Economic implications of FDA platelet bacterial guidance compliance options: Comparison of single-step strategies.

BACKGROUND: Bloodborne pathogens pose a major safety risk in transfusion medicine. To mitigate the risk of bacterial contamination in platelet units, FDA issues updated guidance materials on various bacterial risk control strategies (BRCS). This analysis presents results of a budget impact model updated to include 5- and 7-day pathogen reduced (PR) and large volumed delayed sampling (LVDS) BRCS. STUDY DESIGN AND METHODS: Model base-case parameter inputs were based on scientific literature, a survey distributed to 27 US hospitals, and transfusion experts' opinion. The outputs include hospital budget and shelf-life impacts for 5- and 7-day LVDS, and 5- and 7-day PR units under three different scenarios: (1) 100% LVDS, (2) 100% PR, and (3) mix of 50% LVDS - and 50% PR. RESULTS: Total annual costs from the hospital perspective were highest for 100% LVDS platelets (US$2.325M) and lowest for 100% PR-7 units (US$2.170M). Net budget impact after offsetting annual costs by outpatient reimbursements was 5.5% lower for 5-day PR platelets as compared to 5-day LVDS (US$1.663 vs. US$1.760M). A mix of 7-day LVDS and 5-day PR platelets had net annual costs that were 1.3% lower than for 100% 7-day LVDS, but 1.3% higher than for 100% 5-day PR. 7-day PR platelets had the longest shelf life (4.63 days), while 5-day LVDS had the shortest (2.00 days). DISCUSSION: The model identifies opportunities to minimize transfusion center costs for 5- and 7-day platelets. Budget impact models such as this are important for understanding the financial implications of evolving FDA guidance and new platelet technologies.

Economic Analyses of Pathogen-Reduction Technologies in Blood Transfusion: A Systematic Literature Review.

BACKGROUND: Technologies used in the processing of whole blood and blood component products, including pathogen reduction, are continuously being adopted into blood transfusion workflows to improve process efficiencies. However, the economic implications of these technologies are not well understood. With the advent of these new technologies and regulatory guidance on bacterial risk-control strategies, an updated systematic literature review on this topic was warranted. OBJECTIVE: The objective of this systematic literature review was to summarize the current literature on the economic analyses of pathogen-reduction technologies (PRTs). METHODS: A systematic literature review was conducted using the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) guidelines to identify newly published articles in PubMed, MEDLINE Complete, and EconLit from 1 January 2000 to 17 July 2019 related to economic evaluations of PRTs. Only full-text studies in humans published in English were included in the review. Both budget-impact and cost-effectiveness studies were included; common outcomes included cost, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs). RESULTS: The initial searches identified 433 original abstracts, of which 16 articles were included in the final data extraction and reporting. Seven articles presented cost-effectiveness analyses and nine assessed budget impact. The introduction of PRT increased overall costs, and ICER values ranged widely across cost-effectiveness studies, from below $US150,000/QALY to upwards of $US20,000,000/QALY. This wide range of results was due to a multitude of factors, including comparator selection, target patient population, and scenario analyses included. CONCLUSIONS: Overall, the results of economic evaluations of bacterial risk-control strategies, regardless of mechanism, were highly dependent on the current screening protocols in place. The optimization of blood transfusion safety may not result in decisions made at the willingness-to-pay thresholds commonly seen in pharmaceutical evaluations. Given the critical public health role of blood products, and the potential safety benefits introduced by advancements, it is important to continue building this body of evidence with more transparency and data source heterogeneity. This updated literature review provides global context when making local decisions for the coverage of new and emerging bacterial risk-control strategies.

Assessment of NO2 observations during DISCOVER-AQ and KORUS-AQ field campaigns.

