Bayesian value-of-infomation analysis: an application to a policy model of Alzheimer's disease

A framework is presented that distinguishes the conceptually separate decisions of which treatment strategy is optimal from the question of whether more information is required to inform this choice in the future. The authors argue that the choice of treatment strategy should be based on expected utility, and the only valid reason to characterize the uncertainty surrounding outcomes of interest is to establish the value of acquiring additional information. A Bayesian decision theoretic approach is demonstrated through a probabilistic analysis of a published policy model of Alzheimer’s disease. The expected value of perfect information is estimated for the decision to adopt a new pharmaceutical for the population of patients with Alzheimer’s disease in the United States. This provides an upper bound on the value of additional research. The value of information is also estimated for each of the model inputs. This analysis can focus future research by identifying those parameters where more precise estimates would be most valuable and indicating whether an experimental design would be required. We also discuss how this type of analysis can also be used to design experimental research efficiently (identifying optimal sample size and optimal sample allocation) based on the marginal cost and marginal benefit of sample information. Value-of-information analysis can provide a measure of the expected payoff from proposed research, which can be used to set priorities in research and development. It can also inform an efficient regulatory framework for new healthcare technologies: an analysis of the value of information would define when a claim for a new technology should be deemed substantiated and when evidence should be considered competent and reliable when it is not cost-effective to gather any more information

Model parameter estimation and uncertainty analysis: a report of the ISPOR-SMDM modeling good research practices task force working group - 6

A model’s purpose is to inform medical decisions and health care resource allocation. Modelers employ quantitative methods to structure the clinical, epidemiological, and economic evidence base and gain qualitative insight to assist decision makers in making better decisions. From a policy perspective, the value of a model-based analysis lies not simply in its ability to generate a precise point estimate for a specific outcome but also in the systematic examination and responsible reporting of uncertainty surrounding this outcome and the ultimate decision being addressed. Different concepts relating to uncertainty in decision modeling are explored. Stochastic (first-order) uncertainty is distinguished from both parameter (second-order) uncertainty and from heterogeneity, with structural uncertainty relating to the model itself forming another level of uncertainty to consider. The article argues that the estimation of point estimates and uncertainty in parameters is part of a single process and explores the link between parameter uncertainty through to decision uncertainty and the relationship to value-of-information analysis. The article also makes extensive recommendations around the reporting of uncertainty, both in terms of deterministic sensitivity analysis techniques and probabilistic methods. Expected value of perfect information is argued to be the most appropriate presentational technique, alongside cost-effectiveness acceptability curves, for representing decision uncertainty from probabilistic analysis

The cost-effectiveness of an adjuvanted quadrivalent influenza vaccine in the United Kingdom

In the United Kingdom (UK), both the MF59-adjuvanted quadrivalent influenza vaccine (aQIV) and the high-dose QIV (QIV-HD) are preferred for persons aged 65 years and older but only aQIV is reimbursed by the National Health Service (NHS). The objective was to determine the potential cost-effectiveness of vaccinating adults aged 65 years and above with aQIV compared with QIV-HD in the UK. A dynamic transmission model, calibrated to match infection data from the UK, was used to estimate the impact of vaccination in 10 influenza seasons. Vaccine effectiveness was based on a meta-analysis that concluded the vaccines were not significantly different. Vaccine coverage, physician visits, hospitalizations, deaths, utility losses and NHS costs were estimated using published UK sources. The list price of aQIV was £11.88 while a range of prices were tested for QIV-HD. The price of the trivalent high-dose vaccine (TIV-HD) is £20.00 but a list price for QIV-HD is not yet available. The projected differences between the vaccines in terms of clinical cases and influenza treatment costs are minimal. Our analysis demonstrates that in order to be cost-effective, the price of QIV-HD must be similar to that of aQIV and may range from £7.57 to £12.94 depending on the relative effectiveness of the vaccines. The results of the analysis were most sensitive to variation in vaccine effectiveness and the rate of hospitalization due to influenza. Given the evidence, aQIV is cost-saving unless QIV-HD is priced lower than the existing list price of TIV-HD

The Cost-Effectiveness of Expanding Vaccination with a Cell-Based Influenza Vaccine to Low Risk Adults Aged 50 to 64 Years in the United Kingdom

Background: In response to COVID-19, the UK National Health Service (NHS) extended influenza vaccination in 50- to 64-year-olds from at-risk only to all in this age group for the 2020/21 season. The objective of this research is to determine the cost-effectiveness of continuing to vaccinate all with a quadrivalent cell-based vaccine (QIVc) compared to returning to an at-risk only policy after the pandemic resolves. Methods: A dynamic transmission model, calibrated to match infection data from the UK, was used to estimate the clinical and economic impact of vaccination across 10 influenza seasons. The base case effectiveness of QIVc was 63.9% and the list price was GBP 9.94. Results: Vaccinating 50% of all 50- to 64-year-olds with QIVc reduced the average annual number of clinical infections (−682,000), hospitalizations (−5800) and deaths (−740) in the UK. The base case incremental cost per quality-adjusted life-year gained (ICER) of all compared to at-risk only was GBP6000 (NHS perspective). When the cost of lost productivity was considered, vaccinating all 50-to 64-year-olds with QIVc became cost-saving. Conclusion: Vaccinating all 50- to 64-year-olds with QIVc is likely to be cost-effective. The NHS should consider continuing this policy in future seasons

