is to determine recent trends in hospital admissions and healthcare resource utilization and identify covariates associated with hospital costs and mortality for hospitalized adult patients with a primary SSSI diagnosis in the United States. METHODS: We performed a retrospective cross-sectional analysis (years 2005-2011) of data from the US Healthcare Cost and Utilization Project National Inpatient Sample. Recent trends, patient characteristics, and healthcare resource utilization for patients hospitalized with a primary SSSI diagnosis were evaluated. Descriptive and bivariate analyses were conducted to assess patient and hospital characteristics. RESULTS: A total of 1.8% of hospital admissions for the years 2005 through 2011 were for adult patients with a SSSI primary diagnosis. SSSI-related hospital admissions significantly changed during the study period (P < .001 for trend) ranging from 1.6% (in 2005) to 2.0% (in 2011). Mean hospital length of stay (LOS) decreased from 5.4 days in the year 2005 to 5.0 days in the year 2011 (overall change, P < .001) with no change in hospital costs. Patients with postoperative wound infections had the longest hospital stays (adjusted mean, 5.81 days; 95% confidence interval (CI), 5.80-5.83) and highest total costs (adjusted mean, $9388; 95% CI, $9366-$9410). Year of hospital admission was strongly associated with mortality; infection type, all patient refined diagnosis related group severity of illness level, and LOS were strongly associated with hospital costs. CONCLUSIONS: Hospital admissions for adult patients in the United States with a SSSI primary diagnosis continue to increase. Decreasing hospital inpatient LOS and mortality rate may be due to improved early treatment. Future research should focus on identifying alternative treatment processes for patients with SSSI that could shift management from inpatient to outpatient treatment settings.

Modeling the economic impact of linezolid versus vancomycin in confirmed nosocomial pneumonia caused by methicillin-resistant Staphylococcus aureus.

INTRODUCTION: We compared the economic impacts of linezolid and vancomycin for the treatment of hospitalized patients with methicillin-resistant Staphylococcus aureus (MRSA)-confirmed nosocomial pneumonia. METHODS: We used a 4-week decision tree model incorporating published data and expert opinion on clinical parameters, resource use and costs (in 2012 US dollars), such as efficacy, mortality, serious adverse events, treatment duration and length of hospital stay. The results presented are from a US payer perspective. The base case first-line treatment duration for patients with MRSA-confirmed nosocomial pneumonia was 10 days. Clinical treatment success (used for the cost-effectiveness ratio) and failure due to lack of efficacy, serious adverse events or mortality were possible clinical outcomes that could impact costs. Cost of treatment and incremental cost-effectiveness per successfully treated patient were calculated for linezolid versus vancomycin. Univariate (one-way) and probabilistic sensitivity analyses were conducted. RESULTS: The model allowed us to calculate the total base case inpatient costs as $46,168 (linezolid) and $46,992 (vancomycin). The incremental cost-effectiveness ratio favored linezolid (versus vancomycin), with lower costs ($824 less) and greater efficacy (+2.7% absolute difference in the proportion of patients successfully treated for MRSA nosocomial pneumonia). Approximately 80% of the total treatment costs were attributed to hospital stay (primarily in the intensive care unit). The results of our probabilistic sensitivity analysis indicated that linezolid is the cost-effective alternative under varying willingness to pay thresholds. CONCLUSION: These model results show that linezolid has a favorable incremental cost-effectiveness ratio compared to vancomycin for MRSA-confirmed nosocomial pneumonia, largely attributable to the higher clinical trial response rate of patients treated with linezolid. The higher drug acquisition cost of linezolid was offset by lower treatment failure-related costs and fewer days of hospitalization.

Health economic evaluation of patients treated for nosocomial pneumonia caused by methicillin-resistant Staphylococcus aureus: secondary analysis of a multicenter randomized clinical trial of vancomycin and linezolid.

