Regulatory Decision-making Process Research Articles

Safety Aspects in Dry Storage of Spent Nuclear Fuel in Long Term Operation for Brazilian Nuclear Power Plants

The use of Dry Casks Storage Systems (DCSS) as a strategy for Spent Nuclear Fuel (SNF) management is a solution widely used by several countries. It should be noted that this approach was originally conceived as a temporary / supplementary storage solution, since the ultimate solution is the reprocessing or the storage of SNF in Finals Repositories of radioactive material. Taking into account the limited storage capacity of Angra I and II Spent Fuel Pool, the Nuclear Power Plants Operator has submitted to the Brazilian Nuclear Regulatory Body (CNEN) the design of the Dry Storage Unit (UAS) as an alternative to SNF management. This work performs a Safety Evaluation applying the methodology defined in NUREG 1927 [2]. Three Structures, Systems and Components (SSC), classified as ITS (Important to safety), were selected. Following the methodology, materials and service environments were identified for those SSCs previously selected. In a second moment the ageing mechanisms and degradation effects to be considered in the UAS Long Term Operation were presented. As a result of this Safety Evaluation, some recommendations were extracted. These recommendations together with those found in the literature can guide the regulatory decision-making process regarding to the license renewal of UAS in Brazilian territory.

Are economists Kings? Economic evidence and discretionary assessments at the UK utility regulatory agencies

Abstract UK sectoral regulatory authorities are hybrid communities of, among others, lawyers and economists. Since the liberalization of essential services, expert economists enjoy broad discretionary powers in advancing the agencies’ broad statutory objectives. Yet, despite the significant societal impact of economic regulation, existing scholarship in the fields of competition law and regulation and public law has, with very few exceptions, disregarded these actors and the very essence of their work. This article aims to address this gap in the literature by blending theoretical with empirical insights deriving from 14 semi-structured elite interviews with regulatory economists in the regulatory agencies for energy (Office for Gas and Electricity Markets), telecoms (Office for Communications), and water (Office of Water Services). It explores the increased reliance on economics in the regulatory decision-making process and the impact this has had on the authorities’ decision-making and discretion, when making complex trade-offs between the various goals of the regulatory enterprise. In doing so, it puts forward a theoretical framework inspired by Craig Parsons’ typology of political action so as to identify and examine the nature and scope of the constraints that inform and shape the influence of economics in the exercise of regulatory discretion. This endeavour is significant in the sense that it is the first of its kind and, in that it provides a normative framework of analysis that can be applied in other areas of regulation heavily infused with and influenced by economic evidence and analysis, such as ‘pure’ competition law enforcement by both sectoral and competition authorities.

Users' Modifications to Electronic Nicotine Delivery Systems (ENDS): Interviews with ENDS Enthusiasts.

Users’ modifications to electronic nicotine delivery systems (ENDS) products could increase initiation, inhibit cessation, or change the toxicity of the product. This study aims to begin to identify consumers’ common ENDS modification behaviors. We conducted audio-recorded, in-depth one-on-one interviews with 13 adult ENDS users in the metropolitan Atlanta area, who self-reported extensive modification experience. Modifications to coils, batteries, and e-liquids were commonly mentioned. Participants indicated that users modified devices to produce large clouds, change levels of nicotine delivery, alter tastes of e-liquids, and experience different throat hits. Because manufacturers have changed product characteristics to be in line with consumer preferences, interviewees indicated that fewer users currently engage in modifications to coils and batteries compared to the more widespread practice a few years ago. Hobbyists continue to perform modifications and many users continue to misuse or abuse e-liquids, despite the view that fewer users currently alter their ENDS than in the past. The Food and Drug Administration (FDA) regulatory actions that limit certain product characteristics may unintentionally increase the likelihood that users will once again make more extensive modifications to their products, and this should be considered as part of the FDA’s regulatory decision-making process.

Structured benefit-risk evaluation for medicinal products: review of quantitative benefit-risk assessment findings in the literature.

