Pharmacoeconomic analysis of antifungal therapy for primary treatment of invasive candidiasis caused by Candida albicans and non-albicans Candida species.

BACKGROUND: Cost-effectiveness studies of echinocandins for the treatment of invasive candidiasis, including candidemia, are rare in Asia. No study has determined whether echinocandins are cost-effective for both Candida albicans and non-albicans Candida species. There have been no economic evaluations that compare non-echinocandins with the three available echinocandins. This study was aimed to assess the cost-effectiveness of individual echinocandins, namely caspofungin, micafungin, and anidulafungin, versus non-echinocandins for C. albicans and non-albicans Candida species, respectively. METHODS: A decision tree model was constructed to assess the cost-effectiveness of echinocandins and non-echinocandins for invasive candidiasis. The probability of treatment success, mortality rate, and adverse drug events were extracted from published clinical trials. The cost variables (i.e., drug acquisition) were based on Taiwan's healthcare system from the perspective of a medical payer. One-way sensitivity analyses and probability sensitivity analyses were conducted. RESULTS: For treating invasive candidiasis (all species), as compared to fluconazole, micafungin and caspofungin are dominated (less effective, more expensive), whereas anidulafungin is cost-effective (more effective, more expensive), costing US$3666.09 for each life-year gained, which was below the implicit threshold of the incremental cost-effectiveness ratio in Taiwan. For C. albicans, echinocandins are cost-saving as compared to non-echinocandins. For non-albicans Candida species, echinocandins are cost-effective as compared to non-echinocandins, costing US$652 for each life-year gained. The results were robust over a wide range of sensitivity analyses and were most sensitive to the clinical efficacy of antifungal treatment. CONCLUSIONS: Echinocandins, especially anidulafungin, appear to be cost-effective for invasive candidiasis caused by C. albicans and non-albicans Candida species in Taiwan.

Economic evaluation of azoles as primary prophylaxis for the prevention of invasive fungal infections in Spanish patients undergoing allogeneic haematopoietic stem cell transplant.

Patients undergoing allogeneic haematopoietic stem cell transplantation (alloHSCT) are at risk of developing invasive fungal infections (IFIs). Even with introduction of oral triazole antifungal agents (fluconazole, itraconazole, posaconazole and voriconazole) IFI-associated morbidity and mortality rates and economic burden remain high. Despite their proven efficacy, it is currently unknown which is the most cost-effective antifungal prophylaxis (AFP) agent. To determine the costs and outcomes associated with AFP, a decision-analytic model was used to simulate treatment in a hypothetical cohort of 1000 patients undergoing alloHSCT from the perspective of the Spanish National Health System. Generic itraconazole was the least costly AFP (€162) relative to fluconazole (€500), posaconazole oral suspension (€8628) or voriconazole (€6850). Compared with posaconazole, voriconazole was associated with the lowest number of breakthrough IFIs (36 vs 60); thus, the model predicted fewer deaths from breakthrough IFI for voriconazole (24) than posaconazole (33), and the lowest predicted costs associated with other licensed antifungal treatment and IFI treatment in a cohort of 1000. Voriconazole resulted in cost savings of €4707 per patient compared with posaconazole. Itraconazole demonstrated a high probability of being cost-effective. As primary AFP in alloHSCT patients 180 days posttransplant, voriconazole was more likely to be cost-effective than posaconazole regarding cost per additional IFI and additional death avoided.

Cost-effectiveness analysis of anidulafungin for the treatment of candidaemia and other forms of invasive candidiasis.

