Cost-effectiveness of avelumab first-line maintenance therapy for adult patients with locally advanced or metastatic urothelial carcinoma in France.

BACKGROUND: This study evaluated the cost-effectiveness of avelumab first-line (1L) maintenance therapy plus best supportive care (BSC) versus BSC alone for adults with locally advanced or metastatic urothelial carcinoma (la/mUC) that had not progressed following platinum-based chemotherapy in France. METHODS: A three-state partitioned survival model was developed to assess the lifetime costs and effects of avelumab plus BSC versus BSC alone. Data from the phase 3 JAVELIN Bladder 100 trial (NCT02603432) were used to inform estimates of clinical and utility values considering a 10-year time horizon and a weekly cycle length. Cost data were estimated from a collective perspective and included treatment acquisition, administration, follow-up, adverse event-related hospitalization, transport, post-progression, and end-of-life costs. Health outcomes were measured in quality-adjusted life-years (QALYs) and life-years gained. Costs and clinical outcomes were discounted at 2.5% per annum. Incremental cost-effectiveness ratios (ICERs) were used to compare cost-effectiveness and willingness to pay in France. Uncertainty was assessed using a range of sensitivity analyses. RESULTS: Avelumab plus BSC was associated with a gain of 2.49 QALYs and total discounted costs of €136,917; BSC alone was associated with 1.82 QALYs and €39,751. Although avelumab plus BSC was associated with increased acquisition costs compared with BSC alone, offsets of -€20,424 and -€351 were observed for post-progression and end-of-life costs, respectively. The base case analysis ICER was €145,626/QALY. Sensitivity analyses were consistent with the reference case and showed that efficacy parameters (overall survival, time to treatment discontinuation), post-progression time on immunotherapy, and post-progression costs had the largest impact on the ICER. CONCLUSIONS: This analysis demonstrated that avelumab plus BSC is associated with a favorable cost-effectiveness profile for patients with la/mUC who are eligible for 1L maintenance therapy in France.

Mineral oil hydrocarbons in foods: is the data reliable?

The contamination of foods with mineral oil hydrocarbons (MOH) is a serious concern, requiring in most cases tedious mitigation measures that span across the whole food supply chain. A major issue today is the significant variability of the results generated by laboratories. This study was therefore designed to achieve a deeper insight into the analytical procedures used by commercial laboratories, identifying possible gaps and suggesting improvements that will enhance the reliability of the MOH data, an important prerequisite for risk assessment. In total six different food matrices, i.e. infant formula (IF), cocoa butter, cocoa powder, biscuits, fruit-based baby food containing biscuit and roast and ground coffee were subjected to comparative inter-laboratory studies, as well as one vegetable oil analysed within the frame of a professionally conducted proficiency test. The results indicate that on some matrices with possibly low amounts of MOH contamination, the current methodologies cannot reliably conclude whether or not a food sample is indeed contaminated with mineral oils (<10 mg/kg food). Urgently needed are: (i) an aligned and fully validated sample preparation strategy tested on a range of different food matrices; (ii) a confirmation of positive flame ionisation detection (FID) results by confirmatory methods such as mass spectrometry - in line with the CEN Standard and the Joint Research Centre (JRC) Guidance Document, (iii) a more detailed root-cause analysis in the reports of laboratories through the use of mineral oil markers, and (iv) a fully validated official method for the concerned foods with a limit of application <10 mg/kg food.

Survival benefit, disease progression and quality-of-life outcomes of abiraterone acetate plus prednisone versus docetaxel in metastatic hormone-sensitive prostate cancer: A network meta-analysis.

