Decision-making in a phase II clinical trial: a new approach combining Bayesian and frequentist concepts

The aim of a phase H clinical trial is to decide whether or not to develop an experimental therapy further through phase III clinical evaluation. In this paper, we present a Bayesian approach to the phase H trial, although we assume that subsequent phase III clinical trials will hat,e standard frequentist analyses. The decision whether to conduct the phase III trial is based on the posterior predictive probability of a significant result being obtained. This fusion of Bayesian and frequentist techniques accepts the current paradigm for expressing objective evidence of therapeutic value, while optimizing the form of the phase II investigation that leads to it. By using prior information, we can assess whether a phase II study is needed at all, and how much or what sort of evidence is required. The proposed approach is illustrated by the design of a phase II clinical trial of a multi-drug resistance modulator used in combination with standard chemotherapy in the treatment of metastatic breast cancer. Copyright (c) 2005 John Wiley & Sons, Ltd.

Assembly and maintenance of the sarcomere night and day

The assembly of sarcomeric proteins into the highly organized structure of the sarcomere is an ordered and complex process involving an array of structural and associated proteins. The sarcomere has shown itself to be considerably more complex than ever envisaged and may be considered one of the most complex macromolecular assemblies in biology. Studies over the last decade have helped to put a new face on the sarcomere, and, as such, the sarcomere is being redefined as a dynamic network of proteins capable of generating force and signalling with other cellular compartments and metabolic enzymes capable of controlling many facets of striated myocyte biology.

Competitive strategy revisited: contested concepts and dynamic capabilities

Strategy is a contested concept. The generic literature is characterized by a diverse range of competing theories and alternative perspectives. Traditional models of the competitive strategy of construction firms have tended to focus on exogenous factors. In contrast, the resource-based view of strategic management emphasizes the importance of endogenous factors. The more recently espoused concept of dynamic capabilities extends consideration beyond static resources to focus on the ability of firms to reconfigure their operating routines to enable responses to changing environments. The relevance of the dynamics capabilities framework to the construction sector is investigated through an exploratory case study of a regional contractor. The focus on how firms continuously adapt to changing environments provides new insights into competitive strategy in the construction sector. Strong support is found for the importance of path dependency in shaping strategic choice. The case study further suggests that strategy is a collective endeavour enacted by a loosely defined group of individual actors. Dynamic capabilities are characterized by an empirical elusiveness and as such are best construed as situated practices embedded within a social and physical context.

Exposing the myth of the 1:5:200 ratio relating initial cost, maintenance and staffing costs of office buildings

In an attempt to focus clients' minds on the importance of considering the construction and maintenance costs of a commercial office building (both as a factor in staff productivity and as a fraction of lifetime staff costs) there is an often-quoted ratio of costs of 1:5:200, where for every one pound spent on construction cost, five are spent on maintenance and building operating costs and 200 on staffing and business operating costs. This seems to stem from a paper published by the Royal Academy of Engineering, in which no data is given and no derivation or defence of the ratio appears. The accompanying belief that higher quality design and construction increases staff productivity, and simultaneously reduces maintenance costs, how ever laudable, appears unsupported by research, and carries all the hallmarks of an "urban myth". In tracking down data about real buildings, a more realistic ratio appears to depend on a huge variety of variables, as well as the definition of the number of "lifetime" years. The ill-defined origins of the original ratio (1:5:200) describing these variables have made replication impossible. However, by using published sources of data, we have found that for three office buildings, a more realistic ratio is 1:0.4:12. As there is nothing in the public domain about what comprised the original research that gave rise to 1:5:200, it is not possible to make a true comparison between these new calculations and the originals. Clients and construction professionals stand to be misled because the popularity and widespread use of the wrong ratio appears to be mis-informing important investment and policy decisions.

A system's model for maintenance support and decision making in building services systems

Modern buildings are designed to enhance the match between environment, spaces and the people carrying out work, so that the well-being and the performance of the occupants are all in harmony. Building services are systems that facilitate a healthy working environment within which workers productivity can be optimised in the buildings. However, the maintenance of these services is fraught with problems that may contribute to up to 50% of the total life cycle cost of the building. Maintenance support is one area which is not usually designed into the system as this is not common practice in the services industry. The other areas of shortfall for future designs are; client requirements, commissioning, facilities management data and post occupancy evaluation feedback which needs to be adequately planned to capture and document this information for use in future designs. At the University of Reading an integrated approach has been developed to assemble the multitude of aspects inherent in this field. The means records required and measured achievements for the benefit of both building owners and practitioners. This integrated approach can be represented in a Through Life Business Model (TLBM) format using the concept of Integrated Logistic Support (ILS). The prototype TLBM developed utilises the tailored tools and techniques of ILS for building services. This TLBM approach will facilitate the successful development of a databank that would be invaluable in capturing essential data (e.g. reliability of components) for enhancing future building services designs, life cycle costing and decision making by practitioners, in particular facilities managers.

Horses for courses: Relating innovation diffusion concepts to the stage of the diffusion process

The research uses a sociological perspective to build an improved, context specific understanding of innovation diffusion within the UK construction industry. It is argued there is an iterative interplay between actors and the social system they occupy that directly influences the diffusion process as well as the methodology adopted. The research builds upon previous findings that argued a level of best fit for the three innovation diffusion concepts of cohesion, structural equivalence and thresholds. That level of best fit is analysed here using empirical data from the UK construction industry. This analysis allows an understanding of how the relative importance of these concepts' actually varies within the stages of the innovation diffusion process. The conclusion that the level of relevance fluctuates in relation to the stages of the diffusion process is a new development in the field.

A novel repair model for imperfect maintenance

Commonly used repair rate models for repairable systems in the reliability literature are renewal processes, generalised renewal processes or non-homogeneous Poisson processes. In addition to these models, geometric processes (GP) are studied occasionally. The GP, however, can only model systems with monotonously changing (increasing, decreasing or constant) failure intensities. This paper deals with the reliability modelling of failure processes for repairable systems where the failure intensity shows a bathtub-type non-monotonic behaviour. A new stochastic process, i.e. an extended Poisson process, is introduced in this paper. Reliability indices are presented, and the parameters of the new process are estimated. Experimental results on a data set demonstrate the validity of the new process.

A novel repair model for imperfect maintenance

The basic repair rate models for repairable systems may be homogeneous Poisson processes, renewal processes or nonhomogeneous Poisson processes. In addition to these models, geometric processes are studied occasionally. Geometric processes, however, can only model systems with monotonously changing (increasing, decreasing or constant) failure intensity. This paper deals with the reliability modelling of the failure process of repairable systems when the failure intensity shows a bathtub type non-monotonic behaviour. A new stochastic process, an extended Poisson process, is introduced. Reliability indices and parameter estimation are presented. A comparison of this model with other repair models based on a dataset is made.