Correction: Cost-effectiveness of talazoparib for patients with locally advanced or metastasized breast cancer in Germany.

[This corrects the article DOI: 10.1371/journal.pone.0278460.].

Cost-effectiveness of talazoparib for patients with locally advanced or metastasized breast cancer in Germany.

This study evaluated factors that influence the cost-effectiveness of talazoparib, particularly for patients with a germline breast-cancer-gene-(brca)-mutation and locally advanced or metastasized breast cancer within the context of the German healthcare system. We constructed a partitioned survival model to compare medical costs and treatment effectiveness for patients with such cancers over 45 months. Transition probabilities were derived from survival data from a randomized Phase-III EMBRACA trial, utilities based on published reports, and costs in Euros, which included costs for drug acquisition, clinical monitoring, and treatment of adverse events. Willingness-to-pay thresholds were set to be multiples of the current German per capita gross domestic product. Treatment with talazoparib led to a gain of 0.32 life-years (0.22 quality-adjusted life-years). The mean total cost of €84,003 for talazoparib and €12,741 for standard therapy resulted in an incremental cost-effectiveness ratio of €223,246 per life-year and €323,932 per quality-adjusted life-year gained, indicating that talazoparib is unlikely to be cost-effective at current pricing.

Geriatric assessment for older adults admitted to the emergency department: A systematic review and meta-analysis.

BACKGROUND: Older adults are the most frequent users of emergency services. Comprehensive geriatric assessment (CGA) can help identify high-risk older adults at an early stage. We conducted a systematic review and meta-analysis to identify and evaluate CGA tools used in the emergency department (ED), analyze their predictive validity for adverse outcomes and recommend tools for this particular situation. METHODS: We systematically searched Medline, Web of Science and CENTRAL for eligible articles published in peer-reviewed journals that observed patients ≥65 years admitted to the ED, used at least one assessment tool and reported adverse outcomes of interest. We performed a descriptive analysis and a bivariate meta-analysis of the diagnostic accuracy and predictive validity of the assessment tools for the chosen adverse outcomes. RESULTS: 28 eligible studies were included. The pooled sensitivity (95% CI) of the assessment tools for predicting mortality within short (28-90 days) and long (180-365 days) periods after the first ED visit was 0.77 (0.61-0.89) and 0.79 (0.46-0.96), respectively, with specificity (95% CI) values of 0.45 (0.32-0.59) and 0.37 (0.14-0.65). These findings indicate that the tools used in the included studies had modest predictive accuracy for mortality and were more appropriate for identifying individuals at high risk of readmission in the short term than in the long term. CONCLUSIONS: Early use of assessment tools in the ED might improve clinical decision making and reduce negative outcomes for older adults.

Comparative cost-effectiveness of cabozantinib as second-line therapy for patients with advanced hepatocellular carcinoma in Germany and the United States.

BACKGROUND: Cabozantinib was approved by the European Medicines Agency and the Federal Drug Administration as an option for sorafenib-resistant advanced hepatocellular carcinoma, increasing overall survival and progression-free survival compared with placebo. We evaluated the cost-effectiveness of cabozantinib in the second-line setting for patients with an advanced hepatocellular carcinoma from the German statutory health insurance perspective compared with an US scenario using US prices. METHODS: A Markov model was developed to compare the costs and effectiveness of cabozantinib with best supportive care in the second-line treatment of advanced hepatocellular carcinoma over a lifetime horizon. Health outcomes were measured in discounted life years and discounted quality-adjusted life years. Survival probabilities were estimated using parametric survival distributions based on CELESTIAL trial data. Utilities were derived from the literature. Costs contained drugs, monitoring and adverse events measured in US Dollars. Model robustness was addressed in univariable, scenario and probabilistic sensitivity analyses. RESULTS: Cabozantinib generated a gain of 0.18 life years (0.15 quality-adjusted life years) compared with best supportive care. The total mean cost per patient was $56,621 for cabozantinib and $2064 for best supportive care in the German model resulting in incremental cost-effectiveness ratios for cabozantinib of $306,778/life year and $375,470/quality-adjusted life year. Using US prices generated costs of $177,496 for cabozantinib and $4630 for best supportive care and incremental cost-effectiveness ratios of $972,049/life year and $1,189,706/quality-adjusted life year. CONCLUSIONS: Our analysis established that assuming a willingness-to-pay threshold of $163,371/life year (quality-adjusted life year) for the German model and $188,559/life year (quality-adjusted life year) for the US model, cabozantinib is not cost-effective compared with best supportive care. Sensitivity analyses showed that cabozantinib was not cost-effective in almost all our scenarios.

Estimating extra length of stay due to healthcare-associated infections before and after implementation of a hospital-wide infection control program.

