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 Sparse Implementation of the Average Information Algorithm for Factor Analytic and Reduced Rank Variance Models

Factor analytic variance models have been widely considered for the analysis of multivariate data particularly in the psychometrics area. Recently Smith, Cullis & Thompson (2001) have considered their use in the analysis of multi‐environment data arising from plant improvement programs. For these data, the size of the problem and the complexity of the variance models chosen to account for spatial heterogeneity within trials implies that standard algorithms for fitting factor analytic models can be computationally expensive. This paper presents a sparse implementation of the average information algorithm (Gilmour, Thompson & Cullis, 1995) for fitting factor analytic and reduced rank variance models.     

Mapping water quality by local scoring

The mean density of bacteria in a water body is commonly monitored using quantal assay. This paper describes the use of local scoring in estimating the spatial distribution of mean density from quantal assay results at a set of point locations. An application to estimating the mean density of fecal conform bacteria in a coastal pond is presented. Model diagnostics based on a parametric bootstrap are also presented.     

The Poverty Reduction Strategy Approach Six Years On: An Examination of Principles and Practice in Uganda

It is over six years since the World Bank and the IMF started promoting a PRS approach to development management in low‐income countries. The 2005 review endorsed the approach, but highlighted the need for a renewed focus on the principles underpinning it: country ownership; results orientation; comprehensiveness; partnership focus; and long‐term outlook. Uganda is often hailed as one of the best PRS performers. This article finds that Uganda's Poverty Eradicaton Action Plan (PEAP) has brought significant gains to development management, but that its performance against several of the PRS principles is disappointing. A return to these principles could improve the practice of the government and development partners around the PEAP – a finding likely to be applicable to many countries implementing a PRS.