Medical resource utilization of abiraterone acetate plus prednisone added to androgen deprivation therapy in metastatic castration-naive prostate cancer: Results from LATITUDE.

BACKGROUND: Abiraterone acetate plus prednisone (AA+P), when added to androgen deprivation therapy (ADT), demonstrated significant improvements in overall survival and disease progression over dual placebos added to ADT in the LATITUDE clinical trial (NCT01715285). The objective of this study was to assess event-driven medical resource utilization (MRU) of ADT plus AA+P (ADT+AA+P) versus ADT plus dual placebos (ADT+placebos) in LATITUDE. METHODS: Event-driven MRU data from LATITUDE while patients were on treatment were used for analyses. Types of MRU included overnight hospitalizations and length of stay (LOS), emergency room (ER) visits, radiotherapy, surgery, imaging, and specialist and general practitioner (GP) visits. Rates by treatment (per 100 person-years) and rate ratios comparing ADT+AA+P with ADT+placebos were estimated with zero-inflated Poisson regression. The difference in the average hospital LOS between arms was assessed with repeated measures regression analyses. Reasons for hospitalization were explored. Sensitivity analyses were conducted to assess the robustness of the results. RESULTS: A total of 1199 patients were enrolled in LATITUDE. Significantly lower rates of hospitalization (a 24% reduction), imaging (a 36% reduction), and radiotherapy (a 50% reduction) were observed with ADT+AA+P versus ADT+placebos. There was a nonsignificant trend of lower rates of specialist visits and surgery. The rates of ER and GP visits and the average LOS per hospitalization episode were similar across arms. The most common hospitalization reasons were genitourinary, musculoskeletal, and respiratory tract symptoms/disorders. The results remained consistent in a sensitivity analysis. CONCLUSIONS: Adding AA+P to ADT does not increase MRU and leads to lower rates of hospitalization, imaging, and radiotherapy. This likely reflects the more favorable clinical outcomes with ADT+AA+P therapy.

Modeling Clinical Outcomes in Prostate Cancer: Application and Validation of the Discrete Event Simulation Approach.

OBJECTIVES: Treatment landscape in prostate cancer has changed dramatically with the emergence of new medicines in the past few years. The traditional survival partition model (SPM) cannot accurately predict long-term clinical outcomes because it is limited by its ability to capture the key consequences associated with this changing treatment paradigm. The objective of this study was to introduce and validate a discrete-event simulation (DES) model for prostate cancer. METHODS: A DES model was developed to simulate overall survival (OS) and other clinical outcomes based on patient characteristics, treatment received, and disease progression history. We tested and validated this model with clinical trial data from the abiraterone acetate phase III trial (COU-AA-302). The model was constructed with interim data (55% death) and validated with the final data (96% death). Predicted OS values were also compared with those from the SPM. RESULTS: The DES model's predicted time to chemotherapy and OS are highly consistent with the final observed data. The model accurately predicts the OS hazard ratio from the final data cut (predicted: 0.74; 95% confidence interval [CI] 0.64-0.85 and final actual: 0.74; 95% CI 0.6-0.88). The log-rank test to compare the observed and predicted OS curves indicated no statistically significant difference between observed and predicted curves. However, the predictions from the SPM based on interim data deviated significantly from the final data. CONCLUSIONS: Our study showed that a DES model with properly developed risk equations presents considerable improvements to the more traditional SPM in flexibility and predictive accuracy of long-term outcomes.

Incidence-based cost-of-illness model for metastatic breast cancer in the United States.

OBJECTIVES: This study aims to estimate the annual U.S. societal costs associated with treatment of metastatic breast cancer (MBC) patients using an incidence-based cost-of-illness (COI) framework. METHODS: An incidence-based COI model was constructed in which MBC patients were simulated from diagnosis through active treatment, palliative care, and death over 5 years. Key model parameters included: annual incidence of breast cancer in the metastatic stage, utilization of cancer therapies and other medical care resources, treatment-related adverse events, unit costs, work days missed by patient and caregiver, and wage rates. Overall survival was based on SEER data and costs were assigned to living patients monthly, according to their disease management phase. The outcomes measures were total discounted societal costs, cost/year, and cost/patient-year. RESULTS: The annual incidence of MBC in the United States in 2007 was estimated to be 49,674 patients (de novo and progressed from earlier stages). The total discounted cost to society attributable to MBC was $12.2 billion for the incident cohort, or $98,571 per patient-year. The 5-year direct medical cost of this incident cohort was $9.3 billion, or $75,415 per patient-year. Treatment-related costs (active treatment, toxicity management, and medical follow-up) contributed 44 percent of MBC expenditure, followed by palliative/best supportive care costs (31 percent). Lost productivity accounted for approximately 21 percent of the total cost ($2.6 billion over 5 years or $21,153 per patient-year). CONCLUSIONS: The societal burden of MBC in the United States is substantial. Earlier detection and effective treatment could lead to a significant decrease in costs while improving overall disease prognosis.