BACKGROUND: Candidaemia and other forms of invasive candidiasis (C/IC) in the intensive care unit are challenging conditions that are associated with high rates of mortality. New guidelines from the European Society for Clinical Microbiology and Infectious Diseases strongly recommend echinocandins for the first-line treatment of C/IC. Here, a cost-effectiveness model was developed from the United Kingdom perspective to examine the costs and outcomes of antifungal treatment for C/IC based on the European Society for Clinical Microbiology and Infectious Diseases guidelines. METHODS: Costs and treatment outcomes with the echinocandin anidulafungin were compared with those for caspofungin, micafungin and fluconazole. The model included non-neutropenic patients aged ≥16 years with confirmed C/IC who were receiving intravenous first-line treatment. Patients were categorised as either a clinical success or failure (patients with persistent/breakthrough infection); successfully treated patients switched to oral therapy, while patients categorised as clinical failures switched to a different antifungal class. Other inputs were all-cause mortality at 6 weeks, costs of treatment-related adverse events and other medical resource utilisation costs. Resource use was derived from the published literature and from discussion with clinical experts. Drug-acquisition/administration costs were taken from standard United Kingdom costing sources. RESULTS: The model indicated that first-line anidulafungin could be considered cost-effective versus fluconazole (incremental cost-effectiveness ratio £813 per life-year gained) for the treatment of C/IC. Anidulafungin was cost-saving versus caspofungin and micafungin due to lower total costs and a higher rate of survival combined with a higher probability of clinical success. DISCUSSION: European Society for Clinical Microbiology and Infectious Diseases guidelines recommend echinocandins for the first-line treatment of C/IC; our model indicated that anidulafungin marries clinical effectiveness and cost-effectiveness. CONCLUSIONS: From the United Kingdom perspective, anidulafungin was cost-effective compared with fluconazole for the treatment of C/IC and was cost-saving versus the other echinocandins.

Characterizing fatigue associated with sunitinib and its impact on health-related quality of life in patients with metastatic renal cell carcinoma.

BACKGROUND: Using phase 3 trial data for sunitinib versus interferon (IFN)-α in treatment-naive patients with metastatic renal cell carcinoma, retrospective analyses characterized sunitinib-associated fatigue and its impact on patient-reported health-related quality of life (HRQoL). METHODS: Patients received sunitinib at a dose of 50 mg/day on a schedule of 4 weeks on/2 weeks off (375 patients) or IFN-α at a dose of 9 MU subcutaneously 3 times per week (360 patients). HRQoL was self-assessed using the Functional Assessment of Cancer Therapy-Kidney Symptom Index-15-item (FKSI-15) questionnaire, with fatigue assessed using its Disease-Related Symptoms subscale. Fatigue was also assessed by providers using Common Terminology Criteria for Adverse Events (CTCAE). A repeated-measures model (M1) and random intercept-slope model (M2) characterized sunitinib-associated fatigue over time. Another repeated-measures model examined the relationship between HRQoL scores and CTCAE fatigue grade. RESULTS: M1 demonstrated that the initial increase in patient-reported fatigue with sunitinib was worst during cycle 1, with mean values numerically better at subsequent cycles; most pairwise comparisons of consecutive CTCAE fatigue cycle means were not found to be statistically significant. M2 demonstrated that the overall trend (slope) for patient-reported and CTCAE fatigue with sunitinib was not statistically different from 0. The relationship between most HRQoL scores and CTCAE fatigue was close to linear regardless of treatment, with lower scores (worse HRQoL) corresponding to higher fatigue grade. The majority of HRQoL scores were better with sunitinib versus IFN-α for the same CTCAE fatigue grade. CONCLUSIONS: Patients reported worse fatigue during the first sunitinib cycle. However, in subsequent consecutive cycles, less fatigue was reported with no statistically significant worsening. CTCAE fatigue assessment may not fully capture patient treatment experience.

Analyzing overall survival in randomized controlled trials with crossover and implications for economic evaluation.

BACKGROUND: Offering patients in oncology trials the opportunity to cross over to active treatment at disease progression is a common strategy to address ethical issues associated with placebo controls but may lead to statistical challenges in the analysis of overall survival and cost-effectiveness because crossover leads to information loss and dilution of comparative clinical efficacy. OBJECTIVES: We provide an overview of how to address crossover, implications for risk-effect estimates of survival (hazard ratios) and cost-effectiveness, and how this influences decisions of reimbursement agencies. Two case studies using data from two phase III sunitinib oncology trials are used as illustration. METHODS: We reviewed the literature on statistical methods for adjusting for crossover and recent health technology assessment decisions in oncology. RESULTS: We show that for a trial with a high proportion of crossover from the control arm to the investigational arm, the choice of the statistical method greatly affects treatment-effect estimates and cost-effectiveness because the range of relative mortality risk for active treatment versus control is broad. With relatively frequent crossover, one should consider either the inverse probability of censoring weighting or the rank-preserving structural failure time model to minimize potential bias, with choice dependent on crossover characteristics, trial size, and available data. A large proportion of crossover favors the rank-preserving structural failure time model, while large sample size and abundant information about confounding factors favors the inverse probability of censoring weighting model. When crossover is very infrequent, methods yield similar results. CONCLUSIONS: Failure to correct for crossover may lead to suboptimal decisions by pricing and reimbursement authorities, thereby limiting an effective drug's potential.

