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.

ICTs and decision-making: findings from the Poverty Assessor

Pro-poor decision making depends on an understanding of the complexities and interrelationships between household livelihood, demographic, and economic factors. This article describes the design and implementation of the Poverty Assessor, a software programme to assist practitioners, policy makers, and researchers in visualising the direct impacts on poverty of specific livelihood factors and events among populations living in poverty. The software enables users to upload their own data and profile households in relation to the national poverty line, by selecting from a range of demographic and livelihood indicators. The authors present findings from the programme, using a dataset from Bolivia.

A hypoplastic model of skeletal muscle development displaying reduced foetal myoblast cell numbers, increased oxidative myofibres and improved specific tension capacity

The major component of skeletal muscle is the myofibre. Genetic intervention inducing over-enlargement of myofibres beyond a certain threshold through acellular growth causes a reduction in the specific tension generating capacity of the muscle. However the physiological parameters of a genetic model that harbours reduced skeletal muscle mass have yet to be analysed. Genetic deletion of Meox2 in mice leads to reduced limb muscle size and causes some patterning defects. The loss of Meox2 is not embryonically lethal and a small percentage of animals survive to adulthood making it an excellent model with which to investigate how skeletal muscle responds to reductions in mass. In this study we have performed a detailed analysis of both late foetal and adult muscle development in the absence of Meox2. In the adult, we show that the loss of Meox2 results in smaller limb muscles that harbour reduced numbers of myofibres. However, these fibres are enlarged. These myofibres display a molecular and metabolic fibre type switch towards a more oxidative phenotype that is induced through abnormalities in foetal fibre formation. In spite of these changes, the muscle from Meox2 mutant mice is able to generate increased levels of specific tension compared to that of the wild type.

Climate change and the British Uplands: evidence for decision-making

We summarise the work of an interdisciplinary network set up to explore the impacts of climate change in the British Uplands. In this CR Special, the contributors present the state of knowledge and this introduction synthesises this knowledge and derives implications for decision makers. The Uplands are valued semi-natural habitats, providing ecosystem services that have historically been taken for granted. For example, peat soils, which are mostly found in the Uplands, contain around 50% of the terrestrial carbon in the UK. Land management continues to be a driver of ecosystem service delivery. Degraded and managed peatlands are subject to erosion and carbon loss with negative impacts on biodiversity, carbon storage and water quality. Climate change is already being experienced in British Uplands and is likely to exacerbate these pressures. Climate envelope models suggest as much as 50% of British Uplands and peatlands will be exposed to climate stress by the end of the 21st century under low and high emissions scenarios. However, process-based models of the response of organic soils to this climate stress do not give a consistent indication of what this will mean for soil carbon: results range from a very slight increase in uptake, through a clear decline, to a net carbon loss. Preserving existing peat stocks is an important climate mitigation strategy, even if new peat stops forming. Preserving upland vegetation cover is a key win–win management strategy that will reduce erosion and loss of soil carbon, and protect a variety of services such as the continued delivery of a high quality water resource.

On-line prediction of cheese making using backscatter of near infrared indices light

The potential of a fibre optic sensor, detecting light backscatter in a cheese vat during coagulation and syneresis, to predict curd moisture, fat loses and curd yield was examined. Temperature, cutting time and calcium levels were varied to assess the strength of the predictions over a range of processing conditions. Equations were developed using a combination of independent variables, milk compositional and light backscatter parameters. Fat losses, curd yield and curd moisture content were predicted with a standard error of prediction (SEP) of +/- 2.65 g 100 g(-1) (R-2 = 0.93), +/- 0.95% (R-2 = 0.90) and +/- 1.43% (R-2 = 0.94), respectively. These results were used to develop a model for predicting curd moisture as a function of time during syneresis (SEP = +/- 1.72%; R-2 = 0.95). By monitoring coagulation and syneresis, this sensor technology could be employed to control curd moisture content, thereby improving process control during cheese manufacture. (c) 2007 Elsevier Ltd. All rights reserved..

Dynamic simulation for closed loops in heating systems with decision-making support

Nowadays utilising the proper HVAC system is essential both in extreme weather conditions and dense buildings design. Hydraulic loops are the most common parts in all air conditioning systems. This article aims to investigate the performance of different hydraulic loop arrangements in variable flow systems. Technical, economic and environmental assessments have been considered in this process. A dynamic system simulation is generated to evaluate the system performance and an economic evaluation is conducted by whole life cost assessment. Moreover, environmental impacts have been studied by considering the whole life energy consumption, CO2 emission, the embodied energy and embodied CO2 of the system components. Finally, decision-making in choosing the most suitable hydraulic system among five well-known alternatives has been proposed.

Decision making for HVAC&R system selection for a typical office building in the UK

Demands for thermal comfort, better indoor air quality together with lower environmental impacts have had ascending trends in the last decade. In many circumstances, these demands could not be fully covered through the soft approach of bioclimatic design like optimisation of the building orientation and internal layout. This is mostly because of the dense urban environment and building internal energy loads. In such cases, heating, ventilation, air-conditioning and refrigeration (HVAC&R) systems make a key role to fulfill the requirements of indoor environment. Therefore, it is required to select the most proper HVAC&R system. In this study, a robust decision making approach for HVAC&R system selection is proposed. Technical performance, economic aspect and environmental impacts of 36 permutations of primary and secondary systems are taken into account to choose the most proper HVAC&R system for a case study office building. The building is a representative for the dominant form of office buildings in the UK. Dynamic performance evaluation of HVAC&R alternatives using TRNSYS package together with life cycle energy cost analysis provides a reliable basis for decision making. Six scenarios broadly cover the decision makers' attitudes on HVAC&R system selection which are analysed through Analytical Hierarchy Process (AHP). One of the significant outcomes reveals that, despite both the higher energy demand and more investment requirements associated with compound heating, cooling and power system (CCHP); this system is one of the top ranked alternatives due to the lower energy cost and C02 emissions. The sensitivity analysis reveals that in all six scenarios, the first five top ranked alternatives are not changed. Finally, the proposed approach and the results could be used by researchers and designers especially in the early stages of a design process in which all involved bodies face the lack of time, information and tools for evaluation of a variety of systems.

