A cost analysis of SIR-Spheres yttrium-90 resin microspheres versus tyrosine kinase inhibitors in the treatment of unresectable hepatocellular carcinoma in France,Italy, Spain and the UK

Abstract

Background and aims: A wide range of treatment options are available for hepatocellular carcinoma (HCC), including systemic treatment with tyrosine kinase inhibitors (TKIs) such as sorafenib and lenvatinib, immunotherapies, locoregional therapies such as selective internal radiation therapy (SIRT) and treatments with curative intent such as resection, radiofrequency ablation and liver transplantation. Given the substantial economic burden associated with HCC treatment, the aim of the present analysis was to establish the cost of using SIRT with SIR-Spheres yttrium-90 (Y-90) resin microspheres versus TKIs from healthcare payer perspectives in France, Italy, Spain and the United Kingdom (UK).

Methods: A cost model was developed to capture the costs of initial systemic treatment with sorafenib (95%) or lenvatinib (5%) versus SIRT in patients with HCC in Barcelona Clinic Liver Cancer (BCLC) stages B and C. A nested Markov model was utilized to model transitions between progression-free survival (PFS), progression and death, in addition to transitions between subsequent treatment lines. Cost and resource use data were identified from published sources in each of the four countries.

Results: Relative to TKIs, SIRT with SIR-Spheres Y-90 resin microspheres were found to be cost saving in all four country settings, with the additional costs of the microspheres and the SIRT procedure being more than offset by reductions in drug and drug administration costs, and treatment of adverse events. Across the four country settings, total cost savings with SIR-Spheres Y-90 resin microspheres fell within the range 5.4–24.9% and SIRT resulted in more patients ultimately receiving treatments with curative intent (4.6 vs. 1.4% of eligible patients).

Conclusion: SIR-Spheres Y-90 resin microspheres resulted in cost savings relative to TKIs in the treatment of unresectable HCC in all four country settings, while increasing the proportion of patients who become eligible for treatments with curative intent.     

Air pollution-mortality models: A demonstration of the effects of random measurement error

Errors of measurement have long been recognized as a chronic problem in statistical analysis. Although there is a vast statistical literature of multiple regression models estimating the air pollution-mortality relationship, this problem has been largely ignored. It is well known that pollution measures contain error, but the consequences of this error for regression estimates is not known. We use Lave and Seskin's air pollution model to demonstrate the consequences of random measurement error. We assume a range of 0% to 50% of the variance of the pollution measures is due to error. We find large differences in the estimated effects on mortality of the pollution variables as well as the other explanatory variables once this measurement error is taken into account. These results cast doubt on the usual regression estimates of the mortality effects of air pollution. More generally our results demonstrate the consequences of random measurement error in the explanatory variable of a multiple regression analysis and the misleading conclusions that may result in policy research if this error is ignored.     

Structural instability of the core

Let σ be a q-rule, where any coalition of size q, from the society of size n, is decisive. Let w(n,q)= 2q-n+1 and let W be a smooth ‘policy space’ of dimension w. Let U(W)^N be the space of all smooth profiles on W, endowed with the Whitney topology. It is shown that there exists an ‘instability dimension’ w^*(σ) with 2w^*(σ)w(n,q) such that:

1. (i) if ww^*(σ), and W has no boundary, then the core of σ is empty for a dense set of profiles in U(W)^N (i.e., almost always),

2. (ii) if ww^*(σ)+1, and W has a boundary, then the core of σ is empty, almost always,

3. (iii) if ww^*(σ)+1 then the cycle set is dense in W, almost always,

4. (iv) if ww^*(σ)+2 then the cycle set is also path connected, almost always.

The method of proof is first of all to show that if a point belongs to the core, then certain generalized symmetry conditions in terms of ‘pivotal’ coalitions of size 2q−n must be satisfied. Secondly, it is shown that these symmetry conditions can almost never be satisfied when either W has empty boundary and is of dimension w(n,q) or when W has non-empty boundary and is of dimension w(n,q)+1.     

PROPRIETORIAL CONTROL IN FAMILY FIRMS: SOME FUNCTIONS OF 'QUASI-ORGANIC' MANAGEMENT SYSTEMS

The purpose of this paper is to investigate the strategies of managerial control which are used by the proprietors of family-owned business enterprises. Interviews with the proprietors and senior managers of businesses in the building industry illustrate the ‘quasi-organic’ nature of management structures. These grant some autonomy to senior managers without threatening proprietorial decision-making prerogatives. Although the family firm has certain distinctive features, similar control strategies designed to ensure that delegated decisions are ‘reliable’ and ‘responsible’ are evident in various types of business enterprise. There is, then, scope for further comparative research within a conceptual framework which does not entirely divorce the family firm from other business organizations.     

The measurement and decomposition of nonuse values: A critical review

We critically review the literature that claims that existence values, or nonuse values in general, are a large and measurable component of total value for certain environmental resources. Our concern is not with the question “do nonuse values exist?” For some individuals they surely do. Rather, our concern is with two interrelated questions: are there operationally meaningful theorems which might lead to the specific measurement of nonuse values, and do we in fact have a body of credible evidence which shows that nonuse values, particularly components of any nonuse value, are “large”? We find nothing in the way of operationally meaningful hypotheses which would permit the estimation of values attributable to specific motives of individuals. We find no credible basis for claims related to either the measurement of existence and other motive-related values or claims for the “large” relative size of such values. In short, we question the conventional wisdom that such values are measurable and that they are significant as a component of total value.     

Finding a Nash equilibrium in spatial games is an NP-complete problem

Summary. We consider the class of (finite) spatial games. We show that the problem of determining whether there exists a Nash equilibrium in which each player has a payoff of at least k is NP-complete as a function of the number of players.Received: 15 September 2002, Revised: 9 March 2003, JEL Classification Numbers: C72.Correspondence to: H. HallerWe thank a referee for helpful comments. The hospitality of the Institute of Economics, University of Copenhagen, and the Institute for Advanced Studies, Vienna, is gratefully acknowledged by the third author.     

Asymmetric FDI and tax-treaty bargaining: theory and evidence

Tax treaties are often viewed as a mechanism for eliminating tax competition, however, this approach ignores the need for bargaining over the treaty's terms. This paper focuses on how bargaining can affect the withholding taxes set under the treaty. In a simple framework, we develop hypotheses about patterns in treaty tax rates. A key determinant for these patterns is the relative size of bilateral foreign direct investment (FDI) activity. In plausible situations, more asymmetric countries will negotiate treaties with higher tax rates. This theory is then tested using 1992 data from US and Organization for Economic Cooperation and Development (OECD) bilateral tax treaties. Overall, the data supports the prediction that greater asymmetric FDI activity increases the negotiated tax rates.