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.

The Use and Effectiveness of Ceftazidime-Avibactam in Real-World Clinical Practice: EZTEAM Study.

INTRODUCTION: Ceftazidime-avibactam has proven activity against multidrug-resistant (MDR) bacteria in clinical trials and real-world studies. This study was conducted to describe the patterns of use of ceftazidime-avibactam (including indications and associated antibiotics), and the effectiveness and safety of ceftazidime-avibactam in real-world clinical practice. METHODS: This non-interventional medical chart review study was conducted in 11 countries across the European and Latin American (LATAM) regions. Consecutive patients treated in clinical practice with at least one dose of ceftazidime-avibactam for an approved indication per country label since 01 January 2018 (or launch date in the country if posterior) were enrolled. Effectiveness analyses were conducted in patients treated with ceftazidime-avibactam for at least 72 h. RESULTS: Of the 569 eligible patients enrolled, 516 (90.7%) were treated for at least 72 h (354 patients from Europe and 162 patients from LATAM); 390 patients (75.7%) had switched from another antibiotic line for Gram-negative coverage. Infection sources were intra-abdominal, urinary, respiratory, bloodstream infections, and other infections (approximately 20% each). K. pneumoniae was the most common microorganism identified in the latest microbiological evaluation before starting ceftazidime-avibactam (59.3%). Two-thirds of microorganisms tested for susceptibility were MDR, of which 89.3% were carbapenem-resistant. The common MDR mechanisms for K. pneumoniae were carbapenemase (33.9%), oxacillinase 48 (25.2%), extended-spectrum beta-lactamase (21.5%), or metallo-beta-lactamase (14.2%) production. Without prior patient exposure, 17 isolates (mostly K. pneumoniae) were resistant to ceftazidime-avibactam. Treatment success was achieved in 77.3% of patients overall (88.3% among patients with urinary infection), regardless of first or second treatment line. In-hospital mortality rate was 23.1%. Adverse events were reported for six of the 569 patients enrolled. CONCLUSION: This study provides important real-world evidence on treatment patterns, effectiveness, and safety of ceftazidime-avibactam in clinical practice through its recruitment in the European and LATAM regions. Ceftazidime-avibactam is one of the antibiotics to consider for treatment of MDR bacteria. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT03923426.

Ceftaroline Fosamil for the Empiric Treatment of Hospitalized Adults with cSSTI: An Economic Analysis from the Perspective of the Spanish National Health System.

Purpose: Complicated skin and soft tissue infections (cSSTI) are associated with high healthcare resource use and costs. The emergency nature of cSSTI hospitalizations requires starting immediate empiric intravenous (IV) antibiotic treatment, making the appropriate choice of initial antibiotic therapy crucial. Patients and Methods: The use of ceftaroline fosamil (CFT) as an alternative to other IV antibiotic therapies for the empiric treatment of hospitalized adults with cSSTI (vancomycin, linezolid, daptomycin, cloxacillin, tedizolid) was evaluated through cost consequences analysis. The model structure was a decision tree accounting for four different pathways: patients demonstrating early response (ER) either discharged early (with oral antibiotic) or remaining in hospital to continue the initial therapy; non-responders either remaining on the initial IV therapy or switching to a second-line antibiotic. The model perspective was the Spanish National Health System. Results: CFT resulted in average percentage of patients discharged early (PDE) of 24.6% (CI 19.49-30.2%) with average total cost per patient of €6763 (€6268-€7219). Vancomycin, linezolid, daptomycin and tedizolid resulted in average PDE of 22% (17.34-27.09%), 26.4% (20.5-32.32%), 28.6% (22.08-35.79%) and 26.5% (20.39-33.25%), respectively, for a total cost per patient of €6,619 (€5,902-€6,929), €6,394 (€5,881-€6,904), €6,855 (€5,800-€7,410) and €7,173 (€6,608-€7,763), respectively. Key model drivers were ER and antibiotic treatment duration, with hospital costs accounting for over 83% of the total expenditures. Conclusion: Given its clinical and safety profile, CFT is an acceptable choice for cSSTI empiric therapy providing comparable ER and costs to other relevant antibiotic options.

