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.     

Foreign-born and native-born migration in the U.S.: evidence from linked IRS administrative and census survey records

Journal of Population Research - This paper details efforts to link administrative records from the Internal Revenue Service (IRS) to American Community Survey (ACS) and 2010 Census microdata for...     

Behavior, Belonging, and Belief: A Theory of Ritual Practice

A new model of ritual based on Durkheim's ([1912] 1995) theory is developed. It is argued that ritual practices generate belief and belonging in participants by activating multiple social–psychological mechanisms that interactively create the characteristic outcomes of ritual. Specifically, the distinctive elements of ritual practice are shown to induce altered subjective states and effortful and/or anomalous behaviors, which are subsequently misattributed in such a way that belief and belonging are created or maintained around the focus of ritual attention. These processes are traced in detail, and the resulting model is shown to be empirically credible, comprehensive, and theoretically fertile.     

TEACHING PROFESSIONAL WRITING TO FAMILY THERAPISTS: THREE APPROACHES

The authors present three educational approaches designed to demystify the writing process and to support better writing skills among family therapists. One framework is an academic course in professional writing, another is a writing seminar for family therapy and physician trainees within a medical school setting, and the third is a 2-hour continuing education writing workshop for family therapists. Each is replicable within a variety of settings.     

Measuring agreement between two statistics with applications to age standardization

Summary.  We detail a general method for measuring agreement between two statistics. An application is two ratios of directly standardized rates which differ only by the choice of the standard. If the statistics have a high value for the coefficient of agreement then the expected squared difference between the statistics is small relative to the variance of the average of the two statistics, and inferences vary little by changing statistics. The estimation of a coefficient of agreement between two statistics is not straightforward because there is only one pair of observed values, each statistic calculated from the data. We introduce estimators of the coefficient of agreement for two statistics and discuss their use, especially as applied to functions of standardized rates.     

Bayesian analysis of mixture modelling using the multivariate t distribution

A finite mixture model using the multivariate t distribution has been shown as a robust extension of normal mixtures. In this paper, we present a Bayesian approach for inference about parameters of t-mixture models. The specifications of prior distributions are weakly informative to avoid causing nonintegrable posterior distributions. We present two efficient EM-type algorithms for computing the joint posterior mode with the observed data and an incomplete future vector as the sample. Markov chain Monte Carlo sampling schemes are also developed to obtain the target posterior distribution of parameters. The advantages of Bayesian approach over the maximum likelihood method are demonstrated via a set of real data.     

Consumption and Saving Behavior of Older and Younger Baby Boomers in Korea

The 1998 Korean Survey of Family Income and Expenditures was used to examine the overall consumption and saving behavior of Korean baby boomers and compared the differences in consumption and saving behavior between older and younger boomers. The t -test results indicated that the younger boomers allocated a significantly higher percentage of their expenditures on food away from home, household appliances, transportation and communication than did the older boomers, whereas the older boomers spent higher amounts and allocated larger budget shares on their children's education than did the younger boomers. The results of Ordinary Least-Squares (OLS) regression analysis showed that, holding other factors constant, older boomers not only spent significantly more in the total consumption expenditures and education expenditures, but older boomers also saved significantly less than did younger boomers.     

Assessment of influence in non-linear measurement error models

We consider the assessment of outliers and influential observation in non-linear measurement error models. Residuals, leverage measures and case-deletiondiagonostics are examined. The method of local influence is also applied to the models. In particular, the perturbation of measurement error variances has been found useful in assessing the adequancy of the model assumptions. A numerical example is given to illustrate the application of the diagonostics.