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Kathleen A. Getz - One of the best experts on this subject based on the ideXlab platform.
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The Impact of Collaborative and Risk-Sharing Innovation Approaches on Clinical and Regulatory Cycle Times
Therapeutic Innovation & Regulatory Science, 2014Co-Authors: Joseph A Dimasi, Kathleen A. GetzAbstract:During the past decade, high risk, cost, and inefficiency have driven pharmaceutical and biotechnology companies to enter into collaborative and shared innovation approaches, including mergers and acquisitions, joint development, and in-licensing. These approaches can interrupt the drug development process and affect program-level clinical and Regulatory Cycle times. To examine these potential impacts, detailed development histories were obtained for 289 new molecular and biologics entities that received FDA approval between 2000 and 2011. Approximately half the drugs analyzed had their clinical development activity interrupted by a collaborative or shared innovation approach, with in-licensing as the most common. The total duration (clinical plus approval phases) for interrupted development programs was 20% longer—an additional 14.8 months (median)—than that of uninterrupted development programs ( P
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the impact of collaborative and risk sharing innovation approaches on clinical and Regulatory Cycle times
Therapeutic Innovation & Regulatory Science, 2014Co-Authors: Joseph A Dimasi, Kathleen A. GetzAbstract:During the past decade, high risk, cost, and inefficiency have driven pharmaceutical and biotechnology companies to enter into collaborative and shared innovation approaches, including mergers and acquisitions, joint development, and in-licensing. These approaches can interrupt the drug development process and affect program-level clinical and Regulatory Cycle times. To examine these potential impacts, detailed development histories were obtained for 289 new molecular and biologics entities that received FDA approval between 2000 and 2011. Approximately half the drugs analyzed had their clinical development activity interrupted by a collaborative or shared innovation approach, with in-licensing as the most common. The total duration (clinical plus approval phases) for interrupted development programs was 20% longer—an additional 14.8 months (median)—than that of uninterrupted development programs (P <.05). Approval phase length differences between uninterrupted and interrupted programs were not statistically significant. The results of this study provide important benchmarks and new insights for portfolio planning, forecasting, and management.
K M Gwilliam - One of the best experts on this subject based on the ideXlab platform.
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Bus transport: Is there a Regulatory Cycle?
Transportation Research Part A: Policy and Practice, 2008Co-Authors: K M GwilliamAbstract:In 1983 Douglas Needham's "The Economics and Politics of Regulation" propounded the dynamic nature of the Regulatory phenomenon in a world of uncertainty, change and multiple, often conflicting, economic interests. The book's publication coincided with the early years of transport deregulation in the United States, but predated recognition in the transport sector of the significant distinction between competition "in the market" and "for the market". It did not therefore consider whether fluctuations between the domination of administration and that of free market forms, and between public and private sector responsibility for production of major utilities, were inherently perennial or whether there was a potential stable long term combination of public role as procurer and private sector role as supplier of these public utility services. This paper addresses that question in the context of two decades of experience of Regulatory reform in the field of bus transport in developing and transitional economies as well as in industrialized countries. It analyzes a number of drivers of the Cycle, including the adaptive, self-seeking behavior of suppliers and unrealistic aspirations of politicians, which ensure that stability will be hard to achieve, and concludes by setting out the structural and institutional requirements for a more robust and stable Regulatory outcome.
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Bus transport: is there a Regulatory Cycle?
2007Co-Authors: K M GwilliamAbstract:This paper addresses the question of whether fluctuations between the domination of administration and that of free market forms, and between public and private sector responsibility for production of major utilities, was inherently perennial or whether there was a potential stable long term combination of public role as procurer and private sector role as supplier of these public utility services. That raises three main questions, namely 1. is there a Regulatory Cycle in the bus transport sector? 2. if so, how is it generated? and, 3, is it inevitable? This paper addresses those questions, in the context of two decades of experience of Regulatory reform in the field of public passenger transport, documented mainly through papers from previous Thredbo conferences. (a) For the covering entry of this conference, please see ITRD abstract no. E215911.
Peter Wilkinson - One of the best experts on this subject based on the ideXlab platform.
