Literature-related discovery (LRD): Potential treatments for Multiple Sclerosis

Literature-related discovery (LRD) is the linking of two or more literature concepts that have heretofore not been linked (i.e., disjoint), in order to produce novel, interesting, plausible, and intelligible knowledge (i.e., potential discovery). The open discovery systems (ODS) component of LRD starts with a problem to be solved, and generates solutions to that problem through potential discovery. We have been using ODS LRD to identify potential treatments or preventative actions for challenging medical problems, among myriad other applications. The previous three papers in this Special Issue describe the application of ODS LRD to Raynaud's Phenomenon (RP), cataracts, and Parkinson's Disease (PD).Multiple Sclerosis (MS) is a progressive neurodegenerative disorder (typically preceded by periods of remission and relapse), affecting mainly people in their early-mid life. MS is characterized by changes in sensation (hypoesthesia), muscle weakness, abnormal muscle spasms, or difficulty to move; difficulties with coordination and balance (ataxia); problems in speech (Dysarthria) or swallowing (Dysphagia), visual problems (Nystagmus, optic neuritis, or diplopia), fatigue and acute or chronic pain syndromes, bladder and bowel difficulties, cognitive impairment, or emotional symptomatology (mainly depression).We selected the subject of MS because of its global prevalence, and its apparent intractability to all treatments except for palliative remediation mainly through drugs or surgery. Our first goal was to identify non-drug non-surgical treatments that would 1) prevent the occurrence, or 2) reduce the progression rate, or 3) stop the progression, or 4) maybe even reverse the progression, of MS. Our second goal was to demonstrate that we could again solve an ODS problem (using LRD) with no prior knowledge of any results or prior work (unlike the case of the RP problem). As in the ‘cataract’ and PD examples, we used the MeSH taxonomy of MEDLINE to restrict potential discoveries to selected semantic classes, and to identify potential discoveries efficiently. Our third goal was to generate large amounts of potential discovery in more than an order of magnitude less time than required for the RP study. The discovery generation methodology has been developed to the point where ODS LRD problems can be solved with no results or knowledge of any prior work.     

Costs of Taxation and Benefits of Public Goods with Multiple Taxes and Goods

The fact that raising taxes can increase taxed labor supply through income effects is frequently and erroneously used to justify greater public good provision than indicated by traditional, compensated analyses. We develop a model including multiple public goods and taxes and derive measures of the marginal benefits of public goods and the Marginal Cost of Funds (MCF) using both compensated and uncompensated measures. We confirm that the desirability of tax‐financed public projects is independent of the method used. An important innovation is to show that the benefits of public goods must be adjusted by a benefit multiplier not previously seen in the literature if an uncompensated MCF is used.     

Implications of Real-world Adherence on Cost-effectiveness Analysis in Multiple Sclerosis

Abstract

Objectives:

Adherence to medication is essential for optimal outcomes, especially for chronic diseases such as multiple sclerosis (MS). Studies in MS indicate that lower adherence is associated with an increased risk of relapse, hospitalization or emergency room (ER) visits, and higher medical costs. A previous investigation assessed the cost per relapse avoided for patients with MS receiving first-line disease modifying therapies (DMTs); however, the model assumed 100% adherence.

Methods:

Because real-world utilization patterns influence the actual effectiveness of medications, this analysis assessed the impact of real-world adherence from a US commercial payer perspective, using updated costs.

Results:

As was seen in the original study, in this revised model, fingolimod was associated with the lowest cost per relapse avoided ($90,566), followed by SC IFN β-1b (Extavia: $127,024), SC IFN β-1b (Betaseron: $137,492), SC IFN β-1a ($144,016), glatiramer acetate ($160,314), and IM IFN β-1a ($312,629). The model inputs that had the greatest impact on the results were adherence-adjusted relative relapse rate reduction (RRR) of fingolimod, the wholesale acquisition costs of fingolimod, and the average number of relapses in untreated patients with MS.

Limitations:

The estimates of DMT adherence are from a single claims database study of a large national pharmacy benefit manager that only measured adherence, not actual relapses, and the model does not incorporate manufacturer discounts and rebates, which are not publicly available.

Conclusion:

These results suggest that economic analyses of MS therapies should incorporate real-world adherence rates where available, rather than relying exclusively on trial-based efficacy estimates when considering the economic value of treatment alternatives, and that highly efficacious therapies with low adherence may yield real-world efficacy that is substantially lower than that observed in closely monitored clinical trials.     

