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.     

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.     

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.     

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.     

MINING ERROR VARIANCE AND HITTING PAY-DIRT:

According to traditional error theory, sentiment measurements vary unsystematically from individual to individual. However, we find some patterned deviation in sentiments that characterize subsets of respondents within a seemingly homogeneous population. After demonstrating the existence of such patterns, we report an exploratory study aimed at identifying social characteristics of people with different patterns of sentiments. People embedded in multiple social networks have exaggerated sentiments that contour cultural patterns, and people with few social associations have attenuated sentiments conveying cultural detachment. In addition, people with disciplinary parents and romantic privation have some distinctive sentiments, depending on their gender.     

How Welfare Policies Affect Adolescents' School Outcomes: A Synthesis of Evidence From Experimental Studies

Using data from 8 random assignment studies and employing meta‐analytic techniques, this article provides systematic evidence that welfare and work policies targeted at low‐income parents have small adverse effects on some school outcomes among adolescents ages 12 to 18 years at follow‐up. These adverse effects were observed mostly for school performance outcomes and occurred in programs that required mothers to work or participate in employment‐related activities and those that encouraged mothers to work voluntarily. The most pronounced negative effects on school outcomes occurred for the group of adolescents who had a younger sibling, possibly because of the increased home and sibling care responsibilities they assumed as their mothers increased their employment.     

Measuring Substance Abuse Treatment Need Among Adults in Florida: A Social Indicators Approach

Determining the size and demographiccharacteristics of substance abuse populationsis extremely important for implementing publicpolicies aimed at the control of substanceabuse. Such information not only assists in theallocation of limited treatment resources bythe state, but also in the monitoring ofsubstance abuse trends over time and in theevaluation of innovative policy initiatives. Inthis study, we develop three composite measuresof treatment need. We then use these measuresto estimate treatment need for alcohol abuseand for controlled substance abuse within eachof Florida's 67 counties. This study providesan important empirical component of communityplanning, quantifying and, to a limited degree,specifying the level of need for the substanceabuse treatment of community residents. Anadditional benefit is the development of a costeffective and unobtrusive methodology fordetermining empirically when levels of need arechanging so that treatment levels can beadjusted accordingly. With proper use,policymakers can readily employ the methodologydeveloped in this study in Florida andelsewhere to make better-informed decisions inthe allocation of finite substance abusetreatment resources.