Economic evaluation of new targeted therapies for the first-line treatment of patients with metastatic renal cell carcinoma.

OBJECTIVE: • To assess the economic value of targeted therapies as first-line metastatic renal cell carcinoma (mRCC) treatment in the US and Sweden by indirect comparison of survival data. METHODS: • A Markov model simulated disease progression, adverse events and survival with sunitinib vs sorafenib in the US and bevacizumab plus interferon-α (IFN-α) in both countries. • Results, in life-years (LYs), progression-free LYs (PFLYs), quality-adjusted LYs (QALYs) gained and treatment costs (2008 USD) were obtained through deterministic and probabilistic analyses over the patient's lifetime. RESULTS: • Sunitinib was more effective and less costly than sorafenib (gains of 0.52 PFLYs, 0.16 LYs and 0.17 QALYs and savings/patient of $13,576 in the US) and bevacizumab plus IFN-α (gains of 0.19 PFLYs, 0.23 LYs and 0.16 QALYs in both countries and savings/patient of $67,798 and $47,264 in the US and Sweden, respectively). • Results were most influenced by hazard ratios for progression-free and overall survival and treatment costs, making results generalizable across other countries if relative costs were to fall within the ranges of those in the US and Sweden. CONCLUSION: • The present analyses suggest that first-line mRCC treatment with sunitinib is a cost-effective alternative to sorafenib and bevacizumab plus IFN-α.

Cost-effectiveness Comparison of Ceftazidime/Avibactam Versus Meropenem in the Empirical Treatment of Hospital-acquired Pneumonia, Including Ventilator-associated Pneumonia, in Italy.

PURPOSE: Ceftazidime/avibactam (CAZ-AVI) is a fixed-dose combination antibiotic approved in Europe and the United States for patients with hospital-acquired pneumonia, including ventilator-associated pneumonia (HAP/VAP). The economic benefits of a new drug such as CAZ-AVI are required to be assessed against those of available comparators, from the perspective of health care providers and payers, through cost-effectiveness and cost-utility analyses. The objective of this analysis was to compare the cost-effectiveness of CAZ-AVI versus meropenem in the empirical treatment of appropriate hospitalized patients with HAP/VAP caused by gram-negative pathogens, from the perspective of publicly funded health care in Italy (third-party perspective, based on the data from the REPROVE (Ceftazidime-Avibactam Versus Meropenem In Nosocomial Pneumonia, Including Ventilator-Associated Pneumonia) clinical study; ClinicalTrials.gov NCT01808092). METHODS: A patient-level, sequential simulation model of the HAP/VAP clinical course was developed using spreadsheet software. The analysis focused on direct medical costs. The time horizon of the model selected was 5 years, with an annual discount rate of 3% on costs and quality-adjusted life-years (QALYs). Clinical inputs for treatment comparisons were mainly obtained from the REPROVE clinical study data. In addition to clinical outcomes observed in the trial, the model incorporated impact of resistance pathogens, based on data from published studies and expert opinion. Certain assumptions were made for some model parameters due to a lack of data. FINDINGS: The analysis demonstrated that the intervention sequence (CAZ-AVI followed by colistin + high-dose meropenem) versus the comparator sequence (meropenem followed by colistin + high-dose meropenem) provided a better clinical cure rate (+13.52%), which led to a shorter hospital stay (-0.40 days per patient), and gains in the number of life-years (+0.195) and QALYs (+0.350) per patient. The intervention sequence had an estimated net incremental total cost of €1254 ($1401) per patient, and the estimated incremental cost-effectiveness ratio was €3581 ($4000) per QALY gained, well below the willingness-to-pay threshold of €30,000 ($33,507) per QALY in Italy. IMPLICATIONS: The model results showed that CAZ-AVI is expected to provide clinical benefits in hospitalized patients with HAP/VAP in Italy at an acceptable cost compared to meropenem.

