Issues in applying recent CPMP ‘Points to Consider’ and FDA guidance documents with biostatistical implications

The International Conference on Harmonisation guideline ‘Statistical Principles for Clinical Trials’ was adopted by the Committee for Proprietary Medicinal Products (CPMP) in March 1998, and consequently is operational in Europe. Since then more detailed guidance on selected topics has been issued by the CPMP in the form of ‘Points to Consider’ documents. The intent of these was to give guidance particularly to non‐statistical reviewers within regulatory authorities, although of course they also provide a good source of information for pharmaceutical industry statisticians. In addition, the Food and Drug Administration has recently issued a draft guideline on data monitoring committees. In November 2002 a one‐day discussion forum was held in London by Statisticians in the Pharmaceutical Industry (PSI). The aim of the meeting was to discuss how statisticians were responding to some of the issues covered in these new guidelines, and to document consensus views where they existed. The forum was attended by industry, academic and regulatory statisticians. This paper outlines the questions raised, resulting discussions and consensus views reached. It is clear from the guidelines and discussions at the workshop that the statistical analysis strategy must be planned during the design phase of a clinical trial and carefully documented. Once the study is complete the analysis strategy should be thoughtfully executed and the findings reported. Copyright © 2003 John Wiley & Sons, Ltd.     

A simple estimator for a shared frailty regression model

Summary. We propose a simple estimation procedure for a proportional hazards frailty regression model for clustered survival data in which the dependence is generated by a positive stable distribution. Inferences for the frailty parameter can be obtained by using output from Cox regression analyses. The computational burden is substantially less than that of the other approaches to estimation. The large sample behaviour of the estimator is studied and simulations show that the approximations are appropriate for use with realistic sample sizes. The methods are motivated by studies of familial associations in the natural history of diseases. Their practical utility is illustrated with sib pair data from Beaver Dam, Wisconsin.     

Asthma Patients' Activities and Air Pollution: A Semiparametric Censored Regression Analysis

Asthma patients' health status may be especially sensitive to some types of air pollution, but the evidence on this is mixed. We explore the effects of ground-level ozone on asthma patient's activities, breaking apart the usual aggregated category of leisure into indoor and outdoor activities, and differentiating those by whether the activities were active or inactive. Applying the semiparametric censored estimation method we demonstrate that even though the period over which activities were observed was relatively low in ozone levels, there is a significant impact of ozone on a few activities. The (non-ozone) economic and demographic variables in the model play significant roles in explaining the allocation of time among seven activities, suggesting the suitability of the approach for other household decision-making contexts.     

Bayesian locally optimal design of knockout tournaments

The elimination or knockout format is one of the most common designs for pairing competitors in tournaments and leagues. In each round of a knockout tournament, the losers are eliminated while the winners advance to the next round. Typically, the goal of such a design is to identify the overall best player. Using a common probability model for expressing relative player strengths, we develop an adaptive approach to pairing players each round in which the probability that the best player advances to the next round is maximized. We evaluate our method using simulated game outcomes under several data-generating mechanisms, and compare it to random pairings, to the standard knockout format, and to two variants of the standard format.     

The Development of Affect Specificity in Infants' Use of Emotion Cues

This study examined the emergence of affect specificity in infancy. In this study, infants received verbal and facial signals of 2 different, negatively valenced emotions (fear and sadness) as well as neutral affect via a television monitor to determine if they could make qualitative distinctions among emotions of the same valence. Twenty 12‐ to 14‐month‐olds and 20 16‐ to 18‐month‐olds were examined. Results suggested that younger infants showed no evidence of referential specificity, as they responded similarly to both the target and distracter toys, and showed no evidence of affect specificity, showing no difference in play between affect conditions. Older infants, in contrast, showed evidence both of referential and affect specificity. With respect to affect specificity, 16‐ to 18‐month‐olds touched the target toy less in the fear condition than in the sad condition and showed a larger proportion of negative facial expressions in the sad condition versus the fear condition. These findings suggest a developmental emergence after 15 months of age for affect specificity in relating emotional messages to objects.     

Modeling External Risks in Project Management

To ascertain the viability of a project, undertake resource allocation, take part in bidding processes, and other related decisions, modern project management requires forecasting techniques for cost, duration, and performance of a project, not only under normal circumstances, but also under external events that might abruptly change the status quo. We provide a Bayesian framework that provides a global forecast of a project's performance. We aim at predicting the probabilities and impacts of a set of potential scenarios caused by combinations of disruptive events, and using this information to deal with project management issues. To introduce the methodology, we focus on a project's cost, but the ideas equally apply to project duration or performance forecasting. We illustrate our approach with an example based on a real case study involving estimation of the uncertainty in project cost while bidding for a contract.     

Educating for Social Justice: Making sense of multicultural and antiracist theory and practice with Canadian teacher activists 1

This paper presents an argument for further engagement between educational scholars and school-based social justice activists. An analysis of one segment of the broad field of social justice education focuses on multicultural and antiracist education, particularly as they are understood in the Canadian socio-political context. A brief overview of the literature from UK and US sources highlights their complex and often overlapping concerns, and the need for more dialogue across national boundaries toward progressive social change. Excerpts from in-depth interviews with four Canadian teacher-activists reveal the potential for educators to take up various debates and findings from the academic literature in their daily struggles to work for social justice.     

New Labour and youth justice

The paper discusses the reasons for the large amount of critical commentary that New Labour's reforms of the youth justice system have attracted. It explores the extent to which there is something ‘new’ about these reforms, suggesting that there are important differences when New Labour's approach is compared with its predecessor's. It then discusses the main lines of critical commentary on the reforms, concluding that much of it is over‐abstract and insufficiently empirically informed. The paper concludes with some ambiguous evidence on what the impact of the reforms has actually been. Copyright © 2003 John Wiley & Sons, Ltd.     

Trait Expressiveness and Marital Satisfaction: The Role of Idealization Processes

This study examined the processes that underlie the association between trait expressiveness and marital satisfaction. A total of 168 newlywed couples participated in a four‐wave, 13‐year longitudinal study of marriage. Cross‐sectional and longitudinal path analyses suggested that expressiveness promotes satisfaction by leading spouses to engage in affectionate behavior and by leading them to idealize their partner. Expressive people formed idealized images of their partner because they brought out the best in their partner's behavior and because they interpreted their partner's behavior in a favorable light. The study extends previous research by showing that the benefits of trait expressiveness extend into the second decade of marriage and by providing a plausible explanation of the connections between trait expressiveness and marital satisfaction.     

General Job Satisfaction From a Developmental Perspective: Exploring Choice—Job Matches at Two Career Stages

The authors explored predictions of general job satisfaction at early and middle adulthood and uncovered several findings about developmental processes associated with job satisfaction. Tests of life‐span career theory propositions revealed that neither choice‐job congruence nor gender added significantly to predictions of job satisfaction at 2 career stages. Earlier occupational choice and current job added to predictions of midcareer (modal age 43 years) job satisfaction, especially for men. The predictability of job satisfaction is apparently influenced by the career stage when satisfaction is appraised.