Exploring current read-across applications and needs among selected U.S. Federal Agencies.
ABSTRACT: Read-across is a well-established data gap-filling technique applied for regulatory purposes. In US Environmental Protection Agency's New Chemicals Program under TSCA, read-across has been used extensively for decades, however the extent of application and acceptance of read-across among U.S. federal agencies is less clear. In an effort to build read-across capacity, raise awareness of the state of the science, and work towards a harmonization of read-across approaches across U.S. agencies, a new read-across workgroup was established under the Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM). This is one of several ad hoc groups ICCVAM has convened to implement the ICCVAM Strategic Roadmap. In this article, we outline the charge and scope of the workgroup and summarize the current applications, tools used, and needs of the agencies represented on the workgroup for read-across. Of the agencies surveyed, the Environmental Protection Agency had the greatest experience in using read-across whereas other agencies indicated that they would benefit from gaining a perspective of the landscape of the tools and available guidance. Two practical case studies are also described to illustrate how the read-across approaches applied by two agencies vary on account of decision context.
Project description:Evaluating how wildlife conservation laws are implemented is critical for safeguarding biodiversity. Two agencies, the U.S. Fish and Wildlife Service and National Marine Fisheries Service (FWS and NMFS; Services collectively), are responsible for implementing the U.S. Endangered Species Act (ESA), which requires federal protection for threatened and endangered species. FWS and NMFS' comparable role for terrestrial and marine taxa, respectively, provides the opportunity to examine how implementation of the same law varies between agencies. We analyzed how the Services implement a core component of the ESA, section 7 consultations, by objectively assessing the contents of >120 consultations on sea turtle species against the requirements in the Services' consultation handbook, supplemented with in-person observations from Service biologists. Our results showed that NMFS consultations were 1.40 times as likely to have higher completeness scores than FWS consultations given the standard in the handbook. Consultations tiered from an FWS programmatic consultation inherited higher quality scores of generally more thorough programmatic consultations, indicating that programmatic consultations could increase the quality of consultations while improving efficiency. Both agencies commonly neglected to account for the effects of previous consultations and the potential for compounded effects on species. From these results, we recommend actions that can improve quality of consultation, including the use of a single database to track and integrate previously authorized harm in new analyses and the careful but more widespread use of programmatic consultations. Our study reveals several critical shortfalls in the current process of conducting ESA section 7 consultations that the Services could address to better safeguard North America's most imperiled species.
Project description:President Trump and his administration have been regarded by news outlets and scholars as one of the most hostile administrations towards scientists and their work. However, no study to-date has empirically measured how federal scientists perceive the Trump administration with respect to their scientific work. In 2018, we distributed a survey to over 63,000 federal scientists from 16 federal agencies to assess their perception of scientific integrity. Here we discuss the results of this survey for a subset of these agencies: Department of Interior (DOI) agencies (the US Fish and Wildlife Service (FWS), the US Geological Survey, and the National Park Service); the Centers for Disease Control and Prevention (CDC); the US Environmental Protection Agency (EPA); the Food and Drug Administration (FDA); and the National Oceanic and Atmospheric Administration (NOAA). We focus our analysis to 10 key questions fitting within three core categories that relate to perceptions of integrity in science. Additionally, we analyzed responses across agencies and compare responses in the 2018 survey to prior year surveys of federal scientists with similar survey questions. Our results indicate that federal scientists perceive losses of scientific integrity under the Trump Administration. Perceived loss of integrity in science was greater at the DOI and EPA where federal scientists ranked incompetent and untrustworthy leadership as top barriers to science-based decision-making, but this was not the case at the CDC, FDA, and NOAA where scientists positively associated leadership with scientific integrity. We also find that reports of political interference in scientific work and adverse work environments were higher at EPA and FWS in 2018 than in prior years. We did not find similar results at the CDC and FDA. These results suggest that leadership, positive work environments, and clear and comprehensive scientific integrity policies and infrastructure within agencies play important roles in how federal scientists perceive their agency's scientific integrity.
Project description:A study was conducted to investigate health care agency central line-associated bloodstream infection (CLABSI) definitions and prevention policies and pare them to the Joint Commission National Patient Safety Goal (NPSG.07.04.01), the Centers for Disease Control and Prevention (CDC) CLABSI prevention recommendations, and a best-practice central line care bundle for inpatients.A telephone-based survey was conducted in 2011 of a convenience sample of home health care agencies associated with children's hematology/oncology centers.Of the 97 eligible home health care agencies, 57 (59%) completed the survey. No agency reported using all five aspects of the National Healthcare and Safety Network/Association for Professionals in Infection Control and Epidemiology CLABSI definition and adjudication process, and of the 50 agencies that reported tracking CLABSI rates, 20 (40%) reported using none. Only 10 agencies (18%) had policies consistent with all elements of the inpatient-focused NPSG.07.04.01, 10 agencies (18%) were consistent with all elements of the home care targeted CDC CLABSI prevention recommendations, and no agencies were consistent with all elements of the central line care bundle. Only 14 agencies (25%) knew their overall CLABSI rate: mean 0.40 CLABSIs per 1,000 central line days (95% confidence interval [CI], 0.18 to 0.61). Six agencies (11%) knew their agency's pediatric CLABSI rate: mean 0.54 CLABSIs per 1,000 central line days (95% CI, 0.06 to 1.01).The policies of a national sample of home health care agencies varied significantly from national inpatient and home health care agency targeted standards for CLABSI definitions and prevention. Future research should assess strategies for standardizing home health care practices consistent with evidence-based recommendations.
