Generic entry into a regulated pharmaceutical market

The aim of this paper is to analyse empirically entry decisions by generic firms intomarkets with tough regulation. Generic drugs might be a key driver of competitionand cost containment in pharmaceutical markets. The dynamics of reforms ofpatents and pricing across drug markets in Spain are useful to identify the impact ofregulations on generic entry. Estimates from a count data model using a panel of 86active ingredients during the 1999 2005 period show that the drivers of genericentry in markets with price regulations are similar to less regulated markets: genericfirms entries are positively affected by the market size and time trend, and negativelyaffected by the number of incumbent laboratories and the number of substitutesactive ingredients. We also find that contrary to what policy makers expected, thesystem of reference pricing restrains considerably the generic entry. Short run brandname drug price reductions are obtained by governments at the cost of long runbenefits from fostering generic entry and post-patent competition into the markets.

Otimização Não Linear de Mínimos Quadrados

O problema de otimização de mínimos quadrados e apresentado como uma classe importante de problemas de minimização sem restrições. A importância dessa classe de problemas deriva das bem conhecidas aplicações a estimação de parâmetros no contexto das analises de regressão e de resolução de sistemas de equações não lineares. Apresenta-se uma revisão dos métodos de otimização de mínimos quadrados lineares e de algumas técnicas conhecidas de linearização. Faz-se um estudo dos principais métodos de gradiente usados para problemas não lineares gerais: Métodos de Newton e suas modificações incluindo os métodos Quasi-Newton mais usados (DFP e BFGS). Introduzem-se depois métodos específicos de gradiente para problemas de mínimos quadrados: Gauss-Newton e Levenberg-Larquardt. Apresenta-se uma variedade de exemplos selecionados na literatura para testar os diferentes métodos usando rotinas MATLAB. Faz-se uma an alise comparativa dos algoritmos baseados nesses ensaios computacionais que exibem as vantagens e desvantagens dos diferentes métodos.

On the throughput-WIP trade-off in queueing systems, diminishing returns and the threshold property: A linear programming approach

We present a new unifying framework for investigating throughput-WIP(Work-in-Process) optimal control problems in queueing systems,based on reformulating them as linear programming (LP) problems withspecial structure: We show that if a throughput-WIP performance pairin a stochastic system satisfies the Threshold Property we introducein this paper, then we can reformulate the problem of optimizing alinear objective of throughput-WIP performance as a (semi-infinite)LP problem over a polygon with special structure (a thresholdpolygon). The strong structural properties of such polygones explainthe optimality of threshold policies for optimizing linearperformance objectives: their vertices correspond to the performancepairs of threshold policies. We analyze in this framework theversatile input-output queueing intensity control model introduced byChen and Yao (1990), obtaining a variety of new results, including (a)an exact reformulation of the control problem as an LP problem over athreshold polygon; (b) an analytical characterization of the Min WIPfunction (giving the minimum WIP level required to attain a targetthroughput level); (c) an LP Value Decomposition Theorem that relatesthe objective value under an arbitrary policy with that of a giventhreshold policy (thus revealing the LP interpretation of Chen andYao's optimality conditions); (d) diminishing returns and invarianceproperties of throughput-WIP performance, which underlie thresholdoptimality; (e) a unified treatment of the time-discounted andtime-average cases.

Exact tests for correlation and for the slope in simple linear regressions without making assumptions

We present an exact test for whether two random variables that have known bounds on their support are negatively correlated. The alternative hypothesis is that they are not negatively correlated. No assumptions are made on the underlying distributions. We show by example that the Spearman rank correlation test as the competing exact test of correlation in nonparametric settings rests on an additional assumption on the data generating process without which it is not valid as a test for correlation.We then show how to test for the significance of the slope in a linear regression analysis that invovles a single independent variable and where outcomes of the dependent variable belong to a known bounded set.

A test of the predictive validity of non-linear QALY models using time trade-off utilities

This paper presents a test of the predictive validity of various classes ofQALY models (i.e., linear, power and exponential models). We first estimatedTTO utilities for 43 EQ-5D chronic health states and next these states wereembedded in health profiles. The chronic TTO utilities were then used topredict the responses to TTO questions with health profiles. We find that thepower QALY model clearly outperforms linear and exponential QALY models.Optimal power coefficient is 0.65. Our results suggest that TTO-based QALYcalculations may be biased. This bias can be avoided using a power QALY model.