A favorable benefit–risk profile remains an essential requirement for marketing authorization of medicinal drugs and devices. Furthermore, prior subjective, implicit and inconsistent ad hoc benefit–risk assessment methods have rightly evolved towards more systematic, explicit or “structured” approaches. Contemporary structured benefit–risk evaluation aims at providing an objective assessment of the benefit–risk profile of medicinal products and a higher transparency for decision making purposes. The use of a descriptive framework should be the preferred starting point for a structured benefit–risk assessment. In support of more precise assessments, quantitative and semi-quantitative methodologies have been developed and utilized to complement descriptive or qualitative frameworks in order to facilitate the structured evaluation of the benefit–risk profile of medicinal products. In addition, quantitative structured benefit–risk analysis allows integration of patient preference data. Collecting patient perspectives throughout the medical product development process has become increasingly important and key to the regulatory decision-making process. Both industry and regulatory authorities increasingly rely on descriptive structured benefit–risk evaluation and frameworks in drug, vaccine and device evaluation and comparison. Although varied qualitative methods are more commonplace, quantitative approaches have recently been emphasized. However, it is unclear how frequently these quantitative frameworks have been used by pharmaceutical companies to support submission dossiers for drug approvals or to respond to the health authorities’ requests. The objective of this study has been to identify and review, for the first time, currently available, published, structured, quantitative benefit–risk evaluations which may have informed health care professionals and/or payor as well as contributed to decision making purposes in the regulatory setting for drug, vaccine and/or device approval.Plain language summary Quantitative evaluation of the benefit–risk balance for medicinal products The review of the benefits and the risks associated with a medicinal product is called benefit–risk assessment. One of the conditions for a medicinal product to receive marketing authorization is to demonstrate a positive benefit–risk balance in which the benefits outweigh the risks. In order to enhance the transparency and consistency in the assessment of benefit–risk balance, frameworks and quantitative methods have been developed for decision making purposes and regulatory approvals of medicinal products. This article considers published quantitative benefit–risk evaluations which may have informed health care professionals and/or payor as well as contributed to decision making purposes in the regulatory setting for drug, vaccine and/or device approval.

Assessing forest governance in Albania

In the last 20 years, Albania has transferred the ownership and the responsibility of the management of 80% of forest area from central government to local government. The process was part of a wide decentralization reform aiming to tackle the challenges related to illegal logging activities, weak institutions, and capacities, unclear laws and regulations, frequent reforms in forest administration, high sector informality etc. Due to decentralization forest governance involve two levels of government and a range of stakeholders with different interests (local communities, forest owners, private sector, etc.). Although the reforms are under implementation, there is a lack of assessments, to analyze the governance challenges for the sector. Therefore, the aim of this paper is to provide an assessment of the status of forest governance in Albania, using a comprehensive analytical framework developed by FAO and PROFOR. The framework is based on three columns (i) policy, legal, institutional and regulatory frameworks, (ii) planning and decision-making processes and (iii) implementation enforcement and compliance. A set of 84 indicators, considered to be relevant for Albania, has been chosen out of 130 indicators proposed by PROFOR. The assessment is carried out through a survey, with a cross-section of 30 experts from various forest-related institutions (state and non-state). The results show that forest governance in Albania is far from good forest governance, despite some positive efforts. The reasons for this are no clear set of policy directions, conflicting or confusing laws, complex forest law and bylaws, no secure access to forest resources by local communities, low capacities of government (central and local) and non-government stakeholders, lack of transparency and accountability etc.

Application of Game Theory against Nature in the Assessment of Technical Solutions Used in River Regulation in the Context of Aquatic Plant Protection

The anthropogenic transformation of riverbeds causes a violation of the dynamic equilibrium of the river and its environment, threatening the ecological safety of aquatic ecosystems and dependent waters. However, the differing results of these transformations are dependent on many factors and it is difficult to determine them precisely before the works start. The designers and contractors of these works are dealing with the riverbed, which in terms of hydromorphological and biological features is variable, unique, and strongly diverse. Thus, decisions are followed by an unknown result concerning changes in the riverbed ecosystems. The aim of this study is to determine the suitability of game theory as a tool supporting decision-making in the design of regulatory works including ecological aspects, as well as an indication of a regulatory works model that would meet the expectations of water users while corresponding to environmentally friendly riverbed regulation. The analysis was made on the basis of observed changes in the number of species in aquatic plant vascular communities—one of the most important elements of a riverbed ecosystem. Using game theory, it is possible to create an effective tool for the design of regulatory works and decision-making process.

