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...     

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.     

Spatial variation in soil inorganic nitrogen across an arid urban ecosystem

We explored variations in inorganic soil nitrogen (N) concentrations across metropolitan Phoenix, Arizona, and the surrounding desert using a probability-based synoptic survey. Data were examined using spatial statistics on the entire region, as well as for the desert and urban sites separately. Concentrations of both NO₃-N and NH₄-N were markedly higher and more heterogeneous amongst urban compared to desert soils. Regional variation in soil NO₃-N concentration was best explained by latitude, land use history, population density, along with percent cover of impervious surfaces and lawn, whereas soil NH₄-N concentrations were related to only latitude and population density. Within the urban area, patterns in both soil NO₃-N and NH₄-N were best predicted by elevation, population density and type of irrigation in the surrounding neighborhood. Spatial autocorrelation of soil NO₃-N concentrations explained 49% of variation among desert sites but was absent between urban sites. We suggest that inorganic soil N concentrations are controlled by a number of ‘local’ or ‘neighborhood’ human-related drivers in the city, rather than factors related to an urban-rural gradient.     

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.     

私人妨害原则与相邻权、地役权

文章剖析了英美物权法上“使用权”的概念 ,并解释了财产权就像“权利集束”这个常用比喻 ,并对美国普通法上财产法中的有关相邻方之间土地纠纷的法规进行了比较分析 ,其中特别比较了普通法上的私人妨害原则和中国物权法草案第 9章所规定的相邻权的概念 ,并将普通法体系中的各种私人土地使用协议和地役权与中国物权法草案第 16章的内容进行了对比。     

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.     

An analysis of other countries’ international public relations in the U.S.

The purpose of this study was to examine the various aspects of international public relations by other countries in the U.S. Based on the Foreign Agency Registration Act (FARA) report in 2002, this study analyzed client, activity types, purpose of activity, and key U.S. partners for activity. This study found that (1) business organizations and central governments were major clients of international public relations in the U.S., (2) meeting with governmental officials and congressional leaders was the primary type of activity followed by information dissemination, and (3) economic purpose led by trade promotion was the primary motive for these activities.