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...     

Institutional Constraints and Deforestation: An Application to Mexico

Following North (1990), this article hypothesizes that effective rural institutions may impose additional costs on tropical deforestation through agricultural conversion. This allows a formal agricultural household analysis of institutional constraints on deforestation and therefore a method of empirically testing whether there is any significant difference in the actual level of forest land conversion under institutional constraints compared to the level of conversion under pure open access. A dynamic panel analysis for agricultural planted area in Mexico at state level and over the 1960–85 period confirms that institutional constraints on land clearing affected deforestation during the pre-NAFTA era.     

Characterizations of two power indices for voting games with r alternatives

In the first three sections of this paper we present a set of axioms which provide a characterization of an extension of the Banzhaf index to voting games with r alternatives, such as the United Nations Security Council where a nation can vote “yes”, “no”, or “abstain”. The fourth section presents a set of axioms which characterizes a power index based on winning sets instead of pivot sets. Received: 4 April 2000/Accepted: 30 April 2001     

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.     

Telecommuting: The future of work, corporate culture, and American society

Conclusion Throughout American history, first on the family farm and now in modern day business institutions, the workplace has been a stabilizing institution in American society that has anchored the ongoing, informal interactions occurring outside the workplace. In 1900, few Americans had a private mode of transportation. Barely 4,000 passenger automobiles were sold in 1900, and while horses were common, they were used primarily for farming, public transportation, and commercial activity in cities. By 1930, nearly 40 million cars had been added to America’s streets. The automobile recast life and work in central cities and eventually the suburbs.     

Efe fathers: one among many? A comparison of forager children's involvement with fathers and other males

The study reported describes Efe (pygmy) forager one-, two-, and three-year-olds' involvement with males. The Efe of northeastern Zaïre were chosen because their social organization allows us to examine hypotheses based on studies in Western, technologically complex societies about the distinctive role fathers play in the lives of their young children. Behavioral observations of Efe children's day-to-day activities with fathers, men and boys were recorded using a focal subject sampling technique (Altmann, 1974). Two behavioral measures were created to capture the extent to which males were involved with children: Social engagement describes males' involvement with children and social attention describes eavesdropping by children on males' everyday activities. Eight one-year-olds, 7 two-year-olds and 8 three-year-olds were each observed for six, one-hour observation sessions that were distributed evenly over the daylight hours. Data were analyzed using the traditional measure of involvement (e.g., adult males) and using a newly developed measure of the involvement of the average individual (e.g., average adult mate). Comparisons at each of the ages showed that fathers were consistently like other men in the extent to which children participated in social activities with them and watched their activities. Only fathers' level of social engagement declined significantly as children grew older. Boys' role relative to other males became increasingly distinctive as children aged. The findings suggest that Efe fathers may not be unique in the same sense assumed by Western study ideals, and raise questions about the special status given to fathers in Western theory and data. The patterning of mate involvement with children is discussed in terms of Efe community life, and in terms of Efe children's developing understanding of their relationship with fathers and other males.