Inference and Decision Making for 21st-Century Drug Development and Approval

ABSTRACT

The cost and time of pharmaceutical drug development continue to grow at rates that many say are unsustainable. These trends have enormous impact on what treatments get to patients, when they get them and how they are used. The statistical framework for supporting decisions in regulated clinical development of new medicines has followed a traditional path of frequentist methodology. Trials using hypothesis tests of “no treatment effect” are done routinely, and the p-value < 0.05 is often the determinant of what constitutes a “successful” trial. Many drugs fail in clinical development, adding to the cost of new medicines, and some evidence points blame at the deficiencies of the frequentist paradigm. An unknown number effective medicines may have been abandoned because trials were declared “unsuccessful” due to a p-value exceeding 0.05. Recently, the Bayesian paradigm has shown utility in the clinical drug development process for its probability-based inference. We argue for a Bayesian approach that employs data from other trials as a “prior” for Phase 3 trials so that synthesized evidence across trials can be utilized to compute probability statements that are valuable for understanding the magnitude of treatment effect. Such a Bayesian paradigm provides a promising framework for improving statistical inference and regulatory decision making.     

Random effects regression mixtures for analyzing infant habituation

Random effects regression mixture models are a way to classify longitudinal data (or trajectories) having possibly varying lengths. The mixture structure of the traditional random effects regression mixture model arises through the distribution of the random regression coefficients, which is assumed to be a mixture of multivariate normals. An extension of this standard model is presented that accounts for various levels of heterogeneity among the trajectories, depending on their assumed error structure. A standard likelihood ratio test is presented for testing this error structure assumption. Full details of an expectation-conditional maximization algorithm for maximum likelihood estimation are also presented. This model is used to analyze data from an infant habituation experiment, where it is desirable to assess whether infants comprise different populations in terms of their habituation time.     

The Persistent Problem of Colorism: Skin Tone, Status, and Inequality

Colorism is a persistent problem for people of color in the USA. Colorism, or skin color stratification, is a process that privileges light-skinned people of color over dark in areas such as income, education, housing, and the marriage market. This essay describes the experiences of African Americans, Latinos, and Asian Americans with regard to skin color. Research demonstrates that light-skinned people have clear advantages in these areas, even when controlling for other background variables. However, dark-skinned people of color are typically regarded as more ethnically authentic or legitimate than light-skinned people. Colorism is directly related to the larger system of racism in the USA and around the world. The color complex is also exported around the globe, in part through US media images, and helps to sustain the multibillion-dollar skin bleaching and cosmetic surgery industries.     

Intersensory Redundancy Enhances Memory in Bobwhite Quail Embryos

Information presented concurrently and redundantly to 2 or more senses (intersensory redundancy) has been shown to recruit attention and promote perceptual learning of amodal stimulus properties in animal embryos and human infants. This study examined whether the facilitative effect of intersensory redundancy also extends to the domain of memory. We assessed bobwhite quail chicks' ability to remember and prefer an individual maternal call presented either unimodally or redundantly and synchronously with patterned light during the period prior to hatching. Embryos provided with unimodal auditory exposure failed to prefer the familiar call over a novel maternal call postnatally at 48 hr and 72 hr following exposure. In contrast, embryos provided with redundant, synchronous audiovisual stimulation significantly preferred the familiar call at 48 hr following exposure, but not at 72 hr. A second experiment provided chicks with a single 10‐min refamiliarization with the familiar call at either 48 hr or 72 hr following hatching. Chicks given only unimodal auditory exposure prior to hatching did not appear to benefit from this brief postnatal refamiliarization, showing no preference for the familiar call at either 72 or 96 hr. Chicks that received redundant audiovisual stimulation prenatally showed a significant preference for the familiar call (following the brief reexpo sure 24 hr earlier) at both 72 and 96 hr of age. These results are the first to demonstrate that redundantly specified information is remembered longer and reactivated more easily than the same information presented unimodally. These findings provide further evidence of the salience of intersensory redundancy in guiding selective attention and perceptual learning during early development.     

Household strategies in the face of resource scarcity in coastal Ghana: are they associated with development priorities?

In many developing regions, women and young girls spend several hours daily in the collection of natural resources. Still the link between these household resource strategies and stakeholder perceptions of development priorities remains unexplored. This project examines this association with survey data representative of the adult population from Ghana’s Coastal Region. Although natural resource scarcity and the sustainability of resource use represent key development challenges, there are others (e.g., energy, sanitation, employment, and educational opportunities). As such, even in the face of natural resource scarcity, individuals may place greater importance on other dimensions of development, especially if household resource strategies are perceived as relatively efficient. The analytical focus here is on water and the results suggest that gender roles shape household water collection strategies, while also shaping these strategies’ perceived opportunity costs. Specifically, Ghanian adults more often see drinking water provision as their primary development need when water sources are distant and/or when male household members collect water (particularly male heads). In the end, I argue that social science inquiry benefits by contextualizing social dynamics within environmental context, particularly within cultural settings in which human subsistence is intimately tied to the state of the natural environment.