Implementing TURF analysis through binary linear programming

This paper introduces the approach of using Total Unduplicated Reach and Frequency analysis (TURF) to design a product line through a binary linear programming model. This improves the efficiency of the search for the solution to the problem compared to the algorithms that have been used to date. The results obtained through our exact algorithm are presented, and this method shows to be extremely efficient both in obtaining optimal solutions and in computing time for very large instances of the problem at hand. Furthermore, the proposed technique enables the model to be improved in order to overcome the main drawbacks presented by TURF analysis in practice.

Generic finiteness of equilibrium payoffs for bimatrix games

It is shown that in any affine space of payoff matrices the equilibriumpayoffs of bimatrix games are generically finite.

The impact of generic reference pricing interventions in the statin market

The objective of this study was to evaluate the intended and unintended impact on pharmaceutical use and sales of three public financing reforms applied to the prescription of statins: a Spanish generic reference pricing (RP) system for lovastatin and simvastatin, and two competing policies introduced by the Andalusian Public Health Service (APHS) for all statins, first a maximum consumer price (MCP) and then a so called quality prescribing incentive for general practitioners (MCP plus PI).This study is designed as an observational, retrospective, interrupted time series analysis with comparison series (APHS and the rest of Spain) of 46 monthly drug use and sales ratios from January 2001 to October 2004 for each active ingredient in the group of statins.RP has been effective at reducing the volume of sales growth of the off-patent statins, yet its overall impact on sales of all statins has been relatively modest. The quantity and volume of sales impact heavily depends on regulatory RP details such as when the system is introduced, how often it is updated, and how the reference price is calculated.

Restless bandits, linear programming relaxations and a primal-dual index heuristic

We develop a mathematical programming approach for the classicalPSPACE - hard restless bandit problem in stochastic optimization.We introduce a hierarchy of n (where n is the number of bandits)increasingly stronger linear programming relaxations, the lastof which is exact and corresponds to the (exponential size)formulation of the problem as a Markov decision chain, while theother relaxations provide bounds and are efficiently computed. Wealso propose a priority-index heuristic scheduling policy fromthe solution to the first-order relaxation, where the indices aredefined in terms of optimal dual variables. In this way wepropose a policy and a suboptimality guarantee. We report resultsof computational experiments that suggest that the proposedheuristic policy is nearly optimal. Moreover, the second-orderrelaxation is found to provide strong bounds on the optimalvalue.

On heuristic and linear models of judgment: Mapping the demand for knowledge

Research on judgment and decision making presents a confusing picture of human abilities. For example, much research has emphasized the dysfunctional aspects of judgmental heuristics, and yet, other findings suggest that these can be highly effective. A further line of research has modeled judgment as resulting from as if linear models. This paper illuminates the distinctions in these approaches by providing a common analytical framework based on the central theoretical premise that understanding human performance requires specifying how characteristics of the decision rules people use interact with the demands of the tasks they face. Our work synthesizes the analytical tools of lens model research with novel methodology developed to specify the effectiveness of heuristics in different environments and allows direct comparisons between the different approaches. We illustrate with both theoretical analyses and simulations. We further link our results to the empirical literature by a meta-analysis of lens model studies and estimate both human andheuristic performance in the same tasks. Our results highlight the trade-off betweenlinear models and heuristics. Whereas the former are cognitively demanding, the latterare simple to use. However, they require knowledge and thus maps of when andwhich heuristic to employ.

O Primal e o Dual na programação Linear

O tema da Programação Linear, com as suas particularizações do Problema dos Transportes e do Problema da Afectação de Recursos, é hoje estudado em cursos diversos onde uma disciplina de Investigação Operacional esteja presente. Trata-se, em última análise, de um problema de cálculo de extremos condicionados, seja de máximo ou de mínimo, que apresenta características muito particulares e de grande elegância simbólica. Também os Problemas dos Transportes e da Afectação de Recursos se podem resolver como problemas de Programação Linear, através do Algoritmo Simplex, embora seja preferível o recurso a algoritmos próprios, de muitíssimo maior simplicidade: o Algoritmo dos Transportes e o Algoritmo Húngaro, respectivamente. De molde a facilitar a compreensão do que realmente está em jogo, consideram-se aqui dois casos de determinação de extremos e de extremos condicionados, mas ao nível do final do ensino secundário.

