Pricing, Patent Loss and the Market For Pharmaceuticals

Empirical studies suggest that entry of generic competitors results in minimal decreases or even increases in brand-name drug prices as well as sharp declines in brand-name advertising. This paper examines circumstances under which this empirical pattern could be observed. The analysis focuses on models where the demand for brand-name pharmaceuticals is divided into two segments, only one of which is cross-price-sensitive. Brand-name firms are assumed to set price and advertising in a Stackelberg context; they allow for responses by generic producers but the latter take decisions by brand-name f inns as given. Brand-name price and advertising responses to entry are shown to depend upon the properties of the reduced-form brand-name demand function. Conditions for positive price responses and negative advertising responses are derived. We also examine the implications for brand-name price levels, and for the brand-name price response to entry, of health sector trends (such as increasing HMO enrollments) that may have the effect of expanding the size of the cross-price-sensitive segment of the market. The paper concludes with a review of recent empirical research and suggestions for future work on the effects of generic entry.

"Generic Entry and the Pricing of Pharmaceuticals"

During the 1980s the share of prescriptions sold by retail pharmacies that was accounted for by generic products roughly doubled. The price response to generic entry of brand-name products has been a source of controversy. In this paper we estimate models of price responses to generic entry in the market for brand-name and generic drugs. We study a sample of 32 drugs that lost patent protection during the early to mid-1980s. Our results provide strong evidence that brand-name prices increase after entry and are accompanied by large price decreases in the price of generic drugs.

A free-piston Stirling engine/linear alternator controls and load interaction test facility

A test facility at LeRC was assembled for evaluating free-piston Stirling engine/linear alternator control options, and interaction with various electrical loads. This facility is based on a 'SPIKE' engine/alternator. The engine/alternator, a multi-purpose load system, a digital computer based load and facility control, and a data acquisition system with both steady-periodic and transient capability are described. Preliminary steady-periodic results are included for several operating modes of a digital AC parasitic load control. Preliminary results on the transient response to switching a resistive AC user load are discussed

Spatial heterogeneity of soil nutrients and plant species in herb-dominated communities of contrasting land use

Recent interest in spatial pattern in terrestrial ecosystems has come from an awareness of theintimate relationship between spatial heterogeneity of soil resources and maintenance of plant species diversity. Soil and vegetation can vary spatially inresponse to several state factors of the system. In this study, we examined fine-scale spatial variability of soil nutrients and vascular plant species in contrasting herb-dominated communities (a pasture and an oldfield) to determine degree of spatial dependenceamong soil variables and plant community characteristics within these communities by sampling at 1-m intervals. Each site was divided into 25 1-m 2 plots. Mineral soil was sampled (2-cm diameter, 5-cm depth) from each of four 0.25-m2 quarters and combined into a single composite sample per plot. Soil organic matter was measured as loss-on-ignition. Extractable NH4 and NO3 were determined before and after laboratory incubation to determine potential net N mineralization and nitrification. Cations were analyzed using inductively coupled plasma emission spectrometry. Vegetation was assessed using estimated percent cover. Most soiland plant variables exhibited sharp contrasts betweenpasture and old-field sites, with the old field having significantly higher net N mineralization/nitrification, pH, Ca, Mg, Al, plant cover, and species diversity, richness, and evenness. Multiple regressions revealedthat all plant variables (species diversity, richness,evenness, and cover) were significantly related to soil characteristics (available nitrogen, organic matter,moisture, pH, Ca, and Mg) in the pasture; in the old field only cover was significantly related to soil characteristics (organic matter and moisture). Both sites contrasted sharply with respect to spatial pattern of soil variables, with the old field exhibiting a higher degree of spatial dependence. These results demonstrate that land-use practices can exert profound influence on spatial heterogeneity of both soil properties and vegetation in herb-dominated communities

Spatial heterogeneity of soil nutrients and plant species in herb-dominated communities of contrasting land use

