An adaptive group sequential design for phase II/III clinical trials that select a single treatment from several

There is increasing interest in combining Phases II and III of clinical development into a single trial in which one of a small number of competing experimental treatments is ultimately selected and where a valid comparison is made between this treatment and the control treatment. Such a trial usually proceeds in stages, with the least promising experimental treatments dropped as soon as possible. In this paper we present a highly flexible design that uses adaptive group sequential methodology to monitor an order statistic. By using this approach, it is possible to design a trial which can have any number of stages, begins with any number of experimental treatments, and permits any number of these to continue at any stage. The test statistic used is based upon efficient scores, so the method can be easily applied to binary, ordinal, failure time, or normally distributed outcomes. The method is illustrated with an example, and simulations are conducted to investigate its type I error rate and power under a range of scenarios.

Using historical lesion volume data in the design of a new phase II clinical trial in acute stroke

Background and Purpose-Clinical research into the treatment of acute stroke is complicated, is costly, and has often been unsuccessful. Developments in imaging technology based on computed tomography and magnetic resonance imaging scans offer opportunities for screening experimental therapies during phase II testing so as to deliver only the most promising interventions to phase III. We discuss the design and the appropriate sample size for phase II studies in stroke based on lesion volume. Methods-Determination of the relation between analyses of lesion volumes and of neurologic outcomes is illustrated using data from placebo trial patients from the Virtual International Stroke Trials Archive. The size of an effect on lesion volume that would lead to a clinically relevant treatment effect in terms of a measure, such as modified Rankin score (mRS), is found. The sample size to detect that magnitude of effect on lesion volume is then calculated. Simulation is used to evaluate different criteria for proceeding from phase II to phase III. Results-The odds ratios for mRS correspond roughly to the square root of odds ratios for lesion volume, implying that for equivalent power specifications, sample sizes based on lesion volumes should be about one fourth of those based on mRS. Relaxation of power requirements, appropriate for phase II, lead to further sample size reductions. For example, a phase III trial comparing a novel treatment with placebo with a total sample size of 1518 patients might be motivated from a phase II trial of 126 patients comparing the same 2 treatment arms. Discussion-Definitive phase III trials in stroke should aim to demonstrate significant effects of treatment on clinical outcomes. However, more direct outcomes such as lesion volume can be useful in phase II for determining whether such phase III trials should be undertaken in the first place. (Stroke. 2009;40:1347-1352.)

Modelling for planning building design - a critique of available approaches

This paper reviews four approaches used to create rational tools to aid the planning and the management of the building design process and then proposes a fifth approach. The new approach that has been developed is based on the mechanical aspects of technology rather than subjective design issues. The knowledge base contains, for each construction technology, a generic model of the detailed design process. Each activity in the process is specified by its input and output information needs. By connecting the input demands of one technology with the output supply from another technology a map or network of design activity is formed. Thus, it is possible to structure a specific model from the generic knowledge base within a KBE system.

Investigation into low power of a 2D Inverse Discrete CosineTransform (IDCT) in FPGAs

Design for low power in FPGA is rather limited since technology factors affecting power are either fixed or limited for FPGA families. This paper investigates opportunities for power savings of a pipelined 2D IDCT design at the architecture and logic level. We report power consumption savings of over 25% achieved in FPGA circuits obtained from clock gating implementation of optimizations made at the algorithmic level(1).

An efficient low power FFT implementation for multiband full-rate ultra-wideband (UWB) receivers

This paper discusses the design, implementation and synthesis of an FFT module that has been specifically optimized for use in the OFDM based Multiband UWB system, although the work is generally applicable to many other OFDM based receiver systems. Previous work has detailed the requirements for the receiver FFT module within the Multiband UWB ODFM based system and this paper draws on those requirements coupled with modern digital architecture principles and low power design criteria to converge on our optimized solution. The FFT design obtained in this paper is also applicable for implementation of the transmitter IFFT module therefore only needing one FFT module for half-duplex operation. The results from this paper enable the baseband designers of the 200Mbit/sec variant of Multiband UWB systems (and indeed other OFDM based receivers) using System-on-Chip (SoC), FPGA and ASIC technology to create cost effective and low power solutions biased toward the competitive consumer electronics market.

