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.     

Does a universal non-contributory social pension make sense for rural China?

China’s pension reform during the past three decades has allowed a majority of China’s population to be covered by a pension scheme. Of particular note has been the New Rural Pension Scheme (NRPS), a voluntary programme introduced starting in 2009. One goal of our analysis is to assess that pension scheme, using a variety of sources of information including data drawn from recent (2013 and 2015) nationwide China Health and Retirement Longitudinal Surveys (CHARLS). Our analysis involves an exploration of differences between the generosity and structure of the NRPS and other pension schemes currently in place. We also explore the feasibility of reforming the current “quasi-social pension” component of the NRPS by substituting a universal non-contributory social pension pillar. In connection with our assessment of the NRPS, we note the unusually low benefit levels for rural China.     

Reviews

Abstract

Michelle DeMars reviews The Indispensable Academic Librarian: Teaching and Collaborating for Change; Norma Durian reviews The Library Outreach Casebook; Trina Boykin Nolen reviews Licensing Digital Content: A Practical Guide for Librarians, Third Edition.     

Multi-valued strategy-proof social choice rules

In this paper we introduce a new definition of strategy-proofness for multi-valued social choice correspondences. We prove two Gibbard-Satterthwaite type results for strategy-proof social choice correspondences. These results show that allowing multiple outcomes as social choices will not necessarily lead to an escape from the Gibbard-Satterthwaite impossibility theorem. Received: 24 January 2001/Accepted: 19 March 2001     

Frustration in Infancy: Implications for Emotion Regulation,Physiological Processes,and Temperament

A study sample of 162 six‐month‐old children was selected from a larger sample of 346 infants on the basis of parents' report of their infants' temperament and a laboratory assessment of temperament. Infants were classified as easily frustrated and less easily frustrated and compared on a number of emotion regulation, physiology, and temperament measures. Results indicated that male and female infants were equally likely to be classified as frustrated and less easily frustrated; however, male infants were less able to regulate physiologically. Easily frustrated infants used different emotion regulation strategies and were observed to be less attentive and more active than less easily frustrated infants when observed in the laboratory. These infants were also characterized by their parents as more active, less attentive, and more distressed to novelty. Infants classified as easily frustrated were more reactive physiologically and less able to regulate physiological reactivity than their less easily frustrated counterparts. It is hypothesized that this cluster of characteristics may constitute a unique temperamental type that may have implications for other types of behavioral functioning. Limitations of the study are that observations are based on a single brief assessment of the infant, modest effect sizes were found, and the study is cross‐sectional.     

Open Road or Blind Alley? Welfare Reform, Mothers, and Children with Disabilities

Welfare reform was examined for 39 Michigan families whose children have significant health or intellectual and behavioral disabilities. As a group, these families received little specialized assistance or services to address their unique needs. Family-cited barriers to self-sufficiency included poorly trained welfare caseworkers, limited public transportation, and inadequate child care. Having an older child was the only discriminating variable between working and non-working mothers. However, working mothers only had temporary positions with no benefits and low pay. All families, whether employed or not, lived below the poverty line.     

Effects of Marriage and Children on Financial Risk Tolerance: A Synthesis of Family Development and Prospect Theory

Family development and prospect theory were used as a framework to predict variability in individuals' subjective financial risk tolerance within distinct family structures. Gender, age, and income were expected to interact with the main effects of family structure (marital status and children). Theory-generated hypotheses were examined in Study 1 (data from university housing respondents, n = 76) and Study 2 (the 1998 Survey of Consumer Finances, n = 4,305). One family structure main effect (child presence) was significant for investment risk tolerance in both studies. Family structure interactions (marital status × age and child × income) were significant for employment risk (Study 1), and child × age was significant for investment risk in Study 2.     

Generating random variates from D-distributions via substitution sampling

Laud et al. (1993) describe a method for random variate generation from D-distributions. In this paper an alternative method using substitution sampling is given. An algorithm for the random variate generation from SD-distributions is also given.