Economic analysis of ceftaroline fosamil for treating community-acquired pneumonia in Spain.

Background: Adults admitted to hospital with community-acquired pneumonia (CAP) impose significant burden upon limited hospital resources. To achieve early response and possibly early discharge, thus reducing hospital expenditure, the choice of initial antibiotic therapy is pivotal.Methods: A cost-consequences model was developed to evaluate ceftaroline fosamil (CFT) as an alternative to other antibiotic therapies (ceftriaxone, co-amoxiclav, moxifloxacin, levofloxacin) for the empiric treatment of hospitalized adults with moderate/severe CAP (PORT score III-IV) from the perspective of the Spanish National Health System (NHS).Findings: Compared with ceftriaxone, the model predicted an increase in the number of CFT-treated patients discharged early (PDE) (30.6% vs. 26.1%) while decreasing initial antibiotic failures (3.8% vs. 7.6%). For patients with pneumococcal pneumonia, CFT was cost-saving vs. ceftriaxone (by 1.2%) and significantly increased PDE (32.1% vs. 24.6%). CFT resulted in cost-saving vs. levofloxacin, due lower initial antibiotic therapy costs and increased PDE (30.6% vs. 14.9%). Moxifloxacin and co-amoxiclav early response rate of 53.63% and 54.24% resulted in cost neutrality vs. CFT, with direct comparison hampered by the significantly different early response criteria utilized in the literature.Conclusions: Despite a higher unit cost, CFT is a reasonable alternative to other agents for adults hospitalized with moderate/severe CAP, given the projected higher PDE achieved with similar or lower total costs.

Estimating the Value of New Antimicrobials in the Context of Antimicrobial Resistance: Development and Application of a Dynamic Disease Transmission Model.

OBJECTIVES: Antimicrobial resistance (AMR) represents a significant threat to patient and population health. The study aim was to develop and validate a model of AMR that defines and quantifies the value of new antibiotics. METHODS: A dynamic disease transmission and cost-effectiveness model of AMR consisting of three components (disease transmission, treatment pathway and optimisation) was developed to evaluate the health economic value of new antibiotics. The model is based on the relationship between AMR, antimicrobial availability and consumption. Model analysis explored the impact of different antibiotic treatment strategies on the development of AMR, patient and population estimates of health benefit, across three common treatment indications and pathogens in the UK. RESULTS: Population-level resistance to existing antimicrobials was estimated to increase from 10.3 to 16.1% over 10 years based on current antibiotic availability and consumption. In comparison, the diversified use of a new antibiotic was associated with significant reduction in AMR (12.8% vs. 16.1%) and quality-adjusted life year (QALY) gains at a patient (7.7-10.3, dependent on antimicrobial efficacy) and population level (3657-8197, dependent on antimicrobial efficacy and the prevalence of AMR). Validation across several real-world data sources showed that the model output does not tend to systematically under- or over-estimate observed data. CONCLUSIONS: The development of new antibiotics and the appropriate use of existing antibiotics are key to addressing the threat of AMR. This study presents a validated model that quantifies the value of new antibiotics through clinical and economic outcomes of relevance, and accounts for disease transmission of infection and development of AMR. In this context, the model may be a useful tool that could contribute to the decision-making process alongside other potential models and expert advice.

Using the Rasch model to validate and enhance the interpretation of the Functional Assessment of Cancer Therapy-Kidney Symptom Index--Disease-Related Symptoms scale.

