Quality-adjusted Survival Research Articles

Tools for Economic Analysis of Patient Management Interventions in Heart Failure Cost-Effectiveness Model: A Web-based program designed to evaluate the cost-effectiveness of disease management programs in heart failure

Heart failure disease management programs can influence medical resource use and quality-adjusted survival. Because projecting long-term costs and survival is challenging, a consistent and valid approach to extrapolating short-term outcomes would be valuable. We developed the Tools for Economic Analysis of Patient Management Interventions in Heart Failure Cost-Effectiveness Model, a Web-based simulation tool designed to integrate data on demographic, clinical, and laboratory characteristics; use of evidence-based medications; and costs to generate predicted outcomes. Survival projections are based on a modified Seattle Heart Failure Model. Projections of resource use and quality of life are modeled using relationships with time-varying Seattle Heart Failure Model scores. The model can be used to evaluate parallel-group and single-cohort study designs and hypothetical programs. Simulations consist of 10,000 pairs of virtual cohorts used to generate estimates of resource use, costs, survival, and incremental cost-effectiveness ratios from user inputs. The model demonstrated acceptable internal and external validity in replicating resource use, costs, and survival estimates from 3 clinical trials. Simulations to evaluate the cost-effectiveness of heart failure disease management programs across 3 scenarios demonstrate how the model can be used to design a program in which short-term improvements in functioning and use of evidence-based treatments are sufficient to demonstrate good long-term value to the health care system. The Tools for Economic Analysis of Patient Management Interventions in Heart Failure Cost-Effectiveness Model provides researchers and providers with a tool for conducting long-term cost-effectiveness analyses of disease management programs in heart failure.

Everolimus plus exemestane versus bevacizumab-based chemotherapy for second-line treatment of hormone receptor-positive metastatic breast cancer in Greece: An economic evaluation study.

BackgroundThe objective of our study was to conduct a cost-effectiveness (CE) study of combined everolimus (EVE) and exemestane (EXE) versus the common clinical practice in Greece for the treatment of postmenopausal women with HR+/HER2- advanced breast cancer (BC) progressing on nonsteroidal aromatase inhibitors (NSAI). The combinations of bevacizumab (BEV) plus paclitaxel (PACL) and BEV plus capecitabine (CAPE) were selected as comparators.MethodA Markov model, consisting of three health states, was used to describe disease progression and evaluate the CE of the comparators from a third-party payer perspective over a lifetime horizon. Efficacy and safety data as well as utility values considered in the model were extracted from the relevant randomized Phase III clinical trials and other published studies. Direct medical costs referring to the year 2014 were incorporated in the model. A probabilistic sensitivity analysis was conducted to account for uncertainty and variation in the parameters of the model. Primary outcomes were patient survival (life-years), quality-adjusted life years (QALYs), total direct costs and incremental cost-effectiveness ratios (ICER).ResultsThe discounted quality-adjusted survival of patients treated with EVE plus EXE was greater by 0.035 and 0.004 QALYs, compared to BEV plus PACL and BEV plus CAPE, respectively. EVE plus EXE was the least costly treatment in terms of drug acquisition, administration, and concomitant medications. The total lifetime cost per patient was estimated at €55,022, €67,980, and €62,822 for EVE plus EXE, BEV plus PACL, and BEV plus CAPE, respectively. The probabilistic analysis confirmed the deterministic results.ConclusionOur results suggest that EVE plus EXE may be a dominant alternative relative to BEV plus PACL and BEV plus CAPE for the treatment of HR+/HER2- advanced BC patients failing initial therapy with NSAIs.Electronic supplementary materialThe online version of this article (doi:10.1186/s12913-015-0971-4) contains supplementary material, which is available to authorized users.

Benefits and risks of contralateral prophylactic mastectomy in women undergoing treatment for sporadic unilateral breast cancer: a decision analysis.

The rate of contralateral prophylactic mastectomy (CPM) is rising rapidly, despite limited evidence about the procedure's relative benefits and harms. The objective of this study is to examine the impact of CPM on life expectancy (LE) and quality-adjusted life expectancy (QALE) in women with sporadic unilateral breast cancer. A Markov model was developed to compare 18 hypothetical cohorts of 45-year-old women with newly diagnosed unilateral, sporadic breast cancer treated with or without CPM. The probability of developing distant metastases by American Joint Committee on Cancer stage and molecular subtype was derived from British Columbia Cancer Agency data. Additional model parameters were identified from the medical literature. Sensitivity analyses were performed to examine the impact of plausible variations in key model parameters on results. CPM improved LE in all cohorts (range 0.06-0.54 years). Stage had more effect on LE than subtype (stage I mean, 0.44 years, stage III mean, 0.11 years). However, after adjusting for quality-of-life, No CPM was favored in all cohorts. Univariate sensitivity analysis demonstrated that the most influential model parameter was the post-CPM health state utility. The preferred strategy shifted from No CPM to CPM when the post-CPM utility exceeded 0.83 (base case value 0.81). PSA indicated that LE gains and QALE decreases were stable in all cohorts. The primary determinant of survival after unilateral breast cancer is stage at diagnosis. Our results suggest that routine CPM would not improve quality-adjusted survival for the majority of women with unilateral sporadic breast cancer.