Entanglement preparation using symmetric multiports

We investigate the entanglement produced by a multi-path interferometer that is composed of two symmetric multiports, with phase shifts applied to the output of the first multiport. Particular attention is paid to the case when we have a single photon entering the interferometer. For this situation we derive a simple condition that characterize the types of entanglement that one can generate. We then show how one can use the results from the single photon case to determine what kinds of multi-photon entangled states one can prepare using the interferometer.Comment: 6 pages, 2 figures, accepted for publication in European Journal of Physics

Quark exchange model for charmonium dissociation in hot hadronic matter

A diagrammatic approach to quark exchange processes in meson-meson scattering is applied to the case of inelastic reactions of the type (Q\barQ)+(q\barq)\rightarrow (Q\barq) + (q\barQ), where $Q$ and $q$ refer to heavy and light quarks, respectively. This string-flip process is discussed as a microscopic mechanism for charmonium dissociation (absorption) in hadronic matter. The cross section for the reaction $J/\psi + \pi \to D+ \bar D$ is calculated using a potential model, which is fitted to the meson mass spectrum. The temperature dependence of the relaxation time for the \J/Psi distribution in a homogeneous thermal pion gas is obtained. The use of charmonium for the diagnostics of the state of hot hadronic matter produced in ultrarelativistic nucleus-nucleus collisions is discussed.Comment: 24 pages, 3 tables, 7 figure

Entanglement preparation using symmetric multiports

We investigate the entanglement produced by a multi-path interferometer that is composed of two symmetric multiports, with phase shifts applied to the output of the first multiport. Particular attention is paid to the case when we have a single photon entering the interferometer. For this situation we derive a simple condition that characterize the types of entanglement that one can generate. We then show how one can use the results from the single photon case to determine what kinds of multi-photon entangled states one can prepare using the interferometer.Comment: 6 pages, 2 figures, accepted for publication in European Journal of Physics

Physics Opportunities with the 12 GeV Upgrade at Jefferson Lab

This white paper summarizes the scientific opportunities for utilization of the upgraded 12 GeV Continuous Electron Beam Accelerator Facility (CEBAF) and associated experimental equipment at Jefferson Lab. It is based on the 52 proposals recommended for approval by the Jefferson Lab Program Advisory Committee.The upgraded facility will enable a new experimental program with substantial discovery potential to address important topics in nuclear, hadronic, and electroweak physics.Comment: 64 page

Resident Cellular Components of the Human Lung Current Knowledge and Goals for Research on Cell Phenotyping and Function

The purpose of the workshop was to identify still obscure or novel cellular components of the lung, to determine cell function in lung development and in health that impacts on disease, and to decide promising avenues for future research to extract and phenotype these cells. Since robust technologies are now available to identify, sort, purify, culture, and phenotype cells, progress is now within sight to unravel the origins and functional capabilities of lung cells in developmental stages and in disease. The Workshop's agenda was to first discuss the lung's embryologic development, including progenitor and stem cells, and then assess the functional and structural cells in three main compartments of the lung: (1) airway cells in bronchial and bronchiolar epithelium and bronchial glands (basal, secretory, ciliated, Clara, and neuroendocrine cells); (2) alveolar unit cells (Type 1 cells, Type 2 cells, and fibroblasts in the interstitium); and (3) pulmonary vascular cells (endothelial cells from different vascular structures, smooth muscle cells, and adventitial fibroblasts). The main recommendations were to: (1) characterize with better cell markers, both surface and nonsurface, the various cells within the lung, including progenitor cells and stem cells; (2) obtain more knowledge about gene expression in specific cell types in health and disease, which will provide insights into biological and pathologic processes; (3) develop more methodologies for cell culture, isolation, sorting, co-culture, and immortalization; and (4) promote tissue banks to facilitate the procurement of tissue from normal and from diseased lung for analysis at all levels

Detector Description and Performance for the First Coincidence Observations between LIGO and GEO

For 17 days in August and September 2002, the LIGO and GEO interferometer gravitational wave detectors were operated in coincidence to produce their first data for scientific analysis. Although the detectors were still far from their design sensitivity levels, the data can be used to place better upper limits on the flux of gravitational waves incident on the earth than previous direct measurements. This paper describes the instruments and the data in some detail, as a companion to analysis papers based on the first data.Comment: 41 pages, 9 figures 17 Sept 03: author list amended, minor editorial change