Skilloscopy: Bayesian modeling of decision makers' skill

This paper proposes and demonstrates an approach, Skilloscopy, to the assessment of decision makers. In an increasingly sophisticated, connected and information-rich world, decision making is becoming both more important and more difficult. At the same time, modelling decision-making on computers is becoming more feasible and of interest, partly because the information-input to those decisions is increasingly on record. The aims of Skilloscopy are to rate and rank decision makers in a domain relative to each other: the aims do not include an analysis of why a decision is wrong or suboptimal, nor the modelling of the underlying cognitive process of making the decisions. In the proposed method a decision-maker is characterised by a probability distribution of their competence in choosing among quantifiable alternatives. This probability distribution is derived by classic Bayesian inference from a combination of prior belief and the evidence of the decisions. Thus, decision-makers’ skills may be better compared, rated and ranked. The proposed method is applied and evaluated in the gamedomain of Chess. A large set of games by players across a broad range of the World Chess Federation (FIDE) Elo ratings has been used to infer the distribution of players’ rating directly from the moves they play rather than from game outcomes. Demonstration applications address questions frequently asked by the Chess community regarding the stability of the Elo rating scale, the comparison of players of different eras and/or leagues, and controversial incidents possibly involving fraud. The method of Skilloscopy may be applied in any decision domain where the value of the decision-options can be quantified.

A model of the hemodynamic response and oxygen delivery to brain

A recent nonlinear system by Friston et al. (2000. NeuroImage 12: 466–477) links the changes in BOLD response to changes in neural activity. The system consists of five subsystems, linking: (1) neural activity to flow changes; (2) flow changes to oxygen delivery to tissue; (3) flow changes to changes in blood volume and venous outflow; (4) changes in flow, volume, and oxygen extraction fraction to deoxyhemoglobin changes; and finally (5) volume and deoxyhemoglobin changes to the BOLD response. Friston et al. exploit, in subsystem 2, a model by Buxton and Frank coupling flow changes to changes in oxygen metabolism which assumes tissue oxygen concentration to be close to zero. We describe below a model of the coupling between flow and oxygen delivery which takes into account the modulatory effect of changes in tissue oxygen concentration. The major development has been to extend the original Buxton and Frank model for oxygen transport to a full dynamic capillary model making the model applicable to both transient and steady state conditions. Furthermore our modification enables us to determine the time series of CMRO2 changes under different conditions, including CO2 challenges. We compare the differences in the performance of the “Friston system” using the original model of Buxton and Frank and that of our model. We also compare the data predicted by our model (with appropriate parameters) to data from a series of OIS studies. The qualitative differences in the behaviour of the models are exposed by different experimental simulations and by comparison with the results of OIS data from brief and extended stimulation protocols and from experiments using hypercapnia.

Responsibility effects in decision making under risk

We systematically explore decision situations in which a decision maker bears responsibility for somebody else's outcomes as well as for her own in situations of payoff equality. In the gain domain we confirm the intuition that being responsible for somebody else's payoffs increases risk aversion. This is however not attributable to a 'cautious shift' as often thought. Indeed, looking at risk attitudes in the loss domain, we find an increase in risk seeking under responsibility. This raises issues about the nature of various decision biases under risk, and to what extent changed behavior under responsibility may depend on a social norm of caution in situations of responsibility versus naive corrections from perceived biases. To further explore this issue, we designed a second experiment to explore risk-taking behavior for gain prospects offering very small or very large probabilities of winning. For large probabilities, we find increased risk aversion, thus confirming our earlier finding. For small probabilities however, we find an increase of risk seeking under conditions of responsibility. The latter finding thus discredits hypotheses of a social rule dictating caution under responsibility, and can be explained through flexible self-correction models predicting an accentuation of the fourfold pattern of risk attitudes predicted by prospect theory. An additional accountability mechanism does not change risk behavior, except for mixed prospects, in which it reduces loss aversion. This indicates that loss aversion is of a fundamentally different nature than probability weighting or utility curvature. Implications for debiasing are discussed.

Willingness-to-pay for a probabilistic flood forecast: a risk-based decision-making game

Probabilistic hydro-meteorological forecasts have over the last decades been used more frequently to communicate forecastuncertainty. This uncertainty is twofold, as it constitutes both an added value and a challenge for the forecaster and the user of the forecasts. Many authors have demonstrated the added (economic) value of probabilistic over deterministic forecasts across the water sector (e.g. flood protection, hydroelectric power management and navigation). However, the richness of the information is also a source of challenges for operational uses, due partially to the difficulty to transform the probability of occurrence of an event into a binary decision. This paper presents the results of a risk-based decision-making game on the topic of flood protection mitigation, called “How much are you prepared to pay for a forecast?”. The game was played at several workshops in 2015, which were attended by operational forecasters and academics working in the field of hydrometeorology. The aim of this game was to better understand the role of probabilistic forecasts in decision-making processes and their perceived value by decision-makers. Based on the participants’ willingness-to-pay for a forecast, the results of the game show that the value (or the usefulness) of a forecast depends on several factors, including the way users perceive the quality of their forecasts and link it to the perception of their own performances as decision-makers.