Modelling the cost-effectiveness of public awareness campaigns for the early detection of non-small-cell lung cancer.

Background:Survival rates in lung cancer in England are significantly lower than in many similar countries. A range of Be Clear on Cancer (BCOC) campaigns have been conducted targeting lung cancer and found to improve the proportion of diagnoses at the early stage of disease. This paper considers the cost-effectiveness of such campaigns, evaluating the effect of both the regional and national BCOC campaigns on the stage distribution of non-small-cell lung cancer (NSCLC) at diagnosis.Methods:A natural history model of NSCLC was developed using incidence data, data elicited from clinical experts and model calibration techniques. This structure is used to consider the lifetime cost and quality-adjusted survival implications of the early awareness campaigns. Incremental cost-effectiveness ratios (ICERs) in terms of additional costs per quality-adjusted life-years (QALYs) gained are presented. Two scenario analyses were conducted to investigate the role of changes in the ‘worried-well' population and the route of diagnosis that might occur as a result of the campaigns.Results:The base-case theoretical model found the regional and national early awareness campaigns to be associated with QALY gains of 289 and 178 QALYs and ICERs of £13 660 and £18 173 per QALY gained, respectively. The scenarios found that increases in the ‘worried-well' population may impact the cost-effectiveness conclusions.Conclusions:Subject to the available evidence, the analysis suggests that early awareness campaigns in lung cancer have the potential to be cost-effective. However, significant additional research is required to address many of the limitations of this study. In addition, the estimated natural history model presents previously unavailable estimates of the prevalence and rate of disease progression in the undiagnosed population.

The PRIME trial: Quality-adjusted survival in patients with RAS wild-type (WT) metastatic colorectal cancer (mCRC) receiving first-line therapy with panitumumab plus FOLFOX versus FOLFOX alone.

3543 Background: The pivotal phase III PRIME trial demonstrated that, compared with FOLFOX alone, panitumumab plus FOLFOX prolongs overall survival (OS) and progression-free survival (PFS) in patie...

Abstract 336: Cost-effectiveness of Implantable Cardiac Monitor-guided Intermittent Anticoagulation for Paroxysmal Atrial Fibrillation

Background: Patients with atrial fibrillation (AF) and stroke risk factors are recommended for treatment with long-term anticoagulation, even when rhythm control interventions result in a low AF burden. A strategy of guiding anticoagulation with novel oral anticoagulants (NOACs) based on daily transmissions from an implantable cardiac monitor (ICM) in CHADS 2 1 or 2 AF patients has recently been explored in a single-arm pilot study. The aim of our study was to evaluate the cost-effectiveness of this strategy versus projected outcomes with the current standard of continuous anticoagulation. Methods: We developed a Markov model using data from the Rhythm Evaluation for AntiCoagulaTion With COntinuous Monitoring (REACT.COM) pilot study (N=59) and previously completed anticoagulant trials to calculate the costs and quality-adjusted life years (QALYs) associated with ICM-guided intermittent anticoagulation for AF vs. standard care. The model time horizon was 3 years (the battery life of an ICM). Health state utilities were estimated from the pilot study population using the SF-12. Costs were based on current Medicare reimbursement. Results: In the pilot study, over 14±4 months of follow-up 18/59 patients were observed to have 35 AF episodes, 60% of which spontaneously terminated and 63% were asymptomatic. The protocol resulted in a >90% reduction in anticoagulant use relative to standard continuous treatment. There were no strokes, 2 (3.4%) TIAs, 2 major bleeding events (on aspirin) and 3 minor bleeding events with the ICM-guided strategy. The model projected total 3-year costs of $10,558 for the ICM-guided strategy vs. $12,898 for literature-based expected outcomes with continuous anticoagulation. Projected QALYs were 2.46 for both groups. Detailed sensitivity and scenario analyses are ongoing. Conclusions: Based on the REACT.COM pilot study, a strategy of intermittent, ICM-guided oral anticoagulation with NOACs was cost-saving relative to expected outcomes with continuous anticoagulation, with equivalent quality-adjusted survival. This strategy requires validation in a larger, randomized study.

Long-term cost-effectiveness of providing full coverage for preventive medications after myocardial infarction.

