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.     

Dimensions of Social Stratification and Their Relation to Mortality: A Comparison Across Gender and Life Course Periods in Finland

Social Indicators Research - Differences in mortality between groups with different socioeconomic positions (SEP) are well-established, but the relative contribution of different SEP measures is...     

Missing item imputation for quality-of-life instruments with application to asthma quality-of-life questionnaires

There has been increasing use of quality-of-life (QoL) instruments in drug development. Missing item values often occur in QoL data. A common approach to solve this problem is to impute the missing values before scoring. Several imputation procedures, such as imputing with the most correlated item and imputing with a row/column model or an item response model, have been proposed. We examine these procedures using data from two clinical trials, in which the original asthma quality-of-life questionnaire (AQLQ) and the miniAQLQ were used. We propose two modifications to existing procedures: truncating the imputed values to eliminate outliers and using the proportional odds model as the item response model for imputation. We also propose a novel imputation method based on a semi-parametric beta regression so that the imputed value is always in the correct range and illustrate how this approach can easily be implemented in commonly used statistical software. To compare these approaches, we deleted 5% of item values in the data according to three different missingness mechanisms, imputed them using these approaches and compared the imputed values with the true values. Our comparison showed that the row/column-model-based imputation with truncation generally performed better, whereas our new approach had better performance under a number scenarios.     

欧洲主权债务危机:起因、演进、治理

阐述了目前在欧洲两种治理债务危机的思路发生的激烈碰撞;其中以“紧缩换援助”的治理债务危机思路遭到许多经济学家的质疑和希腊等重灾国的激烈反对,以促进结构改革和经济增长来摆脱欧债危机的主张正在获得越来越多的支持;指出欧盟必须适时转变治理危机的思路,并从五个方面提出治理危机的措施,尝试为欧债危机的解决找到出路.     

Comparing Observed and Unobserved Components of Childhood: Evidence From Finnish Register Data on Midlife Mortality From Siblings and Their Parents

In this study, we argue that the long arm of childhood that determines adult mortality should be thought of as comprising an observed part and its unobserved counterpart, reflecting the observed socioeconomic position of individuals and their parents and unobserved factors shared within a family. Our estimates of the observed and unobserved parts of the long arm of childhood are based on family-level variance in a survival analytic regression model, using siblings nested within families as the units of analysis. The study uses a sample of Finnish siblings born between 1936 and 1950 obtained from Finnish census data. Individuals are followed from ages 35 to 72. To explain familial influence on mortality, we use demographic background factors, the socioeconomic position of the parents, and the individuals’ own socioeconomic position at age 35 as predictors of all-cause and cause-specific mortality. The observed part—demographic and socioeconomic factors, including region; number of siblings; native language; parents’ education and occupation; and individuals’ income, occupation, tenancy status, and education—accounts for between 10 % and 25 % of the total familial influence on mortality. The larger part of the influence of the family on mortality is not explained by observed individual and parental socioeconomic position or demographic background and thus remains an unobserved component of the arm of childhood. This component highlights the need to investigate the influence of childhood circumstances on adult mortality in a comprehensive framework, including demographic, social, behavioral, and genetic information from the family of origin.     

Summary indices of the age distribution of a population

In this paper a method for characterizing the age distribution of a population by means of an ‘index word’ is outlined. It is shown that the method can be applied to yield approximations to population forecasts.     

Am I a leader? Examining leader identity development over time

The extent to which someone thinks of him- or herself as a leader (i.e., leader identity) is subject to change in a dynamic manner because of experience and structured intervention, but is rarely studied as such. In this study, we map the trajectories of leader identity development over a course of a seven-week leader development program. Drawing upon identity theory (Kegan, 1983) and self-perception theory (Bem, 1972), we propose that changes in self-perceived leadership skills are associated with changes in leader identity. Using latent growth curve modeling and latent change score analyses as our primary analytical approaches, we analyzed longitudinal data across seven measurement points (N = 98). We find leader identity to develop in a J-shaped pattern. As hypothesized, we find that these changes in leader identity are associated with, and potentially shaped by, changes in leadership skills across time.     

Gender differences in entrepreneurial intentions: A TPB multi-group analysis at factor and indicator level

Previous research suggests that diverse factors predict gender differences in entrepreneurial intent. Our paper integrates and expands on previous findings using the Theory of Planned Behavior (TPB), including the deeper-level measurement model, allowing for a better understanding of the origin of differences. The results of a survey with business students indicate that the effect of gender on entrepreneurial intentions is mediated via personal attitudes and perceived behavioral control but not social norms. More precisely, vis-à-vis their male counterparts, women are more driven toward entrepreneurship by motives to ‘get organized’ (balance) that are less dominant in predicting personal attitude. Moreover, female students are somewhat less driven toward entrepreneurship by beliefs of internal control that are more dominant in predicting perceived control. Finally, while female students are also more motivated to comply with normative role models, this did not influence their entrepreneurial intentions over and above perceived behavioral control and personal attitude. We discuss both practical and theoretical implications of our findings.