AIM: Androgen deprivation therapy (ADT) has long been the gold standard for patients with metastatic hormone-sensitive prostate cancer (mHSPC). Clinical trials have demonstrated significant survival benefits when docetaxel (DOC) or abiraterone acetate (AA) and prednisone (P) are added to ADT, necessitating comparison of these combination treatments. METHODS: A systematic review of randomised controlled trials (RCTs) of AA-/ADT-/DOC-containing treatment regimens in newly diagnosed patients with high-risk and/or high-volume mHSPC identified three RCTs (LATITUDE, CHAARTED and GETUG-AFU 15). Network meta-analyses (NMAs) using fixed effects Bayesian methods were performed to compare relative benefits of each treatment on overall survival (OS), radiographic progression-free survival (rPFS) and quality of life (QoL) measured by the Brief Pain Inventory, and the Functional Assessment of Cancer Therapy-Prostate questionnaire. One trial, STAMPEDE, was assessed in exploratory OS analyses. RESULTS: The hazard ratio (HR) for OS ranged from 0.85 to 0.92, with the Bayesian probability of AA + P + ADT being better than DOC + ADT ranging between 72% and 87%. For rPFS, the HR ranged between 0.71 and 0.76 (Bayesian probability range: 93%-97%). Exploratory analyses including STAMPEDE found similar trends. AA + P + ADT also showed improved QoL compared with DOC + ADT for at least 1 year of therapy, with results being more pronounced at 3 months. CONCLUSION: Our findings suggest that AA + P + ADT is at least as effective as DOC + ADT in reducing the risk of death in men with mHSPC and better at preventing disease progression and improving QoL. The NMA provides useful insights to clinicians and other decision-makers on the relative efficacy of treatment options for men with mHSPC.

Expected cost effectiveness of high-dose trivalent influenza vaccine in US seniors.

OBJECTIVES: Seniors are particularly vulnerable to complications resulting from influenza infection. Numerous influenza vaccines are available to immunize US seniors, and practitioners must decide which product to use. Options include trivalent and quadrivalent standard-dose inactivated influenza vaccines (IIV3 and IIV4 respectively), as well as a high-dose IIV3 (HD). Our research examines the public health impact, budget impact, and cost-utility of HD versus IIV3 and IIV4 for immunization of US seniors 65 years of age and older. METHODS: Our model was based on US influenza-related health outcome data. Health care costs and vaccine prices were obtained from the Centers for Medicare and Medicaid Services. Efficacies of IIV3 and IIV4 were estimated from various meta-analyses of IIV3 efficacy. The results of a head-to-head randomized controlled trial of HD vs. IIV3 were used to estimate relative efficacy of HD. Conservatively, herd protection was not considered. RESULTS: Compared to IIV3, HD would avert 195,958 cases of influenza, 22,567 influenza-related hospitalizations, and 5423 influenza-related deaths among US seniors. HD generates 29,023 more Quality Adjusted Life Years (QALYs) and a net societal budget impact of $154 million. The Incremental Cost Effectiveness Ratio (ICER) for this comparison is $5299/QALY. 71% of the probabilistic sensitivity analysis (PSA) simulations were <$100,000/QALY. Compared to IIV4, HD would avert 169,257 cases of influenza, 21,222 hospitalizations and 5212 deaths. HD generates 27,718 more QALYs and a net societal budget impact of -$17 million and as such dominates IIV4. For this comparison, 81% of PSA simulations were <$100,000/QALY. CONCLUSIONS: HD is expected to achieve significant reductions in influenza-related morbidity and mortality. Further, HD is a cost effective alternative to both IIV3 and IIV4 in seniors. Our conclusions were robust in the face of sensitivity analyses.

Interfacial properties of oleosins and phospholipids from rapeseed for the stability of oil bodies in aqueous medium.

Oleosins are plant proteins associated with phospholipids in seed oil bodies. The ability of oleosins to aid in the emulsification and stabilization of oil bodies is well known, but little information is available on their interaction with phospholipids at the interface between oil bodies and aqueous medium. Oil body reconstitution at various phospholipid/oleosin ratios was carried out to observe how rapeseed oleosins of 20kDa and rapeseed phospholipids affect oil body stability. Phospholipids are needed to stabilize oil droplets, but oleosins are mandatory to avoid coalescence. We thus characterized how phospholipids affect the interfacial properties of oleosins at pHs 5.5 and 8.5, by analyzing the adsorption kinetics and interfacial dilational rheology. We observed a synergic effect between oleosins and phospholipids in increasing surface pressure at both pHs. This kind of effect was also observed for the dilational modulus at pH 5.5. A thermodynamic approach highlights these synergic interactions between oleosins and phospholipids through a positive deviation from ideality.