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.     

Predicting the Risk of Biological Invasions Using Environmental Similarity and Transport Network Connectedness

Understanding the risk of biological invasions associated with particular transport pathways and source regions is critical for implementing effective biosecurity management. This may require both a model for physical connectedness between regions, and a measure of environmental similarity, so as to quantify the potential for a species to be transported from a given region and to survive at a destination region. We present an analysis of integrated biosecurity risk into Australia, based on flights and shipping data from each global geopolitical region, and an adaptation of the “range bagging” method to determine environmental matching between regions. Here, we describe global patterns of environmental matching and highlight those regions with many physical connections. We classify patterns of global invasion risk (high to low) into Australian states and territories. We validate our analysis by comparison with global presence data for 844 phytophagous insect pest species, and produce a list of high‐risk species not previously known to be present in Australia. We determined that, of the insect pest species used for validation, the species most likely to be present in Australia were those also present in geopolitical regions with high transport connectivity to Australia, and those regions that were geographically close, and had similar environments.     

Cyclical Evolution of the Global Right

An understanding of the current right‐wing national and transnational social movements can benefit from comparing them to the global and national conditions operating during their last appearance in the first half of the twentieth century and by carefully comparing twentieth‐century fascism with the neofascist and right‐wing populist movements that have been emerging in the twenty‐first century. This allows us to assess the similarities and differences, and to gain insights about what could be the consequences of the reemergence of populist nationalism and fascist movements. Our study uses the comparative evolutionary world‐systems perspective to study the Global Right from 1800 to the present. We see fascism as a form of capitalism that emerges when the capitalist project is in crisis. World historical waves of right‐wing populism and fascism are caused by the cycles of globalization and deglobalization, the rise and fall of hegemonic core powers, long business cycles (the Kondratieff wave), and interactions with both Centrist Liberalism and the Global Left. We consider how crises of the global capitalist system have produced right‐wing backlashes in the past, and how a future terminal crisis of capitalism could lead to a reemergence of a new form of authoritarian global governance or a reorganized global democracy in the future.     

Acculturative stress in the adjustment of immigrant families

This study reviews the issue of acculturative stress in immigrant families. Acculturative stress includes behaviors experienced by immigrants that are a direct consequence of the process of acculturation and adaptation to a new society. A number of stressors impacting on the acculturation of immigrant families is discussed. These stressors include lack of English language skills, employment and economic status, educational background, family life, and sociopolitical and immigration status.     

Media Publicity and the Voluntary Sector: The Case of Nonprofit Organizations in New York City

Media publicity is an important resource for contemporary voluntary associations, but very little is actually known about the resources and organizational characteristics that are most important for getting media attention. To address this question, we collected and analyzed data on the organizational attributes and news publicity of 739 nonprofit organizations in New York City. We find that an organization's income, paid staff, membership size, and library resources are significantly related to getting media publicity, whereas the number of chapter affiliations is inversely related to publicity. Association type is also a significant factor that influences an organization's ability to get publicity. We discuss the implications that these findings have for current debates about advocacy and civic engagement in the nonprofit sector.     

Empirical likelihood confidence intervals for the mean of a population containing many zero values

If a population contains many zero values and the sample size is not very large, the traditional normal approximation‐based confidence intervals for the population mean may have poor coverage probabilities. This problem is substantially reduced by constructing parametric likelihood ratio intervals when an appropriate mixture model can be found. In the context of survey sampling, however, there is a general preference for making minimal assumptions about the population under study. The authors have therefore investigated the coverage properties of nonparametric empirical likelihood confidence intervals for the population mean. They show that under a variety of hypothetical populations, these intervals often outperformed parametric likelihood intervals by having more balanced coverage rates and larger lower bounds. The authors illustrate their methodology using data from the Canadian Labour Force Survey for the year 2000.     

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.