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.     

Secondary analysis of dangerousness among death sentenced capital murderers

The theory of incapacitation involves reducing an offender's ability or capacity to commit further crimes. Capital punishment accomplishes this goal. An executed murderer never murders again. However, we do not execute all murderers, only capital murderers. This policy produces several research questions. Do capital murderers present a special risk to society? Are capital murderers more likely to murder or commit other violent crimes again than other murderers or the average citizen? To answer these questions, many states require a prediction of future dangerousness of a newly convicted murderer. To what extent has the judgment of future dangerousness matched actuarial data of subsequent murders and serious crimes? Using a secondary analysis, this investigation attempted to assemble available data of postconviction dangerousness of death sentenced capital murderers to create a more comprehensive actuarial account of subsequent dangerousness and to present the data in a common format used by the Federal Bureau of Investigation and the Bureau of Justice Statistics. Across 14 studies identified with relevant data, there were 13 instances of subsequent murder and 462 serious crime or prison rule violations.     

Cognitive and interpersonal abilities related to the primary activities of R&D managers

This study attempted to identify the primary activities performed by R&D managers at different supervisory levels, and the cognitive and interpersonal ability requirements that underlie these activities. A task inventory containing 244 managerial tasks was completed by 117 R&D managers in nine organizations. The 48 tasks which managers rated as having spent the most time were factor analyzed, resulting in the identification of three primary activities: project management, personnel supervision, and strategic planning. Furthermore, these activities varied with supervisory level, with R&D managers performing a wider range of these activities with the progression from first-line to upper-level management.Thirty R&D managers later rated the degree to which 19 cognitive and interpersonal abilities were required for performing these primary activities. Strategic planning was rated as requiring significantly higher levels of oral expression, logical reasoning, originality, fluency of ideas, oral defense, and resistance to premature judgement than was required for the other two primary activities. Personnel supervision required a higher level of social sensitivity than was required for the other two activities. Project management required high levels of information ordering, oral fact- finding ability, problem sensitivity, and oral and written comprehension. Implications of the findings for understanding R&D managerial performance and personnel staffing functions are discussed.     

Effects of Category Order on Answers in Mail and Telephone Surveys1

Abstract Past research suggests that mail surveys encourage a primacy effect, which is a tendency to choose the first answers from a list, whereas telephone surveys encourage a recency effect, a tendency to choose the last answers from a list. This paper summarizes results from 82 new experiments conducted in 12 separate surveys in seven states. Only four of 33 mail survey comparisons exhibited significant primacy effects, while five of 26 experiments in telephone surveys exhibited recency effects. In addition, only three of 23 cross-method comparisons produced a significant primacy/recency effect in the expected manner. The conclusion is that the prevalence of primacy and recency effects has been over-estimated by past research and a new theoretical approach that takes into account multiple causation is needed for examining these effects.     

‘There’s a lot of places I’d like to go and things I’d like to do’: the daily living experiences of adults with mild to moderate intellectual disabilities during a time of personalised social care reform in the United Kingdom

Adult social care services in the United Kingdom have undergone a period of transformation over recent years, characterised by a drive towards personalised care. Concurrently, social care budgets have been significantly reduced. This study aimed to explore the daily living experiences of adults with mild/moderate intellectual disabilities, who are at risk of no longer meeting eligibility criteria for statutory support. Focus group discussions, which included both people with intellectual disabilities and support workers, were analysed thematically. Two broad themes are presented: independence and agency; and social capital and well-being. While some participants echoed ideas central to the personalisation narrative, a number of contextual barriers to achieving greater independence and agency were discussed. Moreover, greater independence was not a desired goal for all participants. The findings highlight the potential mismatch between personalised social care, as delivered within significant budget constraints, and the needs of adults with intellectual disabilities.     

Odd-Burr generalized family of distributions with some applications

We study a new family of continuous distributions with two extra shape parameters called the Burr generalized family of distributions. We investigate the shapes of the density and hazard rate function. We derive explicit expressions for some of its mathematical quantities. The estimation of the model parameters is performed by maximum likelihood. We prove the flexibility of the new family by means of applications to two real data sets. Furthermore, we propose a new extended regression model based on the logarithm of the Burr generalized distribution. This model can be very useful to the analysis of real data and provide more realistic fits than other special regression models.     

Documenting Pornography Use in America: A Comparative Analysis of Methodological Approaches

Estimates of pornography use in the United States range widely. We explore the reasons for the variation in such estimates among U.S. adults using data from four different recent nationally representative samples—each of which asked a different type of question about pornography use. We attribute the notable variation in estimates to differences in question wording and answer options, and assert that a survey question asking respondents about their most recent use of pornography minimizes recall bias and is better poised to assess the overall prevalence of pornography in a population than is the more common approach of asking respondents about their historical general-use pattern. When we privileged the most-recent-use approach, survey data from 2014 reveal that 46% of men and 16% of women between the ages of 18 and 39 intentionally viewed pornography in a given week. These numbers are notably higher than most previous population estimates employing different types of questions. The results have ramifications for methods of surveying sensitive self-reported behaviors and for contextualizing scholars’ claims as well as popular conversations about the reach and implications of pornography use in the United States.     

“Big Fish in a Small Pond”: Chinese Migrant Shopkeepers in South Africa

The steady growth of Chinese migrants to South Africa in the past decade provides an opportunity to use Sen's (2001, Development as Freedom. Oxford: Oxford University Press) capabilities approach in the field of immigration. This theoretical framing reveals that the Chinese employ, what I call, a small pond migration strategy – utilizing mobility to maximize their social, economic, and human capital. I argue that the Chinese move to South Africa because of a desire to venture out of China and pursue freedoms associated with being one's own boss. Once in South Africa, they choose to stay because of comfortable weather and a slower pace of life, despite losing freedoms associated with high crime in Johannesburg. The findings suggest alternative ways of understanding factors of migration as well as a model that explains migration from more developed countries to less developed ones.     

The influence of FDA advisory information and black box warnings on individual use of prescription antidepressants

We examine how use of antidepressant medications is influenced by Food and Drug Administration (FDA) warnings about the increased risk of suicidality associated with pediatric antidepressant use. With individual-level data on antidepressant use from the Medical Expenditure Panel Survey, we consider whether consumer responses to FDA warnings differ among targeted (children) and non-targeted (adult) age-groups. Because the warning labels specifically mentioned new users, we examine separately the effects of the warnings on initiations of antidepressant therapy and on continued use of antidepressants. We find evidence consistent with reduced initiation of antidepressant use among the intended population of children, and that usage among children with more highly educated parents responded earlier to FDA information. However, we also find spillover effects of reduced initiation among the non-targeted population of adults. Overall, our results indicate that the FDA warning may have led consumers to perceive risks beyond those specifically mentioned.