Adherence to drugs that are prescribed after myocardial infarction remains suboptimal. Although eliminating patient cost sharing for secondary prevention increases adherence and reduces rates of major cardiovascular events, the long-term clinical and economic implications of this approach have not been adequately evaluated. We developed a Markov model simulating a hypothetical cohort of commercially insured patients who were discharged from the hospital after myocardial infarction. Patients received β-blockers, renin-angiotensin system antagonists, and statins without cost sharing (full coverage) or at the current level of insurance coverage (usual coverage). Model inputs were extracted from the Post Myocardial Infarction Free Rx Event and Economic Evaluation trial and other published literature. The main outcome was an incremental cost-effectiveness ratio as measured by cost per quality-adjusted life year gained. Patients receiving usual coverage lived an average of 9.46 quality-adjusted life years after their event and incurred costs of $171,412. Patients receiving full coverage lived an average of 9.60 quality-adjusted life years and incurred costs of $167,401. Compared with usual coverage, full coverage would result in greater quality-adjusted survival (0.14 quality-adjusted life years) and less resource use ($4011) per patient. Our results were sensitive to alterations in the risk reduction for post-myocardial infarction events from full coverage. Providing full prescription drug coverage for evidence-based pharmacotherapy to commercially insured post-myocardial infarction patients has the potential to improve health outcomes and save money from the societal perspective over the long-term. https://www.clinicaltrials.gov. Unique identifier: NCT00566774.

Gemcitabine/dexamethasone/cisplatin vs cytarabine/dexamethasone/cisplatin for relapsed or refractory aggressive-histology lymphoma: cost-utility analysis of NCIC CTG LY.12.

The NCIC CTG LY.12 study showed that gemcitabine, dexamethasone, and cisplatin (GDP) were noninferior to dexamethasone, cytarabine, and cisplatin (DHAP) in patients with relapsed or refractory aggressive histology lymphoma prior to autologous stem cell transplantation. We conducted an economic evaluation from the perspective of the Canadian public healthcare system based on trial data. The primary outcome was an incremental cost utility analysis comparing costs and benefits associated with GDP vs DHAP. Resource utilization data were collected from 519 Canadian patients in the trial. Costs were presented in 2012 Canadian dollars and disaggregated to highlight the major cost drivers of care. Benefit was measured as quality-adjusted life-years (QALYs) based on utilities translated from prospectively collected quality-of-life data. All statistical tests were two-sided. The mean overall costs of treatment per patient in the GDP and DHAP arms were $19 961 (95% confidence interval (CI) = $17 286 to $24 565) and $34 425 (95% CI = $31 901 to $39 520), respectively, with an incremental difference in direct medical costs of $14 464 per patient in favor of GDP (P < .001). The predominant cost driver for both treatment arms was related to hospitalizations. The mean discounted quality-adjusted overall survival with GDP was 0.161 QALYs and 0.152 QALYs for DHAP (difference = 0.01 QALYs, P = .146). In probabilistic sensitivity analysis, GDP was associated with both cost savings and improved quality-adjusted outcomes compared with DHAP in 92.6% of cost-pair simulations. GDP was associated with both lower costs and similar quality-adjusted outcomes compared with DHAP in patients with relapsed or refractory lymphoma. Considering both costs and outcomes, GDP was the dominant therapy.

Cost-effectiveness of heat and moisture exchangers compared to usual care for pulmonary rehabilitation after total laryngectomy in Poland.

The beneficial physical and psychosocial effects of heat and moisture exchangers (HMEs) for pulmonary rehabilitation of laryngectomy patients are well evidenced. However, cost-effectiveness in terms of costs per additional quality-adjusted life years (QALYs) has not yet been investigated. Therefore, a model-based cost-effectiveness analysis of using HMEs versus usual care (UC) (including stoma covers, suction system and/or external humidifier) for patients after laryngectomy was performed. Primary outcomes were costs, QALYs and incremental cost-effectiveness ratio (ICER). Secondary outcomes were pulmonary infections, and sleeping problems. The analysis was performed from a health care perspective of Poland, using a time horizon of 10 years and cycle length of 1 year. Transition probabilities were derived from various sources, amongst others a Polish randomized clinical trial. Quality of life data was derived from an Italian study on similar patients. Data on frequencies and mortality-related tracheobronchitis and/or pneumonia were derived from a Europe-wide survey amongst head and neck cancer experts. Substantial differences in quality-adjusted survival between the use of HMEs (3.63 QALYs) versus UC (2.95 QALYs) were observed. Total health care costs/patient were 39,553 PLN (9465 Euro) for the HME strategy and 4889 PLN (1168 Euro) for the UC strategy. HME use resulted in fewer pulmonary infections, and less sleeping problems. We could conclude that given the Polish threshold of 99,000 PLN/QALY, using HMEs is cost-effective compared to UC, resulting in 51,326 PLN/QALY (12,264 Euro/QALY) gained for patients after total laryngectomy. For the hospital period alone (2 weeks), HMEs were cost-saving: less costly and more effective.

Evaluating the clinical impact of a genomic classifier in prostate cancer using individualized decision analysis.

