Decision-theoretic designs for dose-finding clinical trials with multiple outcomes

A decision-theoretic framework is proposed for designing sequential dose-finding trials with multiple outcomes. The optimal strategy is solvable theoretically via backward induction. However, for dose-finding studies involving k doses, the computational complexity is the same as the bandit problem with k-dependent arms, which is computationally prohibitive. We therefore provide two computationally compromised strategies, which is of practical interest as the computational complexity is greatly reduced: one is closely related to the continual reassessment method (CRM), and the other improves CRM and approximates to the optimal strategy better. In particular, we present the framework for phase I/II trials with multiple outcomes. Applications to a pediatric HIV trial and a cancer chemotherapy trial are given to illustrate the proposed approach. Simulation results for the two trials show that the computationally compromised strategy can perform well and appear to be ethical for allocating patients. The proposed framework can provide better approximation to the optimal strategy if more extensive computing is available.

An extension of the continual reassessment method using decision theory

The primary goal of a phase I trial is to find the maximally tolerated dose (MTD) of a treatment. The MTD is usually defined in terms of a tolerable probability, q*, of toxicity. Our objective is to find the highest dose with toxicity risk that does not exceed q*, a criterion that is often desired in designing phase I trials. This criterion differs from that of finding the dose with toxicity risk closest to q*, that is used in methods such as the continual reassessment method. We use the theory of decision processes to find optimal sequential designs that maximize the expected number of patients within the trial allocated to the highest dose with toxicity not exceeding q*, among the doses under consideration. The proposed method is very general in the sense that criteria other than the one considered here can be optimized and that optimal dose assignment can be defined in terms of patients within or outside the trial. It includes as an important special case the continual reassessment method. Numerical study indicates the strategy compares favourably with other phase I designs.

A Bayesian decision approach for sample size determination in phase II trials

Stallard (1998, Biometrics 54, 279-294) recently used Bayesian decision theory for sample-size determination in phase II trials. His design maximizes the expected financial gains in the development of a new treatment. However, it results in a very high probability (0.65) of recommending an ineffective treatment for phase III testing. On the other hand, the expected gain using his design is more than 10 times that of a design that tightly controls the false positive error (Thall and Simon, 1994, Biometrics 50, 337-349). Stallard's design maximizes the expected gain per phase II trial, but it does not maximize the rate of gain or total gain for a fixed length of time because the rate of gain depends on the proportion: of treatments forwarding to the phase III study. We suggest maximizing the rate of gain, and the resulting optimal one-stage design becomes twice as efficient as Stallard's one-stage design. Furthermore, the new design has a probability of only 0.12 of passing an ineffective treatment to phase III study.

Bayesian and Decision Tree Approaches for Pattern Recognition Including Feature Measurement Costs

The minimum cost classifier when general cost functionsare associated with the tasks of feature measurement and classification is formulated as a decision graph which does not reject class labels at intermediate stages. Noting its complexities, a heuristic procedure to simplify this scheme to a binary decision tree is presented. The optimizationof the binary tree in this context is carried out using ynamicprogramming. This technique is applied to the voiced-unvoiced-silence classification in speech processing.

Human mating in the informal market for sperm donation: Preferences and decision making

Choosing a mate is one of the largest (economic) decisions humans make. This thesis investigates this large scale decision and how the process is changing with the advent of the internet and the growing market for online informal sperm donation. This research identifies individual factors that influence female mating preferences. It explores the roles of behavioural traits and physical appearance, preferences for homogamy and hypergamy, and personality, and how these impact the decision to choose a donor. Overall, this thesis makes contributions to both the literature on human behaviour, and that on decision-making in extreme and highly important situations.

Patient decision aids in routine maternity care: Benefits, barriers, and new opportunities

Background and aim Participation in decision-making, supported by comprehensive and quality information provision, is increasingly emphasised as a priority for women in maternity care. Patient decision aids are tools that can offer women greater access to information and guidance to participate in maternity care decision-making. Relative to their evaluation in controlled settings, the implementation of patient decision aids in routine maternity care has received little attention and our understanding of which approaches may be effective is limited. This paper critically discusses the application of patient decision aids in routine maternity care and explores viable solutions for promoting their successful uptake. Discussion A range of patient decision aids have been developed for use within maternity care, and controlled trials have highlighted their positive impact on the decision-making process for women. Nevertheless, evidence of successful patient decision aid implementation in real world health care settings is lacking due to practical and ideological barriers that exist. Patient-directed social marketing campaigns are a relatively novel approach to patient decision aid delivery that may facilitate their adoption in maternity care, at least in the short-term, by overcoming common implementation barriers. Social marketing may also be particularly well suited to maternity care, given the unique characteristics of this health context. Conclusions The potential of social marketing campaigns to facilitate patient decision aid adoption in maternity care highlights the need for pragmatic trials to evaluate their effectiveness. Identifying which sub-groups of women are more or less likely to respond to these strategies will further direct implementation.