State of Wyoming v. U.S. Dep’t of the Interior Confused Agency Overlap with Preclusion: BLM Had Authority to Promulgate the Fracking Rule for Public Lands, Not Tribal Lands

State of Wyoming v. U.S. Dep’t of the Interior Confused Agency Overlap with Preclusion: BLM Had Authority to Promulgate the Fracking Rule for Public Lands, Not Tribal Lands

De facto regulatory decision-making processes in telecommunications regulation: explaining influence relationships with exponential random graph models

AbstractResearch on regulation has focussed on explaining the independence of sector regulators and assessing the effects of regulations on markets. This article broadens the scope of such research by studying and explaining how regulatory actors interact at the de facto level in a multi-actor regulatory arrangement when making regulatory decisions in the telecommunications sector of Colombia. We propose that regulatory decisions depend on the manner in which actors influence each other. In this article, we are not only focussing on the policy outcome itself but also on the regulatory decision-making process. We performed a social network analysis and used an exponential random graph model to analyse the data. Our findings suggest that actors’ level of influence is affected by the access they have to other organisations, the divergence of positions they have with these other organisations and the power resources of an organisation. In addition, there are structural network characteristics that affect regulatory decisionmaking.

PMU100 - MAPPING BENEFIT-RISK DECISION-MAKING PROCESSES AND IDENTIFYING DECISION POINTS WITH THE POTENTIAL TO INCLUDE PATIENT PREFERENCE INFORMATION THROUGHOUT THE MEDICAL PRODUCT LIFECYCLE

Patient preference information (PPI) has not been effectively integrated in decision-making throughout the medical product lifecycle (MPLC). A first step requires an understanding of existing processes and decision points to know how to incorporate PPI to improve patient-centric decision making. The aims were to: 1) identify the decision-making processes and decision points throughout the MPLC for stakeholders, and 2) determine which decision points have potential to include PPI. A 3-step approach was conducted, including a scoping literature review identifying relevant white and grey literature, validation meetings with stakeholders to confirm decision-making processes, and semi-structured interviews with representatives of 3 stakeholder groups (industry n=24, regulatory n=22, HTA n=24). The literature review was conducted using five scientific databases, and interviews were conducted within seven different European countries and the US. Six decision points were identified for industry decision-making process: 1) Select & prioritize targets and leads; 2) Prioritize studies; 3) Prioritize assets; 4) Optimize & Prioritize assets; 5) Regulatory Submission & Launch; and 6) Manage MPLC & Prioritize opportunities. Four decisions points for the regulatory decision-making process: 1) Submission and validation; 2) Scientific opinion; 3) Orphan designation; and 4) Commission decision. Six decision points for HTA decision-making: 1) Filtration; 2) Prioritization; 3) Appraisal; 4) Filtration II; 5) Prioritization II; and 6) Appraisal II. PPI is currently not considered required information to be submitted for decision-making, but has the potential to be included at most key decision points. Currently, PPI is not considered as obligatory information to submit for any of the MPLC decision points, nor is it a pre-set criterium for decision-making. PPI is considered an important component by most stakeholders to inform future decision-making across the MPLC. Acknowledgement: This work received support from the EU/EFPIA Innovative Medicines Initiative [2] Joint Undertaking PREFER grant n° 115966

Intestinal Metabolism and Bioaccumulation of Sucralose In Adipose Tissue In The Rat