INTRODUCTION: Healthcare-associated infections (HAIs) are a major health concern and have substantial effects on morbidity and mortality and increase healthcare costs. We investigated the effect of a hospital-wide program for the prevention of HAIs on additional length of stay (LOS). METHODS: We analyzed data from a prospective, single-center, quasi-experimental study with two surveillance periods before and after implementation of an infection prevention intervention program. HAI diagnosis was made according to surveillance definition criteria established by the US Centers for Disease Control and Prevention. A multistate model was used to estimate additional LOS for patients with HAI in both surveillance periods. RESULTS: During the first and second periods, 1,568 and 2,336 HAIs were identified among 26,943 and 35,211 patients, respectively. For HAI patients exclusively treated in a general ward, additional LOS was 8.4 (95% confidence interval, CI: 6.8-10.0) days in the first period and 9.6 (95% CI: 8.3-11.0) days in the second period (p = 0.26). For HAI patients treated in both an intensive care unit (ICU) and a general ward, additional LOS was 8.1 (95% CI: 6.3-9.9) days in the first period to 7.3 (95% CI: 6.1-8.5) days in the second period (p = 0.47). CONCLUSIONS: Healthcare-associated infections prolong LOS. A hospital-wide infection control program did not alter the prolongation of LOS.

Economic burden of surgical site infections in patients undergoing cardiac surgery†.

OBJECTIVES: This study aimed to determine the additional costs and length of stay (LOS) due to surgical site infections (SSIs) after coronary artery bypass grafting (CABG) at Jena University Hospital. METHODS: The data of 999 consecutive patients who underwent CABG from January 2013 to December 2014 were collected. We extracted the number, type and duration of antimicrobial therapy and V.A.C.® therapy (negative pressure wound therapy) treatments and calculated the additional SSI-related costs based on the hospital's perspective. We also evaluated the prolongation of LOS using a multistate model and calculated the costs due to the additional LOS. RESULTS: In total, 983 patients were included in our analysis, and 126 patients with SSIs following CABG were identified during the study period; 124 patients with SSIs (98.4%) were discharged alive. The mean cost of antimicrobial therapy to treat the SSIs was €818 [95% confidence interval (CI) 392-1245], and the mean cost of V.A.C. therapy was €1179 (95% CI 748-1610) per infected patient. The mean additional LOS due to SSIs (±standard error) was estimated to be 9.3 ± 2.6 days. The cost per SSI-infected patient attributable to the additional LOS was €9444 (95% CI 4242-14 645). CONCLUSIONS: SSIs following CABG are associated with an additional LOS and a significant economic burden depending on the classification of SSI. A very important component of the additional cost is the prolongation of LOS. Therefore, it is essential to shorten the hospital stay due to SSIs as far as possible.

Cost-effectiveness of allergic rhinitis treatment: An exploratory study.

Allergic rhinitis is serious public health problems and one of the most common chronic diseases worldwide. We aimed to assess the cost-effectiveness of clinically relevant treatment options for allergic rhinitis using evidence-based literature. In addition, we aimed to develop recommendations for allergic rhinitis treatment based on health economic facts. We searched MEDLINE via PubMed from 2009 to 2014 to identify all therapeutic options described in the current literature and selected randomized controlled trials that used a symptom score, had at least one placebo control group and used adult patients. We analyzed the side effects and the number of cases in which treatment was discontinued for each treatment option. Local antihistamines were the most cost-effective local therapy and are recommended due to the low number of complications. Regarding systemic therapies, although the use of oral steroids is indeed significantly cost-effective, this treatment was found to be associated with strong side effects. Sublingual immunotherapy was identified as the most cost-effective immunotherapy and exhibits a good side-effect profile. Overall, local therapy with antihistamines was found to be the most cost-effective option of all therapies. This study showed that there are only minor differences between sublingual and subcutaneous immunotherapy. Based on our results, we recommend the use of an international, uniform nasal symptom score to facilitate the comparison of clinical trials on allergic rhinitis in the future.

Cost-effectiveness of the long-term use of temozolomide for treating newly diagnosed glioblastoma in Germany.

Concomitant radiochemotherapy followed by six cycles of temozolomide (= short term) is considered as standard therapy for adults with newly diagnosed glioblastoma. In contrast, open-end administration of temozolomide until progression (= long-term) is proposed by some authors as a viable alternative. We aimed to determine the cost-effectiveness of long-term temozolomide therapy for patients newly diagnosed with glioblastoma compared to standard therapy. A Markov model was constructed to compare medical costs and clinical outcomes for both therapy types over a time horizon of 60 months. Transition probabilities for standard therapy were calculated from randomized controlled trial data by Stupp et al. The data for long-term temozolomide therapy was collected by matching a cohort treated in the Department of Neurosurgery at Jena University Hospital. Health utilities were obtained from a previous cost utility study. The cost perspective was based on health insurance. The base case analysis showed a median overall survival of 17.1 months and a median progression-free survival of 7.4 months for patients in the long-term temozolomide therapy arm. The cost-effectiveness analysis using all base case parameters in a time-dependent Markov model resulted in an incremental effectiveness of 0.022 quality-adjusted life-years (QALYs). The incremental cost-effectiveness ratio (ICER) was €351,909/QALY. Sensitivity analyses showed that parameters with the most influence on ICER were the health state utility of progression in both therapy arms. Although open-ended temozolomide therapy is very expensive, the ICER of this therapy is comparable to that of the standard temozolomide therapy for patients newly diagnosed with glioblastoma.

