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.     

The Effect of Learning Experiences and Context on Infant Imitation and Generalization

Over the first years of life, infants gradually develop the ability to retrieve their memories across cue and contextual changes. Whereas maturational factors drive some of these developments in memory ability, experiences occurring within the learning event may also impact infants' ability to retrieve memories in new situations. In 2 experiments we examined whether it was possible to facilitate 12‐month‐old infants' generalization of learning in the deferred imitation paradigm by varying experiences before or during the demonstration session, or during the retention interval. In Experiment 1, altering the length, timing, or variability of training had no impact on generalization; infants showed a low, but consistent level of memory retrieval. In Experiment 2, infants who experienced a unique context for encoding and retrieval exhibited generalization; infants who experienced the context prior to the demonstration session, or during the retention interval, did not. Specificity is a robust feature of infant memory and is not substantially altered by encoding experiences in an observational learning paradigm. Previous history with a learning environment can, however, impact the flexibility of memory retrieval.     

Spaces of Participation in Pre‐School: Arenas for Establishing Power Orders?

This article reports an ethnographic study of pre‐school children's social knowledge domains. Results show how the children's shared knowledge concerning social status and social differentiation in the group was strengthened and confirmed during a traditional teacher‐led ring game, where they were supposed to choose a friend. We suggest that from the perspective of the children, the game situation may be understood as, at the same time, a space of participation and an arena for establishing the power order. From the perspective of the teacher, pedagogical intentions may be challenged as they encounter and are mediated and interpreted by children's peer‐cultures.     

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.     

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.