A Bayesian adaptive marker‐stratified design for molecularly targeted agents with customized hierarchical modeling

It is well known that the treatment effect of a molecularly targeted agent (MTA) may vary dramatically, depending on each patient's biomarker profile. Therefore, for a clinical trial evaluating MTA, it is more reasonable to evaluate its treatment effect within different marker subgroups rather than evaluating the average treatment effect for the overall population. The marker‐stratified design (MSD) provides a useful tool to evaluate the subgroup treatment effects of MTAs. Under the Bayesian framework, the beta‐binomial model is conventionally used under the MSD to estimate the response rate and test the hypothesis. However, this conventional model ignores the fact that the biomarker used in the MSD is, in general, predictive only for the MTA. The response rates for the standard treatment can be approximately consistent across different subgroups stratified by the biomarker. In this paper, we proposed a Bayesian hierarchical model incorporating this biomarker information into consideration. The proposed model uses a hierarchical prior to borrow strength across different subgroups of patients receiving the standard treatment and, therefore, improve the efficiency of the design. Prior informativeness is determined by solving a “customized” equation reflecting the physician's professional opinion. We developed a Bayesian adaptive design based on the proposed hierarchical model to guide the treatment allocation and test the subgroup treatment effect as well as the predictive marker effect. Simulation studies and a real trial application demonstrate that the proposed design yields desirable operating characteristics and outperforms the existing designs

Patents versus patenting: implications of intellectual property protection for biological research

A new survey shows scientists consider the proliferation of intellectual property protectionto have a strongly negative effect on research.patents, biology, intellectual property, material transfer agreements

A Compensatory Liability Regime to Promote the Exchange of Microbial Genetic Resources for Research and Benefit Sharing

Female rhesus macaques were immunized with HIV virus-like particles (HIV-VLPs) or HIV DNA administered as sequential combinations of mucosal (intranasal) and systemic (intramuscular) routes, according to homologous or heterologous prime-boost schedules. The results show that in rhesus macaques only the sequential intranasal and intramuscular administration of HIV-VLPs, and not the intranasal alone, is able to elicit humoral immune response at the systemic as well as the vaginal level.funding agencies|Simian Vaccine Evaluation Unit (SVEU) of the Division of AIDS||European Community|201433|</p

Synergies in Wireless Telephony: Evidence from the Broadband PCS Auctions

We examine bid data from the first two broadband PCS spectrum auctions for evidence of value synergies. First, we estimate a benchmark regression for the determinants of final auction prices. Then, we include variables reflecting the extent to which bidders ultimately won or already owned the adjacent wireless properties. Consistent with geographic synergies in an ascending-bid auction, prices were higher when the highest-losing bidder had adjacent licenses. The footprints of winning bidders suggest that they were often successful in realizing these synergies.Auctions; Multi-Object Auctions; Spectrum Auctions

Multilateral Versus Regional Trading Arrangements: Substitutes Or Compliments?

We summarise salient developments in the interaction of the multilateral trading system and multilateral trading agreements (MTAs) on the one hand and regional trading agreements (RTAs) on the other. We then consider the economic effects of RTAs, comparing customs unions with free trade agreements. We argue, contrary to much received wisdom, that either may produce more economic benefits than the other, depending on the specific context in which they are introduced. There follows a discussion of the political economy effects of RTAs. Some of these have unfavourable, some neutral and some favourable effects on the progress of further MTAs. We conclude that the case against RTAs as eroding the MTS and inhibiting further MTA negotiations, as expounded by such economists as Krueger and Bhagwati, is not well founded. There remain grounds for optimism that the process of competitive liberalisation in RTAs will lead eventually to further multilateral liberalisation.customs unions, free trade areas, multilateral agreements, multilateral trading system, regional agreements, rules of origin, scale economies, trade creation, trade diversion.

Horses as Sources of Proprietary Information: Commercialization, Conservation, and Compensation Pursuant to the Convention on Biological Diversity

Horses indigenous to East and Southeast (E/SE) Asia, including native, landrace, feral, and wild populations, embody valuable genetic diversity. Conservation efforts for animals have largely been driven by humane altruism, with little consideration for the information value of genomes. Yet, if horses are viewed as archives of information as well as objects of affection, their conservation shifts to a market-based paradigm. Horse genetic resources (GR) likely contain significant value to the lucrative global horse industry, including veterinary applications such as diagnostics, therapeutics, genetic markers, gene therapies, and cloning technologies. As biotechnology becomes increasingly sophisticated, mining of horse GR will accelerate, thus facilitating identification, inventorying, bioprospecting, and commercialization of genetic information. Yet, establishing a value chain that balances equitable compensation for commercial applications while promoting conservation of horse populations remains a challenge. Recommendations presented here include establishing regional and national human resource and institutional capacity (competent national authorities), that catalog eco-geographical inventories of horse GR; monitor, manage, market and direct equitable value chains from horse to genetic information to commercial products; and ensure revenue flow back to support conservation. This system will foster market incentives to build capacity for sustainable conservation of the diverse horse populations of E/SE Asia

Patenting and licensing of university research: promoting innovation or undermining academic values?

Since the 1980s in the US and the 1990s in Europe, patenting and licensing activities by universities have massively increased. This is strongly encouraged by governments throughout the Western world. Many regard academic patenting as essential to achieve 'knowledge transfer' from academia to industry. This trend has far-reaching consequences for access to the fruits of academic research and so the question arises whether the current policies are indeed promoting innovation or whether they are instead a symptom of a pro-intellectual property (IP) culture which is blind to adverse effects. Addressing this question requires both empirical analysis (how real is the link between academic patenting and licensing and 'development' of academic research by industry?) and normative assessment (which justifications are given for the current policies and to what extent do they threaten important academic values?). After illustrating the major rise of academic patenting and licensing in the US and Europe and commenting on the increasing trend of 'upstream' patenting and the focus on exclusive as opposed to non-exclusive licences, this paper will discuss five negative effects of these trends. Subsequently, the question as to why policymakers seem to ignore these adverse effects will be addressed. Finally, a number of proposals for improving university policies will be made

National Authority for Health: France

Provides an overview of France's National Authority for Health, which defines best-care standards and assesses the benefit and effectiveness of new technologies for inclusion on benefits lists. Examines its use of comparative effectiveness research

A projection model of the contributory pension expenditure of the spanish social security system: 2004-2050

The need for long-term fiscal projections is self evident. Of these projections, pension expenditure is one of the most important since firstly it represents a large share of total expenditure, and secondly because of the positive correlation between this variable and demographic ageing. In this paper, we develop a model to project contributory pension expenditures in the Spanish Social Security System disaggregating the results by pension category, social security regime and sex. The most salient of the results obtained is the expected steady growth of total expenditure in contributory pensions. This would lie around 15% of GDP around 2045 compared to its initial level of barely 8% even though the baseline scenario incorporates a substantial recovery of employment and female participation rates. By pension categories, retirement pensions are those that determine the tendency of total expenditure evolution. Interesting conclusions can also be extracted from the analysis by sex. For instance, even accounting for an increase in female retirement pensions due to their higher participation, the corresponding increase in widow male pensions implies a higher total increase of the total number of contributory pensions accruing to men.Pensions system, sustainability, public expenditure.