PURPOSE: Results from studies comparing health care resource use (HCRU), costs of treatment, and cost-effectiveness of linezolid compared with vancomycin therapy in the treatment of hospitalized patients with methicillin-resistant Staphylococcus aureus (MRSA) nosocomial pneumonia are limited in the published literature. We therefore conducted an analysis to compare the HCRU, costs of treatment, and cost-effectiveness of linezolid compared with vancomycin in the treatment of hospitalized patients with MRSA nosocomial pneumonia using data from a Phase IV clinical trial. The economic effect of moderate to severe adverse events (MSAEs) and the development of renal failure were also evaluated. METHODS: We performed a post hoc analysis of data from a Phase IV, double-blind, randomized, comparator-controlled, multicenter trial that compared linezolid and vancomycin treatment in patients with MRSA nosocomial pneumonia. HCRU and costs were compared based on treatment, development of MSAEs, and development of renal failure using data from the modified intent-to-treat population. Predictors of costs were evaluated using generalized linear models. A piggyback cost-effectiveness analysis was conducted to assess the incremental cost-effectiveness ratio of linezolid versus vancomycin, given the significantly higher clinical success of linezolid compared with vancomycin found in the trial. FINDINGS: Overall, HCRU and costs were similar between the linezolid and vancomycin treatment groups; drug costs were significantly higher and dialysis costs significantly lower for linezolid- compared with vancomycin-treated patients. Total treatment costs were approximately $8000 higher (P = .046) for patients who developed renal failure compared with those who did not. Renal failure occurred more commonly in patients randomized to receive vancomycin (15%) compared with linezolid (4%; P < .001). Region, ventilator-associated pneumonia, clinical failure, and development of renal failure were associated with significantly higher total costs. The point estimate incremental cost-effectiveness ratio for linezolid compared with vancomycin was $16,516 per treatment success, with linezolid dominant in 24% and dominated in <2% of bootstrapped samples. IMPLICATIONS: This phase 4 clinical trial conducted in patients with MRSA-confirmed nosocomial pneumonia reveals that linezolid- compared with vancomycin-treated patients had similar HCRU and total overall costs. Fewer patients developed renal failure during the study while taking linezolid compared with vancomycin, and patients with a documented MSAE or renal failure had increased HCRU and costs. In summary, linezolid may be a cost-effective treatment strategy in MRSA-confirmed nosocomial pneumonia.

Antibiotic treatment patterns across Europe in patients with complicated skin and soft-tissue infections due to meticillin-resistant Staphylococcus aureus: a plea for implementation of early switch and early discharge criteria.

This retrospective observational medical chart review aimed to describe country-specific variations across Europe in real-world meticillin-resistant Staphylococcus aureus (MRSA) complicated skin and soft-tissue infection (cSSTI) treatment patterns, antibiotic stewardship activity, and potential opportunities for early switch (ES) from intravenous (i.v.) to oral formulations and early discharge (ED) from hospital using standardised data collection and criteria and economic implications of these opportunities. Patients were randomly sampled from 12 countries (Austria, Czech Republic, France, Germany, Greece, Ireland, Italy, Poland, Portugal, Slovakia, Spain and the UK), aged ≥18 years, with documented MRSA cSSTI, hospitalised between 1 July 2010 and 30 June 2011, discharged alive by 31 July 2011. Of 1502 patients, 1468 received MRSA-targeted therapy. Intravenous-to-oral switch rates ranged from 2.0% to 20.2%, i.v. length of therapy from 10.1 to 18.6 days and hospital length of stay (LoS) from 15.2 to 25.0 days across Europe. Of 341 sites, 82.9% had antibiotic steering committees, 23.7% had i.v.-to-oral switch antibiotic protocols and 12.9% had ED protocols for MRSA cSSTI. ES and ED eligibility ranged from 12.0% (Slovakia) to 56.3% (Greece) and from 10% (Slovakia) to 48.2% (Portugal), respectively. Potential cost savings per ED-eligible patient ranged from €414 (Slovakia) to €2703 (France). MRSA cSSTI treatment patterns varied widely across countries, but further reductions in i.v. therapy, hospital LoS and associated costs could be realised. These data provide insight into clinical practice patterns across diverse European healthcare systems and identify potential opportunities for local clinicians and policy-makers to improve clinical care and cost-effectiveness of this therapeutic area.

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.

Aspergillosis in Intensive Care Unit (ICU) patients: epidemiology and economic outcomes.

BACKGROUND: Few data are available regarding the epidemiology of invasive aspergillosis (IA) in ICU patients. The aim of this study was to examine epidemiology and economic outcomes (length of stay, hospital costs) among ICU patients with IA who lack traditional risk factors for IA, such as cancer, transplants, neutropenia or HIV infection. METHODS: Retrospective cohort study using Premier Inc. Perspective™ US administrative hospital database (2005-2008). Adults with ICU stays and aspergillosis (ICD-9 117.3 plus 484.6) who received initial antifungal therapy (AF) in the ICU were included. Patients with traditional risk factors (cancer, transplant, neutropenia, HIV/AIDS) were excluded. The relationship of antifungal therapy and co-morbidities to economic outcomes were examined using Generalized linear models. RESULTS: From 6,424 aspergillosis patients in the database, 412 (6.4%) ICU patients with IA were identified. Mean age was 63.9 years and 53% were male. Frequent co-morbidities included steroid use (77%), acute respiratory failure (76%) and acute renal failure (41%). In-hospital mortality was 46%. The most frequently used AF was voriconazole (71% received at least once). Mean length of stay (LOS) was 26.9 days and mean total hospital cost was $76,235. Each 1 day lag before initiating AF therapy was associated with 1.28 days longer hospital stay and 3.5% increase in costs (p < 0.0001 for both). CONCLUSIONS: Invasive aspergillosis in ICU patients is associated with high mortality and hospital costs. Antifungal timing impacts economic outcomes. These findings underscore the importance of timely diagnosis, appropriate treatment, and consideration of Aspergillus as a potential etiology in ICU patients.