BackgroundCurrently there is controversy surrounding the optimal way to treat patients with prostate cancer in the post-prostatectomy setting. Adjuvant therapies carry possible benefits of improved curative results, but there is uncertainty in which patients should receive adjuvant therapy. There are concerns about giving toxicity to a whole population for the benefit of only a subset. We hypothesized that making post-prostatectomy treatment decisions using genomics-based risk prediction estimates would improve cancer and quality of life outcomes.MethodsWe developed a state-transition model to simulate outcomes over a 10 year horizon for a cohort of post-prostatectomy patients. Outcomes included cancer progression rates at 5 and 10 years, overall survival, and quality-adjusted survival with reductions for treatment, side effects, and cancer stage. We compared outcomes using population-level versus individual-level risk of cancer progression, and for genomics-based care versus usual care treatment recommendations.ResultsCancer progression outcomes, expected life-years (LYs), and expected quality-adjusted life-years (QALYs) were significantly different when individual genomics-based cancer progression risk estimates were used in place of population-level risk estimates. Use of the genomic classifier to guide treatment decisions provided small, but statistically significant, improvements in model outcomes. We observed an additional 0.03 LYs and 0.07 QALYs, a 12% relative increase in the 5-year recurrence-free survival probability, and a 4% relative reduction in the 5-year probability of metastatic disease or death.ConclusionsThe use of genomics-based risk prediction to guide treatment decisions may improve outcomes for prostate cancer patients. This study offers a framework for individualized decision analysis, and can be extended to incorporate a wide range of personal attributes to enable delivery of patient-centered tools for informed decision-making.

A Markov Decision Model to Guide Treatment of Recurrent Colonic Diverticulitis

Although colonic diverticulitis is a common disorder, there is no clear treatment strategy for patients with recurrent episodes of diverticulitis. We investigated whether colonic resection or conservative or medical treatments have the greatest effects on quality-adjusted life-years (QALYs). A Markov model simulating patients with 2 episodes of non-surgically treated diverticulitis was used to simulate all relevant outcomes of each treatment strategy. A 1-year cycle length with 10-year follow-up period was used to allow for chance of recurrent diverticulitis. Primary outcome was QALYs gained from each strategy. Factors considered were morbidity, mortality, chance of colostomy formation, risk of recurrence, and persistence of abdominal pain. The probabilities of clinical events were determined by using the best available published data. A strategy in which colonic resection was performed after 2 episodes of diverticulitis was associated with the lowest quality-adjusted survival (a gain of 8.66 QALYs) and highest chance of stoma formation (1.1%) but the lowest chance of a mild (3.5%) or severe (1.1%) recurrence. The strategies of colonic resection or conservative or medical treatment after the third episode of diverticulitis were comparable in terms of quality-adjusted survival, providing 8.78, 8.76, and 8.74 QALYs, respectively. Probabilistic sensitivity analysis did not change these results. Persistent abdominal complaints were lowest in the medical treatment strategy. Elective surgery after 2 episodes of diverticulitis should be questioned in terms of QALYs. After the third episode of diverticulitis, surgical or conservative or medical treatments provide similar QALYs, but rates of abdominal symptoms are lower with the medical treatment strategy. This Markov decision model has limitations when the individual patient and physician face a complex decision weighing early and long-term risks and benefits of elective surgery or conservative management.

An economic analysis of autologous hematopoietic stem cell transplantation (AHSCT) in the treatment of new onset type 1 diabetes.

Autologous hematopoietic stem cell transplantation (AHSCT) is an emerging treatment option in new onset type 1 diabetes (T1DM), leading to a remission of the T1DM for a longer time period in up to 50 % of patients. The aim of the study was to analyze the cost-effectiveness of this treatment option compared with standard insulin therapy. The medical records of patients who had undergone immunoablation with AHSCT for new onset T1DM were analyzed for the cost-effectiveness of the treatment using the IMS CORE Diabetes Model. The expected survival of patients with T1DM treated solely with insulin (without transplantation) was estimated to be 34.4 years, and their quality-adjusted survival was 13.8 QALY, whereas the expected survival of the patients treated with AHSCT was 34.9 years when the HbA1c benefit over standard treated patients lasted for 2, 35.4 years with 8-year benefit and even up to 40.3 years with the lifelong benefit scenario. Values under the threshold of ICER were reached after 8 years of sustained benefit in terms of HbA1c concentration. If discounting was not applied, the threshold values were reached after 3 years of HbA1c benefit over the standard group, independent of insulin use after transplantation. The results of our study show that hematopoietic stem cell transplantation could be cost-effective in treating new onset T1DM, providing that the benefits of the transplantation lasted over 3-8 years, depending on application of discounting.

Quality-adjusted survival in patients with RAS wild-type (WT) metastatic colorectal cancer (mCRC) receiving first-line therapy with panitumumab plus FOLFOX versus FOLFOX alone in the PRIME trial.