Recent interest in spatial pattern in terrestrial ecosystems has come from an awareness of theintimate relationship between spatial heterogeneity of soil resources and maintenance of plant species diversity. Soil and vegetation can vary spatially inresponse to several state factors of the system. In this study, we examined fine-scale spatial variability of soil nutrients and vascular plant species in contrasting herb-dominated communities (a pasture and an oldfield) to determine degree of spatial dependenceamong soil variables and plant community characteristics within these communities by sampling at 1-m intervals. Each site was divided into 25 1-m 2 plots. Mineral soil was sampled (2-cm diameter, 5-cm depth) from each of four 0.25-m2 quarters and combined into a single composite sample per plot. Soil organic matter was measured as loss-on-ignition. Extractable NH4 and NO3 were determined before and after laboratory incubation to determine potential net N mineralization and nitrification. Cations were analyzed using inductively coupled plasma emission spectrometry. Vegetation was assessed using estimated percent cover. Most soiland plant variables exhibited sharp contrasts betweenpasture and old-field sites, with the old field having significantly higher net N mineralization/nitrification, pH, Ca, Mg, Al, plant cover, and species diversity, richness, and evenness. Multiple regressions revealedthat all plant variables (species diversity, richness,evenness, and cover) were significantly related to soil characteristics (available nitrogen, organic matter,moisture, pH, Ca, and Mg) in the pasture; in the old field only cover was significantly related to soil characteristics (organic matter and moisture). Both sites contrasted sharply with respect to spatial pattern of soil variables, with the old field exhibiting a higher degree of spatial dependence. These results demonstrate that land-use practices can exert profound influence on spatial heterogeneity of both soil properties and vegetation in herb-dominated communities

Ariel - Volume 6 Number 1

Editors John Lammie Curt Cummings Frank Chervenak J.D. Kanofsky Mark Dembert Entertainment Robert Breckenridge Joe Conti Gary Kaskey Photographer Larry Glazerman Overseas Editor Mike Sinason Circulation Jay Amsterdam Humorist Jim McCann Staff Ken Jaffe Bob Sklaroff Halley Faus

An engineered cardiac reporter cell line identifies human embryonic stem cell-derived myocardial precursors.

Unlike some organs, the heart is unable to repair itself after injury. Human embryonic stem cells (hESCs) grow and divide indefinitely while maintaining the potential to develop into many tissues of the body. As such, they provide an unprecedented opportunity to treat human diseases characterized by tissue loss. We have identified early myocardial precursors derived from hESCs (hMPs) using an α-myosin heavy chain (αMHC)-GFP reporter line. We have demonstrated by immunocytochemistry and quantitative real-time PCR (qPCR) that reporter activation is restricted to hESC-derived cardiomyocytes (CMs) differentiated in vitro, and that hMPs give rise exclusively to muscle in an in vivo teratoma formation assay. We also demonstrate that the reporter does not interfere with hESC genomic stability. Importantly, we show that hMPs give rise to atrial, ventricular and specialized conduction CM subtypes by qPCR and microelectrode array analysis. Expression profiling of hMPs over the course of differentiation implicate Wnt and transforming growth factor-β signaling pathways in CM development. The identification of hMPs using this αMHC-GFP reporter line will provide important insight into the pathways regulating human myocardial development, and may provide a novel therapeutic reagent for the treatment of cardiac disease

Graphical approaches for the control of generalised error rates

When simultaneously testing multiple hypotheses, the usual approach in the context of confirmatory clinical trials is to control the familywise error rate (FWER), which bounds the probability of making at least one false rejection. In many trial settings, these hypotheses will additionally have a hierarchical structure that reflects the relative importance and links between different clinical objectives. The graphical approach of Bretz et al. (2009) is a flexible and easily communicable way of controlling the FWER while respecting complex trial objectives and multiple structured hypotheses. However, the FWER can be a very stringent criterion that leads to procedures with low power, and may not be appropriate in exploratory trial settings. This motivates controlling generalised error rates, particularly when the number of hypotheses tested is no longer small. We consider the generalised familywise error rate (k-FWER), which is the probability of making k or more false rejections, as well as the tail probability of the false discovery proportion (FDP), which is the probability that the proportion of false rejections is greater than some threshold. We also consider asymptotic control of the false discovery rate (FDR), which is the expectation of the FDP. In this paper, we show how to control these generalised error rates when using the graphical approach and its extensions. We demonstrate the utility of the resulting graphical procedures on three clinical trial case studies.Biometrika Trust; Medical Research Council, Grant/Award Numbers: MC∖UU∖00002/6, MR/N028171/