Real-world costs of transvenous lead extraction: the challenge for reimbursement.

AIMS: Transvenous lead extraction is challenging, often requiring specialist equipment and prolonged hospital admission. A single tariff or itemized costs may be available for reimbursement. Due to limited data relating to the costs of transvenous extraction, it is unclear whether either form of reimbursement is adequate. We aim to describe accurately the total real-world costs of managing patients undergoing transvenous extraction at a single, large centre. We further aim to consider the additional costs of device reimplantation. METHODS AND RESULTS: At a single UK extraction centre, a retrospective, patient level service line analysis was undertaken, during a complete financial year. Seventy-four patients required transvenous extraction (47 infected and 27 non-infected; 156 leads). Sixty-nine procedures (93%) were performed under general anaesthesia, with a median time in theatre of 95 min [interquartile range (IQR) 71-120]. Specialist extraction tools were required for 130 leads (83%). The median hospitalization duration was 3 days (IQR 1-8). The mean cost of extraction was £9228 (±4099); infected £10 727 (±4178) and non-infected £6619 (±2269). With the additional costs of device reimplantation, the overall mean cost rose to £17 574 (±12 882); infected £22 615 (±13 343) and non-infected £8801 (±5007). At the time of this study, the UK NHS tariff was £2530 for elective and £4764 for non-elective extraction, covering barely half of the real costs. CONCLUSION: We demonstrated a substantial difference between the real-world cost of extraction and the UK NHS tariff. Extracting centres should scrutinize their practice, including the timing of reimplantation.

Trastuzumab uptake in HER2-positive breast cancer patients: a systematic review and meta-analysis of observational studies.

Overexpression of the HER2 gene is predictive of treatment benefit with trastuzumab therapy for breast cancer (BC) patients. The study objective was to investigate whether all eligible patients with HER2-positive BC initiated trastuzumab therapy. A systematic search was conducted through PubMed, Web of Science PsycINFO, Cumulative Index to Nursing and Allied Health Literature (CINAHL) and Cochrane Library. From 2651 studies identified, 107 observational studies were included for full text review, of which 26 met the inclusion criteria and an additional 7 studies were identified through citation searching. Two independent reviewers extracted data for accuracy and completeness. From 33 observational studies, 14,644 patients were exposed to trastuzumab therapy. Age range varied across studies; the youngest cohort had a median age of 50 and the oldest had a median age of 84. Sample sizes ranged from 11 to 1928 and included patients from 10 countries. Studies were heterogenous and few studies accounted for confounders. We identified large variability in uptake of trastuzumab in HER2-positive early BC patients (9.1-100%) and metastatic BC patients (50.8-84.0%). The pooled uptake was 71.3% (95% CI 64.6-77.9%), with high heterogeneity (I2 = 99.05%). The most conservative predictors of higher uptake included younger age (OR 2.09; 95% CI 1.36-3.20) and lower Charlson Comorbidity Index of patients (OR 1.62; 95% CI 1.32-1.99). In addition, tumour characteristics including higher tumour grade (OR 1.73; 95% CI 1.23-2.45), larger tumour size (OR 1.80; 95% CI 1.54-2.10), advanced tumour stage (OR 2.07; 95% CI 1.44-2.96) and hormone receptor negative tumor (OR 1.54; 95% CI 1.35-1.77) were associated with higher uptake. The uptake of trastuzumab therapy varied widely between studies and across subgroups suggesting that there may be some inequalities in the use of this agent. However, our findings should be interpreted with caution due to study heterogeneity and potential confounding, and thus additional studies of individual level data which control for confounders are needed to understand more about inequalities in uptake.

Utilization and Expenditure of Anti-cancer Medicines in Kosovo: Findings and Implications.

