Optimal composite scores for longitudinal clinical trials under the linear mixed effects model

Clinical trials of chronic, progressive conditions use rate of change on continuous measures as the primary outcome measure, with slowing of progression on the measure as evidence of clinical efficacy. For clinical trials with a single prespecified primary endpoint, it is important to choose an endpoint with the best signal‐to‐noise properties to optimize statistical power to detect a treatment effect. Composite endpoints composed of a linear weighted average of candidate outcome measures have also been proposed. Composites constructed as simple sums or averages of component tests, as well as composites constructed using weights derived from more sophisticated approaches, can be suboptimal, in some cases performing worse than individual outcome measures. We extend recent research on the construction of efficient linearly weighted composites by establishing the often overlooked connection between trial design and composite performance under linear mixed effects model assumptions and derive a formula for calculating composites that are optimal for longitudinal clinical trials of known, arbitrary design. Using data from a completed trial, we provide example calculations showing that the optimally weighted linear combination of scales can improve the efficiency of trials by almost 20% compared with the most efficient of the individual component scales. Additional simulations and analytical results demonstrate the potential losses in efficiency that can result from alternative published approaches to composite construction and explore the impact of weight estimation on composite performance. Copyright © 2016. The Authors. Pharmaceutical Statistics Published by John Wiley & Sons Ltd.     

The relevance of Kuhn's model of science to discipline development in sociology «1»

Thomas Kuhn's model of scientific development during the last two decades is reviewed critically in light of its increasing popularity in the sociology of sociology literature. This model, along with recent criticisms and rebuttals by Kuhn, is described, and the circularity of this position as a basis for paradigm development is noted. Several problems are identified for contemporary sociology. We conclude that Kuhn's model can not be used as a strategy for generating a scientific paradigm for the discipline of sociology and, at best, Kuhn's work serves only as a heuristic device for discipline analysis.     

Social Environmental Variation, Plasticity Genes, and Aggression: Evidence for the Differential Susceptibility Hypothesis

Although G×E studies are typically based on the assumption that some individuals possess genetic variants that enhance their vulnerability to environmental adversity, the differential susceptibility perspective posits that these individuals are simply more susceptible to environmental influence than others. An important implication of this model is that those persons most vulnerable to adverse social environments are the same ones who reap the most benefit from environmental support. The present study tested several implications of this proposition. Using longitudinal data from a sample of several hundred African Americans, we found that relatively common variants of the dopamine receptor gene and the serotonin transporter gene interact with social environmental conditions to predict aggression in a manner consonant with differential susceptibility. When the social environment was adverse, individuals with these genetic variants manifested more aggression than other genotypes, whereas when the environment was supportive they demonstrated less aggression than other genotypes. Further, we found that these genetic variants interact with environmental conditions to foster various cognitive schemas and emotions in a manner consistent with differential susceptibility and that a latent construct formed by these schemas and emotions mediated the effect of gene by environment interaction on aggression.     

Governmentalities of Volunteering: A Study of Regional Western Australia

The aim of this article is to investigate the governmentalities of volunteering in regional Western Australia. Drawing on interviews with 25 consenting volunteers and their managers, a thematic analysis revealed the experiences and perceptions of the research participants. Two distinct governmentalities exist: one reflecting neo-liberal governmentality and the other reflective of classic liberalism. Whilst this study is limited to regional Western Australia, the results suggest that there are variations in ‘governmentalities’ of volunteering comprising a mix of sometimes contradictory elements. This article also demonstrates the usefulness of governmentality for expanding the understanding of volunteering that has the potential to illuminate vital elements of the volunteer sector, which are being missed. There are many niches where volunteer groups exist or are emerging that are not visible and out of reach of the control techniques commonly used by governments adopting advanced (neo) liberal governmentalities.     

Understanding Food Insecurity Among Latino Immigrant Families in Rural America

Using ecological theory, this study investigated how low-income rural Latino immigrant families succeeded or failed to meet their food needs over time. Interviews with ten families purposively selected to represent consistently food secure, fragile, and consistently food insecure groups were intensively analyzed using a case study approach. Achieving and maintaining food security was a complicated task and a constant struggle for families. Success or failure was influenced by factors at multiple ecological levels including family characteristics, access to social networks and community support, and the local economy. These findings can inform practitioners and policymakers seeking to identify strategies and policies that will support Latino immigrant families as they work toward improving their well-being.     

Mechanisms of Family Impact on African American Adolescents' HIV‐Related Behavior

A longitudinal model that tested mediating pathways between protective family processes and HIV‐related behavior was evaluated with 195 African American youth. Three waves of data were collected when the youth were 13, 15, and 19 years old. Evidence of mediation and temporal priority were assessed for 3 constructs: academic engagement, evaluations of prototypical risk‐taking peers, and affiliations with risk‐promoting peers. Structural equation modeling indicated that protective family processes assessed during early adolescence were associated with HIV‐related behavior during emerging adulthood and that academic engagement, evaluations of prototypical risk‐taking peers, and affiliations with risk‐promoting peers accounted for this association. Evidence of a specific pathway emerged: protective family processes→academic engagement→negative evaluations of prototypical risk‐taking peers→affiliations with risk‐promoting peers→HIV‐related behavior. Academic engagement also was a direct predictor of HIV‐related risk behavior.     

Covariate imbalance and precision in measuring treatment effects

Covariate adjustment can increase the precision of estimates by removing unexplained variance from the error in randomized experiments, although chance covariate imbalance tends to counteract the improvement in precision. The author develops an easy measure to examine chance covariate imbalance in randomization by standardizing the average covariate difference between the treatment and control condition. The standardized covariate difference must not exceed an upper bound in order to gain precision in covariate adjusted analysis. The author then shows how to select an adequate sample size to mitigate chance covariate imbalance and improve precision in small pilot studies.