Cost-effectiveness of warfarin: trial versus "real-world" stroke prevention in atrial fibrillation.

BACKGROUND AND PURPOSE: Previous cost-effectiveness analyses analyzed warfarin for stroke prevention in randomized trial settings. Given the complexities of warfarin treatment, cost-effectiveness should be examined within a real-world setting. METHODS: Our model followed patients with atrial fibrillation at moderate to high risk of stroke through primary and recurrent ischemic stroke, hemorrhages--intracranial and extracranial, and the resulting disability. Four scenarios were examined: (1) all patients start on warfarin with perfect control, that is, international normalized ratio (INR) values always within range; (2) all patients start on warfarin with trial-like control, where INR can fall outside the recommended range; (3) all patients start on warfarin with real-world INR control; and (4) real-world prescription (and control) of warfarin, aspirin, or neither for warfarin-eligible patients. Reported warfarin discontinuation rates were used. Main outcomes were total number of events, quality adjusted life years, and costs in a US setting. RESULTS: The total number of primary and recurrent ischemic strokes in a 1,000-patient cohort (age 70 years, lifetime analysis) was 626, 832, 984, and 1,171 in scenarios 1 to 4, respectively. The corresponding mean quality adjusted life years per patient were 7.21, 6.92, 6.75, and 6.67 for scenarios 1 to 4, respectively. Costs per patient were $68,039, $77,764, $84,518, and $87,248 in scenarios 1 to 4, respectively. If "perfect" adherence to warfarin was assumed, except for discontinuations for clinical reasons, strokes would decrease to 503, 737, 909, and 1,120 in scenarios 1 to 4, respectively. CONCLUSIONS: Clinical and cost outcomes are strongly dependent on the quality of anticoagulation and rates of warfarin discontinuation. Clinicians should work to improve both. Policy makers should use real-world INR control and warfarin discontinuation rates when assessing cost-effectiveness.

Model-based simulation to explore the cost-effectiveness of following practice guidelines for triglyceride and low-density lipoprotein cholesterol control among patients with diabetes mellitus and mixed dyslipidemia.

BACKGROUND: The National Cholesterol Education Program Adult Treatment Panel III guidelines recommend maintaining lipid levels within particular targets to reduce the risk of coronary heart disease (CHD) events. OBJECTIVE: The objective of this simulation study was to evaluate the cost-effectiveness of following guideline-recommended care compared with current practice or usual care for patients with diabetes mellitus (DM) and mixed dyslipidemia (ie, high low-density lipoprotein cholesterol [LDL-C] and triglyceride [TG] levels). METHODS: A simulation model using a US health care payer perspective was designed to predict changes in lipid levels (LDL-C, TG, high-density lipoprotein cholesterol, and total cholesterol) and long-term CHD risk. Data about patients with DM and uncontrolled TG and/or LDL-C were taken from an electronic medical records database to develop the description of current care (eg, statin, fibrate, or no medication) and cholesterol levels. Patients with uncontrolled lipid levels who were not following guideline recommendations were assumed to be receiving combination treatment (ie, coadministration of statin and fibrate) or monotherapy for the uncontrolled lipids under guideline care. Results from a previous study were used to project incremental benefits of combination treatment compared with monotherapy. CHD events were predicted based on risk equations. A 20-year model of direct costs and quality-adjusted life-years (QALYs) was created. RESULTS: Among patients switched to guideline therapy, the model predicted 72% achieved 2 lipid targets and 44% achieved 3 lipid targets in 1 year. Over 20 years, in a modeled sample of 1000 patients, 176 myocardial infarction and angina events would be avoided by following guideline care. Total present value of costs for drug treatment and medical care for CHD events would be $33,626 per patient for guideline treatment versus $25,264 per patient for current care. The discounted QALY gain would be 0.18 per patient for an incremental cost per QALY of $50,315. CONCLUSIONS: The results of this model simulation suggest that for patients with DM and mixed dyslipidemia, following treatment guidelines rather than current practice (including combination therapy rather than monotherapy) would result in more patients achieving lipid targets, fewer CHD events, and more QALYs gained at a reasonable cost (less than $109,000) per QALY.

