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.     

External knowledge search,absorptive capacity and radical innovation in high-technology firms

Open innovation and absorptive capacity are two concepts based on the idea that companies can leverage the knowledge generated externally to improve their innovation performance. The aim of this paper is to analyse the joint effect of open innovation and absorptive capacity on a firm's radical innovation. Open innovation is expressed in terms of external search breadth and depth strategies and absorptive capacity is described by distinguishing between potential and realized absorptive capacity. In order to test our hypotheses, we carried out empirical research in firms operating in high-technology industries. The results indicate that internal routines and processes for absorbing external knowledge help explain radical innovation as they show a significant effect of potential and realized absorptive capacity. Also, there is a moderating effect of absorptive capacity on open innovation. Specifically, potential absorptive capacity exerts a positive effect on the relationship between external search breadth and depth and radical innovation. Realized absorptive capacity moderates the influence of external search breadth. These findings confirm the complementary nature of absorptive capacity and open innovation search strategies on radical innovation.     

Ethical Numbers: Ethics Training in U.S. Graduate Statistics Programs, 2013–2014

As important members of research teams, statisticians bear an ethical responsibility to analyze, interpret, and report data honestly and objectively. One way of reinforcing ethical responsibilities is through required courses covering a variety of ethics-related topics at the graduate level. We assessed ethics requirements for graduate-level statistics training programs in the United States for the 2013–2014 academic year using the websites of 88 universities, examining 103 biostatistics programs, and 136 statistics degree programs. We categorized programs’ ethics training requirements as required or not required. Thirty-one (35.1%) universities required an ethics course for at least some degree students. Sixty-two (25.5%) degree programs required an ethics course for at least some students. The majority (77.4%) of required courses were worth 0 or 1 credit. Of the 177 programs without an ethics requirement, 19 (10.7%) listed an ethics elective. Although a single ethics course is insufficient for instilling an ethical approach to science, degree programs that model expectations through coursework point to the value of ethics in science. More training programs should prepare statisticians to consider the ethical dimensions of their work through required coursework. Supplementary materials for this article are available online.     

Applying kaizen to the schedule in a concurrent environment

Not only ETO (Engineering to Order), but even serial production industry should know how to deal with projects and their schedule: plant commissioning, shutdown, introducing new products and similar circumstances should be managed with adequate planning and resource allocation techniques to create a schedule useful in decision making during the execution. The current complex reality, with evolving technologies and fierce pressure to reach the market as soon as possible, pushes the project managers to use more advanced techniques than waterfall planning, such as agile or lean. It also requires them to take a holistic view and manage concurrent tasks in complex projects. The contributions of this paper are two: the proposal to control specific parallel groups of waterfall activities under uncertain environments, which can lead to iterations and reworks, as a single concurrent Activity Managed by Kanban Methods (AMKM). This activity can be subsequently embedded into traditional scheduling approaches as CPM-PERT. The second contribution is the feasibility of its application in industrial environments due to the affordability of simulation software. Two use cases are shown as evidence. It is not a disruptive proposal, but a kaizen action based on very mature technologies. Finally, it is suggested some improvements to be implemented in Project Management Software due to this ‘kaizen’ proposal.     

Sex Related Factors in the Perception of Threatening Facial Expressions

This study replicated and extended previously reported sex differences involving both viewer and target in the recognition of threatening facial expressions. Based on the assumption that the evolved cognitive mechanisms mediating anger recognition would have been designed by natural selection to operate quickly in the interests of survival, brief tachistoscopic presentation of stimulus photographs was used. Additionally, in contrast to prior published studies, the statistical methods of signal detection research were used to control for the confounding effects of non-random guessing. The main hypothesis, that anger posed by males would be more accurately perceived than anger posed by females, was supported. A secondary hypothesis, that female-posed anger would be more accurately perceived by women than by men, received partial support. Testosterone levels, measured inferentially in terms of diurnal cycles, failed to show the hypothesized positive relationship to accuracy of anger perception.     

Family Ties and Peso Signs: Challenges for Career Counseling in the Philippines

The article's 1st section provides an overview of the historical development of career counseling in the Philippines from an economic‐political perspective. The 2nd section raises current challenges and concerns, highlighting the need for a career counseling model that would address, among other things, Filipinos' valued characteristics of close family ties and desire for economic progress.     

International and intercultural issues in English teaching textbooks: the case of Spain

The sociocultural content of foreign language textbooks has become a concern of scholars and practitioners owing to the fact that the traditional emphasis on purely linguistic issues has been expanded to embrace a language in context approach. This paper studies the English‐speaking communities that are described in English language teaching textbooks marketed in Spain. It examines to what extent an international and/or intercultural approach is a constituent element in their design.     

Why sociology does not need to be saved: Analytic reflections on public sociologies

After reviewing the debate about public sociologies in the American Sociological Association over the past few years, we offer a response to calls for “saving sociology” from the Burawoy approach as well as an analytic critique of the former ASA president's “For Public Sociology” address. While being sympathetic to the basic idea of public sociologies, we argue that the “reflexive” and “critical” categories of sociology, as Burawoy has conceptualized them, are too ambiguous and value-laden to allow for empirical investigation of the different major orientations of sociological research and the ways the discipline can address non-academic audiences. Debates about the future of sociology should be undertaken with empirical evidence, and we need a theoretical approach that can allow us to compare both disciplines and nations as well as taking into account the institutional context of the universities in which we operate. Research into the conditions under which professional, critical, policy, and public sociologies could work together for the larger disciplinary and societal good is called for instead of overheated rhetoric both for and against public sociologies.