537 Background: The pivotal phase III PRIME trial demonstrated that, compared with FOLFOX alone, panitumumab plus FOLFOX prolongs overall survival and progression-free survival in patients with RASWT mCRC without having a detrimental effect on overall quality of life. The objective of this analysis was to use the quality-adjusted time without symptoms of disease or toxicity of treatment (Q-TWiST) method to compare quality-adjusted survival between the treatment arms of PRIME. Methods: Patients with RASWT mCRC from each treatment arm of PRIME were included in this analysis, and the area under the survival curve (AUSC) was estimated using the nonparametric Kaplan-Meier method (48 months follow-up). The AUSC was partitioned into three health states: toxicity (TOX), time without symptoms of disease progression or toxicity (TWiST, i.e., PFS minus TOX), and relapse (REL, i.e., OS minus PFS). The durations of the health states were then adjusted using utility weights derived from patient-reported EuroQoL 5 measures. The null hypothesis of no difference between treatment arms was tested based on the normal approximation, with standard errors calculated by the bootstrap method. In the primary analysis, TOX consisted of grade 3 and 4 adverse events. A sensitivity analysis, with grade 2, 3, and 4 adverse events classified as TOX, was performed. Results: Of 1,183 patients with mCRC who were randomized, 512 patients had RAS WT tumors (panitumumab plus FOLFOX, n=259; FOLFOX alone, n=253) and were included in this analysis. Patients receiving panitumumab plus FOLFOX had a significantly longer Q-TWiST (20.5 months) than patients receiving FOLFOX alone (18.2 months) resulting in 2.3 ± 1.0 (SE) additional quality-adjusted months (p&lt;0.03). The sensitivity analysis yielded similar results, indicating that the analysis was robust. Conclusions: This Q-TWiST analysis showed that in a previously untreated RAS WT mCRC population, patients treated with panitumumab plus FOLFOX had a significantly improved duration of quality-adjusted survival compared with patients treated with FOLFOX alone. Clinical trial information: NCT00364013.

High-dose chemotherapy followed by autologous haematopoietic cell transplantation for children, adolescents and young adults with first recurrence of Ewing sarcoma

BACKGROUND Ewing sarcoma is a solid tumour, which is the second most common primary bone malignancy in children, often occurring in the long bones and pelvis. An incidence rate of 4.5 per million a year is reported, with a peak incidence of 11 per million at the age of 12 years. Despite more intensive chemotherapy, 30% to 40% of young people with Ewing sarcoma will have recurrence of the disease. Less than 30% of young people with a recurrence of Ewing sarcoma are alive at 24 months, and less than 10% are alive at 48 months. High-dose chemotherapy (HDC), followed by autologous haematopoietic cell transplantation (AHCT), is used in a variety of paediatric groups with diverse solid tumours. The hypothesis is that HDC regimens may overcome resistance to standard polychemotherapy, and this way may eradicate minimal residual disease, leading to improved survival after a first recurrence of disease. OBJECTIVES To assess the efficacy of HDC with AHCT versus conventional chemotherapy in improving event-free survival, overall survival, quality-adjusted survival, and progression-free survival in children, adolescents, and young adults with first recurrence of Ewing sarcoma, and to determine the toxicity of the treatment. SEARCH METHODS We searched CENTRAL, MEDLINE, Embase, conference proceedings from the SIOP, ASPHO, CTOS, ASBMT, EBMT, and EMSOS, and two trial registries in January 2020. We also searched reference lists of relevant articles and review articles. SELECTION CRITERIA We planned to include randomised controlled trials (RCTs) or (historical) controlled clinical trials (CCTs) comparing the effectiveness of HDC plus AHCT with conventional chemotherapy for children, adolescents, and young adults (up to 30 years old at the date of diagnostic biopsy) with a first recurrence of Ewing sarcoma. DATA COLLECTION AND ANALYSIS We used standard methodological procedures expected by Cochrane. MAIN RESULTS We did not identify any eligible studies. AUTHORS' CONCLUSIONS Since we did not identify any eligible studies, we are unable to draw any conclusions about the efficacy and toxicity of HDC with AHCT versus conventional chemotherapy in children, adolescents, and young adults with a first recurrence of Ewing sarcoma. Further high-quality research is urgently needed.

Iron Supplementation Adjunct to Erythropoiesis Stimulating Agents Is Cost Saving for Chemotherapy-Related Anemia in the Era of Biosimilars