Cost-effectiveness of linezolid versus vancomycin for hospitalised patients with complicated skin and soft-tissue infections in Germany.

This study used a decision analytic model approach to evaluate the cost-effectiveness of linezolid versus vancomycin in the empirical treatment of complicated skin and soft-tissue infection (cSSTI) due to suspected methicillin-resistant Staphylococcus aureus (MRSA) from the German hospital and health care system perspective. Clinical probabilities were obtained from trial data, resource utilisation and MRSA prevalence rates were obtained through German physician interviews, and costs from published sources were applied to resource units. Outcomes included total cost/patient and cure. The estimated first-line cure rate for linezolid-treated patients was 90.1% versus 85.5% for vancomycin; total cure rates after two lines of treatment were 98.4% and 98.1%, respectively. Average total cost/episode was 8,232 euro for linezolid versus 9,206 euro for vancomycin. The model outcomes were sensitive to changes in length of stay (LOS), isolation days, rate of confirmed MRSA and price of linezolid. Linezolid was expected to result in a shorter intravenous treatment duration and shorter LOS that offset its higher acquisition cost versus vancomycin in cSSTI in Germany.

How inducing covariation in simulated HDL-C, triglyceride, and total cholesterol data affects Framingham risk equation results.

OBJECTIVE: To assess the effect of inducing covariation among simulated high-density lipoprotein (HDL-C), triglyceride, and total cholesterol values on Framingham risk equation results. METHODS: National Health and Nutrition Examination Survey (NHANES) data were used to estimate means and standard deviations for HDL-C, triglyceride, and total cholesterol for all Type II diabetic patients (N = 293) and patients with metabolic syndrome (N = 2303). NHANES data were also used to estimate correlations between HDL-C, triglyceride, and total cholesterol. Data were simulated and bootstrapped for 1000 replications of the numbers of patients in NHANES. Four-year risks of coronary heart disease were estimated using the Framingham risk equation that includes a nonlinear Weibull function. The differences in means, with and without correlation, were compared to zero to determine whether not inducing correlation was associated with bias. The ratios of variances with and without correlation were compared to one to determine whether not inducing correlation was associated with a different level of precision. All simulation results were compared with bootstrapping results. RESULTS: Bootstrapping maintained the correlation in the original data. Inducing correlation leads to more precise estimates that are closer to the bootstrapped estimates for Framingham equations not including triglycerides. Using the Framingham equation for women with triglycerides, the correlated simulation data produce less precise estimates than the uncorrelated data; the uncorrelated data are more precise than the bootstrapped results. CONCLUSION: Not inducing correlation can affect results that combine multiple simulated parameters using nonlinear functions. Researchers engaged in modeling should consider the value of inducing correlation in their simulated data.

A comparison of costs and hospital length of stay associated with intravenous/oral linezolid or intravenous vancomycin treatment of complicated skin and soft-tissue infections caused by suspected or confirmed methicillin-resistant Staphylococcus aureus in elderly US patients.

OBJECTIVES: This study compared the costs and hospital length of stay (LOS) and duration of intravenous therapy associated with intravenous/oral linezolid or intravenous vancomycin treatment of complicated skin and soft-tissue infections (cSSTIs) caused by suspected or confirmed methicillin-resistant Staphylococcus aureus (MRSA) in elderly US patients. METHODS: Data were obtained from elderly (>or=65 years) US patients participating in a multinational randomized trial of hospitalized cSSTI patients treated with linezolid or vancomycin. Costs (hospital and total) from the provider perspective were estimated for intent-to-treat (ITT) patients (ie, all those receiving >or=1 dose) using national 2003 costs (ward, medication, intravenous administration). LOS for inpatient care, duration of intravenous linezolid and vancomycin therapy (ITT and MRSA groups), and cure rates were evaluated. RESULTS: Of 717 enrolled subjects, 163 (23%) were elderly (87 linezolid, 76 vancomycin), with no significant differences in demographic characteristics between the linezolid and vancomycin groups. Mean hospitalization and total costs were lower with linezolid compared with vancomycin (hospitalization: US $4510 vs US $6478, P<0.001; total: US $6009 vs US $7329, P=0.03). Linezolid was associated with a 3.5-day reduction in LOS and a 9.5-day reduction in the duration of intravenous therapy compared with vancomycin in the ITT group (both, P<0.001). Cure rates were comparable between linezolid and vancomycin in both the ITT group (88.7% vs 81.4%, respectively) and the MRSA group (80.0% vs 71.4%). In multivariate analyses of the ITT group, linezolid patients were 57% less likely than vancomycin patients to have a LOS >7 days (odds ratio = 0.43; 95% CI, 0.21-0.87). Chronic renal failure, malnutrition, and a diagnosis of infected ulcer predicted an LOS >7 days. CONCLUSIONS: In this analysis of data from elderly patients with cSSTI caused by suspected or confirmed MRSA, linezolid treatment was associated with reductions in the costs of care, LOS, and duration of intravenous treatment without affecting the clinical outcomes. Although the use of a subset of patients from a larger trial that did not focus on the elderly can be seen as a study limitation, the elderly represent an important population when evaluating health care resource use and costs.