OBJECTIVES: The Functional Assessment of Cancer Therapy-Kidney Symptom Index-Disease-Related Symptoms (FKSI-DRS) was developed to assess patients' kidney-cancer-related symptoms. The Rasch rating scale, a one-parameter logistic item response model, may enhance FKSI-DRS interpretation and validate its measurement properties. METHODS: We applied the Rasch model to FKSI-DRS data from a randomized phase 3 trial in which first-line sunitinib therapy showed superiority to interferon-alfa in patients with metastatic renal cell carcinoma. Of 750 enrolled patients, 668 patients completed the questionnaire on cycle 1, day 28 and were evaluated in the current study. The nine FKSI-DRS items were analyzed to enhance interpretation of the summary score by using an item characteristic curve that related score to probability of reporting specific symptoms. RESULTS: The Rasch model fitted the FKSI-DRS well: 8 of 9 items had acceptable infit and outfit statistics (<1.5, >0.5); item difficulty spanned a wide range (-3.23 to 1.64 logits); and the five response categories performed adequately. The item characteristic curve offered enhanced interpretation of FKSI-DRS: For example, an FKSI-DRS score of 27 (mean baseline score for total sample) indicated a 47% chance of reporting "no" to "lack of energy," although a two-point difference between sunitinib and interferon-alfa, averaged across all assessments (29 vs. 27), corresponded to sunitinib achieving a 28% increase (13% absolute difference) in the probability of reporting "no" to "lack of energy" (60% vs. 47%). CONCLUSIONS: Data suggest that the FKSI-DRS is an adequate measure of symptom status in patients with metastatic renal cell carcinoma. The Rasch model supports its validation and enhances its interpretation.

Value of hospital antimicrobial stewardship programs [ASPs]: a systematic review.

Background: Hospital antimicrobial stewardship programs (ASPs) aim to promote judicious use of antimicrobials to combat antimicrobial resistance. For ASPs to be developed, adopted, and implemented, an economic value assessment is essential. Few studies demonstrate the cost-effectiveness of ASPs. This systematic review aimed to evaluate the economic and clinical impact of ASPs. Methods: An update to the Dik et al. systematic review (2000-2014) was conducted on EMBASE and Medline using PRISMA guidelines. The updated search was limited to primary research studies in English (30 September 2014-31 December 2017) that evaluated patient and/or economic outcomes after implementation of hospital ASPs including length of stay (LOS), antimicrobial use, and total (including operational and implementation) costs. Results: One hundred forty-six studies meeting inclusion criteria were included. The majority of these studies were conducted within the last 5 years in North America (49%), Europe (25%), and Asia (14%), with few studies conducted in Africa (3%), South America (3%), and Australia (3%). Most studies were conducted in hospitals with 500-1000 beds and evaluated LOS and change in antibiotic expenditure, the majority of which showed a decrease in LOS (85%) and antibiotic expenditure (92%). The mean cost-savings varied by hospital size and region after implementation of ASPs. Average cost savings in US studies were $732 per patient (range: $2.50 to $2640), with similar trends exhibited in European studies. The key driver of cost savings was from reduction in LOS. Savings were higher among hospitals with comprehensive ASPs which included therapy review and antibiotic restrictions. Conclusions: Our data indicates that hospital ASPs have significant value with beneficial clinical and economic impacts. More robust published data is required in terms of implementation, LOS, and overall costs so that decision-makers can make a stronger case for investing in ASPs, considering competing priorities. Such data on ASPs in lower- and middle-income countries is limited and requires urgent attention.

Cost-effectiveness analysis comparing ceftazidime/avibactam (CAZ-AVI) as empirical treatment comparing to ceftolozane/tazobactam and to meropenem for complicated intra-abdominal infection (cIAI).