▪Background: International guidelines recommend erythropoiesis stimulating agents (ESA) to improve chemotherapy-related anemia (CRA), however, two meta-analyses proved that intravenous iron (II) improves the chance of obtaining a response to ESA by 28% (Gafter-Gvili 2013, Petrelli 2012). Recently, biosimilar ESAs have been approved for CRA, we therefore aimed at comparing the cost-effectiveness of different therapeutic strategies for CRA eventually including II and/or biosimilar ESAs.Methods: A decision model was built comparing 5 strategies: no ESA, brand ESA, brand ESA plus II, biosimilar ESA, biosimilar ESA plus II. Ferric gluconate was assumed to be administered 125 mg per week for 6 weeks overall: 4 infusions were planned in days different from chemotherapy administration. ESA was started at hemoglobin values lower than 11 g/dl. The model included a Markov tree of 13 health states representing hemoglobin level during 26 therapy weeks. Weekly probability of hemoglobin improvement by 1 g/dL was estimated to be 10% with ESA and 15% with ESA plus II but null without ESA. The efficacy of biosimilar ESA was assumed to be the same as ESA. Weekly probability of death was assumed to be 0.4% (Pedrazzoli 2008). The rate of severe events during II infusion was assumed to be 0.2% per week without fatal events. Quality of life at different hemoglobin levels was driven from literature. The economic analysis was run in the perspective of the Health Care System and of the society. II administration was charged €50 and blood transfusion €400. Indirect costs for iron infusions and transfusions planned in days not devoted to chemotherapy was estimated to be €100 for transportation and care-giver time. Based on local data, the per-unit cost of biosimilar ESA versus brand ESA was considered to be 1 in 5.All the analyses were run TreeAgePro2014. Microsimulations and first-order MonteCarlo analysis were run.Results: ESA improve quality-adjusted survival of patients from 14.51 to 14.82 quality-adjusted weeks but II adjunct increased the gain to 15.20 weeks. In the perspective of the health-care system, the management of cancer-related anemia without ESA costs €1,550, while ESA therapy increased the costs by €618 (biosimilars) and €2,933 (brand); ESA plus II increased the costs by €359 and €2,437, respectively. Therefore, the adjunct of II reduced overall health-care costs by €259 in the biosimilar strategy and €496 in the brand ESA strategy. Societal costs similarly increased with ESA use, but the increment was lower: €584 with biosimilar ESA and €2,866 with brand ESA. II allowed to achieve minimal savings in the biosimilar strategy, while savings were €288 in the brand ESA strategy. Savings to the health-care system and to the society were even higher (further €300 to the healthcare-system and €90 to the society) in the hypothesis that liposomial oral iron (30 mg per day for 60 days) achieved similar results as II, at €1 per day charged to the patient (in Italy liposomal iron it is not refunded). Ferric carboxymaltose 750 mg single administration at a cost of €280 might compete with multiple ferric gluconate administrations. Finally, we explored the efffect of threshold hemoglobin: starting ESA at hemoglobin levels lower than 10 g/dl instead of 11 g/dl allowed to reduce health-care costs of ESA therapy by €172, but quality of life was increased by only 0.14 and 0.59 weeks, without and with II, respectively.Conclusions: Rational allocation of health-care resources imposes to choose the most convenient therapeutic strategy among those recommended by practice guidelines. Intravenous iron allows to save health-care and society resources and to improve quality of life by a more rapid hematopoietic response to ESA. Different iron formulations need to be tested in association with ESA in this setting in order to improve the efficiency of avilable therapeutic strategies. Cost-effectiveness analyses should be shared by clinicians and hospital pharmacy to adopt the most effective and efficient therapeutic strategies. DisclosuresNo relevant conflicts of interest to declare.

Risk-Benefit Trade-Off of Pediatric-Inspired Versus Hyper-CVAD Protocols for Philadelphia Negative Acute Lymphocytic Leukemia (ALL) in Adolescents and Young Adults: A Modeling Analysis

BackgroundAlthough treatment outcomes for childhood acute lymphocytic leukemia (ALL) have dramatically improved in recent years, treatment outcomes in adolescents and young adults (AYA, ages 16-39) have remained inferior due to unfavorable cytogenetic features associated with increasing age and differences in treatment for this population. Pediatric-inspired protocols include L-asparaginase for induction and intensification phases, which are thought to be less tolerable and to lead to increased adverse events in adults. As a result, they are not widely used in the AYA population. Although non-comparative studies suggest improved survival in AYA patients treated with pediatric-inspired protocols, the long-term risk-benefit profile of treating AYAs with a pediatric-inspired ALL protocol is unknown. We utilized an exploratory decision-analytic approach to model the survival and quality-adjusted survival of a pediatric-inspired protocol versus hyper-CVAD, a widely utilized adult protocol, in AYA patients with Philadelphia negative ALL.MethodsPatient outcomes were simulated using a 6-state Markov model including complete response (CR), no CR, first relapse, second CR, second relapse, and death. Hyper-CVAD protocol outcomes were modeled by fitting a Weibull distribution to the progression free survival curve of AYA patients from a single-center study of 288 patientsa; we utilized comparable patient data from a retrospective study of 85 patients treated with a pediatric-inspired regimenb to estimate a relative progression difference (HR = 0.51), and used this estimate to model survival for pediatric-inspired protocol patients. We estimated health state utilities (quality of life) based on treatment stage, and assumed the pediatric protocol had a 0.10 disutility compared to hyper-CVAD prior to the maintenance phase of treatment. Our analysis compared total life years and quality-adjusted life years (QALYs) between treatment protocols at 1 year, 5 years, and 10 years. [Display omitted] ResultsTreatment with the pediatric-inspired protocol led to a 0.04 increase in life years but a 0.01 decrease in QALYs at 1 year. By years 5 and 10, the pediatric-inspired protocol resulted in 0.18 and 0.24 increases in life years and 0.25 and 0.32 increases in QALYs, respectively, relative to hyper-CVAD. The lower quality of life associated with the induction and intensification phases of pediatric treatment was largely offset by more favorable progression-free survival and overall survival in comparison to hyper-CVAD.TableOutcomePediatricHyper-CVADDifference1 YearLife Years0.8150.7740.041QALYs0.5070.513-0.0065 YearsLife Years1.8821.6330.250QALYs1.3621.1790.18210 YearsLife Years2.1201.8020.318QALYs1.5641.3240.241ConclusionsOur exploratory analysis suggests Philadelphia negative AYA patients treated with a pediatric-inspired protocol experience a decrease in QALYs versus hyper-CVAD during the initial stages of treatment for ALL. However, the pediatric protocol leads to an increase in life years throughout all treatment stages and an increase in QALYs in the long-term following the initial stages of treatment. Ongoing work will incorporate treatment and adverse event costs to estimate the cost-effectiveness of pediatric-inspired versus hyper-CVAD protocols.a Kantarjian H. et al. Cancer 2004; 2788-801.b Storring JM, et al. BJH 2009; 76-85.Analysis support: This analysis was supported by Jazz Pharmaceuticals. DisclosuresGuzauskas:Jazz Pharmaceuticals: Consultancy. Villa:Jazz Pharmaceuticals: Employment, Equity Ownership. Off Label Use: Defibrotide is an investigational treatment for hepatic veno-occlusive disease in the United States.. Vanhove:Jazz Pharmaceuticals: Employment, Equity Ownership. Veenstra:Jazz Pharmaceuticals: Consultancy.

