A review and validation of overall survival extrapolation in health technology assessments of cancer immunotherapy by the National Institute for Health and Care Excellence: how did the initial best estimate compare to trial data subsequently made available?

Background: Validation of overall survival (OS) extrapolations of immune-checkpoint inhibitors (ICIs) during the National Institute for Health and Care Excellence (NICE) Single Technology Assessment (STA) process is limited due to data still maturing at the time of submission. Inaccurate extrapolation may lead to inappropriate decision-making. The availability of more mature trial data facilitates a retrospective analysis of the plausibility and validity of initial extrapolations. This study compares these extrapolations to subsequently available longer-term data.

Methods: A systematic search of completed NICE appraisals of ICIs from March 2000 to December 2017 was performed. A targeted search was also undertaken to procure published OS data from the pivotal clinical trials for each identified STA made available post-submission to NICE. Initial Kaplan-Meier curves and associated extrapolations from NICE documentation were extracted to compare the accuracy of OS projections versus the most mature data.

Results: The review identified 11 STAs, of which 10 provided OS data upon submission to NICE. The extrapolations undertaken considered parametric or piecewise survival models. Additional data cut-offs provided a mean of 18 months of OS beyond the end of the original data. Initial extrapolations typically under-estimated OS from the most mature data cut-off by 0.4–2.7%, depending on the choice of assessment method and use of the manufacturer- or ERG-preferred extrapolation.

Conclusion: Long-term extrapolation of OS is required for NICE STAs based on initial immature OS data. The results of this study demonstrate that the initial OS extrapolations employed by manufacturers and ERGs generally predicted OS reasonably well when compared to more mature data (when available), although on average they appeared to underestimate OS. This review and validation shows that, while the choice of OS extrapolation is uncertain, the methods adopted are generally aligned with later-published follow-up data and appear appropriate for informing HTA decisions.     

Charges in the Industrial Water Sector: Comparison Between Ireland and Spain

The European Treaty supports the application of the polluter pays principle in all environmental policies including the Water Framework Directive. This paper assesses the efficiency of water-charging systems in two European regions. The regions examined are the South west region of Ireland and the Navarre region in Spain which were selected because they are similar in terms of economic indicators but different in terms of water pricing structures. The paper describes the development and application of a simple model to analyse data on water-charging systems from these two regions. We present the results of a detailed scenario-based investigation illustrating the differences between experience, composition and basis, impact and constraints on the application of water charges for both regions. The key findings are that existing water charges do not provide incentives for users to use water efficiently and thereby do not contribute effectively to the environmental objectives of the Water Framework Directive.     

SOCIAL COOPERATIVES IN ITALY: ECONOMIC ANTECEDENTS AND REGIONAL DISTRIBUTION

Social cooperatives represent the most notable form of non‐profit organizations operating in Italy in the social services field, the birth and development of which has been strongly linked to, and conditioned by, the needs and resources of territories and communities. This paper intends to demonstrate how certain socio‐economic factors, recognized in economic literature as antecedents of the development of social enterprises, may account for the spread of social cooperatives in different Italian regions. Furthermore, the research results demonstrate an inter‐regional differentiation of the shape social cooperation has entered into in Italy.     

Social Position and Behaviour: A Formalization

Modern society has witnessed anever-increasing development in the social sciences;partly due to changes in mentality, and partly due tothe growing requirements of the economic and political world – requirements which frequently takeon the guise of necessity, as for instance in thecases of market research and electoral opinion polls.Such development has produced an increasing paralleldemand for mathematical accuracy and exactitude inthese fields.The intention here is to rationalize the basic logicand methodology of the sociological procedure; anintention, it is hoped, which could be influential inimproving practical sociological work by rendering itmore comprehensible. This requires the employment offairly sophisticated mathematical and statisticalnotions.Section 1 outlines the definitions considered essential for the rationalization of the basiclogic framework previously described.Section 2 discusses the general concept of statisticalvariance. Section 3 introduces the notion of ``heterogeneity'and offers several propositions linked to this concept.Section 5 revolves around the notion of ``inaccuracy'.Section 6 presents a theorem relating to theimmersion of metric spaces in Banach spaces, andshows how the theorem can be used to constructtheoretically satisfactory immersion algorithms.Section 7 together with the material, which ispreviously introduced in Section 4, outlines thecluster analysis and the principal components methodologies.     

Temporary hires and innovative investments

The flexicurity approach claims a positive effect of flexible labour on firm performance, also through an increased ability to innovate. Critics consider it a deregulation of the labour market, decreasing investment in human capital and innovation. We contribute to this broad debate providing an estimate of the relationships linking innovative investment, substitution investment, permanent hires and temporary hires. In particular, we aim at affirming or denying that innovative investments are accompanied by a specific kind of workforce, being it stable or flexible. In doing so, we contribute to bridge the gap among two quite separate strands of literature, as existing literature usually analyses capital and labour separately. Estimating a nonlinear recursive equation system we highlight a significant increase in the likelihood of hiring on a permanent base when the firm innovates; this holds till 2008. Afterward, during the crisis, innovating firms are more likely to hire using temporary contracts instead, a possible signal of a cost saving strategy adopted in a loose labour market by firms still able to innovate. Furthermore, both permanent and temporary hires never depend on increases in labour costs; however, substitution investment increases when labour cost increases, maybe in an attempt to increase labour productivity through a more efficient capital equipment.     

财富对创业的异质性影响——基于三省农户的实证分析

文章从动态视角重新考察了财富与创业的关系,并基于中国农村固定观察点的调查数据进行了实证分析,研究发现财富对创业的影响并非简单的单调关系。当农户资产处于0-98.70分位数区间(0<资产<26.84万元)时,农户资产越多越倾向于创业,这与静态模型的预测相同;但当资产处于98.70分位数之后的区间(资产≥26.84万元)时,样本自选择偏差的存在使二者呈负相关关系,即资产越多,创业概率越低,支持了动态模型的理论预测。文章还使用人情收入作为资产的工具变量来解决模型中可能存在的内生性问题,发现此结论依然稳健。     

Multinationals without Advantages

We question the widespread argument that firms embarking on foreign direct investments must possess some specific advantages to offset the penalties of operating across national and cultural boundaries. A simple model shows that firms might invest abroad to capture local advantages through geographical proximity of plant location, rather than to exploit existing ones. Because of spatially bounded spillovers, laggard firms might use foreign investments to acquire location-specific knowledge, whereas leading firms might prefer costly exports to avoid the dissipation of their advantages.
JEL classification: F 23; O 32; L 22