BACKGROUND AND OBJECTIVE: The Ministry of Health (MoH) leads and organizes health policy in Kosovo, which includes procurement and provision of medicines, including anti-cancer medicines, which compose a special group of medicines. However, there has been limited analysis of the utilization and expenditure on anti-cancer medicines in Kosovo; consequently, the objective of this study is to undertake research to provide future guidance on the use of anti-cancer medicines. METHOD: National drug utilization data is available in Kosovo. Utilization and expenditure on anti-cancer medicines [Anatomical Therapeutic Chemical (ATC) code L], initially from 2011 to 2013, especially for anti-cancer medicines on the essential medicines list was analysed from national data. In addition, current systems for procuring and managing anti-cancer medicines in Kosovo was documented. RESULTS: There was appreciable variability in the utilization of anti-cancer medicines over the years, with low or limited use of some anti-cancer medicines on the Essential Medicine List. This is a concern in view of their essential medicine status. From 2011 to 2013, €16.49 million was spent on anti-cancer medicines (ATC L). The process of selection of new medicines begins with suggestions from doctors at the University Clinical Centre in Kosovo. CONCLUSION: The analysis has shown appreciable variation with current utilization patterns for anti-cancer medicines in Kosovo. This needs to be addressed as part of improving the drug management process to optimize patient care within available resources. Future years and reforms need to be assessed to improve current utilization and expenditure patterns.

The Implementation of Managed Entry Agreements in Central and Eastern Europe: Findings and Implications.

BACKGROUND: Managed entry agreements (MEAs) are a set of instruments to facilitate access to new medicines. This study surveyed the implementation of MEAs in Central and Eastern Europe (CEE) where limited comparative information is currently available. METHOD: We conducted a survey on the implementation of MEAs in CEE between January and March 2017. RESULTS: Sixteen countries participated in this study. Across five countries with available data on the number of different MEA instruments implemented, the most common MEAs implemented were confidential discounts (n = 495, 73%), followed by paybacks (n = 92, 14%), price-volume agreements (n = 37, 5%), free doses (n = 25, 4%), bundle and other agreements (n = 19, 3%), and payment by result (n = 10, >1%). Across seven countries with data on MEAs by therapeutic group, the highest number of brand names associated with one or more MEA instruments belonged to the Anatomical Therapeutic Chemical (ATC)-L group, antineoplastic and immunomodulating agents (n = 201, 31%). The second most frequent therapeutic group for MEA implementation was ATC-A, alimentary tract and metabolism (n = 87, 13%), followed by medicines for neurological conditions (n = 83, 13%). CONCLUSIONS: Experience in implementing MEAs varied substantially across the region and there is considerable scope for greater transparency, sharing experiences and mutual learning. European citizens, authorities and industry should ask themselves whether, within publicly funded health systems, confidential discounts can still be tolerated, particularly when it is not clear which country and party they are really benefiting. Furthermore, if MEAs are to improve access, countries should establish clear objectives for their implementation and a monitoring framework to measure their performance, as well as the burden of implementation.

Evaluating the use of plerixafor in stem cell mobilisation - an economic analysis of the PHANTASTIC trial.

Plerixafor is an effective haematopoietic stem cell mobilising agent in candidates for autologous transplantation, including patients with myeloma and lymphoma. Here we compare 98 plerixafor recipients in the PHANTASTIC trial with 151 historic controls mobilised by conventional chemotherapy (each with granulocyte colony-stimulating factor, G-CSF). Seventy (71.4%) plerixafor-mobilised patients achieved the composite primary endpoint of ≥4 × 10(6) CD34+ cells kg(-1) in ≤2 aphereses and no clinically significant neutropenia, compared to 48 (31.8%) historic controls (P < 0.001), and this significant advantage was maintained in scenario analyses testing components of this composite endpoint. A patient-level cost analysis was undertaken for 249 patients, which included the cost of remobilising patients where initial mobilisation had failed. Combined mean treatment cost for plerixafor mobilised patients was £12,679 compared with £11,694 for historical controls. However, plerixafor produces an average saving of £3,828 per lymphoma patient but average cost increase by £5,245 per myeloma patient. The present data demonstrate cost-effectiveness for plerixafor as a first line mobilisation agent, certainly for lymphoma patients, where substantial resource savings and achievement of the primary endpoint are likely. J. Clin. Apheresis 31:434-442, 2016. © 2015 Wiley Periodicals, Inc.

A Single-Center Randomized Trial of Intraoperative Zero-Balanced Ultrafiltration During Cardiopulmonary Bypass for Patients With Impaired Kidney Function Undergoing Cardiac Surgery.