The Costs of Cooperation

Public goods production is not necessarily desirable and involves higher costs than is often recognized. Specifically, public goods production may require that a small minority of individuals can collude at the expense of others or impose strategic sanctions on non-contributors. These facilities may have negative as well as positive effects. The same conditions that support public goods production also support business cartels and racial discrimination, for instance. We examine the implications of this perspective for modern debates on economic policy, civic virtue, communitarianism, and libertarianism.     

A discrete choice experiment to determine UK patient preference for attributes of disease modifying treatments in Multiple Sclerosis

Aims: The recent licensing of Disease Modifying Treatments (DMTs) for Multiple Sclerosis (MS) has increased available treatment options. The aim of this study was to explore MS patients’ preference for the different attributes of DMTs in the UK.

Materials and methods: Attributes (treatment characteristics) for inclusion in the discrete choice experiment (DCE) were determined through published literature and interviews with 12 people with MS. Seven attributes were selected. Participants were presented with three hypothetical treatment options sampled from included attributes and asked for their most/least preferred options. The influence of patient characteristics and demographics on patient preference was also investigated.

Results: The DCE was completed by 350 people with MS (81% female, mean age?=?39). Results showed that method of taking medication was the strongest determinant of preference (27%; relative importance out of 100%), followed by relapse free rate (21%) and symptom progression (14%). Risk of fatigue (8%) and type of monitoring (6%) were the weakest determinants of preference. Once-daily oral treatment was preferred over all other methods of administration. Participant characteristics did not influence data on strength of preference.

Limitations: This study assumed adequate participant understanding of the discrete choice experiment task, and recruitment targeted those with access to the internet.

Conclusions: These results, derived from people with MS in the UK, should be used to inform individual discussions with patients about DMT choices.     

The Costs of Inflation Revisited

Neoclassical treatments of inflation understate the costs associated with inflation, even at very low levels. A comparative institutions perspective that recognizes the epistemological properties of prices and the institutional process by which inflation takes place, reveals the costs of inflation to be both larger and more widespread than standard treatments suggest. This paper makes use of insights from Austrian economics, public choice theory, and the new institutional economics to argue that inflation imposes costs by undermining the coordinative properties of the price system. Not only are there the direct costs of increased economic error, but actors also divert resources away from direct want-satisfaction into attempts to either prevent or cope with the increased degree of uncertainty inflation imposes. These resource costs are best understood from a comparative institutions perspective, as traditional measures of economic well-being, such as GDP, cannot distinguish between exchanges that directly satisfy wants, and exchanges that are attempts to correct or prevent utility-diminishing activities. The analogy between these coping costs and rent-seeking behavior is explored. In addition, inflation imposes costs by undermining the coordinative properties of markets and inducing actors to, on the margin, prefer to seek wealth or allocate resources through the political process.     

Multiple Buyers, Rent‐Defending and the Observed Social Costs of Monopoly

This paper uses analytical and experimental methods to assess the effects of fracturing the interests of agents seeking to maintain the competitive status quo in a rent‐seeking contest for a monopoly franchise. Theoretically, it is shown that while "rent‐defending" can ameliorate the social costs of rent‐seeking, these beneficial effects deteriorate quickly as the interests of those seeking to maintain the status quo become fractured. Experimental results indicate that overbidding is persistent when bidders have different sharing rules. In fact, the observed social costs of rent‐seeking often increase just when rent‐defending has the greatest predicted ameliorative effect.     

Competition in Markets for Depletable Resources with Setup Costs

This paper analyzes the impact on exhaustible resource markets of setup costs, a sparsely analyzed category of nonconvex production technologies. This paper proves that, even under idealized circumstances for competition, a competitive equilibrium will fail to exist in the presence of setup costs, for any utility and cost functions such that a planner would exploit exhaustible resource pools sequentially.JEL classifications: Q3, C62     

城市生态环境可持续发展能力研究

建设生态城市是一种国际趋势,也备受中国政府的关注,目前各级政府均提出了建立生态省(市、县)的目标.而如何保持城市生态环境的可持续发展,需要有一套科学的指标体系和评价方法.本文讨论了国内外城市生态环境可持续发展研究进展,建立了城市生态环境可持续发展评价指标体系,提出了城市生态环境可持续发展的对策.     

The Costs of China's State-owned Enterprises

MOCT-MOST: Economic Policy in Transitional Economies -     

The price elasticity of demand for pharmaceuticals amongst high-income older Australians: a natural experiment

Most high-income older Australians became eligible for a pharmaceutical concession through a 1999 policy change. I exploit this natural experiment to estimate their price elasticity of demand for pharmaceuticals. The preferred model is a nonlinear Instrumental Variable (IV) regression, estimated on nationally representative repeated cross-sectional survey data using the Generalized Method of Moments (GMM). No significant evidence is found for endogenous take-up, and so cross-sectional estimates are also considered. Taking all of the results into account, the ‘headline’ estimate is ?0.1, implying that quantity demanded is not highly responsive to price.     

