Economic Evaluation of Tocilizumab Monotherapy Compared to Adalimumab Monotherapy in the Treatment of Severe Active Rheumatoid Arthritis

AbstractObjectivesTo estimate the cost-effectiveness of tocilizumab (TCZ) monotherapy (Mono) versus adalimumab (ADA) Mono from the US payer perspective in patients with rheumatoid arthritis for whom methotrexate is inappropriate.MethodsWe compared TCZ Mono (8 mg/kg monthly) with ADA Mono (40 mg every other week), using efficacy results from a head-to-head study, ADalimumab ACTemrA (ADACTA). We calculated the incremental cost per responder (achievement of American College of Rheumatology [ACR] 20% improvement criteria, ACR 50% improvement criteria, ACR 70% improvement criteria, or low disease activity score) for TCZ versus ADA at 6 months. A patient-level simulation was used to estimate the lifetime incremental cost per quality-adjusted life-year (QALY) of initiating treatment with TCZ Mono versus ADA Mono. Both drugs are followed by an etanercept-certolizumab-palliative care sequence. Nonresponders discontinue at 6 months; responders experience a constant probability of discontinuation. Discontinuers move to the next treatment. ACR responses produce changes in the Health Assessment Questionnaire (HAQ) score. We mapped the HAQ score to utility to estimate QALYs. Costs include those related to hospitalization and those related to treatment (drug acquisition, administration, and monitoring). Probabilistic and one-way sensitivity analyses were conducted, along with several scenario analyses.ResultsCompared with ADA, TCZ was more effective, with an estimated 6-month incremental cost ranging from $6,570 per additional low disease activity score achiever to$14,265 per additional ACR 70% improvement criteria responder. The lifetime incremental cost-effectiveness ratio was $36,944/QALY.ConclusionsTCZ Mono is projected to be cost-effective compared with ADA Mono in patients with severe rheumatoid arthritis for whom methotrexate is not appropriate, from a US payer perspective

Interaction of urea with frequency and amount of distillers grains supplementation for growing steers on a high forage diet

Two studies were conducted to determine interactions of urea inclusion to a dried distillers grains plus solubles (DDGS; 29.4% crude protein, 5.48% ether extract) supplement fed at two amounts and two frequencies to steers on a high forage diet. In Exp. 1, 120 (247 kg; SD = 20) steers were fed individually for 84 d. Steers received ad libitum grass hay (6.8% crude protein) and one of eight treatments. Treatment design was a 2 × 2 × 2 factorial. Supplement was fed daily or three times per week, amount of supplement fed was 6.36 kg dry matter (DM)/week [0.37% body weight (BW); LO] or 12.73 kg DM/week (0.74% BW; HI) and contained either no urea or 1.3% urea on a DM basis. Steer BW was measured at the start and end of the trial and hay DM intake (DMI) was measured weekly. In Exp. 2, ruminally cannulated steers (310 kg; SD = 25) were used in a row-column design with eight steers and six 14-d periods. Treatments assigned were the same as Exp. 1, except that supplement was fed at 0.4% of BW (LO) or 0.8% of BW (HI) and supplement was fed either daily (DY) or every other day (ALT). Hay DMI, rumen ammonia-N, rumen pH, in situ neutral detergent fiber (NDF) disappearance, and rumination were measured. In Exp. 1, average daily gain (ADG) was affected by amount of supplement with steers on HI gaining 0.30 kg/d more (P \u3c 0.01) than LO. Hay DMI was reduced by increased amount of supplement (0.39 kg/d; P \u3c 0.01) and by decreased frequency of supplementation (0.54 kg/d; P \u3c 0.01). In Exp. 2, hay DMI was also reduced due to increased amount of supplement and decreased frequency of supplementation (P \u3c 0.01). Rumen pH was decreased on the day of supplement feeding for steers on ALT (P \u3c 0.01) and reduced for steers fed HI vs. LO. There was no difference in NDF digestibility between DY and ALT (P \u3e 0.05). For ALT steers, there was reduction (P \u3c 0.01) in in situ NDF disappearance for the HI compared to LO amount of supplementation on the day of supplementation. Infrequent supplementation of DDGS results in no difference in ADG but decreased hay DMI compared to daily supplementation. Urea had no effect on digestion or ADG, suggesting rumen degradable protein was not deficient when supplementing DDGS. There is little change in rumen fermentation parameters between frequency of supplement feeding, indicating that forage digestion is not impacted by supplementation frequency. Dried distillers grains can be supplemented infrequently without a reduction in animal performance

Cost‐effectiveness analysis of low‐dose direct oral anticoagulant (DOAC) for the prevention of cancer‐associated thrombosis in the United States

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154607/1/cncr32724.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154607/2/cncr32724_am.pd

Design and Implementation of an Underwater Sound Recording Device

To monitor the underwater sound and pressure waves generated by anthropogenic activities such as underwater blasting and pile driving, an autonomous system was designed to record underwater acoustic signals. The underwater sound recording device (USR) allows for connections of two hydrophones or other dynamic pressure sensors, filters high frequency noise out of the collected signals, has a gain that can be independently set for each sensor, and allows for 2 h of data collection. Two versions of the USR were created: a submersible model deployable to a maximum depth of 300 m, and a watertight but not fully submersible model. Tests were performed on the USR in the laboratory using a data acquisition system to send single-frequency sinusoidal voltages directly to each component. These tests verified that the device operates as designed and performs as well as larger commercially available data acquisition systems, which are not suited for field use. On average, the designed gain values differed from the actual measured gain values by about 0.35 dB. A prototype of the device was used in a case study to measure blast pressures while investigating the effect of underwater rock blasting on juvenile Chinook salmon and rainbow trout. In the case study, maximum positive pressure from the blast was found to be significantly correlated with frequency of injury for individual fish. The case study also demonstrated that the device withstood operation in harsh environments, making it a valuable tool for collecting field measurements