Background: The rising incidence of resistance to currently available antibiotics among pathogens, particularly Gram-negative pathogens, in complicated intra-abdominal infections (cIAIs) has become a challenge for clinicians. Ceftazidime/avibactam (CAZ-AVI) is a fixed-dose antibiotic approved in Europe and the United States for treating (in combination with metronidazole) cIAI in adult hospitalised patients who have limited or no alternative treatment options. The approval was based on the results of RECLAIM, a Phase III, parallel-group, comparative study (RECLAIM 1 [NCT01499290] and RECLAIM 2 [NCT01500239]). The objective of our study was to assess the cost-effectiveness of CAZ-AVI plus metronidazole compared with 1) ceftolozane/tazobactam plus metronidazole and 2) meropenem, as an empiric treatment for the management of cIAI in Italy. Methods: A sequential, patient-level simulation model, with a 5-year time horizon and 3% annual discount rate (applied to both costs and health benefits), was developed using Microsoft Excel® to demonstrate the clinical course of the disease. The impact of resistant pathogens was included as an additional factor. Results: In the base-case analysis, the CAZ-AVI sequence (CAZ-AVI plus metronidazole followed by a colistin + tigecycline + high-dose meropenem combination after treatment failure), when compared to sequences for ceftolozane/tazobactam (ceftolozane/tazobactam plus metronidazole followed by colistin + tigecycline + high-dose meropenem after treatment failure) and meropenem (meropenem followed by colistin + tigecycline + high-dose meropenem after treatment failure), had better clinical outcomes with higher cure rates (93.04% vs. 91.52%; 92.98% vs. 90.24%, respectively), shorter hospital stays (∆ = - 0.38 and ∆ = - 1.24 days per patient, respectively), and higher quality-adjusted life years (QALYs) gained per patient (4.021 vs. 3.982; 4.019 vs. 3.960, respectively). The incremental cost effectiveness ratio in the CAZ-AVI sequence was €4099 and €15,574 per QALY gained versus each comparator sequence, respectively, well below the willingness-to-pay threshold of €30,000 per QALY accepted in Italy. Conclusions: The model results demonstrated that CAZ-AVI plus metronidazole could be a cost-effective alternative when compared with other antibiotic treatment options, as it is expected to provide better clinical benefits in hospitalised patients with cIAI in Italy.

Cost-effectiveness analysis of ceftazidime/avibactam compared to imipenem as empirical treatment for complicated urinary tract infections.

Ceftazidime/avibactam (CAZ-AVI) is a novel, fixed-dose combination antibiotic that has been approved in Europe and the United States for patients with complicated urinary tract infections (cUTIs) based on results of a Phase III, randomized, comparative study (RECAPTURE study). The present analysis evaluated cost-effectiveness of CAZ-AVI as an empirical treatment for hospitalized patients with cUTIs from the Italian publicly funded healthcare (third-party payer) perspective. A sequential, patient-level simulation model was developed that followed the clinical course of cUTI and generated 5000 pairs of identical patients (CAZ-AVI or imipenem as empirical treatment). The model included additional impact of resistant pathogens; patients who did not respond to empirical treatment were switched to second-line treatment of colistin+high dose carbapenem in both groups. The time horizon of the model was five years, with an annual discount rate of 3% applied to both costs and quality-adjusted life-years (QALYs). The analysis demonstrated that an intervention sequence (CAZ-AVI followed by colistin+high dose carbapenem) compared with a comparator sequence (imipenem followed by colistin+high dose carbapenem) was associated with a net incremental cost of €1015 per patient but provided better health outcomes in terms of clinical cure (97.65% vs. 91.08%; ∆ = 6.57%), shorter hospital stays (10.65 vs. 12.55 days; ∆ = 1.90 days), and QALYs gained per patient (4.190 vs. 4.063; ∆ = 0.126). The incremental cost-effectiveness ratio was €8039/QALY, which is well below the willingness-to-pay threshold of €30 000/QALY in Italy. The results showed that CAZ-AVI is expected to be a cost-effective treatment compared with imipenem for cUTI in Italy.

Treatment of immunocompromised patients with suspected invasive fungal infections: economic analysis of diagnostic-driven versus empirical strategies in Algeria and Egypt.