Cost-Effectiveness of Kidney Transplantation From DCD in Italy

IntroductionKidney transplantation represents the best therapeutic option for patients with end-stage renal disease (ESRD), providing the best outcomes for survival, quality of life, and cost-effectiveness. To increase kidney donations, in 2007, the Italian IRCCS Policlinico San Matteo Foundation in Pavia designed and conducted Programma Alba, a protocol for organ donation after cardiac death (DCD). This study evaluated the costs and health outcomes of DCD transplantation and in all types of transplants compared with current clinical practice. Patients and MethodsA Markov-based model was used to assess costs and health outcomes for new ESRD patients for 2008 to 2013. A health care founder perspective was used. Data sources were the Italian National Institute of Statistics and the Lombardy Registry of Dialysis and Transplantation. A microcosting analysis was performed to calculate costs related to clinical pathways for DCD. We assessed costs, survival, quality-adjusted survival, and cost-effectiveness. FindingsChanging the actual practice pattern for new patients with ESRD and increasing the availability of kidneys from DCD to 10 extra transplants per year will induce an incremental cost per quality-adjusted life-year of €4255. Increases in transplantation to reach an extra 10% by transplant type would result in reduced costs and increased patient survival and quality of life compared with the current scenario. InterpretationOur data show that increasing DCD transplants would result in a cost-effective policy to expand the kidney donor pool compared with current ESRD treatment patterns. Italian policies should make an effort to increase transplant rates to optimize cost-effectiveness in ESRD service supply.

Economic evaluation of ivabradine in the treatment of chronic heart failure in Greece.

BackgroundThe objective of our study was to assess the cost-effectiveness of ivabradine plus standard care (SoC) in chronic heart failure (CHF) patients with sinus rhythm and a baseline heart rate ≥ 75 b.p.m. in Greece, in comparison with current SoC alone.MethodsAn existing cost-effectiveness model consisting of two health states, was adapted to the Greek health care setting. All clinical inputs of the model (i.e. mortality rates, hospitalization rates, NYHA class distribution and utility values) were estimated from SHIFT trial data. All costing data used in the model reflects the year 2013 (in €). An incremental cost effectiveness ratio (ICER) per quality-adjusted life year (QALY) gained was calculated. Deterministic and probabilistic sensitivity analyses (PSA) were conducted. The horizon of analysis was over patient life time and both cost and outcomes were discounted at 3.5% per year. The analysis was conducted from a Greek third party-payer perspective.ResultsThe Markov analysis revealed that the discounted quality-adjusted survival was 4.27 and 3.99 QALYs in the ivabradine plus SoC and SoC alone treatment arms, respectively. The cumulative lifetime total cost per patient was €8,665 and €5,873, for ivabradine plus SoC and SoC alone, respectively. The ICER for ivabradine plus SoC versus SoC alone was estimated as €9,986 per QALY gained. The PSA showed that the likelihood of ivabradine plus SoC being cost-effective at a threshold of €36,000/QALY was found to be 95%.ConclusionsIvabradine plus SoC may be regarded as a cost-effective option for the treatment in CHF patients in Greece.Electronic supplementary materialThe online version of this article (doi:10.1186/s12913-014-0631-0) contains supplementary material, which is available to authorized users.