ABSTRACTThe aim of this study was to (1) determine if the organochlorine artificial sweetener sucralose is metabolized in rat intestine with repeated dosing and (2) examine whether sucralose might bioaccumulate in rat adipose tissue. Sucralose was administered to 10 rats by gavage daily for 40 days at an average dosage of 80.4 mg/kg/day. The dosages were within the range utilized in historical toxicology studies submitted for regulatory approval in North America, Europe, and Asia. Feces and urine were collected individually from each animal for every 24-hr period during the 40-day dosing period. Analysis of the urine and fecal extracts by ultra-high performance liquid chromatography tandem mass spectrometry (UHPLC–MS/MS) revealed two new biotransformation products that have not previously been reported. These two metabolites are both acetylated forms of sucralose that are less polar and hence more lipophilic than sucralose itself. These metabolites were present in urine and feces throughout the sucralose dosing period and still detected at low levels in the urine 11 days after discontinuation of sucralose administration and 6 days after sucralose was no longer detected in the urine or feces. The finding of acetylated sucralose metabolites in urine and feces do not support early metabolism studies, on which regulatory approval was based, that claimed ingested sucralose is excreted unchanged (i.e. not metabolized). The historical metabolic studies apparently failed to detect these metabolites in part because investigators used a methanol fraction from feces for analysis along with thin layer chromatography and a low-resolution linear radioactivity analyzer. Further, sucralose was found in adipose tissue in rats two weeks after cessation of the 40-day feeding period even though this compound had disappeared from the urine and feces. Thus, depuration of sucralose which accumulated in fatty tissue requires an extended period of time after discontinuation of chemical ingestion. These new findings of metabolism of sucralose in the gastrointestinal tract (GIT) and its accumulation in adipose tissue were not part of the original regulatory decision process for this agent and indicate that it now may be time to revisit the safety and regulatory status of this organochlorine artificial sweetener

Emerging technologies for food and drug safety

Emerging technologies are playing a major role in the generation of new approaches to assess the safety of both foods and drugs. However, the integration of emerging technologies in the regulatory decision-making process requires rigorous assessment and consensus amongst international partners and research communities. To that end, the Global Coalition for Regulatory Science Research (GCRSR) in partnership with the Brazilian Health Surveillance Agency (ANVISA) hosted the seventh Global Summit on Regulatory Science (GSRS17) in Brasilia, Brazil on September 18–20, 2017 to discuss the role of new approaches in regulatory science with a specific emphasis on applications in food and medical product safety. The global regulatory landscape concerning the application of new technologies was assessed in several countries worldwide. Challenges and issues were discussed in the context of developing an international consensus for objective criteria in the development, application and review of emerging technologies. The need for advanced approaches to allow for faster, less expensive and more predictive methodologies was elaborated. In addition, the strengths and weaknesses of each new approach was discussed. And finally, the need for standards and reproducible approaches was reviewed to enhance the application of the emerging technologies to improve food and drug safety. The overarching goal of GSRS17 was to provide a venue where regulators and researchers meet to develop collaborations addressing the most pressing scientific challenges and facilitate the adoption of novel technical innovations to advance the field of regulatory science.

Learning the effects of psychotropic drugs during pregnancy using real-world safety data: a paradigm shift toward modern pharmacovigilance

The growing evidence on psychotropic drug safety in pregnancy has been possible thanks to the increasing availability of real-world data, i.e. data not collected in conventional randomised controlled trials. Use of these data is a key to establish psychotropic drug effects on foetal, child, and maternal health. Despite the inherent limitations and pitfalls of observational data, these can still be informative after a critical appraisal of the collective body of evidence has been done. By valuing real-world safety data, and making these a larger part of the regulatory decision-making process, we move toward a modern pregnancy pharmacovigilance. The recent uptake of real-world safety data by health authorities has set the basis for an important paradigm shift, which is integrating such data into drug labelling. The recent safety assessment of sodium valproate in pregnant and childbearing women is probably one of the first examples of modern pregnancy pharmacovigilance.

Measuring bank efficiency and market power in the household and corporate credit markets considering credit risks

The aim of this paper is to estimate the efficiency of Hungarian banks with several models and to calculate the Lerner index for both the household and the corporate credit market. We apply stochastic frontier analysis (SFA) and data envelopment analysis (DEA) models to estimate the efficiency and calculate profit and cost efficiency with and without taking credit losses into consideration. In terms of cost efficiency, banks are nearly homogeneous and improved their efficiency after the crisis. Banks, however, are extremely heterogeneous in terms of profit efficiency. During the crisis, a gradual improvement could be observed across the sector after the initial downturn. Since the operating conditions of the household and the corporate credit markets are different, we estimated the intensity of competition separately for both the markets. While the Lerner index showed strong market power in the household credit market, the corporate credit market was characterised by intense competition. Regarding efficiency, various models often resulted in different conclusions, especially in the case of cost efficiency. Therefore we recommend that the regulatory decision-making process should always consider the results of several models. Moreover, the Lerner indices demonstrate that it might be important to use disaggregated models when modelling the features of credit markets.