NASA's Deriving Information on Surface Conditions from Column and Vertically Resolved Observations Relevant to Air Quality (DISCOVER-AQ, conducted in 2011-2014) campaign in the United States and the joint NASA and National Institute of Environmental Research (NIER) Korea-United States Air Quality Study (KORUS-AQ, conducted in 2016) in South Korea were two field study programs that provided comprehensive, integrated datasets of airborne and surface observations of atmospheric constituents, including nitrogen dioxide (NO2), with the goal of improving the interpretation of spaceborne remote sensing data. Various types of NO2 measurements were made, including in situ concentrations and column amounts of NO2 using ground- and aircraft-based instruments, while NO2 column amounts were being derived from the Ozone Monitoring Instrument (OMI) on the Aura satellite. This study takes advantage of these unique datasets by first evaluating in situ data taken from two different instruments on the same aircraft platform, comparing coincidently sampled profile-integrated columns from aircraft spirals with remotely sensed column observations from ground-based Pandora spectrometers, intercomparing column observations from the ground (Pandora), aircraft (in situ vertical spirals), and space (OMI), and evaluating NO2 simulations from coarse Global Modeling Initiative (GMI) and high-resolution regional models. We then use these data to interpret observed discrepancies due to differences in sampling and deficiencies in the data reduction process. Finally, we assess satellite retrieval sensitivity to observed and modeled a priori NO2 profiles. Contemporaneous measurements from two aircraft instruments that likely sample similar air masses generally agree very well but are also found to differ in integrated columns by up to 31.9 %. These show even larger differences with Pandora, reaching up to 53.9 %, potentially due to a combination of strong gradients in NO2 fields that could be missed by aircraft spirals and errors in the Pandora retrievals. OMI NO2 values are about a factor of 2 lower in these highly polluted environments due in part to inaccurate retrieval assumptions (e.g., a priori profiles) but mostly to OMI's large footprint (> 312 km2).

Economic Implications of Pathogen Reduced and Bacterially Tested Platelet Components: A US Hospital Budget Impact Model.

BACKGROUND: US FDA draft guidance includes pathogen reduction (PR) or secondary rapid bacterial testing (RT) in its recommendations for mitigating risk of platelet component (PC) bacterial contamination. An interactive budget impact model was created for hospitals to use when considering these technologies. METHODS: A Microsoft Excel model was built and populated with base-case costs and probabilities identified through literature search and a survey of US hospital transfusion service directors. Annual costs of PC acquisition, testing, wastage, dispensing/transfusion, sepsis, shelf life, and reimbursement for a mid-sized hospital that purchases all of its PCs were compared for four scenarios: 100% conventional PCs (C-PC), 100% RT-PC, 100% PR-PC, and 50% RT-PC/50% PR-PC. RESULTS: Annual total costs were US$3.64, US$3.67, and US$3.96 million when all platelets were C-PC, RT-PC, or PR-PC, respectively, or US$3.81 million in the 50% RT-PC/50% PR-PC scenario. The annual net cost of PR-PC, obtained by subtracting annual reimbursements from annual total costs, is 6.18% above that of RT-PC. Maximum usable shelf lives for C-PC, RT-PC, and PR-PC are 3.0, 5.0, and 3.6 days, respectively; hospitals obtain PR-PC components earliest at 1.37 days. CONCLUSION: The model predicts minimal cost increase for PR-PC versus RT-PC, including cost offsets such as elimination of bacterial detection and irradiation, and reimbursement. Additional safety provided by PR, including risk mitigation of transfusion-transmission of a broad spectrum of viruses, parasites, and emerging pathogens, may justify this increase. Effective PC shelf life may increase with RT, but platelets can be available sooner with PR due to elimination of bacterial detection, depending on blood center logistics.

Carcinogenicity assessment of baricitinib in Tg.rasH2 mice and Sprague-Dawley (Crl:CD) rats.

Baricitinib is a potent and selective Janus kinase (JAK)1 and JAK2 inhibitor, and is approved for the treatment of moderately to severely active RA in adults in Europe, Japan, and other countries. This study evaluated the carcinogenic potential of baricitinib in Tg. rasH2 mice and Sprague-Dawley (Crl:CD) rats. Baricitinib was administered daily by oral gavage to Crl:CD rats for up to 94 weeks (dose levels of 0, 1, 3, or 8 mg/kg for males and 0, 3, 8, or 25 mg/kg for females) and to Tg. rasH2 mice for 26 weeks (dose levels of 0, 15, 40, or 300 mg/kg for males and 0, 10, 30, or 150 mg/kg for females). Baricitinib was well tolerated with no incidence of compound-related neoplasms at any dose levels in rats and mice. In mice, non-neoplastic events observed were bone marrow hypocellularity and increased adipocytes. In rats, baricitinib administration was associated with a dose-dependent increase in survival, with a decreased incidence of neoplasm (hematopoietic and mammary), potentially secondary to drug-related decreased weight gain. The incidence of proliferative changes such as neoplastic and hyperplastic lesions in the mammary glands of females and in the livers of males and females also decreased. In conclusion, baricitinib is not considered to be carcinogenic.