Integrating value of research into NCI Clinical Trials Cooperative Group research review and prioritization: A pilot study

BackgroundThe Institute of Medicine has called for approaches to help maximize the return on investments (ROI) in cancer clinical trials. Value of Research (VOR) is a health economics technique that estimates ROI and can inform research prioritization. Our objective was to evaluate the impact of using VOR analyses on the clinical trial proposal review process within the SWOG cancer clinical trials consortium.MethodsWe used a previously developed minimal modeling approach to calculate VOR estimates for 9 phase II/III SWOG proposals between February 2015 and December 2016. Estimates were presented to executive committee (EC) members (N = 12) who determine which studies are sent to the National Cancer Institute for funding consideration. EC members scored proposals from 1 (best) to 5 based on scientific merit and potential impact before and after receiving VOR estimates. EC members were surveyed to assess research priorities, proposal evaluation process satisfaction, and the VOR process.ResultsValue of Research estimates ranged from −$2.1B to$16.46B per proposal. Following review of VOR results, the EC changed their score for eight of nine proposals. Proposal rankings were different in pre‐ vs postscores (P value: 0.03). Respondents had mixed views of the ultimate utility of VOR for their decisions with most supporting (42%) or neutral (41%) to the idea of adding VOR to the evaluation process.ConclusionsThe findings from this pilot study indicate use of VOR analyses may be a useful adjunct to inform proposal reviews within NCI Cooperative Clinical Trials groups.The Instiztute of Medicine has called for approaches to help maximize the return on investments in cancer clinical trials. The findings from this pilot study indicate use of value of research analyses may be a useful adjunct to inform proposal reviews within NCI Cooperative Clinical Trials groups.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/146484/1/cam41657.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/146484/2/cam41657_am.pd

Exploring the Cost Effectiveness of Shared Decision Making for Choosing between Disease-Modifying Drugs for Relapsing-Remitting Multiple Sclerosis in the Netherlands:A State Transition Model

Background Up to 31% of patients with relapsing-remitting multiple sclerosis (RRMS) discontinue treatment with disease-modifying drug (DMD) within the first year, and of the patients who do continue, about 40% are nonadherent. Shared decision making may decrease nonadherence and discontinuation rates, but evidence in the context of RRMS is limited. Shared decision making may, however, come at additional costs. This study aimed to explore the potential cost-effectiveness of shared decision making for RRMS in comparison with usual care, from a (limited) societal perspective over a lifetime. Methods An exploratory economic evaluation was conducted by adapting a previously developed state transition model that evaluates the cost-effectiveness of a range of DMDs for RRMS in comparison with the best supportive care. Three potential effects of shared decision making were explored: 1) a change in the initial DMD chosen, 2) a decrease in the patient's discontinuation in using the DMD, and 3) an increase in adherence to the DMD. One-way and probabilistic sensitivity analyses of a scenario that combined the 3 effects were conducted. Results Each effect separately and the 3 effects combined resulted in higher quality-adjusted life years (QALYs) and costs due to the increased utilization of DMD. A decrease in discontinuation of DMDs influenced the incremental cost-effectiveness ratio (ICER) most. The combined scenario resulted in an ICER of euro17,875 per QALY gained. The ICER was sensitive to changes in several parameters. Conclusion This study suggests that shared decision making for DMDs could potentially be cost-effective, especially if shared decision making would help to decrease treatment discontinuation. Our results, however, may depend on the assumed effects on treatment choice, persistence, and adherence, which are actually largely unknown

LSST: from Science Drivers to Reference Design and Anticipated Data Products

(Abridged) We describe here the most ambitious survey currently planned in the optical, the Large Synoptic Survey Telescope (LSST). A vast array of science will be enabled by a single wide-deep-fast sky survey, and LSST will have unique survey capability in the faint time domain. The LSST design is driven by four main science themes: probing dark energy and dark matter, taking an inventory of the Solar System, exploring the transient optical sky, and mapping the Milky Way. LSST will be a wide-field ground-based system sited at Cerro Pach\'{o}n in northern Chile. The telescope will have an 8.4 m (6.5 m effective) primary mirror, a 9.6 deg$^2$ field of view, and a 3.2 Gigapixel camera. The standard observing sequence will consist of pairs of 15-second exposures in a given field, with two such visits in each pointing in a given night. With these repeats, the LSST system is capable of imaging about 10,000 square degrees of sky in a single filter in three nights. The typical 5$\sigma$ point-source depth in a single visit in $r$ will be $\sim 24.5$ (AB). The project is in the construction phase and will begin regular survey operations by 2022. The survey area will be contained within 30,000 deg$^2$ with $\delta<+34.5^\circ$, and will be imaged multiple times in six bands, $ugrizy$, covering the wavelength range 320--1050 nm. About 90\% of the observing time will be devoted to a deep-wide-fast survey mode which will uniformly observe a 18,000 deg$^2$ region about 800 times (summed over all six bands) during the anticipated 10 years of operations, and yield a coadded map to $r\sim27.5$. The remaining 10\% of the observing time will be allocated to projects such as a Very Deep and Fast time domain survey. The goal is to make LSST data products, including a relational database of about 32 trillion observations of 40 billion objects, available to the public and scientists around the world.Comment: 57 pages, 32 color figures, version with high-resolution figures available from https://www.lsst.org/overvie

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements