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 hospitalacquired 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 V1254 ($1401) per patient, and the estimated incremental cost-effectiveness ratio was V3581 ($4000) per QALY gained, well below the willingness-topay threshold of V30,000 ($33,507) per QALY in Italy. Implications: The model results showed that CAZAVI is expected to provide clinical benefits in hospitalized patients with HAP/VAP in Italy at an acceptable cost compared to meropenem

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

Abstract 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

Development and Test of a New Method for Preference Measurement for Multistate Health Profiles

This dissertation aims at developing and testing a new method that can better capture preferences for multistate health profiles. The motivation arose from the failure of the QALY (Quality-Adjusted Life Year) model in adequately capturing preferences in multistate health profiles. The current QALY-based technique captures preferences for multistate health profiles by evaluating each health state in the profile independently of other states. As the past literature showed, this additive independence condition does not hold in practice and hence such approach is inadequate. To address this issue, this study proposes a novel approach to measure preferences for multistate health profiles by looking at two consecutive health states at a time. It hypothesizes that an evaluation of the future health state is dependent or "conditioned" on the level of the preceding, or current, health state. Characteristics of the current health state that are suspected to impact the resulting conditional preference scores for future health state are systematically explored in a carefully designed empirical study. The interested factors include duration of the current health state, direction of change and amplitude of change between the current and future health states. A 2Ph.D.Committee Chair: Sainfort, Francois; Committee Member: Bostrom, Ann; Committee Member: Flowers, Christopher; Committee Member: Jacko, Julie; Committee Member: Vidakovic, Bran

Cost effectiveness of apixaban versus aspirin for stroke prevention in patients with non-valvular atrial fibrillation in Belgium

Evidence indicates that vitamin K antagonists (VKAs) and oral anticoagulant therapy are under-utilised for stroke prevention in patients with non-valvular atrial fibrillation (AF), and patients who decline or cannot tolerate such treatment are often prescribed aspirin instead. Apixaban has been shown in the AVERROES trial to be superior to aspirin in preventing stroke and systemic embolism without significantly increasing the risk of major bleeding among patients with AF who are unsuitable for VKA therapy. This study estimates the economic implications and potential cost effectiveness of apixaban compared with aspirin in such individuals from the perspective of healthcare payers in Belgium. A Markov model was developed to evaluate the clinical and economic impact of apixaban compared with aspirin in patients unsuitable for VKA therapy. The clinical events modelled include ischaemic and haemorrhagic stroke, systemic embolism, intracranial haemorrhage, other major bleeding, clinically relevant non-major bleeding, myocardial infarction, cardiovascular hospitalisation and treatment discontinuations obtained from AVERROES. Outcomes included life-years and quality-adjusted life-years (QALYs) gained, costs and incremental cost-effectiveness ratios (ICERs) over a lifetime. Apixaban was projected to increase life expectancy and QALYs compared with aspirin, with an associated increase in drug acquisition costs. The estimated ICER was a,not sign7,334 per QALY gained with apixaban compared with aspirin. Apixaban is a cost-effective alternative to aspirin for patients with AF in Belgium who decline or cannot tolerate VKA treatment

The Impact of Auditory and Haptic Feedback on Computer Task Performance in Patients with Age-Related Macular Degeneration and Control Subjects With No Known Ocular Disease

PURPOSE: To determine the impact of auditory and haptic (tactile) feedback on computer task performance of patients with age-related macular degeneration (AMD) compared to controls. METHODS: Thirty patients with AMD and 29 similarly aged controls with no known ocular disease completed timed computer icon drag and drop tasks under all four possible conditions of presence or absence of auditory and haptic feedback in a two-factor repeated measures design. Patient recruitment was stratified by best eye acuity: 20/20-20/50; 20/60-20/100; \u3c20/100. Controls had best eye acuity\u3eor=20/30. Task completion time was quantified using final target highlight time (FTHT) and total trial time, measured in milliseconds. RESULTS: Mean+/-standard deviation (SD) FTHT with neither feedback type in the three patient and control groups was, respectively: 1,110+/-356, 1,682+/-1,069, 1,763+/-831, 924+/-533. Auditory feedback improved performance [%FTHT decrease, p-value] in all groups, respectively: 18%, P=0.018; 38%, P=0.054; 57%, P=0.001; 19%, P=0.001. Haptic feedback improved performance in the worst acuity AMD group and controls: 46%, P=0.009; 17%, P=0.038. In the worst acuity AMD group, auditory and/or haptic feedback was associated with a 4-6 second mean (for each task) reduction in total trial time. CONCLUSION: Auditory and haptic feedback can substantially increase performance speed of computer drag and drop tasks for patients with AMD, particularly in those patients with the most compromised vision

Clinical and Economic Implications of Apixaban Versus Aspirin in the Low-Risk Nonvalvular Atrial Fibrillation Patients