The Reorganisation of Provincial Territories in Light of the Imperial Decision-Making Process : Later Roman Arabia and Tres Palaestinae as Case Studies

The dissertation examines Roman provincial administration and the phenomenon of territorial reorganisations of provinces during the Imperial period with special emphasis on the provinces of Arabia and Palaestina during the Later Roman period, i.e., from Diocletian (r. 284 305) to the accession of Phocas (602), in the light of imperial decision-making. Provinces were the basic unit of Roman rule, for centuries the only level of administration that existed between the emperor and the cities of the Empire. The significance of the territorial reorganisations that the provinces were subjected to during the Imperial period is thus of special interest. The approach to the phenomenon is threefold: firstly, attention is paid to the nature and constraints of the Roman system of provincial administration. Secondly, the phenomenon of territorial reorganisations is analysed on the macro-scale, and thirdly, a case study concerning the reorganisations of the provinces of Arabia and Palaestina is conducted. The study of the mechanisms of decision-making provides a foundation through which the collected data of all known major territorial reorganisations is interpreted. The data concerning reorganisations is also subjected to qualitative comparative analysis that provides a new perspective to the data in the form of statistical analysis that is sensitive to the complexities of individual cases. This analysis of imperial decision-making is based on a timeframe stretching from Augustus (r. 30 BC AD 14) to the accession of Phocas (602). The study identifies five distinct phases in the use of territorial reorganisations of the provinces. From Diocletian s reign there is a clear normative change that made territorial reorganisations a regular tool of administration for the decision-making elite for addressing a wide variety of qualitatively different concerns. From the beginning of the fifth century the use of territorial reorganisations rapidly diminishes. The two primary reasons for the decline in the use of reorganisations were the solidification of ecclesiastical power and interests connected to the extent of provinces, and the decline of the dioceses. The case study of Palaestina and Arabia identifies seven different territorial reorganisations from Diocletian to Phocas. Their existence not only testifies to wider imperial policies, but also shows sensitivity to local conditions and corresponds with the general picture of provincial reorganisations. The territorial reorganisations of the provinces reflect the proactive control of the Roman decision-making elite. The importance of reorganisations should be recognised more clearly as part of the normal imperial administration of the provinces and especially reflecting the functioning of dioceses.

Leibniz on Rational Decision-Making

In this study I discuss G. W. Leibniz's (1646-1716) views on rational decision-making from the standpoint of both God and man. The Divine decision takes place within creation, as God freely chooses the best from an infinite number of possible worlds. While God's choice is based on absolutely certain knowledge, human decisions on practical matters are mostly based on uncertain knowledge. However, in many respects they could be regarded as analogous in more complicated situations. In addition to giving an overview of the divine decision-making and discussing critically the criteria God favours in his choice, I provide an account of Leibniz's views on human deliberation, which includes some new ideas. One of these concerns is the importance of estimating probabilities in making decisions one estimates both the goodness of the act itself and its consequences as far as the desired good is concerned. Another idea is related to the plurality of goods in complicated decisions and the competition this may provoke. Thirdly, heuristic models are used to sketch situations under deliberation in order to help in making the decision. Combining the views of Marcelo Dascal, Jaakko Hintikka and Simo Knuuttila, I argue that Leibniz applied two kinds of models of rational decision-making to practical controversies, often without explicating the details. The more simple, traditional pair of scales model is best suited to cases in which one has to decide for or against some option, or to distribute goods among parties and strive for a compromise. What may be of more help in more complicated deliberations is the novel vectorial model, which is an instance of the general mathematical doctrine of the calculus of variations. To illustrate this distinction, I discuss some cases in which he apparently applied these models in different kinds of situation. These examples support the view that the models had a systematic value in his theory of practical rationality.

Formative evaluation to benchmark and improve climate-based decision support for graziers in Western Queelsland

Researchers developing climate-based forecasts, workshops, software tools and information to aid grazier decisions undertook an evaluation study to enhance planning and benchmark impact. One hundred graziers in Western Queensland were randomly selected from 7 shires and surveyed by mail and telephone (43 respondents) to explore levels of knowledge and use of climate information, practices and information needs. We found 36% of respondents apply the Southern Oscillation Index to property decisions but 92% were unaware El Niño Southern Oscillation’s predictive signal in the region is greater for pasture growth than rainfall, suggesting they may not recognise the potential of pasture growth forecasts. Almost 75% of graziers consider they are conservative or risk averse in their attitude to managing their enterprise. Mail respondents (n= 20) if given a 68%, on average, probability of exceeding median rainfall forecast may change a decision; almost two-thirds vary stocking rate based on forage available, last year’s pasture growth or the Southern Oscillation Index; the balance maintain a constant stocking rate strategy; 90% have access to a computer; 75% to the internet and 95% have a fax. This paper presents findings of the study and draws comparisons with a similar study of 174 irrigators in the Northern Murray-Darling Basin (Aust. J. Exp. Ag. 44, 247-257). New insights and information gained are helping the team better understand client needs and plan, design and extend tools and information tailored to grazier knowledge, practice, information needs and preferences. Results have also provided a benchmark against which to measure project impact and have influenced the team to make important changes to their project planning, activities and methods for transferring technology tailored to grazier preferences.