Comparison of hoop-net trapping and visual surveys to monitor abundance of the Rio Grande cooter (Pseudemys gorzugi).

Abundance estimates play an important part in the regulatory and conservation decision-making process. It is important to correct monitoring data for imperfect detection when using these data to track spatial and temporal variation in abundance, especially in the case of rare and elusive species. This paper presents the first attempt to estimate abundance of the Rio Grande cooter (Pseudemys gorzugi) while explicitly considering the detection process. Specifically, in 2016 we monitored this rare species at two sites along the Black River, New Mexico via traditional baited hoop-net traps and less invasive visual surveys to evaluate the efficacy of these two sampling designs. We fitted the Huggins closed-capture estimator to estimate capture probabilities using the trap data and distance sampling models to estimate detection probabilities using the visual survey data. We found that only the visual survey with the highest number of observed turtles resulted in similar abundance estimates to those estimated using the trap data. However, the estimates of abundance from the remaining visual survey data were highly variable and often underestimated abundance relative to the estimates from the trap data. We suspect this pattern is related to changes in the basking behavior of the species and, thus, the availability of turtles to be detected even though all visual surveys were conducted when environmental conditions were similar. Regardless, we found that riverine habitat conditions limited our ability to properly conduct visual surveys at one site. Collectively, this suggests visual surveys may not be an effective sample design for this species in this river system. When analyzing the trap data, we found capture probabilities to be highly variable across sites and between age classes and that recapture probabilities were much lower than initial capture probabilities, highlighting the importance of accounting for detectability when monitoring this species. Although baited hoop-net traps seem to be an effective sampling design, it is important to note that this method required a relatively high trap effort to reliably estimate abundance. This information will be useful when developing a larger-scale, long-term monitoring program for this species of concern.

Surface Sensing for Biofilm Formation in Pseudomonas aeruginosa.

Aggregating and forming biofilms on biotic or abiotic surfaces are ubiquitous bacterial behaviors under various conditions. In clinical settings, persistent presence of biofilms increases the risks of healthcare-associated infections and imposes huge healthcare and economic burdens. Bacteria within biofilms are protected from external damage and attacks from the host immune system and can exchange genomic information including antibiotic-resistance genes. Dispersed bacterial cells from attached biofilms on medical devices or host tissues may also serve as the origin of further infections. Understanding how bacteria develop biofilms is pertinent to tackle biofilm-associated infections and transmission. Biofilms have been suggested as a continuum of growth modes for adapting to different environments, initiating from bacterial cells sensing their attachment to a surface and then switching cellular physiological status for mature biofilm development. It is crucial to understand bacterial gene regulatory networks and decision-making processes for biofilm formation upon initial surface attachment. Pseudomonas aeruginosa is one of the model microorganisms for studying bacterial population behaviors. Several hypotheses and studies have suggested that extracellular macromolecules and appendages play important roles in bacterial responses to the surface attachment. Here, I review recent studies on potential molecular mechanisms and signal transduction pathways for P. aeruginosa surface sensing.

The role of women in nuclear - attracting public participation in regulatory decision-making process

Public participation is vital in demonstrating transparency and enhancing effectiveness of a nuclear regulatory process. As such, it is necessary for nuclear practitioners to involve the public in key nuclear delivery milestones. This paper specifically discusses challenges faced in attracting public participation throughout the nuclear regulatory decision-making process, and highlights the roles of women in nuclear (WiN) in initiating the said public discourse.