Project description:Endocrine disrupting chemicals with estrogenic activity (EA) have been associated with various adverse health effects. US agencies (ICCVAM/NICEATM) tasked to assess in vitro transcription activation assays to detect estrogenic receptor (ER) agonists for EA have recently validated a BG1Luc assay in manual format, but prefer robotic formats. We have developed a robotic BG1Luc EA assay to detect EA that demonstrated 100% concordance with ICCVAM meta-analyses and ICCVAM BG1Luc results in manual format for 27 ICCVAM test substances, i.e. no false negatives or false positives. This robotic assay also consistently assessed other, more problematic ICCVAM test substances such as clomiphene citrate, L-thyroxin, and tamoxifen. Agonist responses using this robotic BG1Luc assay were consistently inhibited by the ER antagonist ICI 182,780, confirming that agonist responses were due to binding to ERs rather than to a non-specific agonist response. This robotic assay also detected EA in complex mixtures of substances such as extracts of personal care products, plastic resins or plastic consumer products. This robotic BG1Luc assay had at least as high accuracy and greater sensitivity and repeatability when compared to its manual version or to the other ICCVAM/OECD validated assays for EA (manual BG1Luc and CERI).
Project description:BACKGROUND:Systematic reviews are increasingly prevalent in environmental health due to their ability to synthesize evidence while reducing bias. Different systematic review methods have been developed by the US National Toxicology Program's Office of Health Assessment and Translation (OHAT), the US Environmental Protection Agency's (EPA) Integrated Risk Information System (IRIS), and by the US EPA under the Toxic Substances Control Act (TSCA), including the approach to assess risk of bias (ROB), one of the most vital steps which is used to evaluate internal validity of the studies. Our objective was to compare the performance of three tools (OHAT, IRIS, TSCA) in assessing ROB. METHODS:We selected a systematic review on polybrominated diphenyl ethers and intelligence quotient and/or attention deficit hyperactivity disorder because it had been endorsed by the National Academy of Sciences. Two reviewers followed verbatim instructions from the tools and independently applied each tool to assess ROB in 15 studies previously identified. We documented the time to apply each tool and the impact the ROB ratings for each tool had on the final rating of the quality of the overall body of evidence. RESULTS:The time to complete the ROB assessments varied widely (mean = 20, 32, and 40?min per study for the OHAT, IRIS, and TSCA tools, respectively). All studies were rated overall "low" or "uninformative" using IRIS, due to "deficient" or "critically deficient" ratings in one or two domains. Similarly, all studies were rated "unacceptable" using the TSCA tool because of one "unacceptable" rating in a metric related to statistical power. Approximately half of the studies had "low" or "probably low ROB" ratings across all domains with the OHAT and Navigation Guide tools. CONCLUSIONS:Tools that use overall ROB or study quality ratings, such as IRIS and TSCA, may reduce the available evidence to assess the harms of environmental exposures by erroneously excluding studies, which leads to inaccurate conclusions about the quality of the body of evidence. We recommend using ROB tools that circumvents these issues, such as OHAT and Navigation Guide. SYSTEMATIC REVIEW REGISTRATION:This review has not been registered as it is not a systematic review.
Project description:To protect biodiversity, conservation laws should be evaluated and improved using data. We provide a comprehensive assessment of how a key provision of the U.S. Endangered Species Act (ESA) is implemented: consultation to ensure federal actions do not jeopardize the existence of listed species. Data from all 24,893 consultations recorded by the National Marine Fisheries Service (NMFS) from 2000-2017 show federal agencies and NMFS frequently agreed (79%) on how federal actions would affect listed species. In cases of disagreement, agencies most often (71%) underestimated effects relative to the conclusions of species experts at NMFS. Such instances can have deleterious consequences for imperiled species. In 22 consultations covering 14 species, agencies concluded that an action would not harm species while NMFS determined the action would jeopardize species' existence. These results affirm the importance of the role of NMFS in preventing federal actions from jeopardizing listed species. Excluding expert agencies from consultation compromises biodiversity conservation, but we identify approaches that improve consultation efficiency without sacrificing species protections.