Background and Purpose— Although recommended by guidelines, the benefits of treating patients with atrial fibrillation with a low–stroke risk score, with aspirin or anticoagulants, have not been clearly established. With advent of safer non–vitamin K antagonist oral anticoagulant, we assessed the clinical and economic implications of 5 mg BID of apixaban versus aspirin among patients with a relative low risk of stroke as assessed using the CHADS 2 (congestive heart failure, hypertension, age&gt;75, diabetes mellitus, stroke/transient ischemic attack) and CHA 2 DS 2 –VASc (congestive heart failure, hypertension, age, diabetes mellitus, stroke/transient ischemic attack, vascular disease) stroke risk classification. Methods— A previously developed and validated Markov model was adapted. A secondary analysis of the Apixaban Versus Acetylsalicylic Acid to Prevent Stroke in Atrial Fibrillation Patients Who Have Failed or Are Unsuitable for Vitamin K Antagonist Treatment (AVERROES) study was conducted to estimate event rates in different low-risk cohorts by treatment. Three cohorts (n=1000) with a CHADS 2 score of 1, CHA 2 DS 2 –VASc score of 1, and CHA 2 DS 2 –VASc of score 2 to 4 were simulated to assess the number of clinical events avoided in terms of strokes and major bleeds, as well as life years gained, quality-adjusted life years gained, costs, and incremental costs per quality-adjusted life year gained. Results— Apixaban was associated with fewer strokes and systemic embolism versus aspirin across all subgroups; however, it caused more major bleeding events. The reduction in systemic embolism offset the increase in major bleeding events leading to increased life expectancy and quality-adjusted life year gains, achieved at an increased cost that was lower than the UK threshold of $44 400 (ie, £30 000) per quality-adjusted life year gained across the 3 cohorts examined. Conclusions— Anticoagulant treatment with apixaban versus aspirin in low-risk patients, as identified using CHADS 2 or CHA 2 DS 2 –VASc, is projected to increase life expectancy and provide clinical benefits that are cost effective. </jats:sec

Stroke and systemic embolism prevention in patients with atrial fibrillation in Belgium: comparative cost effectiveness of new oral anticoagulants and warfarin

Background: Management of non-valvular atrial fibrillation (NVAF) focuses on the use of anticoagulation to mitigate the risk of stroke. Until recently, vitamin K antagonist (VKA) treatment was considered the standard of care, with the emergence of non-VKA oral anticoagulants (NOACs) shifting treatment practice. The objective of this study was therefore to assess the use of warfarin and the NOACs for stroke prevention in patients with NVAF from the perspective of a Belgian healthcare payer using a cost-effectiveness analysis and the efficiency frontier approach. Methods: A previously published Markov model was adapted to the Belgian healthcare setting. Clinical events modelled include ischaemic and haemorrhagic stroke, systemic embolism, intracranial haemorrhage, other major bleeding, clinically relevant non-major bleeding, myocardial infarction, cardiovascular hospitalisation and treatment discontinuations. Efficacy and bleeding data for warfarin and apixaban 5 mg twice daily were obtained from the ARISTOTLE trial, whilst those for other NOACs (rivaroxaban 20 mg once daily, dabigatran 110 mg twice daily, dabigatran 150 mg twice daily) were from published indirect comparisons. Acute medical costs were obtained from reimbursement payments made to Belgian hospitals, whilst long-term medical costs and utility data were derived from the literature. The efficiency frontier was calculated using total costs and quality-adjusted life-years (QALYs) as outcomes. Univariate and probabilistic sensitivity analyses were performed. Result: Warfarin and apixaban were the two optimal treatment choices, as the other three treatment alternatives including dabigatran 110 mg, dabigatran 150 mg switching to dabigatran 110 mg at the age of 80 years and rivaroxaban were extendedly or strictly dominated on the efficiency frontier. Apixaban was a cost-effective alternative vs warfarin at an incremental cost-effectiveness ratio of a,not sign7,212/QALY gained. Conclusions: Amongst NOACs, apixaban may be the most economically efficient alternative to warfarin in NVAF patients who are suitable for VKA treatment and eligible for stroke prevention in Belgium

Cost-effectiveness of Apixaban Compared With Edoxaban for Stroke Prevention in Nonvalvular Atrial Fibrillation

AbstractPurposeThe purpose of this analysis was to assess the cost-effectiveness of apixaban 5 mg BID versus high- and low-dose edoxaban (60 mg and 30 mg once daily) as intended starting dose strategies for stroke prevention in patients from a UK National Health Service perspective.MethodsA previously developed and validated Markov model was adapted to evaluate the lifetime clinical and economic impact of apixaban 5 mg BID versus edoxaban (high and low dose) in patients with nonvalvular atrial fibrillation. A pairwise indirect treatment comparison was conducted for clinical end points, and price parity was assumed between apixaban and edoxaban. Costs in 2012 British pounds, life-years, and quality-adjusted life-years (QALYs) gained, discounted at 3.5% per annum, were estimated.FindingsApixaban was predicted to increase life expectancy and QALYs versus low- and high-dose edoxaban. These gains were achieved at cost-savings versus low-dose edoxaban, thus being dominant and nominal increases in costs versus high-dose edoxaban. The incremental cost-effectiveness ratio of apixaban versus high-dose edoxaban was £6763 per QALY gained.ImplicationsApixaban was deemed to be dominant (less costly and more effective) versus low-dose edoxaban and a cost-effective alternative to high-dose edoxaban