Comparação entre os métodos da transeção linear e fotográfico na avaliação de cobertura vegetal morta, sob dois métodos de preparo, após a colheita da soja

A eficácia da cobertura vegetal morta no controle da erosão pode ser avaliada através de dois indicadores principais: a porcentagem de cobertura do solo pelos resíduos culturais e sua persistência sobre a superfície ao longo do tempo. O preparo do solo, por sua vez, pode exercer influência significativa sobre esses indicadores. O trabalho foi realizado no campo, no município de Eldorado do Sul, Depressão Central do Rio Grande do Sul. Avaliou-se a persistência da cobertura vegetal morta durante um período de pousio, que foi de maio de 1989 a abril de 1990, em sucessão à cultura da soja. Os resíduos dessa cultura foram manejados sem preparo, por escarificação e por gradagem. A porcentagem de cobertura do solo pelos resíduos culturais foi quantificada pelo método fotográfico e pelo da transeção linear. A cultura da soja produziu cobertura vegetal morta em pequena quantidade e de baixa durabilidade. A distribuição dos resíduos na superfície, sem preparo do solo, foi o tratamento que possibilitou melhor correlação (R²) entre os índices de cobertura obtidos pelos dois métodos testados. Nas áreas sob gradagem ou escarificação do solo, os índices de cobertura obtidos pelo método fotográfico foram superiores aos da transeção linear, enquanto, na área sem preparo do solo, houve similaridade entre os resultados dos dois métodos.

Correlação linear e espacial entre o rendimento de grãos do feijoeiro e a resistência mecânica à penetração em um Latossolo Vermelho distrófico

A resistência mecânica à penetração apresentada pelo solo exerce grande influência sobre o desenvolvimento vegetal, uma vez que o crescimento das raízes, assim como o rendimento das culturas, varia de forma inversamente proporcional ao seu valor. No ano agrícola de 2001/2002, na Fazenda Experimental de Ensino e Pesquisa da Faculdade de Engenharia/UNESP - Campus de Ilha Solteira, foram analisados o rendimento de grãos do feijoeiro (PG) e a resistência mecânica à penetração (R), de um Latossolo Vermelho distrófico. O objetivo foi apurar diretrizes relacionadas com o aumento da produtividade agrícola em questão, estudando a correlação linear e a espacial entre a PG e a R. Foi instalada uma rede geoestatística para a coleta dos dados do solo e da planta, estabelecida com espaçamentos de 5 x 5 m e 2,5 x 2,5 m, que continham 120 pontos amostrais distribuídos numa área de 1.875 m². A correlação linear entre a PG e a R foi praticamente nula, uma vez que, dependendo das profundidades estudadas do solo, apresentou coeficientes de correlação (r) menores do que 0,20. A análise geoestatística apresentou boa estrutura de dependência espacial, tanto para a PG quanto para a R, quando analisadas isoladamente. Entretanto, a análise espacial conjunta de tais atributos apresentou-se inconsistente. Assim, com o aumento da resistência mecânica à penetração, em determinada região do solo ocorreu ora aumento, ora diminuição do rendimento de grãos do feijoeiro.

Super-resolution of remotely sensed images with variable-pixel linear reconstruction

This paper describes the development and applications of a super-resolution method, known as Super-Resolution Variable-Pixel Linear Reconstruction. The algorithm works combining different lower resolution images in order to obtain, as a result, a higher resolution image. We show that it can make significant spatial resolution improvements to satellite images of the Earth¿s surface allowing recognition of objects with size approaching the limiting spatial resolution of the lower resolution images. The algorithm is based on the Variable-Pixel Linear Reconstruction algorithm developed by Fruchter and Hook, a well-known method in astronomy but never used for Earth remote sensing purposes. The algorithm preserves photometry, can weight input images according to the statistical significance of each pixel, and removes the effect of geometric distortion on both image shape and photometry. In this paper, we describe its development for remote sensing purposes, show the usefulness of the algorithm working with images as different to the astronomical images as the remote sensing ones, and show applications to: 1) a set of simulated multispectral images obtained from a real Quickbird image; and 2) a set of multispectral real Landsat Enhanced Thematic Mapper Plus (ETM+) images. These examples show that the algorithm provides a substantial improvement in limiting spatial resolution for both simulated and real data sets without significantly altering the multispectral content of the input low-resolution images, without amplifying the noise, and with very few artifacts.