中央银行金融危机救助的成本-收益分析

维护金融稳定是中央银行的一项基本职能,这决定了中央银行在金融危机救助中的主体地位.但中央银行的金融危机救助能力不是无限的,因为无论哪种救助措施都不是无成本的.文章通过成本-收益分析方法,考察了中央银行对金融危机救助的成本与收益,既包括直接成本与直接收益,又包括隐性成本与间接收益,并通过建立成本.收益模型,考察最优的中央银行金融危机救助应满足的条件,结合我国中央银行金融危机救助的实际,提出成本收益分析对我国的启示.     

慢性乙型肝炎患者住院费用及其影响因素分析

本研究利用南京市医疗保险中心数据库的信息,对599名慢性乙型肝炎患者的住院信息进行分析。分析结果显示,慢性乙型肝炎患者平均次均住院费用为12927元;住院费用结构分析发现,药品费用在总费用中的比例为60％,明显高于其它费用;对慢性乙型肝炎患者的住院费用进行回归分析,结果显示年龄、疾病进展、抗病毒药物、手术治疗与否、抢救与否是影响住院费用的重要因素。     

The Optimality of a Zero Inflation Rate with Menu Costs: Australia

This paper juxtaposes the policy trend towards a zero inflation rate against the theoretical standard of optimal deflation at the real interest rate. It extends an example monetary economy to include a simple form of nominal adjustment costs and calibrates the model with recent evidence on Australian money demand. There is a critical value that the calibrated parameter for menu costs must exceed in order for a zero inflation rate to be optimal. An inflation rate of –2 per cent to 0 per cent is found to be optimal. The quantitative results, of whether inflation-adjustment costs imply a zero inflation rate policy for Australia, are tempered by the abstraction of the model and its sensitivity to parameters. Qualitatively, the paper shows the effects of changes in the adjustment cost function and in the structural parameters.     

跨国公司的兼并收购成本

跨国公司的并购活动不但规模日益增大,而且通过利用资本市场并购活动能更顺利地进行。这种国际间资本流动需要考虑成本,跨国公司的并购成本可以从并购过程所涉及的各项进行分析,包括对目标公司的评估成本、协商确认并购活动、并购进行过程。评估目标公司成本常采用现金流折现法,也可采用基于古诺模型的公司评估方法,更多地考虑市场因素,多角度分析目标公司的可能价格。     

The Costs of Deception: Evidence from Psychology

Recently, it has been argued that the evidence in social science research suggests that deceiving participants in an experiment does not lead to a significant loss of experimental control. Based on this assessment, experimental economists were counseled to lift their de facto prohibition against deception to capture its potential benefits. To the extent that this recommendation is derived from empirical studies, we argue that it draws on a selective sample of the available evidence. Building on a systematic review of relevant research in psychology, we present two major results: First, the evidence suggests that the experience of having been deceived generates suspicion that in turn is likely to affect the judgment and decision making of a non-negligible number of participants. Second, we find little evidence for the reputational spillover effects that have been hypothesized by a number of authors in psychology and economics (e.g., Kelman, H.C., 1967. Psychological Bulletin. 67, 1–11; Davis, D.D. and Holt, C.A., 1993. Experimental Economics. Princeton University Press, Princeton). Based on a discussion of the methodological costs and benefits of deception, we conclude that experimental economists' prohibition of deception is a sensible convention that economists should not abandon.     

The Effect of Privatization on Public Transit Costs

In an effort to reduce operating deficits, increase productivity, and improve the quality of services, the public transit sector has been moving away from public ownership and operation and towards a franchising arrangement whereby a local government authorizes a private firm to manage and operate the city's public transit system. Profit maximization considerations imply that private managers have stronger incentives for cost efficiency. One such example is the city of Indianapolis which began privatization efforts in its transit operations in 1996. Based upon monthly data from January 1991 through March 1997, this study examines the effect of privatization on the city's cost of providing mass transit. The primary implication of the study is that Indianapolis has experienced an annual 2.5% reduction in operating costs since privatizing the management of its public transit system.     

The Use of Dental Services among Older Australians: Does Location Matter?

Based on the National Health Survey of 2005, this study examined the use of dental services among non‐institutionalised older Australians. The results of the regression revealed differences in the frequency of dental visits across the states. The greater the public dental health expenditure per capita in each state the more likely residents of that state were to have visited the dentist in the previous year. Older people residing outside major cities experienced the greatest disadvantage. In addition to the socioeconomic factors reported by studies, in Australia inequalities in access to dental health services was associated with urbanicity and Australian states.