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The Regulatory Cycle stalled? An assessment of current institutional obstacles to Regulatory reform in the provision of road-based public transport in Cape Town, South Africa
Research in Transportation Economics, 2010Co-Authors: Peter WilkinsonAbstract:Wide-ranging and ambitious proposals for the comprehensive transformation of public transport systems in major South African cities, including Cape Town, have now been in play for a decade or more since the country's post-apartheid transition. To date, progress in implementing such proposals has been, at best, much delayed and, in Cape Town, appears to have stalled, and may now be significantly compromised. This paper draws on aspects of the concept of Regulatory Cycles in the bus transport sector to explore some of the key factors which have given rise to this situation, focusing primarily on obstacles embedded in the present institutional framework which governs the provision of road-based public transport in the city. It specifically identifies difficulties in establishing an appropriately mandated and resourced agency at the local level to drive forward the transformation project and the sustained opposition of existing, largely [`]self-regulated' minibus-taxi operators as key factors which have obstructed the introduction of the proposed regime of [`]regulated competition'. A tentative conclusion is offered to the effect that perhaps a partial or [`]hybrid' transformation of the public transport system may be the best - and, indeed, possibly the most appropriate - outcome of the transformation process that can be anticipated under the present and foreseeable future circumstances prevailing in the city.
Hyen Jin Han - One of the best experts on this subject based on the ideXlab platform.
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A theory of deregulation in public transport
Research in Transportation Economics, 2020Co-Authors: Andrei Dementiev, Hyen Jin HanAbstract:Abstract This paper builds a theory of deregulation and roll-out of on-road competition in the public transport sector. Focusing on the dimensions of competition, ownership and authorisation, we identify five distinct Regulatory regimes: public monopoly, regulated monopoly, unregulated monopoly, outsourcing to private monopoly and competition in the market. Our generalised theoretical framework allows for the direct comparison in the social welfare terms of the monopolies' outcomes and the fragmented market structure after deregulation. We formulate a set of parameter restrictions that make competition in the market preferable to public monopoly and competition for the market in the form of outsourcing. We also show the theoretical possibility of a ‘revised’ Regulatory Cycle forming a sequential transition between these identified Regulatory regimes. Our model predicts possible policy reversals and the bypassing of certain phases of the Cycle, that can occur due to technological advances, changes in fiscal constraints and institutional capacity improvements.
Alexander Hoffmann - One of the best experts on this subject based on the ideXlab platform.
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Tunable signal processing through a kinase control Cycle: the IKK signaling node.
Biophysical journal, 2013Co-Authors: Marcelo Behar, Alexander HoffmannAbstract:The transcription factor NFκB, a key component of the immune system, shows intricate stimulus-specific temporal dynamics. Those dynamics are thought to play a role in controlling the physiological response to cytokines and pathogens. Biochemical evidence suggests that the NFκB inducing kinase, IKK, a signaling hub onto which many signaling pathways converge, is regulated via a Regulatory Cycle comprising a poised, an active, and an inactive state. We hypothesize that it operates as a modulator of signal dynamics, actively reshaping the signals generated at the receptor proximal level. Here we show that a Regulatory Cycle can function in at least three dynamical regimes, tunable by regulating a single kinetic parameter. In particular, the simplest three-state Regulatory Cycle can generate signals with two well-defined phases, each with distinct coding capabilities in terms of the information they can carry about the stimulus. We also demonstrate that such a kinase Cycle can function as a signal categorizer classifying diverse incoming signals into outputs with a limited set of temporal activity profiles. Finally, we discuss the extension of the results to other Regulatory motifs that could be understood in terms of the regimes of the three-state Cycle.
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Signal Processing by the Control Cycle of the IKK Kinase in the NFκB Signaling Axis
Biophysical Journal, 2012Co-Authors: Marcelo Behar, Alexander HoffmannAbstract:The inflammatory response transcription factor NFkB, a key component of the immune system, shows intricate stimulus-specific temporal dynamics. It has been proposed that those dynamics play a role controlling the genetic outcome of inflammatory signals and hence the specificity of the cellular response to cytokines and other stimuli. As malfunctions in NFkB signaling are linked to many immune diseases as well as the onset and development of cancers, it is of considerable clinical interest to understand the mechanisms that control NFkB dynamics. Here we focus on IKK, a hub kinase that targets the main negative regulators of NFκB activity and onto which diverse receptor associated signals converge. Biochemical evidence suggests that IKK is regulated via a multi-state Regulatory Cycle and therefore we hypothesize that it can operate as a modulator, actively reshaping the signals generated at the receptor proximal level. Here we demonstrate that the IKK control Cycle can function in at least three dynamical regimes some of them producing signals comprising multiple temporal phases with distinct coding capabilities. In particular, we show that the simplest three-state Regulatory Cycle generates biphasic signals with an early phase well suited for relaying information about stimuli amplitude and a late phase more apt for encoding stimulus duration. This study demonstrates that an actively regulated hub kinase can play a crucial role functioning as a signal “categorizer” classifying complex incoming signals into a limited set of output activities. Expanding the general analysis to a more detailed model of IKK regulation revealed how specific features of IKK and NFkB activities are controlled by the different enzymatic mechanisms within the kinase Cycle.