Balancing Uncertain Risks and Benefits in Human Subjects Research

October, 2005, Revised June, 2007Composed of a variety of scientific and technical experts plus a few lay members, thousands of Institutional Review Boards (IRBs) in the US must identify and assess the potential risks to human research subjects, and balance those risks against the potential benefits of the research. These assessments are laden with uncertainty, however. Most IRBs handle risk and its uncertainty by adopting a version of the precautionary principle, which is largely suggested by the Belmont Report and the Common Rule. To assess scientific merit, IRBs tacitly employ a "sanguinity principle," which treats uncertainty as inevitable in scientific progress. In balancing the uncertainties of human subjects risks and scientific benefits, IRBs use uncertainty as a bridging device that allows the approaches of science and ethics to be reconciled. Nevertheless, the flexibility and lack of consistent oversight of how IRBs apply these principles leads to frustration by investigators who are unclear about the criteria by which their proposals are evaluated

From Experts' Beliefs to Safety Standards: Explaining Preferred Radiation Protection Standards in Polarized Technical Communities

Public policy debates often involve complex, high-stakes issues in which the views of experts within scientific and technical communities play a prominent role. Disputes over appropriate governmental actions concerning global climate change, genetically modified organisms, nuclear waste disposal, cloning, and stem cell research highlight the political importance that can be attached to debates within scientific communities. Not only do these debates influence the kinds of assumed causal relationships that underlie policy alternatives (e.g., the link between CO2 concentrations in the atmosphere and global temperatures, or the dispersal patterns of pollens from genetically modified corn), but also those appointed to advisory and technical policy making positions are often chosen from the participating scientific communities. The appointment to such positions has become an increasingly contentious process; some critics contend that experts’ policy positions have trumped their scientific standing in determining appointments to important science policy boards (Revkin 2004; Mooney 2005)

Confirmation that a specific haplotype of the dopamine transporter gene is associated with Combined-Type ADHD

Objective: The primary purpose of this study was to confirm the association of a specific haplotype of the dopamine transporter gene and attention deficit hyperactivity disorder (ADHD), which could be one source of the heterogeneity seen across published studies. Method: The authors previously reported the association of ADHD with a subgroup of chromosomes containing specific alleles of two variable-number tandem repeat polymorphisms within the 3' untranslated region and intron 8 of the dopamine transporter gene. They now report on this association in a sample of ADHD combined-type probands. Results: The original observations were confirmed, with an overall odds ratio of 1.4 across samples. Conclusions: These data challenge results of meta-analyses suggesting that dopamine transporter variation does not have an effect on the risk for ADHD, and they indicate that further investigation of functional variation in the gene is required. <br/

Preventive digital mental health interventions for children and young people: a review of the design and reporting of research

Abstract: Digital health interventions (DHIs) have frequently been highlighted as one way to respond to increasing levels of mental health problems in children and young people. Whilst many are developed to address existing mental health problems, there is also potential for DHIs to address prevention and early intervention. However, there are currently limitations in the design and reporting of the development, evaluation and implementation of preventive DHIs that can limit their adoption into real-world practice. This scoping review aimed to examine existing evidence-based DHI interventions and review how well the research literature described factors that researchers need to include in their study designs and reports to support real-world implementation. A search was conducted for relevant publications published from 2013 onwards. Twenty-one different interventions were identified from 30 publications, which took a universal (n = 12), selective (n = 3) and indicative (n = 15) approach to preventing poor mental health. Most interventions targeted adolescents, with only two studies including children aged ≤10 years. There was limited reporting of user co-design involvement in intervention development. Barriers and facilitators to implementation varied across the delivery settings, and only a minority reported financial costs involved in delivering the intervention. This review found that while there are continued attempts to design and evaluate DHIs for children and young people, there are several points of concern. More research is needed with younger children and those from poorer and underserved backgrounds. Co-design processes with children and young people should be recognised and reported as a necessary component within DHI research as they are an important factor in the design and development of interventions, and underpin successful adoption and implementation. Reporting the type and level of human support provided as part of the intervention is also important in enabling the sustained use and implementation of DHIs

Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors

Background Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders. Methods We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors. Results Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged. Conclusions Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders.Peer reviewe

A genetic investigation of sex bias in the prevalence of attention-deficit/hyperactivity disorder

Background Attention-deficit/hyperactivity disorder (ADHD) shows substantial heritability and is 2-7 times more common in males than females. We examined two putative genetic mechanisms underlying this sex bias: sex-specific heterogeneity and higher burden of risk in female cases. Methods We analyzed genome-wide autosomal common variants from the Psychiatric Genomics Consortium and iPSYCH Project (20,183 cases, 35,191 controls) and Swedish populationregister data (N=77,905 cases, N=1,874,637 population controls). Results Genetic correlation analyses using two methods suggested near complete sharing of common variant effects across sexes, with rg estimates close to 1. Analyses of population data, however, indicated that females with ADHD may be at especially high risk of certain comorbid developmental conditions (i.e. autism spectrum disorder and congenital malformations), potentially indicating some clinical and etiological heterogeneity. Polygenic risk score (PRS) analysis did not support a higher burden of ADHD common risk variants in female cases (OR=1.02 [0.98-1.06], p=0.28). In contrast, epidemiological sibling analyses revealed that the siblings of females with ADHD are at higher familial risk of ADHD than siblings of affected males (OR=1.14, [95% CI: 1.11-1.18], p=1.5E-15). Conclusions Overall, this study supports a greater familial burden of risk in females with ADHD and some clinical and etiological heterogeneity, based on epidemiological analyses. However, molecular genetic analyses suggest that autosomal common variants largely do not explain the sex bias in ADHD prevalence

Nanotechnology, Risks, and Regulatory Options

Presented on March 27, 2018 at 12:00 p.m. in the Marcus Nanotechnology Building, Room 1117, Georgia Tech.Dr. Richard Barke is an Associate Professor in the School of Public Policy. He received his BS in Physics from the Georgia Institute of Technology and his MA and PhD in Political Science from the University of Rochester. His recent research interests focus on the regulation of risk, the roles of politics within science, and of science within politics. Dr. Barke has written about topics such as the political behavior of scientific disciplines, the impact of university curricula on the organization and advancement of scientific knowledge, the politics of science budgeting in Congress, and how scientists translate scientific findings into policy recommendations. Recent works involve the decision making processes by which science and ethics are reconciled in the regulation of research, particularly research involving human subjects and in nanotechnology. Currently he is writing a book about obstacles to long-term policy making.Runtime: 55:36 minutesThe National Science Foundation estimated that revenues from nano-enabled products grew worldwide from about $340 billion in 2010 to$731 billion in 2012, and more than $1 trillion in 2013. The impact of the nanotechnology revolution is undeniable, with vast potential benefits, from consumer products to industrial products, pharmaceutical and military applications, energy technologies, cosmetics, and so on. But along with these benefits come potential risks. As the EPA wrote in 2016, “nanomaterials are very useful, but there is little research about how they affect human and ecosystem health.” Uncertainties about health, safety, and environmental effects, and even about how to define and classify nanomaterials, have persisted. It is certain that regulatory policies in the U.S. and internationally will attempt to address these risks and balance them with the benefits, but several decades of experience reveals that analogies to previous emerging technologies are difficult and regulators have been hesitant to make definitive decisions. In some ways, the regulatory regime that will emerge may be as innovative as the technology that it addresses. In this talk I will examine some of the legally and politically inescapable procedural and substantive aspects of nanotechnology regulation, and identify some of the directions that American regulatory policy might move