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.     

Loss functions for estimation of extrema with an application to disease mapping

It is often of interest to find the maximum or near maxima among a set of vector‐valued parameters in a statistical model; in the case of disease mapping, for example, these correspond to relative‐risk “hotspots” where public‐health intervention may be needed. The general problem is one of estimating nonlinear functions of the ensemble of relative risks, but biased estimates result if posterior means are simply substituted into these nonlinear functions. The authors obtain better estimates of extrema from a new, weighted ranks squared error loss function. The derivation of these Bayes estimators assumes a hidden‐Markov random‐field model for relative risks, and their behaviour is illustrated with real and simulated data.     

Values and Vegetarianism: An Exploratory Analysis1

The American diet has changed substantially over the last few decades. These changes provide a test for social theory and have substantial effects on the demand for various food products, thus impacting U.S. agriculture. In this paper a rapidly growing dietary choice—vegetarianism—is explored. Prevalence of various forms of vegetarianism is estimated in a representative sample of a suburban population and factors that influence choice of a vegetarian diet are examined. About 7 percent of the sample report they are vegetarians. The prevalence of vegetarianism is not influenced by age, gender, or education, but individuals holding traditional values are less likely to be vegetarian than others. There also is some evidence mat individuals holding altruistic values are more likely than others to be vegetarians.     

Society's search for a legal and ethical basis of physician-assisted suicide

A review of the way physician-assisted suicide (PAS) is being addressed in the United States reveals three models, each functioning out of distinctive concepts of autonomy: (1) litigation, which utilizes philosophical autonomy; (2) legislation, which utilizes political autonomy; and (3) act of conscience by a physician, which utilizes consumer autonomy. Each model raises a correspondingly distinct set of ethical questions and challenges centered around their point of reference-the judicial system, voters, or the doctor-patient relationship. In the end, however, efforts to resolve the challenge of PAS will falter if they do not go beyond these models of autonomy. Religious institutions offer a more constructive setting for facing the life and death decisionmaking of PAS. The challenge for religion is to address PAS in solidarity with sufferers, physicians, and the community, rather than retreating into iconoclastic dogmas.     

Brexit: Be Careful What You Wish For?

In this paper, I focus on the British future from Brexit. The institutional form this will take is not yet fixed. However, one can consider likely outcomes based on dominant economic frameworks. From this perspective, it seems unlikely that Brexit will address the actual grievances that resulted in Brexit. These transcend European Union membership.     

Testing the Vision: Preschool Settings as Places for Meeting,Bonding and Bridging

The OECD (2006 Starting Strong II: Early Childhood Education and Care. OECD Publishing: Paris) envisions early childhood education and care settings as meeting places for diverse social groups; places that build social capital. This vision was assessed in a comparison of three preschools types: full‐fee paying, subsidised‐fee and publicly funded. The social composition within each was examined and the connectedness of the children (n = 472) who attended compared. Publicly funded preschools had more socially diverse populations. The quantity of social connectedness did not differ but children in publicly funded preschools described higher quality social relationships. Not all preschool settings are socially diverse but, where they are, the quality of relationships is highest.     

Pollutant Ground Concentrations of Nonneutrally Buoyant Particles

A methodology is suggested for the estimation of the mass density and the cumulative ground deposition of a nonvolatile, nonneutrally buoyant, air pollutant (liquid or solid) released from a polluted column (following an explosion caused during routine operation in, e.g., the chemical industry or due to any kind of hostile act) and deposited on the ground via gravitational settling. In many cases, the deposited mass due to gravitational settling constitutes a significant fraction of the original inventory released from the source. Implementation of the methodology in preliminary risk assessments can serve as an efficient tool for emergency planning for both immediate and long‐term measures such as evacuation and decontamination. The methodology considers, inter alia, an estimation of the critical particle diameter, particle size, and mass distributions along the polluted column. This methodology was developed to apply in rural regions since proper application of relevant meteorological input data can be accomplished mainly for such areas.     

Sampling schemes for price index construction: a performance comparison across the classification of individual consumption by purpose food groups

Five sampling schemes (SS) for price index construction – one cut-off sampling technique and four probability-proportional-to-size (pps) methods – are evaluated by comparing their performance on a homescan market research data set across 21 months for each of the 13 classification of individual consumption by purpose (COICOP) food groups. Classifications are derived for each of the food groups and the population index value is used as a reference to derive performance error measures, such as root mean squared error, bias and standard deviation for each food type. Repeated samples are taken for each of the pps schemes and the resulting performance error measures analysed using regression of three of the pps schemes to assess the overall effect of SS and COICOP group whilst controlling for sample size, month and population index value. Cut-off sampling appears to perform less well than pps methods and multistage pps seems to have no advantage over its single-stage counterpart. The jackknife resampling technique is also explored as a means of estimating the standard error of the index and compared with the actual results from repeated sampling.