EVALUATION OF HUMAN HEALTH RISKS ASSOCIATED WITH PESTICIDE DIETARY INTAKE - AN OVERVIEW ON QUANTITATIVE UNCERTAINTY ANALYSIS

The probabilistic estimation and the risk analysis of the exposure to pesticides through the ingestion of plants and food products is an important task for ensuring informed decision making and appropriate consumer protection. Monte Carlo-based methods are powerful tools in this regard, allowing for the empirical estimation of the distribution of exposure values, as well as for carrying out a corresponding uncertainty analysis. Such findings are important for assessing the exposure risk for multiple categories of the general population, divided by age groups, body weight, food consumption etc. The general model used for determining the exposure allows for a detailed assessment and analysis of the distribution of exposure values along a determined range, and of the probabilities of occurrence for acute and chronic exposure levels, while also accounting for potential uncertainties in the input parameters. Researchers in the related fields propose various probabilistic approaches using several distribution shapes to estimate each parameter of the model. Furthermore, the related literature contains a series of guidelines for carrying out the aforementioned tasks, for various types of data with a wide assortment of distributions. Consequently, this study presents a general framework and characterization of exposure as a result of food consumption, as well as common practices for carrying out an assessment of exposure levels, with an emphasis on significant related work from the state-of-the-art in the field. The findings of the present study indicate that probabilistic approaches are powerful tools for aiding the regulatory decision-making process in the case of acute or chronic dietary exposure.

Guidelines for performing systematic reviews in the development of toxicity factors

The Texas Commission on Environmental Quality (TCEQ) developed guidance on conducting systematic reviews during the development of chemical-specific toxicity factors. Using elements from publicly available frameworks, the TCEQ systematic review process was developed in order to supplement the existing TCEQ Guidelines for developing toxicity factors (TCEQ Regulatory Guidance 442). The TCEQ systematic review process includes six steps: 1) Problem Formulation; 2) Systematic Literature Review and Study Selection; 3) Data Extraction; 4) Study Quality and Risk of Bias Assessment; 5) Evidence Integration and Endpoint Determination; and 6) Confidence Rating. This document provides guidance on conducting a systematic literature review and integrating evidence from different data streams when developing chemical-specific reference values (ReVs) and unit risk factors (URFs). However, this process can also be modified or expanded to address other questions that would benefit from systematic review practices. The systematic review and evidence integration framework can improve regulatory decision-making processes, increase transparency, minimize bias, improve consistency between different risk assessments, and further improve confidence in toxicity factor development.

In silico weight of evidence assessment of drug-induced liver injury in humans

Emerging technologies are playing a major role in the generation of new approaches to assess the safety of both foods and drugs. However, the integration of emerging technologies in the regulatory decision-making process requires rigorous assessment and consensus amongst international partners and research communities. To that end, the Global Coalition for Regulatory Science Research (GCRSR) in partnership with the Brazilian Health Surveillance Agency (ANVISA) hosted the seventh Global Summit on Regulatory Science (GSRS17) in Brasilia, Brazil on September 18–20, 2017 to discuss the role of new approaches in regulatory science with a specific emphasis on applications in food and medical product safety. The global regulatory landscape concerning the application of new technologies was assessed in several countries worldwide. Challenges and issues were discussed in the context of developing an international consensus for objective criteria in the development, application and review of emerging technologies. The need for advanced approaches to allow for faster, less expensive and more predictive methodologies was elaborated. In addition, the strengths and weaknesses of each new approach was discussed. And finally, the need for standards and reproducible approaches was reviewed to enhance the application of the emerging technologies to improve food and drug safety. The overarching goal of GSRS17 was to provide a venue where regulators and researchers meet to develop collaborations addressing the most pressing scientific challenges and facilitate the adoption of novel technical innovations to advance the field of regulatory science.

Separation and assembly of deep sequencing data into discrete sub-population genomes.

Sequence heterogeneity is a common characteristic of RNA viruses that is often referred to as sub-populations or quasispecies. Traditional techniques used for assembly of short sequence reads produced by deep sequencing, such as de-novo assemblers, ignore the underlying diversity. Here, we introduce a novel algorithm that simultaneously assembles discrete sequences of multiple genomes present in populations. Using in silico data we were able to detect populations at as low as 0.1% frequency with complete global genome reconstruction and in a single sample detected 16 resolved sequences with no mismatches. We also applied the algorithm to high throughput sequencing data obtained for viruses present in sewage samples and successfully detected multiple sub-populations and recombination events in these diverse mixtures. High sensitivity of the algorithm also enables genomic analysis of heterogeneous pathogen genomes from patient samples and accurate detection of intra-host diversity, enabling not just basic research in personalized medicine but also accurate diagnostics and monitoring drug therapies, which are critical in clinical and regulatory decision-making process.