Statistical modeling for Bayesian extrapolation of adult clinical trial information in pediatric drug evaluation

Children represent a large underserved population of “therapeutic orphans,” as an estimated 80% of children are treated off‐label. However, pediatric drug development often faces substantial challenges, including economic, logistical, technical, and ethical barriers, among others. Among many efforts trying to remove these barriers, increased recent attention has been paid to extrapolation; that is, the leveraging of available data from adults or older age groups to draw conclusions for the pediatric population. The Bayesian statistical paradigm is natural in this setting, as it permits the combining (or “borrowing”) of information across disparate sources, such as the adult and pediatric data. In this paper, authored by the pediatric subteam of the Drug Information Association Bayesian Scientific Working Group and Adaptive Design Working Group, we develop, illustrate, and provide suggestions on Bayesian statistical methods that could be used to design improved pediatric development programs that use all available information in the most efficient manner. A variety of relevant Bayesian approaches are described, several of which are illustrated through 2 case studies: extrapolating adult efficacy data to expand the labeling for Remicade to include pediatric ulcerative colitis and extrapolating adult exposure‐response information for antiepileptic drugs to pediatrics.     

Compatibility,Leisure, and Satisfaction in Marital Relationships

This study challenges the prevailing view that marital companionship promotes marital satisfaction. By following a cohort of married couples for over a decade and by incorporating several methodological improvements—such as refining the measurement of marital satisfaction, determining how much spouses enjoy doing the leisure activities they pursue together and apart, and using diary data to portray marital leisure patterns—we found that the association between companionship and satisfaction is less robust than previously believed, and that it depends on how often spouses pursue activities that reflect their own and their partner's leisure preferences. Over time, involvement in leisure liked by husbands but disliked by wives, whether as a couple or by husbands alone, is both a cause and a consequence of wives' dissatisfaction.     

Modified quasi-profile likelihoods from estimating functions

We discuss higher-order adjustments for a quasi-profile likelihood for a scalar parameter of interest, in order to alleviate some of the problems inherent to the presence of nuisance parameters, such as bias and inconsistency. Indeed, quasi-profile score functions for the parameter of interest have bias of order O(1)$\mathrm{O}(1)$, and such bias can lead to poor inference on the parameter of interest. The higher-order adjustments are obtained so that the adjusted quasi-profile score estimating function is unbiased and its variance is the negative expected derivative matrix of the adjusted profile estimating equation. The modified quasi-profile likelihood is then obtained as the integral of the adjusted profile estimating function. We discuss two methods for the computation of the modified quasi-profile likelihoods: a bootstrap simulation method and a first-order asymptotic expression, which can be simplified under an orthogonality assumption. Examples in the context of generalized linear models and of robust inference are provided, showing that the use of a modified quasi-profile likelihood ratio statistic may lead to coverage probabilities more accurate than those pertaining to first-order Wald-type confidence intervals.     

Analysis of growth curve data by using cubic smoothing splines

Longitudinal data frequently arises in various fields of applied sciences where individuals are measured according to some ordered variable, e.g. time. A common approach used to model such data is based on the mixed models for repeated measures. This model provides an eminently flexible approach to modeling of a wide range of mean and covariance structures. However, such models are forced into a rigidly defined class of mathematical formulas which may not be well supported by the data within the whole sequence of observations. A possible non-parametric alternative is a cubic smoothing spline, which is highly flexible and has useful smoothing properties. It can be shown that under normality assumption, the solution of the penalized log-likelihood equation is the cubic smoothing spline, and this solution can be further expressed as a solution of the linear mixed model. It is shown here how cubic smoothing splines can be easily used in the analysis of complete and balanced data. Analysis can be greatly simplified by using the unweighted estimator studied in the paper. It is shown that if the covariance structure of random errors belong to certain class of matrices, the unweighted estimator is the solution to the penalized log-likelihood function. This result is new in smoothing spline context and it is not only confined to growth curve settings. The connection to mixed models is used in developing a rough testing of group profiles. Numerical examples are presented to illustrate the techniques proposed.     

Reports of Conferences,Institutes, and Seminars

In the span of four weeks, from late March to early April 2008, three important technical services conferences were held: the Electronic Resources & Libraries Conference, the New England Technical Services Librarians Conference, and the North Carolina Serials Conference.     

Realistic Major Previews in the School‐to‐College Transition of Italian High School Students

Industrial/organizational researchers have reported that realistic job previews diminish prospective workers' expectations but promote the satisfaction and persistence of those who ultimately accept a job assignment. The authors applied this strategy to the context of school‐to‐college transition; 354 Italian high school students were provided with a 2‐hour lecture designed to simulate exposure to a college major of their choice. Students showed moderate pre‐post increases in subject matter knowledge but reported small decreases in interests and outcome expectations (but not self‐efficacy) related to the academic major to which they were exposed.     

'You've gotta learn how to play the game': homeless women's use of gender performance as a tool for preventing victimization

As a masculinist space, ‘the streets’ present a variety of dangers to homeless women, a fact that has received too little attention within the social science literature. This study utilizes data drawn from interviews with homeless women and service providers in Edinburgh, San Francisco, Vancouver, Montreal and Ottawa, to explore the complex survival strategies that homeless women develop to prevent criminal victimization. Through women's words, we see that gender is understood strategically as performance. Four gender performances are identified and discussed: the ‘femininity simulacrum’, the ‘masculinity simulacrum’, ‘genderlessness’ and ‘passing’. We discussed how each of these performances is employed in the pursuit of safety and security in frequently violent and chaotic social spaces.