Cost of Purchased Versus Produced Plasma from Donor Recruitment Through Transfusion.

BACKGROUND: Plasma is used to treat acquired coagulopathy or thrombotic thrombocytopenic purpura, or to reverse warfarin effect. Scant data are available, however, about its costs. OBJECTIVE: To estimate total costs of plasma from production through administration, from the perspective of a US hospital blood donor center (BDC). STUDY DESIGN AND METHODS: Six sequential decision analytic models were constructed and informed by primary and secondary data on time, tasks, personnel, and supplies for donation, processing, and administration. Expected values of the models were summed to yield the BDC's total cost of producing, preparing, and transfusing plasma. Costs ($US 2015) are reported for a typical patient using three units of plasma. Models assume plasma was obtained from whole blood donation and transfused in an inpatient setting. Univariate sensitivity analyses were performed to test the impact of changing inputs for personnel costs and adverse event (AE) rates and costs. RESULTS: BDC production cost of plasma was $91.24/patient ($30.41/unit), a $30.16/patient savings versus purchased plasma. Administration and monitoring costs totaled $194.64/patient. Sensitivity analyses indicated that modifying BDC personnel costs during donation and processing has little impact on total plasma costs. However, the probability and cost of transfusion-associated circulatory overload (TACO) have a significant impact on costs. CONCLUSION: Plasma produced by our BDC may be less costly than purchased plasma. Though plasma processes have multiple tasks involving staff time, these are not the largest cost driver. Major plasma-related AEs are uncommon, but are the biggest driver of total plasma costs.

Establishing an antigen-negative red blood cell inventory in a hospital-based blood bank.

BACKGROUND: Our blood bank is part of a large academic institution with an active sickle cell anemia program. We provide sickle patients with blood phenotypically matched for C/c, E/e, and K antigens. Since licensed reagents are available for phenotyping C/c, E/e, and K on an automated blood analyzer, we decided to evaluate whether establishing our own inventory of blood negative for those antigens would result in cost savings and decreased turnaround time (TAT). STUDY DESIGN AND METHODS: Antigen typing of blood units for C/c, E/e, and K was validated. From March 1, 2012, to August 31, 2012, a total of 1033 units from our own donor center and from our suppliers were phenotyped. We compared direct cost savings and TAT for blood availability with historical data before we began phenotyping. RESULTS: Thirty-eight percent of typed antigen-negative (AG-) units were transfused to sickle patients. An additional 35% were transfused to nonsickle patients needing AG- blood. Twenty-one percent were used by patients without antibodies to prevent outdating. The remaining 6% had not yet been transfused by the end of the study period. From March 1, 2011, to August 31, 2011, we spent almost $200,000 on obtaining AG- blood. In the 6 months since we started antigen typing, we have saved approximately $110,000, the majority of which resulted from AG- blood provided to sickle patients. In addition, TAT for AG- units from our inventory significantly improved to 1 to 2 hours versus approximately 6 hours when obtained from our suppliers. CONCLUSION: Establishing an AG- inventory in a hospital-based blood bank is cost-effective and time-efficient.

Assessment of the ultraviolet radiation field in ocean waters from space-based measurements and full radiative-transfer calculations.

Quantitative assessment of the UV effects on aquatic ecosystems requires an estimate of the in-water radiation field. Actual ocean UV reflectances are needed for improving the total ozone retrievals from the total ozone mapping spectrometer (TOMS) and the ozone monitoring instrument (OMI) flown on NASA's Aura satellite. The estimate of underwater UV radiation can be done on the basis of measurements from the TOMS/OMI and full models of radiative transfer (RT) in the atmosphere-ocean system. The Hydrolight code, modified for extension to the UV, is used for the generation of look-up tables for in-water irradiances. A look-up table for surface radiances generated with a full RT code is input for the Hydrolight simulations. A model of seawater inherent optical properties (IOPs) is an extension of the Case 1 water model to the UV. A new element of the IOP model is parameterization of particulate matter absorption based on recent in situ data. A chlorophyll product from ocean color sensors is input for the IOP model. Verification of the in-water computational scheme shows that the calculated diffuse attenuation coefficient Kd is in good agreement with the measured Kd.