A taxonomy and economic consequences of nursing home falls.

BACKGROUND: Falls are a primary cause of injury and disability in the nursing home environment and can be costly to treat. We propose a taxonomy of nursing home falls that accounts for both the severity of fall consequences and the duration of the treatment episode. No other systematic approach of this kind has been previously described. METHODS: We defined a 9-level taxonomy of fall types and outcomes. Components of each fall category include resource use during the acute, convalescent, and long-term phases of treatment. Three variants of each category describe typical, best-case and worst-case fall episodes. Treatment costs were estimated for each fall category by applying unit costs from national databases and published sources to projected medical resource utilisation. Long-term costs reflect adjustment in Medicare per diem reimbursement rates associated with change in patient status subsequent to the fall. RESULTS: The most common and least costly fall category was category 1 -- non-injurious, which accounted for 30% of falls and a 1-year cost of US dollars 319 per event (range US dollars 71-550). The least common and most costly was fall category 9 -- multiple injuries, which accounted for 1% of falls and a 1-year cost of US dollars 22,368 (range US dollars 9,969-64,382). CONCLUSIONS: The falls taxonomy represents a unique approach to estimating the cost of nursing home falls and offers a tool for evaluating the cost-effectiveness of fall prevention strategies. A validation study should be performed to confirm the magnitude of fall frequency and cost estimates.

Comparison of the cost-effectiveness of new oral anticoagulants for the prevention of stroke and systemic embolism in atrial fibrillation in a UK setting.

PURPOSE: Three new oral anticoagulants (NOACs) have recently become available in the United Kingdom as an alternative to warfarin in the prevention of stroke and systemic embolism in atrial fibrillation. This study examines the relative cost-effectiveness of dabigatran (BID dosing of 150 mg or 110 mg based on patient age), rivaroxaban, and apixaban from a UK payer perspective. METHODS: A previously published model that follows up patients through treatment of atrial fibrillation during a lifetime was adapted to allow comparison of the 3 NOACs and warfarin. Acute thromboembolic and bleeding events, as well as long-term consequences of stroke, intracranial hemorrhage, and acute myocardial infarction, were tracked. Relative efficacy was calculated from a formal indirect treatment comparison using data from the 3 key trials (Randomized Evaluation of Long-Term Anticoagulation Therapy, Rivaroxaban Once-daily oral direct factor Xa inhibition Compared with vitamin K antagonism for prevention of stroke and Embolism Trial in Atrial Fibrillation, and Apixaban for the Prevention of Stroke in Subjects With Atrial Fibrillation) of the NOACs. Data from the rivaroxaban trial were adjusted for the difference in international normalized ratio control among warfarin patients versus the other 2 trials. Model outputs included total costs, event rates, and quality-adjusted life-years. FINDINGS: Among the patients taking NOACs, those taking dabigatran had the highest total QALYs (7.68 QALYs), followed by apixaban (7.63 QALYs) and rivaroxaban (7.47 QALYs). Patients taking dabigatran had the lowest total lifetime costs (£23,342), followed by apixaban (£24,014) and rivaroxaban (£25,220). The differences between dabigatran and apixaban were modest but consistent in sensitivity analyses, with the directionality only changing at the limits of the CIs for the relative risks of ischemic stroke or intracranial hemorrhage or when assuming that both treatment discontinuation and post-event disability rates differ by drug. IMPLICATIONS: Dabigatran was found to be economically dominant over rivaroxaban and apixaban in the UK setting. These economic findings are based on relative clinical efficacy from an indirect treatment comparison and would benefit from any data of direct comparisons of the NOACs in the future.