OBJECTIVES: The authors investigated whether zero-balance ultrafiltration (Z-BUF) during bypass significantly improves clinical and cost outcomes or biomarkers of kidney injury for patients with preoperative kidney impairment (estimated glomerular filtration rate [eGFR]<60 mL/minute) undergoing cardiac surgery. DESIGN: A single-center randomized controlled trial recruited, patients between 2010 and 2013, with a 12-months follow-up. SETTING: Hospital. PARTICIPANTS: One hundred ninety-nine patients undergoing cardiac surgery with cardiopulmonary bypass (CPB). INTERVENTIONS: Patients were assigned randomly to receive zero-balance ultrafiltration (Z-BUF) or not, with stratification for degree of kidney dysfunction and diabetes. MEASUREMENTS AND MAIN RESULTS: The authors assessed clinical efficacy and kidney function biomarkers. Cumulative probability of discharge from the intensive care unit (ICU) was assessed by Kaplan-Meier plots and was found not to be significantly different between the two trial arms (p = 0.61). After adjusting for EuroSCORE, diabetes, eGFR, cardioplegia types and type of surgery in a Cox proportional hazard model, hazard ratios (HR) for ICU length of stay between the Z-BUF and no-Z-BUF groups was not significantly different: HR (95% CI): 0.89 (0.66, 1.20; p = 0.44). In contrast, significant reductions in postoperative chest infections and the composite of clinical endpoints (death, strokes, and myocardial infarctions) in the Z-BUF group were observed. In addition, Z-BUF significantly abrogated the rise in the kidney damage markers urinary NGAL/creatinine ratio, urea, creatinine and eGFR during CPB and adverse events risks. CONCLUSIONS: Z-BUF during bypass surgery is associated with significant reductions in morbidity and biomarkers of CPB-induced acute kidney injury soon after CPB, which are indicative of clearance of inflammatory/immune mediators from the circulation.

Optimizing decision making and resource allocation in palliative care.

Optimizing resource allocation in end-of-life care is one of the most difficult issues currently being addressed within the U.K. National Health Service. Decision rules and cost-effectiveness thresholds that would appear to be appropriate for acute interventions may significantly under value extensions in quantity and quality of life provided to the terminally ill. Arguably, the value placed on improving quantity and quality of life is dependent on the context in which they are derived. In such circumstances, we can either adjust cost-effectiveness thresholds to ensure that end-of-life interventions have a less stringent cost-effectiveness hurdle to overcome or we can derive an entirely new evaluative framework that better captures the true value of interventions focusing primarily on care rather than cure. Irrespective of the approach taken, optimizing resource allocation in palliative care is crucial in ensuring that overall therapeutic objectives both for individual patients and for this patient group as a whole are achieved to the greatest degree possible.

Using disease registries for pharmacoepidemiological research: a case study of data from a cystic fibrosis registry.

BACKGROUND: The Epidemiologic Registry of Cystic Fibrosis (ERCF) was a multicentre, longitudinal follow-up project of cystic fibrosis patients enrolled at some 200 centres in nine European countries between 1994 and 1999. PURPOSE: We aimed to assess and improve the quality of a subset of data from the ERCF relating to seven English centres (1184 patients), prior to using the data for a long-term cost-effectiveness analysis of dornase alfa (Pulmozyme). Specifically we wanted to assess the completeness and accuracy of the data and the comparability of cases across centres. METHODS: We used a subset of ERCF data relating to seven UK cystic fibrosis (CF) centres. Following initial data editing, key variable data from a sample of patients from five centres were subjected to a detailed verification of ERCF data against original data sources available in the centres. Disagreements between ERCF reports and original data sources were identified and corrected in the study dataset. In addition, centre staff were questioned about relevant clinical and recording practices. RESULTS: Thanks to detailed routine data checking procedures on key variables operated by the ERCF, the rates of disagreement between ERCF data and original data as identified in our verification process on the assessed variables are generally low (0.4-3.7%). Some outcome variables (deaths, hospitalisations) seem to be under-reported by some centres. Episodes of pulmonary exacerbation are difficult to identify and also to verify. Twenty-four patients were registered twice (consecutively in two different centres). There were some differences between centres in their interpretation of recording rules. CONCLUSIONS: Researchers seeking to use disease registry data should consider detailed data quality review processes. Apart from data accuracy, reliable definitions of both critical events as well as their timing are important. The degree of under-reporting, particularly of outcome variables, should be estimated. Information on local clinical and reporting practices is necessary to interpret multi-centre data. Data protection issues may limit the possibilities for detailed data quality assessments of secondary data, as does the accessibility of original data for verification purposes. Our experiences and recommendations may be valuable for those intending to use disease registry data as well as those devising and operating such registries.