Predicting wood value in Queensland Caribbean pine plantations using a decision support system

A decision support system has been developed in Queensland to evaluate how changes in silvicultural regimes affect wood quality, and specifically the graded recovery of structural timber. Models of tree growth, branch architecture and wood properties were developed from data collected in routine Caribbean pine plantations and specific silvicultural experiments. These models were incorporated in software that simulates the conversion of standing trees into logs, and the logs into boards, and generates detailed data on knot location and basic density distribution. The structural grade of each board was determined by simulating the machine stress-grading process, and the predicted graded recovery provided an indicator of wood value. The decision support system improves the basis of decision-making by simulating the performance of elite genetic material under specified silvicultural regimes and by predicting links between wood quality and general stand attributes such as stocking and length of rotation.

Sexual harassment and the corporation in Australia and Japan: The potential for corporate governance of human rights

The authors explore the legal and social undercurrents in Australia and Japan which are encouraging corporations to embrace broader social responsibilities. They consider a case study of sexual harassment and its regulation within Australian corporations, uncovering the legal and social conditions that have led to the adoption of sexual harassment policies. The authors propose a model for determining when corporate governance of sexual harassment is likely to be effective and test the model by reference to the experience of sexual harassment in Japan. They draw some conclusions about what the experience of corporate implementation of management of sexual harassment might mean for other areas of human rights.

Private governance of public rights in Japan: Revisiting the Japanese governance debate

Dramatic growth in the Japanese economy in the postwar period – and its meltdown in the 1990s – has attracted sustained interest in the power dynamics underlying the management of Japan’s administrative state. For a long time, scholars and commentators have debated about who wields power in Japan. The question has been asked in different ways. In the 1970s and 1980s, the question was usually posed as: who orchestrated Japan’s economic miracle in the 1960s and 1970s? Today, the question is usually reframed to: who is accountable for the policy failures that plunged Japan into financial crisis and recession during the 1990s? Yet the core issue remains the same – who governs Japan? (Johnson 1995)...

Moments of flux in intermediary liability for copyright infringement

This chapter provides an overview of a recent shift in regulatory strategies to address copyright infringement toward enlisting the assistance of general purpose Internet Service Providers. In Australia, the High Court held in 2012 that iiNet, a general purpose ISP, had no legal duty to police what its subscribers did with their internet connections. We provide an overview of three recent developments in Australian copyright law since that decision that demonstrate an emerging shift in the way that obligations are imposed on ISPs to govern the actions of their users without relying on secondary liability. The first is a new privately negotiated industry code that introduces a 'graduated response' system that requires ISPs to pass on warnings to subscribers who receive allegations of infringement. The second involves a recent series of Federal Court cases where rightsholders made a partially successful application to require ISPs to hand over the identifying details of subscribers whose households are alleged to have infringed copyright. The third is a new legislative scheme that will require ISPs to block access to foreign websites that 'facilitate' infringement. We argue that these shifts represent a greater sophistication in approaches to enrolling general purpose intermediaries in the regulatory project. We also suggest that these shifts represent a potentially disturbing trend towards enforcement of copyright law in a way that does not provide strong safeguards for the legitimate constitutional due process interests of users. We conclude with a call for greater attention and research to better understand how intermediaries make decisions when governing the conduct of users, how those decisions may be influenced by both state and non-state actors, and how the rights of individuals to due process can be adequately protected.

Climate change and human rights: Intellectual property challenges and opportunities

Mitigating and adapting to the effects of climate change will require innovation and the development of new technologies. Intellectual property laws have a key part to play in the global transfer of climate technologies. However, failures to properly utilize flexibilities in intellectual property regimes or comply with technology transfer obligations under international climate change agreements calls for a human rights based analysis of climate technology transfer. Climate change is an unprecedented challenge and requires unprecedented strategies. Given the substantial impact of climate change on all of humanity and the ethical imperative to act, a complete rethink of traditional intellectual property approaches is warranted. This report proposes a series of intellectual property law policy options, through a human rights framework, aimed at promoting access to technologies to reduce the human suffering caused by climate change.