Background: Invasive fungal infections (IFIs) in immunocompromised patients are associated with high mortality and treatment costs. Identifying appropriate, cost-effective treatment strategies is crucial to reduce the burden of IFIs. This economic assessment compared strategies for treating immunocompromised patients in Algeria and Egypt.Methods: We developed a decision analytic model incorporating clinical and cost inputs associated with a diagnostic-driven (DD) and standard empirical (SE) strategy. Costs and clinical outcomes were used to calculate incremental cost-effectiveness ratios (ICERs) per death avoided.Results: In both countries, 73.8 (DD) and 125.3 (SE) hypothetical patients per 1,000 received antifungal therapy; 73.8 (DD) and 32.7 (SE) had diagnosed IFIs. Survival at 180 days was similar between DD and SE strategies in Algeria (92.0% vs 91.6%) and Egypt (90.2% vs 90.0%). Total costs per patient were lower with the DD than SE strategy (Algeria: $839 vs $1,591; Egypt: $4,077 vs $4,717). ICERs indicated that the DD compared with SE strategy was associated with better clinical outcomes at a lower overall cost in both countries.Conclusion: Diagnostic-driven compared to empirical therapy may be cost-saving in Algeria and Egypt for the management of immunocompromised patients with persistent neutropenic fever, with no increase in mortality.

Epidemiologic and socioeconomic burden of metastatic renal cell carcinoma (mRCC): a literature review.

Renal cell carcinoma (RCC), the most common form of kidney cancer, initially has an asymptomatic clinical course; 25-30% of patients present with metastatic disease at time of diagnosis. Worldwide incidence and mortality rates are rising at a rate of approximately 2-3% per decade. Metastatic RCC (mRCC) is one of the most treatment-resistant malignancies; outcomes are generally poor and median survival after diagnosis is less than one year. Surgery and chemotherapy have limited or no effect, leaving mRCC patients underserved in the realm of cancer treatment. As the world's population ages and the prevalence of risk factors (obesity, hypertension) increases, the burden of mRCC is predicted to increase significantly. With a shift in treatment of mRCC to novel therapies, such as molecularly targeted therapies (MTTs) (e.g., sorafenib and sunitinib), clinicians, payers, and other healthcare decision-makers must re-evaluate the optimal role for new treatments. Timely understanding of the burden of mRCC on individuals and society clearly is needed at this juncture. Using a comprehensive literature review, we assessed the epidemiologic, economic, and health-related quality of life (HRQOL) burdens of mRCC. The annual incidence of mRCC in major European countries, the US, and Japan ranges from 1500 to 8600 cases. However, prevalence data were lacking. The estimated economic burden of mRCC is large; $107-$556 million (2006 USD) in the US and $446 million-$1.6 billion (2006 USD) collectively in select countries worldwide. MTTs have potential to reduce the burden of mRCC and provide substantial value beyond their clinical effectiveness.

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.

Burden and treatment patterns of invasive fungal infections in hospitalized patients in the Middle East: real-world data from Saudi Arabia and Lebanon.

OBJECTIVES: The objective of this study was to document the burden and treatment patterns associated with invasive fungal infections (IFIs) due to Candida and Aspergillus species in Saudi Arabia and Lebanon. METHODS: A retrospective chart review study was conducted using data recorded from 2011 to 2012 from hospitals in Saudi Arabia and Lebanon. Patients were included if they had been discharged with a diagnosis of IFI due to Candida or Aspergillus, which was culture proven or suspected based on clinical criteria. Hospital data were abstracted for a random sample of patients to capture demographics, treatment patterns, hospital resource utilization, and clinical outcomes. Descriptive results were reported. RESULTS: Five hospitals participated and provided data on 102 patients with IFI (51 from Lebanon and 51 from Saudi Arabia). The mean age of the patients was 55 years, and 55% were males. Comorbidities included diabetes (41%), coronary artery disease (24%), leukemia (19%), moderate-to-severe renal disease (16%), congestive heart failure (15%), and chronic obstructive pulmonary disease (15%). Twenty percent of patients received corticosteroids prior to admission and 26% had received chemotherapy in the past 90 days. Inpatient mortality was 42%, and the mean hospital length of stay was 32.4±28.6 days. Fifty-five percent of patients required intensive care unit admission (17.2±14.1 days), 37% required mechanical ventilation (13.7±13.2 days), and 11% required dialysis (14.6±14.2 days). The most commonly used first-line antifungal was fluconazole. CONCLUSION: Patients with IFI in Saudi Arabia and Lebanon frequently have multiple medical comorbidities and may not have traditionally observed IFI risk factors. Efforts to increase use of rapid diagnostic tests and appropriate antifungal treatments may impact the substantial mortality and high length of stay observed in these patients.