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.     

Ecocultural Attributes: Evaluating Ecological Degradation in Terms of Ecological Goods and Services Versus Subsistence and Tribal Values

It is becoming increasingly clear that scientists, managers, lawyers, public policymakers, and the public must decide how to value what is provided by, and is a consequence of, natural resources. While “Western” scientists have clear definitions for the goods and services that ecosystems provide, we contend that these categories do not encompass the full totality of the values provided by natural resources. Partly the confusion results from a limited view of natural resources derived from the need to monetize the value of ecosystems and their component parts. Partly it derives from the “Western” way of separating natural resources from cultural resources or values, and partly it derives from the false dichotomy of assuming that ecosystems are natural, and anything constructed by man is not natural. In this article, we explore the previous assumptions, and suggest that because cultural resources often derive from, and indeed require, intact and unspoiled natural ecosystems or settings, that these values are rightly part of natural resources. The distinction is not trivial because of the current emphasis on cleaning up chemically and radiologically contaminated sites, on restoration of damaged ecosystems, on natural resource damage assessments, and on long‐term stewardship goals. All of these processes depend upon defining natural resources appropriately. Several laws, regulations, and protocols depend upon natural resource trustees to protect natural resources on trust lands, which could lead to the circular definition that natural resources are those resources that the trustees feel they are responsible for. Where subsistence or tribal peoples are involved, the definition of natural resources should be broadened to include those ecocultural attributes that are dependent upon, and have incorporated, natural resources. For example, a traditional hunting and fishing ground is less valued by subsistence peoples if it is despoiled by contamination or physical ecosystem degradation; an Indian sacred ground is tarnished if the surrounding natural environment is degraded; a traditional homeland is less valued if the land itself is contaminated. Our argument is that intact natural resources are essential elements of many cultural resources, and this aspect requires and demands adequate consideration (and may therefore require compensation).     

Was <Emphasis Type="Italic">that</Emphasis> Racist? An Experimental Study of Microaggression Ambiguity and Emotional Reactions for Racial–Ethnic Minority and White Individuals

This study examined racial–ethnic minority and white identified participants’ perceptions of racial microaggressions in four video scenarios involving a white professor and a black student. Participants (N = 261) were randomly assigned to observe a one of the four video conditions. The video involved an interaction with no microaggression, a very ambiguous microaggression, an ambiguous microaggression, or an overt microaggression. Participants rated their observations of (a) negative emotions toward the committer (white professor) and receiver (black student) of the microaggression, (b) positive emotions toward the committer and receiver of the microaggression, (c) perceptions on the degree of biasedness of committer, and (d) degree of positive perceptions of the committer. Analysis compared ratings of two groups, including racial–ethnic minority and white observers. We found a significant difference between the overt condition and other three conditions on negative emotions, positive emotions, and attributions of the professor (i.e., cultural biasedness and positive perceptions). However, there were no differences between the no microaggression, very ambiguous, and ambiguous conditions. No significant differences between racial–ethnic minority and white participants’ ratings were detected. Implications for training, practice, and future research are offered in our discussion.     

‘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.     

Comparing the effectiveness of respondent-driven sampling and quota sampling in migration research

We evaluate the effectiveness in empirical migration research of the respondent-driven sampling (RDS) and the quota sampling with regard to four criteria: quality of the data; sociometric diversity of the sample; geographic coverage of the sample; and cost-effectiveness. We review two surveys of ex-USSR migrants, conducted simultaneously in the Warsaw metropolitan area, each undertaken with the use of one of the two sampling methods. We find that although the RDS was considerably costlier, it enabled faster data collection and posed a lower risk of underestimating the cost of the survey. We also find that the RDS generated higher-quality data, and that it was more successful in surveying short-term circular migrants. This comparative evaluation contributes to the literature on social research methods in that it links the sampling methods with the quality and character of the data, and helps assess the usefulness and applicability of RDS in empirical migration studies.