Compression of Morbidity: In Retrospect and in Prospect

By postponing the age at which chronic infirmity begins,disability and morbidity could be compressed into a shorter period of the average human life span, resulting in a society in which the active and vital years of life would increase in length, the disabilities and frailties of ageing would be postponed,and the total amount of lifetime disability and morbidity would decrease

Early Time Evolution of High Energy Heavy Ion Collisions

We solve the Yang-Mills equations in the framework of the McLerran-Venugopalan model for small times tau after a collision of two nuclei. An analytic expansion around tau=0 leads to explicit results for the field strength and the energy momentum tensor of the gluon field at early times. We then discuss constraints for the energy density, pressure and flow of the plasma phase that emerges after thermalization of the gluon field.Comment: 4 pages, 1 figure; contribution to Quark Matter 2006; submitted to J. Phys.

Quark Recombination and Heavy Quark Diffusion in Hot Nuclear Matter

We discuss resonance recombination for quarks and show that it is compatible with quark and hadron distributions in local thermal equilibrium. We then calculate realistic heavy quark phase space distributions in heavy ion collisions using Langevin simulations with non-perturbative T-matrix interactions in hydrodynamic backgrounds. We hadronize the heavy quarks on the critical hypersurface given by hydrodynamics after constructing a criterion for the relative recombination and fragmentation contributions. We discuss the influence of recombination and flow on the resulting heavy meson and single electron R_AA and elliptic flow. We will also comment on the effect of diffusion of open heavy flavor mesons in the hadronic phase.Comment: Contribution to Quark Matter 2011, submitted to J.Phys.G; 4 pages, 5 figure

CHALLENGES IN CONFRONTING PANDEMIC INFLUENZA USING NOVEL ADJUVANTED VACCINES

Pandemic influenza is a recurring threat throughout history. Characterized by rapid spread and high attack rate, the features of pandemic influenza are grounded in the lack of immunologic experience with pandemic virus subtypes in the majority of the human population alive during the outbreak. Immunization is regarded as a key tool in preparing for, and mitigating, pandemic influenza. Unfortunately, capacity to manufacture sufficient inactivated influenza antigen by currently-licensed processes remains challenging, and this problem is amplified by the very short timeline for production and distribution that may be available. GSK has addressed the pandemic influenza challenge by application of the AS03 adjuvant system, a tocopherol-based emulsion. Vaccines containing AS03 and inactivated split virion influenza antigens manufactured by two distinct processes at GSK’s facilities in Germany and Canada have been evaluated in pre-clinical systems and in humans with closely similar results. AS03 has been shown to provide a marked antigen-sparing effect, especially for difficult antigens such as H5N1. In addition, AS03 added to inactivated influenza vaccines has also allowed induction of cross-reactive humoral and cellular responses to antigenically diverse H5N1 viruses. By broadening cross-reactivity, AS03 might allow stockpiled vaccines to be deployed as a first counter-measure, even if the vaccine antigen available is not closely antigenically matched to the threat virus. The deployment of GSK’s AS03-adjuvanted vaccines Pandemrix™ and Arepanrix™ to confront the recent swine-origin H1N1 pandemic experience has required the management of multiple novel challenges. These have included the rapid conduct of clinical trials to satisfy a range of regulatory and public health needs, real-time evolution of dosing recommendations as the vaccines were used, consideration of the potential interaction of pandemic and seasonal vaccines, the use of non-traditional sources of data for safety and effectiveness, and safety monitoring of mass-vaccination campaigns on an unprecedented scale. GSK’s experience with, and learnings from, some of these challenges will be discussed

Equipoise, design bias, and randomized controlled trials: the elusive ethics of new drug development

The concept of 'equipoise', or the 'uncertainty principle', has been represented as a central ethical principle, and holds that a subject may be enrolled in a randomized controlled trial (RCT) only if there is true uncertainty about which of the trial arms is most likely to benefit the patient. We sought to estimate the frequency with which equipoise conditions were met in industry-sponsored RCTs in rheumatology, to explore the reasons for any deviations from equipoise, to examine the concept of 'design bias', and to consider alternative ethical formulations that might improve subject safety and autonomy. We studied abstracts accepted for the 2001 American College of Rheumatology meetings that reported RCTs, acknowledged industry sponsorship, and had clinical end-points (n = 45), and examined the proportion of studies that favored the registration or marketing of the sponsor's drug. In every trial (45/45) results were favorable to the sponsor, indicating that results could have been predicted in advance solely by knowledge of sponsorship (P < 0.0001). Equipoise clearly was being systematically violated. Publication bias appeared to be an incomplete explanation for this dramatic result; this bias occurs after a study is completed. Rather, we hypothesize that 'design bias', in which extensive preliminary data are used to design studies with a high likelihood of being positive, is the major cause of the asymmetric results. Design 'bias' occurs before the trial is begun and is inconsistent with the equipoise principle. However, design bias increases scientific efficiency, decreases drug development costs, and limits the number of subjects required, probably reducing aggregate risks to participants. Conceptual and ethical issues were found with the equipoise principle, which encourages performance of negative studies; ignores patient values, patient autonomy, and social benefits; is applied at a conceptually inappropriate decision point (after randomization rather than before); and is in conflict with the Belmont, Nuremberg, and other sets of ethical principles, as well as with US Food and Drug Administration procedures. We propose a principle of 'positive expected outcomes', which informs the assessment that a trial is ethical, together with a restatement of the priority of personal autonomy