Cost-effectiveness of new oral anticoagulants in the prevention of stroke in patients with atrial fibrillation.

Atrial fibrillation (AF) is a common arrhythmia and the leading cause of stroke, an event with high human and economic burden. Novel oral anticoagulants have been approved in many markets as alternatives to warfarin for stroke prevention in patients with AF - dabigatran etexilate, apixaban and rivaroxaban. Given the high burden of AF, and given that new treatments can more effectively prevent stroke than warfarin, but at higher drug cost, there has been a need for systematic evaluation of the costs and benefits of these new treatments. In this study, we summarize the findings of a systematic literature review on the cost-effectiveness of the new oral anticoagulants. We find that there is substantial heterogeneity between the studies and their numerical findings, despite using a common set of four trials for their clinical inputs. However, there is broad consensus among them that each of the novel oral anticoagulants is cost-effective versus warfarin or aspirin.

A comparative analysis of models used to evaluate the cost-effectiveness of dabigatran versus warfarin for the prevention of stroke in atrial fibrillation.

BACKGROUND: A number of models exploring the cost-effectiveness of dabigatran versus warfarin for stroke prevention in atrial fibrillation have been published. These studies found dabigatran was generally cost-effective, considering well-accepted willingness-to-pay thresholds, but estimates of the incremental cost-effectiveness ratios (ICERs) varied, even in the same setting. The objective of this study was to compare the findings of the published economic models and identify key model features accounting for differences. METHODS: All aspects of the economic evaluations were reviewed: model approach, inputs, and assumptions. A previously published model served as the reference model for comparisons of the selected studies in the US and UK settings. The reference model was adapted, wherever possible, using the inputs and key assumptions from each of the other published studies to determine if results could be reproduced in the reference model. Incremental total costs, incremental quality-adjusted life years (QALYs), and ICERs (cost per QALY) were compared between each study and the corresponding adapted reference model. The impact of each modified variable or assumption was tracked separately. RESULTS: The selected studies were in the US setting (2), the Canadian setting (1), and the UK setting (2). All models used the Randomized Evaluation of Long-Term Anticoagulation study (RE-LY) as the main source for clinical inputs, and all used a Markov modelling approach, except one that used discrete event simulation. The reference model had been published in the Canadian and UK settings. In the UK setting, the reference model reported an ICER of UK£4,831, whereas the other UK-based analysis reported an ICER of UK£23,082. When the reference model was modified to use the same population characteristics, cost inputs, and utility inputs, it reproduced the results of the other model (ICER UK£25,518) reasonably well. Key reasons for the different results between the two models were the assumptions on the event utility decrement and costs associated with intracranial haemorrhage, as well as the costs of warfarin monitoring and disability following events. In the US setting, the reference model produced an ICER similar to the ICER from one of the US models (US$15,115/QALY versus US$12,386/QALY, respectively) when modelling assumptions and input values were transferred into the reference model. Key differences in results could be explained by the population characteristics (age and baseline stroke risk), utility assigned to events and specific treatments, adjustment of stroke and intracranial haemorrhage risk over time, and treatment discontinuation and switching. The reference model was able to replicate the QALY results, but not the cost results, reported by the other US cost-effectiveness analysis. The parameters driving the QALY results were utility values by disability levels as well as utilities assigned to specific treatments, and event and background mortality rates. CONCLUSIONS: Despite differences in model designs and structures, it was mostly possible to replicate the results published by different authors and identify variables responsible for differences between ICERs using a reference model approach. This enables a better interpretation of published findings by focusing attention on the assumptions underlying the key model features accounting for differences.

Modeling hard clinical end-point data in economic analyses.