Effect of intermittent pneumatic compression on disability, living circumstances, quality of life, and hospital costs after stroke: secondary analyses from CLOTS 3, a randomised trial

The results of the CLOTS 3 trial showed that intermittent pneumatic compression (IPC) reduced the risk of deep vein thrombosis and improved survival in immobile patients with stroke. IPC is now being widely used in stroke units. Here we describe the disability, living circumstances, quality of life, and hospital costs of patients in CLOTS 3. In CLOTS 3, a parallel group trial in 94 UK hospitals, immobile patients with stroke from days 0 to 3 of admission were assigned with a computer-generated allocation sequence in a 1:1 ratio to IPC or no IPC through a central randomisation system. We followed up patients at about 6 months with postal or telephone questionnaire to assess the secondary endpoints: disability (Oxford Handicap Scale [OHS]), living circumstances, health-related quality of life (EQ5D-3L), and hospital costs (based on use of IPC and length of hospital stay). Patients and carers who completed the postal questionnaires were not masked to treatment allocation, but telephone follow-up in non-responders was masked. All analyses were by intention to treat. This trial is registered, number ISRCTN93529999. Between Dec 8, 2008, and Sept 6, 2012, we enrolled 2876 patients, with 1438 in each group. Despite the previously reported reduction in the risk of proximal deep vein thrombosis at 30 days (primary endpoint), there were no significant differences in disability (OHS 0-2 vs 3-6, adjusted odds ratio [OR] 0·98, 95% CI 0·80 to 1·19, p=0·83; adjusted ordinal analysis common OR 0·97, 95% CI 0·86 to 1·11), living circumstances (institutional care vs not; adjusted OR 1·11, 95% CI 0·89 to 1·37; p=0·358), or health-related quality of life (median utility value 0·26, IQR -0·07 to 0·66 with IPC, and 0·27, -0·06 to 0·64, with no IPC; p=0·952). The estimated cost of IPC was £64·10 per patient (SD 28·3). The direct costs of preventing a deep vein thrombosis and death were £1282 (95% CI 785 to 3077) and £2756 (1346 to not estimable), respectively, with IPC. Hospital costs increased by £451 with IPC compared with no IPC because of a longer stay in hospital (mean 44·5 days [SD 37·6] vs 42·8 days [37·2]; mean difference 1·8 days, 95% CI -1·0 to 4·5). By 6 months, despite an increase in survival (IPC 152·5 days [SD 60·6] vs no IPC 148·1 days [64·3]; mean difference 4·5 days, 95% CI -0·2 to 9·1), there was a non-significant increase in quality-adjusted survival associated with IPC (IPC 27·6 days [SD 40·6] vs no IPC 26·7 days [39·6]; mean difference 0·9 days, 95% CI -2·1 to 3·9). IPC is inexpensive, prevents deep vein thrombosis, improves survival but not functional outcomes, and does not lead to a significant gain in quality-adjusted survival. When deciding whether to treat patients with IPC, clinicians need to take into account all these potential effects. National Institute of Health Research Health Technology Assessment Programme, Chief Scientist Office of Scottish Government, and Covidien.

Gasless laparoscopically assisted transhiatal esophagectomy for upper esophageal carcinoma.

Transhiatal esophagectomy frequently is thought to achieve lower morbidity by sacrificing long-term survival at 5 years. With the introduction of the isobaric laparoscopy using abdominal wall lifting, the authors explore gasless laparoscopically assisted transhiatal surgical treatment of upper thoracic or cervical esophageal carcinoma after neoadjuvant chemotherapy. They wish it not only lower morbidity but also similarity to transthoracic esophagectomy, with extended en bloc lymphadenectomy in aspects of median overall, disease-free, and quality-adjusted survival. Between 2011 and 2013, 11 patients with upper thoracic or cervical esophageal carcinoma were treated at the authors' department. Neoadjuvant chemotherapy was administered to these patients. Their clinical data were retrospectively analyzed. The tumor originated from the cervical esophagus in eight of these patients and from upper thoracic esophagus in three of them. None of the patients were receiving preoperation radiotherapy. No operation-related deaths or conversion to open procedure occurred. The mean operative time was 146.0 ± 22.2 min, and the mean intraoperative blood loss was 192.7 ± 25.5 ml. Anastomotic leakage occurred in three cases, pulmonary complications in one case, cardiac complications in two cases, and herniation of part of the colon into the right thorax in one case. Two patients received postoperative auxiliary radiotherapy. All the patients were followed up for 6 months to 3.5 years. During the follow-up period, three patients experienced pulmonary complications at least once. All the patients reported heartburn and regurgitation from time to time after surgery. The survival rate was 63.6%. With neoadjuvant chemotherapy, gasless laparoscopically assisted transhiatal esophagectomy provides a minimally invasive surgical treatment for upper thoracic or cervical esophageal carcinoma. But it seems that the postoperative complications are relatively high. Further study is needed to determine whether it can improve long-term survival.