Optimising the feedback loop of a millimetre-wave absolute photoacoustic power meter using H-infinity control synthesis

An H-infinity control strategy has been developed for the design of controllers used in feedback controlled electrical substitution measurements (FCESM). The methodology has the potential to provide substantial improvements in both response time and resolution of a millimetre-wave absolute photoacoustic power meter.

A parallel convolutional coder including embedded puncturing with application to consumer devices

As consumers demand more functionality) from their electronic devices and manufacturers supply the demand then electrical power and clock requirements tend to increase, however reassessing system architecture can fortunately lead to suitable counter reductions. To maintain low clock rates and therefore reduce electrical power, this paper presents a parallel convolutional coder for the transmit side in many wireless consumer devices. The coder accepts a parallel data input and directly computes punctured convolutional codes without the need for a separate puncturing operation while the coded bits are available at the output of the coder in a parallel fashion. Also as the computation is in parallel then the coder can be clocked at 7 times slower than the conventional shift-register based convolutional coder (using DVB 7/8 rate). The presented coder is directly relevant to the design of modern low-power consumer devices

Expert system aid for design of overload line distribution networks

The use of expert system techniques in power distribution system design is examined. The selection and siting of equipment on overhead line networks is chosen for investigation as the use of equipment such as auto-reclosers, etc., represents a substantial investment and has a significant effect on the reliability of the system. Through past experience with both equipment and network operations, most decisions in selection and siting of this equipment are made intuitively, following certain general guidelines or rules of thumb. This heuristic nature of the problem lends itself to solution using an expert system approach. A prototype has been developed and is currently under evaluation in the industry. Results so far have demonstrated both the feasibility and benefits of the expert system as a design aid.

A clocking technique with power savings in virtex-based pipelined designs

This paper presents the evaluation in power consumption of a clocking technique for pipelined designs. The technique shows a dynamic power consumption saving of around 30% over a conventional global clocking mechanism. The results were obtained from a series of experiments of a systolic circuit implemented in Virtex-II devices. The conversion from a global-clocked pipelined design to the proposed technique is straightforward, preserving the original datapath design. The savings can be used immediately either as a power reduction benefit or to increase the frequency of operation of a design for the same power consumption.

Knowledge transfer: the facilitating attributes in supply-chain partnerships

This article examines the operational characteristics of supply-chain partnerships and identifies the relational attributes that cultivate knowledge transfer in such partnerships. A set of theoretical propositions are developed. A case study of a computer manufacturer's supply chain was conducted to examine their validity. The findings support the view that trust, commitment, interdependence, shared meaning, and balanced power facilitate knowledge transfer in supply-chain partnerships, and that knowledge transfer should be treated as a dynamic multistage process.

A general basis for quarter-power scaling in animals

It has been known for decades that the metabolic rate of animals scales with body mass with an exponent that is almost always <1, >2/3, and often very close to 3/4. The 3/4 exponent emerges naturally from two models of resource distribution networks, radial explosion and hierarchically branched, which incorporate a minimum of specific details. Both models show that the exponent is 2/3 if velocity of flow remains constant, but can attain a maximum value of 3/4 if velocity scales with its maximum exponent, 1/12. Quarterpower scaling can arise even when there is no underlying fractality. The canonical “fourth dimension” in biological scaling relations can result from matching the velocity of flow through the network to the linear dimension of the terminal “service volume” where resources are consumed. These models have broad applicability for the optimal design of biological and engineered systems where energy, materials, or information are distributed from a single source.

Can microgrids make a major contribution to UK energy supply?