OBJECTIVE: The availability of hard clinical end-point data, such as that on cardiovascular (CV) events among patients with type 2 diabetes mellitus, is increasing, and as a result there is growing interest in using hard end-point data of this type in economic analyses. This study investigated published approaches for modeling hard end-points from clinical trials and evaluated their applicability in health economic models with different disease features. METHODS: A review of cost-effectiveness models of interventions in clinically significant therapeutic areas (CV diseases, cancer, and chronic lower respiratory diseases) was conducted in PubMed and Embase using a defined search strategy. Only studies integrating hard end-point data from randomized clinical trials were considered. For each study included, clinical input characteristics and modeling approach were summarized and evaluated. RESULTS: A total of 33 articles (23 CV, eight cancer, two respiratory) were accepted for detailed analysis. Decision trees, Markov models, discrete event simulations, and hybrids were used. Event rates were incorporated either as constant rates, time-dependent risks, or risk equations based on patient characteristics. Risks dependent on time and/or patient characteristics were used where major event rates were >1%/year in models with fewer health states (<7). Models of infrequent events or with numerous health states generally preferred constant event rates. LIMITATIONS: The detailed modeling information and terminology varied, sometimes requiring interpretation. CONCLUSIONS: Key considerations for cost-effectiveness models incorporating hard end-point data include the frequency and characteristics of the relevant clinical events and how the trial data is reported. When event risk is low, simplification of both the model structure and event rate modeling is recommended. When event risk is common, such as in high risk populations, more detailed modeling approaches, including individual simulations or explicitly time-dependent event rates, are more appropriate to accurately reflect the trial data.

Cost-effectiveness of dabigatran etexilate for the prevention of stroke and systemic embolism in UK patients with atrial fibrillation.

OBJECTIVE: To assess the cost-effectiveness of dabigatran etexilate, a new oral anticoagulant, versus warfarin and other alternatives for the prevention of stroke and systemic embolism in UK patients with atrial fibrillation (AF). METHODS: A Markov model estimated the cost-effectiveness of dabigatran etexilate versus warfarin, aspirin or no therapy. Two patient cohorts with AF (starting age of <80 and ≥80 years) were considered separately, in line with the UK labelled indication. Modelled outcomes over a lifetime horizon included clinical events, quality-adjusted life years (QALYs), total costs and incremental cost-effectiveness ratios (ICERs). RESULTS: Patients treated with dabigatran etexilate experienced fewer ischaemic strokes (3.74 dabigatran etexilate vs 3.97 warfarin) and fewer combined intracranial haemorrhages and haemorrhagic strokes (0.43 dabigatran etexilate vs 0.99 warfarin) per 100 patient-years. Larger differences were observed comparing dabigatran etexilate with aspirin or no therapy. For patients initiating treatment at ages <80 and ≥80 years, the ICERs for dabigatran etexilate were £4831 and £7090/QALY gained versus warfarin with a probability of cost-effectiveness at £20 000/QALY gained of 98% and 63%, respectively. For the patient cohort starting treatment at ages <80 years, the ICER versus aspirin was £3457/QALY gained and dabigatran etexilate was dominant (ie, was less costly and more effective) compared with no therapy. These results were robust in sensitivity analyses. CONCLUSIONS: This economic evaluation suggests that the use of dabigatran etexilate as a first-line treatment for the prevention of stroke and systemic embolism is likely to be cost-effective in eligible UK patients with AF.

Dabigatran versus rivaroxaban for the prevention of stroke and systemic embolism in atrial fibrillation in Canada. Comparative efficacy and cost-effectiveness.

Canadian patients with atrial fibrillation (AF) in whom anticoagulation is appropriate have two new choices for anticoagulation for prevention of stroke and systemic embolism--dabigatran etexilate (dabigatran) and rivaroxaban. Based on the RE-LY and ROCKET AF trial results, we investigated the cost-effectiveness of dabigatran (twice daily dosing of 150 mg or 110 mg based on patient age) versus rivaroxaban from a Canadian payer perspective. A formal indirect treatment comparison (ITC) of dabigatran versus rivaroxaban was performed, using dabigatran clinical event rates from RE-LY for the safety-on-treatment population, adjusted to the ROCKET AF population. A previously described Markov model was modified to simulate anticoagulation treatment using ITC results as inputs. Model outputs included total costs, event rates, and quality-adjusted life-years (QALYs). The ITC found when compared to rivaroxaban, dabigatran had a lower risk of intracranial haemorrhage (ICH) (relative risk [RR] = 0.38; 95% confidence interval [CI] 0.21 - 0.67) and stroke (RR = 0.62; 95%CI 0.45-0.87). Over a lifetime horizon, the model found dabigatran-treated patients experienced fewer ICHs (0.33 dabigatran vs. 0.71 rivaroxaban) and ischaemic strokes (3.40 vs. 3.96) per 100 patient-years, and accrued more QALYs (6.17 vs. 6.01). Dabigatran-treated patients had lower acute care and long-term follow-up costs per patient ($52,314 vs. $53,638) which more than offset differences in drug costs ($7,299 vs. $6,128). In probabilistic analysis, dabigatran had high probability of being the most cost-effective therapy at common thresholds of willingness-to-pay (93% at a $20,000/QALY threshold). This study found dabigatran is economically dominant versus rivaroxaban for prevention of stroke and systemic embolism among Canadian AF patients.