Impact of adverse events on costs and quality of life in protease inhibitor-based combination therapy for hepatitis C.

Protease inhibitor with pegylated interferon and ribavirin therapy (PI-PR) increases hepatitis C virus treatment efficacy versus standard of care pegylated interferon and ribavarin therapy [PR]. The adverse event (AE) impact of PI-PR remains under-reported. The authors estimated the AE impact on costs, treatment discontinuation and health-related quality of life (HRQoL) in PI-PR- and PR-treated patients through literature review and cost analysis. HRQoL and safety data were synthesized by instrument, AE and discontinuation rate. AE-related treatment costs were estimated with trial-based AE rates and literature-based protocols, resource utilization and standard costs. No PI-PR study reported HRQoL outcomes. Five PR studies reported that anemia, depression, fatigue and/or influenza-like symptoms negatively affected HRQoL. Decreased HRQoL predicted treatment discontinuation in two PR studies. PI-PR and PR had comparable AE-related treatment discontinuation rates (~12%). Weighted AE-related treatment costs were US$2042, $1835 and $1076 in boceprevir-based PI-PR, PR and telaprevir-based PI-PR, respectively. AE-related burden may increase with PI-PR. Future studies should incorporate AE-related economic and HRQoL outcomes to comprehensively assess costs/benefits.

US hospital database analysis of invasive aspergillosis in the chronic obstructive pulmonary disease non-traditional host.

OBJECTIVES: Invasive aspergillosis (IA) is reported increasingly in non-traditional hosts, typically patients with chronic obstructive pulmonary disease (COPD). Objectives were to describe the excess burden of IA in COPD, including mortality, resource utilization, and costs, as well as to examine the impact of initial antifungal selection on clinical and economic outcomes. METHODS: This retrospective cohort study used national data from 2005 to 2008, from the Premier Perspective hospital database. IA was identified using proxy ICD-9 codes based on published algorithms. The COPD + IA patient cohort was analyzed using descriptive statistics. Excess resource utilization was analyzed by matching cases (COPD + IA) and controls (COPD patients without aspergillosis) on demographic and clinical variables. Multivariate analyses were used to assess the impact of initial antifungal drug selection on outcomes in COPD + IA. RESULTS: In total, 475 COPD + IA patients were identified (mean age 69 years, 50% male, 76% Caucasian). COPD + IA cases had significantly higher costs, length of stay, intensive care unit (ICU) stay, and mortality compared to COPD controls (all p < 0.01). On average, antifungal therapy was initiated on hospital day 6, with mean length of therapy 15 days, and one-third of patients were in the ICU when antifungal treatment was initiated. Most commonly used antifungals were voriconazole, fluconazole, and caspofungin. Patients receiving fluconazole as the initial antifungal, an agent inactive against moulds, had almost two times greater mortality (p = 0.016), two additional hospital days (p = 0.002), and 25% greater costs (p = 0.007), compared to patients receiving voriconazole first-line. Findings were consistent in sub-analyses including ICU patients. LIMITATIONS: 'Invasive' form of aspergillosis was identified using proxy ICD-9 codes based on published literature. Additional limitations stem from the study's non-randomized, retrospective design that is typical with any database analyses. CONCLUSIONS: COPD + IA patients had significantly higher mortality, resource utilization, and costs versus COPD controls. Treatment with an agent active against Aspergillus was associated with better survival and reduced economic burden, therefore this potential etiology of pneumonia should be considered when contemplating antifungal therapy in COPD patients.

Economic evaluation of major knee surgery with recombinant activated factor VII in hemophilia patients with high titer inhibitors and advanced knee arthropathy: exploratory results via literature-based modeling.