Almost all the electricity currently produced in the UK is generated as part of a centralised power system designed around large fossil fuel or nuclear power stations. This power system is robust and reliable but the efficiency of power generation is low, resulting in large quantities of waste heat. The principal aim of this paper is to investigate an alternative concept: the energy production by small scale generators in close proximity to the energy users, integrated into microgrids. Microgrids—de-centralised electricity generation combined with on-site production of heat—bear the promise of substantial environmental benefits, brought about by a higher energy efficiency and by facilitating the integration of renewable sources such as photovoltaic arrays or wind turbines. By virtue of good match between generation and load, microgrids have a low impact on the electricity network, despite a potentially significant level of generation by intermittent energy sources. The paper discusses the technical and economic issues associated with this novel concept, giving an overview of the generator technologies, the current regulatory framework in the UK, and the barriers that have to be overcome if microgrids are to make a major contribution to the UK energy supply. The focus of this study is a microgrid of domestic users powered by small Combined Heat and Power generators and photovoltaics. Focusing on the energy balance between the generation and load, it is found that the optimum combination of the generators in the microgrid- consisting of around 1.4 kWp PV array per household and 45% household ownership of micro-CHP generators- will maintain energy balance on a yearly basis if supplemented by energy storage of 2.7 kWh per household. We find that there is no fundamental technological reason why microgrids cannot contribute an appreciable part of the UK energy demand. Indeed, an estimate of cost indicates that the microgrids considered in this study would supply electricity at a cost comparable with the present electricity supply if the current support mechanisms for photovoltaics were maintained. Combining photovoltaics and micro-CHP and a small battery requirement gives a microgrid that is independent of the national electricity network. In the short term, this has particular benefits for remote communities but more wide-ranging possibilities open up in the medium to long term. Microgrids could meet the need to replace current generation nuclear and coal fired power stations, greatly reducing the demand on the transmission and distribution network.

A robust controller design method for feedback substitution schemes using genetic algorithms

Controllers for feedback substitution schemes demonstrate a trade-off between noise power gain and normalized response time. Using as an example the design of a controller for a radiometric transduction process subjected to arbitrary noise power gain and robustness constraints, a Pareto-front of optimal controller solutions fulfilling a range of time-domain design objectives can be derived. In this work, we consider designs using a loop shaping design procedure (LSDP). The approach uses linear matrix inequalities to specify a range of objectives and a genetic algorithm (GA) to perform a multi-objective optimization for the controller weights (MOGA). A clonal selection algorithm is used to further provide a directed search of the GA towards the Pareto front. We demonstrate that with the proposed methodology, it is possible to design higher order controllers with superior performance in terms of response time, noise power gain and robustness.

Evaluating the likelihood of the adoption of an animal welfare assessment system in European agri-food supply chains

Purpose – The purpose of this paper is to analyse the likelihood of adoption of a recently designed Welfare Assessment System in agri-food supply chains and the factors affecting the adoption decision. The application is carried out for pig and poultry chains. Design/methodology/approach – This research consisted of two main components: interviews with retailers in pig and poultry supply chains in eight different EU countries to explore their perceptions towards the adoption possibilities of the welfare assessment system; and a conjoint analysis designed to evaluate the perceived adoption likelihood of the assessment system by different Standards Formulating Organisations (SFOs). Findings – Stakeholders were found to be especially concerned about the costs of implementation of the system and how it could, or should, be merged with existing assurance schemes. Another conclusion of the study is that the presence of a strong third independent party supporting the implementation of the welfare assessment system would be the most important influence on the decision whether, or not, to adopt it. Originality/value – This research evaluates the adoption possibilities of a novel Welfare Assessment System and presents the views of different supply chain stakeholders on an adoption of such a system. The main factors affecting the adoption decision are identified and analysed. Contrary to expectations, the costs of adoption of a new welfare assessment system were not considered to be the most important factor affecting the decision of supply chain stakeholders about the adoption of this new welfare system.