Impact of linezolid on economic outcomes and determinants of cost in a clinical trial evaluating patients with MRSA complicated skin and soft-tissue infections.

BACKGROUND: In clinical trials, linezolid has demonstrated higher clinical cure rates and shorter hospital duration for patients than has vancomycin for the treatment of complicated skin and soft-tissue infections (cSSTIs). OBJECTIVE: To assess economic outcomes of linezolid versus vancomycin and evaluate determinants of treatment costs for cSSTIs. METHODS: Economic data were obtained from US subjects enrolled in a multinational, open-label, clinical trial of cSSTIs caused by suspected or proven methicillin-resistant Staphylococcus aureus (MRSA). Subjects were randomized to receive intravenous or oral linezolid or intravenous vancomycin for 7-21 days. Costs for each patient were evaluated by applying nationally representative per diem hospital costs by hospital ward. Intravenous administration costs were applied to the duration of intravenous treatment. Factors contributing to the cost of therapy were evaluated using multivariate regression analysis. RESULTS: Seven hundred seventeen US patients were included in the study. Demographics were similar between treatment groups. Length of stay and duration of intravenous therapy were shorter for linezolid-treated patients. Mean +/- SD cost for intent-to-treat population patients treated with linezolid versus vancomycin was 4865 US dollars +/- 4367 versus 5738 US dollars +/- 5190, respectively (p = 0.017), and in the MRSA population was 4881 US dollars +/- 3987 versus 6006 US dollars +/- 5039, respectively (p = 0.041). Factors significantly associated with increased cost included vancomycin therapy, age, and comorbidities, including diabetes. After adjusting for all other factors, treatment with linezolid was associated with significantly lower treatment costs compared with vancomycin. CONCLUSIONS: Linezolid therapy was associated with improved clinical outcomes and significantly lower treatment costs than was vancomycin. The largest cost advantage was demonstrated in patients with documented MRSA cSSTIs.

Atopic dermatitis is associated with a decrement in health-related quality of life.

BACKGROUND: Although atopic dermatitis is a chronic skin disease that can have a major impact on a patient's life, the burden of illness associated with this condition has not been well characterized. OBJECTIVE: To determine the health-related quality of life (HRQL) of patients with atopic dermatitis by disease severity and to compare it with that of the general public and of patients suffering from other chronic illnesses or skin disorders. METHODS: Two hundred and thirty-nine atopic dermatitis patients aged 4-70 years completed the Medical Outcomes Study Short Form-36 Health Survey (SF-36) and the Dermatology Life Quality Index (DLQI) or the Children's Dermatology Life Quality Index. These HRQL scores were compared by self-reported patient disease severity ratings. Health-related quality of life scores were compared with those of the general population and those of patients with other chronic conditions (clinical depression, hypertension, type 2 diabetes) or skin disease (psoriasis). Dermatology Life Quality Index scores were also compared with those of other skin diseases (such as psoriasis, Darier's disease, and Hailey-Hailey disease). RESULTS: Patients with atopic dermatitis had inferior scores on the SF-36 vitality, social functioning, and mental health subscales compared with individuals in the general population. In seven of eight subscales, individuals reporting more severe disease had inferior DLQI and SF-36 scores. Patients with atopic dermatitis had inferior mental health scores compared with those with diabetes or hypertension, and inferior social functioning scores compared with patients with hypertension. When compared with a psoriasis cohort, patients with atopic dermatitis had inferior scores in the role-physical, vitality, social functioning, role-emotional, and mental health SF-36 domains. Patients with atopic dermatitis had similar DLQI scores to patients with other chronic dermatologic diseases. CONCLUSIONS: These results demonstrate that atopic dermatitis has an impact on HRQL, particularly in social functioning and psychological wellbeing. Patient-assessed severity of atopic dermatitis correlates with HRQL decrements, indicating greater HRQL impact with greater disease severity. Atopic dermatitis has as large an impact on HRQL as several chronic conditions and other dermatologic conditions.