Hospital-related cost of sepsis: A systematic review.

OBJECTIVES: This article systematically reviews research on the costs of sepsis and, as a secondary aim, evaluates the quality of economic evaluations reported in peer-reviewed journals. METHODS: We systematically searched the MEDLINE, National Health Service (Abstracts of Reviews of Effects, Economic Evaluation and Health Technology Assessment), Cost-effectiveness Analysis Registry and Web of Knowledge databases for studies published between January 2005 and June 2015. We selected original articles that provided cost and cost-effectiveness analyses, defined sepsis and described their cost calculation method. Only studies that considered index admissions and re-admissions in the first 30 days were published in peer-reviewed journals and used standard treatments were considered. All costs were adjusted to 2014 US dollars. Medians and interquartile ranges (IQRs) for various costs of sepsis were calculated. The quality of economic studies was assessed using the Drummond 10-item checklist. RESULTS: Overall, 37 studies met our eligibility criteria. The median of the mean hospital-wide cost of sepsis per patient was $32,421 (IQR $20,745-$40,835), and the median of the mean ICU cost of sepsis per patient was $27,461 (IQR $16,007-$31,251). Overall, the quality of economic studies was low. CONCLUSIONS: Estimates of the hospital-related costs of sepsis varied considerably across the included studies depending on the method used for cost calculation, the type of sepsis and the population that was examined. A standard model for conducting cost improve the quality of studies on the costs of sepsis.

Economic Evaluation of Interventions for Prevention of Hospital Acquired Infections: A Systematic Review.

OBJECTIVE: This systematic review sought to assess the costs and benefits of interventions preventing hospital-acquired infections and to evaluate methodological and reporting quality. METHODS: We systematically searched Medline via PubMed and the National Health Service Economic Evaluation Database from 2009 to 2014. We included quasi-experimental and randomized trails published in English or German evaluating the economic impact of interventions preventing the four most frequent hospital-acquired infections (urinary tract infections, surgical wound infections, pneumonia, and primary bloodstream infections). Characteristics and results of the included articles were extracted using a standardized data collection form. Study and reporting quality were evaluated using SIGN and CHEERS checklists. All costs were adjusted to 2013 US$. Savings-to-cost ratios and difference values with interquartile ranges (IQRs) per month were calculated, and the effects of study characteristics on the cost-benefit results were analyzed. RESULTS: Our search returned 2067 articles, of which 27 met the inclusion criteria. The median savings-to-cost ratio across all studies reporting both costs and savings values was US $7.0 (IQR 4.2-30.9), and the median net global saving was US $13,179 (IQR 5,106-65,850) per month. The studies' reporting quality was low. Only 14 articles reported more than half of CHEERS items appropriately. Similarly, an assessment of methodological quality found that only four studies (14.8%) were considered high quality. CONCLUSIONS: Prevention programs for hospital acquired infections have very positive cost-benefit ratios. Improved reporting quality in health economics publications is required.

Extra length of stay and costs because of health care-associated infections at a German university hospital.

BACKGROUND: Health care-associated infections (HAIs) can be associated with increased health care costs. We examined extra length of hospital stay (LOS) and associated per diem costs attributable to HAIs in a large academic medical center. METHODS: Data for analysis were acquired in a preinterventional phase of a prospective cohort study (ALERTS) conducted over 12 months in 27 general and 4 intensive care units at Jena University Hospital. HAIs were identified among patients hospitalized for ≥48 hours with at least 1 risk factor for HAI and new antimicrobial therapy; the diagnosis was confirmed by U.S. Centers for Disease Control and Prevention criteria. Extra LOS was estimated by multistate modeling, and associated extra costs were based on average per diem costs for clinical units sampled. RESULTS: Of a total of 22,613 patients hospitalized for ≥48 hours, 893 (3.95%) experienced 1,212 episodes of HAI during 12 months. The associated mean extra LOS ± SEM in general units was 8.45 ± 0.80 days per case and 8.09 ± 0.91 days for patients treated in both general and intensive care units. Additional costs attributable to HAIs were €5,823-€11,840 ($7,453-$15,155) per infected patient. CONCLUSION: HAIs generated substantial extra costs by prolonging hospitalization. Potential clinical and financial savings may be realized by implementing effective infection prevention programs.