OBJECTIVES: People with severe hemophilia suffer from frequent intra-articular hemorrhages, leading to pain, swelling, reduced flexion, and arthropathy. Elective orthopedic surgery using factor VIII (FVIII) replacement to prevent uncontrolled bleeding has been endorsed as an effective treatment option for patients with severe or advanced hemophilic arthropathy. These surgeries reduce pain, restore mobility and function, and reduce the frequency of recurrent joint bleeds. Unfortunately, some patients with hemophilia develop inhibitors to FVIII, which neutralize FVIII activity and render the use of even massive amounts of FVIII replacement ineffective and surgery very risky. For this reason, elective surgical procedures in high-titer inhibitor patients had largely been abandoned until the introduction of new agents, such as recombinant activated factor VII (rFVIIa, NovoSeven, Novo Nordisk A/S, Denmark). rFVIIa has been shown effective for prophylaxis during elective surgery and has therefore improved the feasibility of orthopedic surgery in hemophilia patients with high-titer inhibitors. The present research explored, from a modified US payer perspective, the direct economic and quality of life benefits of four different elective knee surgeries (total knee replacement [TKR], knee arthrodesis [KA], proximal tibial osteotomy, and distal femoral osteotomy) with rFVIIa coverage in hemophilia patients with high-titer inhibitors. METHODS: An exploratory literature-based life-table model was developed to compare the direct medical costs and quality of life of two hypothetical cohorts of high-titer inhibitor patients with frequent bleeding episodes: one undergoing and the other not undergoing elective knee surgery. Knee surgery costs included perioperative rFVIIa costs, inpatient and rehabilitation care, and repeat procedures due to surgery failure, prosthesis loosening or deep infection. Based on efficacy studies, knee surgery was assumed to reduce mean annual bleeding episodes at the affected joint from 9.13 to 1.64. The cost of managing each bleeding episode was estimated at $15 298. Thus, by reducing bleeding episodes, surgery was expected to result in related cost offsets. All costs were expressed in 2006 US dollars. Surgery was also assumed to result in gains in quality of life by reducing pain and reducing bleeding episodes. The impact of pain reduction on quality of life and utility was estimated by simulating EQ-5D scores for a typical patient with and without knee surgery. RESULTS: Based on the model, average knee surgery costs are predicted to range from a low of $694 000 (for KA) to a high of $855 000 (for TKR). However, knee surgery is also expected to reduce the subsequent number of bleeding episodes and resultant costs, leading to long-term costs savings. Due to improvement in pain levels, surgical patients are expected to experience improvements in quality-adjusted life-years (QALYs). Thus, surgery appears to be the preferred strategy (i.e., saves costs and increases QALYs). Based on the assumptions used in the model, the initial cost of knee surgery was offset during the 8th and 10th years for KA and TKR, respectively, with intermediate break-even time for the other surgeries. As expected, cost savings and gains in QALYs increased over time, as well as the cost effective ness of knee surgery. Specifically, the cost per QALY with KA and TKR fell under $50 000/QALY during the 6th and 8th years, respectively, with intermediate time for the other surgeries. CONCLUSIONS: The present exploratory analysis is based on the long-term extrapolation of data from a small number of patients without inhibitors and short-term studies. It suggests that major knee surgery utilizing rFVIIa in hemophilia patients with inhibitors may be cost-effective on average, with expected cost savings apparent within a decade of knee surgery. The present exploratory results should be validated with real-world, longitudinal patient data.

A review of the clinical and economic outcomes of imatinib in Philadelphia chromosome-positive acute lymphoblastic leukemia.

Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) is a rare, high-risk, aggressive form of acute leukemia, affecting primarily adults and the elderly. Patients with high-risk forms of ALL typically have extremely poor prognosis and incur high disease-related costs. Successful use of imatinib in patients with Ph+ chronic myelogenous leukemia (CML) has led to the administration of imatinib in recent clinical studies for patients with Ph+ALL. In this review, the clinical outcomes of imatinib used as a single-agent or in combination with chemotherapy are discussed. In addition, an overview of the economic and quality of life burden associated with high-risk forms of ALL (with Ph+ALL being the most common high risk ALL), as well as the cost-effectiveness of imatinib in Ph+ALL compared with conventional chemotherapy, are presented.

Health economic review of recombinant activated factor VII for treatment of bleeding episodes in hemophilia patients with inhibitors.

Severe hemophilia with inhibitors is a rare disease with substantial clinical, humanistic and economic consequences. This review provides an overview of the role of recombinant activated factor VII (rFVIIa) versus plasma-derived bypassing agents for hemophilia with inhibitors and summarizes the 13 formal economic analyses (6 burden of illness and 7 comparative studies) that have been published in this indication. The findings suggest that the economic impact of rFVIIa has occurred primarily during hospitalization to manage major bleeding episodes and to allow for elective orthopedic surgeries that would not have been attempted prior to rFVIIa. Comparative analyses for on-demand treatment suggest that the total cost of treating a bleeding episode with rFVIIa may be lower than with plasma-based agents due to faster bleeding resolution, higher initial efficacy rates and avoidance of second and third lines of treatment.