Project description:To investigate factors associated with engagement of U.S. Federal Health Agencies via Twitter. Our specific goals are to study factors related to a) numbers of retweets, b) time between the agency tweet and first retweet and c) time between the agency tweet and last retweet.We collect 164,104 tweets from 25 Federal Health Agencies and their 130 accounts. We use negative binomial hurdle regression models and Cox proportional hazards models to explore the influence of 26 factors on agency engagement. Account features include network centrality, tweet count, numbers of friends, followers, and favorites. Tweet features include age, the use of hashtags, user-mentions, URLs, sentiment measured using Sentistrength, and tweet content represented by fifteen semantic groups.A third of the tweets (53,556) had zero retweets. Less than 1% (613) had more than 100 retweets (mean ?=?284). The hurdle analysis shows that hashtags, URLs and user-mentions are positively associated with retweets; sentiment has no association with retweets; and tweet count has a negative association with retweets. Almost all semantic groups, except for geographic areas, occupations and organizations, are positively associated with retweeting. The survival analyses indicate that engagement is positively associated with tweet age and the follower count.Some of the factors associated with higher levels of Twitter engagement cannot be changed by the agencies, but others can be modified (e.g., use of hashtags, URLs). Our findings provide the background for future controlled experiments to increase public health engagement via Twitter.
Project description:Despite substantial investments by government, philanthropic, and commercial sources over the past several decades, traumatic brain injury (TBI) remains an unmet medical need and a major source of disability and mortality in both developed and developing societies. The U.S. Department of Defense neurotrauma research portfolio contains more than 500 research projects funded at more than $700 million and is aimed at developing interventions that mitigate the effects of trauma to the nervous system and lead to improved quality of life outcomes. A key area of this portfolio focuses on the need for effective pharmacological approaches for treating patients with TBI and its associated symptoms. The Neurotrauma Pharmacology Workgroup was established by the U.S. Army Medical Research and Materiel Command (USAMRMC) with the overarching goal of providing a strategic research plan for developing pharmacological treatments that improve clinical outcomes after TBI. To inform this plan, the Workgroup (a) assessed the current state of the science and ongoing research and (b) identified research gaps to inform future development of research priorities for the neurotrauma research portfolio. The Workgroup identified the six most critical research priority areas in the field of pharmacological treatment for persons with TBI. The priority areas represent parallel efforts needed to advance clinical care; each requires independent effort and sufficient investment. These priority areas will help the USAMRMC and other funding agencies strategically guide their research portfolios to ensure the development of effective pharmacological approaches for treating patients with TBI.
Project description:Reputation is of growing interest for the study of public bureaucracies, but a measurement that can discern between the subdimensions of reputation and is validated on real-life audiences has remained elusive. The authors deductively build, test, and cross-validate a survey instrument through two surveys of 2,100 key stakeholders of the European Chemicals Agency, the European Union chemicals regulator. This empirical tool measures an agency's reputation and its building blocks. This scale represents an important contribution to reputation literature, as it allows scholars to distinguish and measure which aspects of reputation public organizations are "known for" and build their claim to authority on, as well as how the profiles of public organizations differ. The authors find that direct stakeholder contact with the agency is necessary for stakeholders to be able to evaluate the separate dimensions of reputation independently. Evidence for Practice This study equips practitioners with a reputation barometer tailored to the public sector. It allows them to measure the reputation of their organization, in a differentiated fashion, among different stakeholder groups.While public organizations increasingly engage in reputation management activities, a potential caveat that emerges from our exercise is that managers might be steering in non-astute directions. While our study shows that, as for private actors, "performance matters," procedural and moral aspects also weigh heavily in the eyes of stakeholders when it comes to public regulators.To secure a positive organizational image and the authority crucial for public agencies to operate, the performance management turn in the public sector may need to be supplemented by an enhanced organizational attention to procedural and moral aspects.
Project description:There are many mechanisms of neurotoxicity that are initiated by the interaction of chemicals with different neurological targets. Under the U.S. Environmental Protection Agency's ToxCast program, the biological activity of thousands of chemicals was screened in biochemical and cell-based assays in a high-throughput manner. Two hundred sixteen assays in the ToxCast screening database were identified as targeting a total of 123 proteins having neurological functions according to the Gene Ontology database. Data from these assays were imported into the Organization for Economic Co-operation and Development QSAR Toolbox and used to predict neurological targets for chemical neurotoxins. Two sets of data were generated: one set was used to classify compounds as active or inactive and another set, composed of AC50s for only active compounds, was used to predict AC50 values for unknown chemicals. Chemical grouping and read-across within the QSAR Toolbox were used to identify neurologic targets and predict interactions for pyrethroids, a class of compounds known to elicit neurotoxic effects in humans. The classification prediction results showed 79% accuracy while AC50 predictions demonstrated mixed accuracy compared with the ToxCast screening data.