Regulatory Appraisal Research Articles

Weight of evidence evaluation of the metabolism disrupting effects of triphenyl phosphate using an expert knowledge elicitation approach

Identification of Endocrine-Disrupting Chemicals (EDCs) in a regulatory context requires a high level of evidence. However, lines of evidence (e.g. human, in vivo, in vitro or in silico) are heterogeneous and incomplete for quantifying evidence of the adverse effects and mechanisms involved. To date, for the regulatory appraisal of metabolism-disrupting chemicals (MDCs), no harmonised guidance to assess the weight of evidence has been developed at the EU or international level. To explore how to develop this, we applied a formal Expert Knowledge Elicitation (EKE) approach within the European GOLIATH project. EKE captures expert judgment in a quantitative manner and provides an estimate of uncertainty of the final opinion. As a proof of principle, we selected one suspected MDC -triphenyl phosphate (TPP) - based on its related adverse endpoints (obesity/adipogenicity) relevant to metabolic disruption and a putative Molecular Initiating Event (MIE): activation of peroxisome proliferator activated receptor gamma (PPARγ). We conducted a systematic literature review and assessed the quality of the lines of evidence with two independent groups of experts within GOLIATH, with the objective of categorising the metabolic disruption properties of TPP, by applying an EKE approach. Having followed the entire process separately, both groups arrived at the same conclusion, designating TPP as a “suspected MDC” with an overall quantitative agreement exceeding 85%, indicating robust reproducibility. The EKE method provides to be an important way to bring together scientists with diverse expertise and is recommended for future work in this area.

A regulatory appraisal of the Saudi Stock Exchange: A study based on secondary data

This paper aims to appraise the Saudi Stock Exchange (Tadawul) with reference to various indicators like performance, structure, market size, share price index, etc. This study is motivated from the reform initiatives the Saudi Stock Exchange passes through in recent years because of the implantation of the nationwide strategy, Vision 2030 (Kumar, 2023). Using a published dataset, this study undertakes an appraisal mindset to highlight the performance of the market over 35 years’ time (from 1985 to 2019). The analysis follows various descriptive statistics reflecting market trends over the periods across selected parameters. The findings of the study imply that the market is improving in every dimension supporting the reform initiatives (Alsuhaibani et al., 2023). The incremental contribution of the current study is to inform policymakers about the response of the market towards various policy interventions. However, the study warrants careful attention of market regulators to observe the gradual changes so that it may receive policy attention as necessary.

Innovations for microbiome targeting interventions - a patent landscape analysis indicating overall patenting activity decline and promising target disease areas.

The human microbiota have been implicated in the aetiology and remedy of a host of disorders. However, due to the pervasive uncertainty inherent in the field of microbiota-targeting interventions and associated issues with establishing rigorous safety and efficacy profiles, regulatory oversight is suboptimal. This can dissuade innovators from further exploring novel and much needed health interventions. Modification of regulatory protocols and practices requires focussed efforts and funding to build the evidence base around future regulatory needs. Such modification can be critically informed by identification of changes and trends in technology fields to facilitate identification of regulatory gaps. To this purpose, this study rigorously collected and analysed patent data from Espacenet - covering the years 2013-2018 - and created a patent landscape analysis of microbiome targeting interventions with a focus on medicinal products. Pertinent patenting activity has declined overall. While, in absolute terms, patents most frequently claimed inventions targeting disorders of the gut and alimentary tract, relative year-on-year interest increases have been substantial for cancer, and disorders of the (neuro-)muscular and respiratory systems - driven by the private sector. Academic stakeholders showed top interest in disorders of the metabolism, anti-infectives, and skeletal and dermatological diseases. Although medicinal preparation claims dominated our dataset, a third of patents claimed food preparations, while only 1% claimed application as a diagnostic. Finally, China is, by an inordinate margin, a market of particular interest for both domestic and foreign innovators, indicating that microbiome targeting intervention innovation for EU and US markets might be frustrated. This study is the first to empirically demonstrate that live biotherapeutic product innovation is decelerating and potentially frustrated, supporting the urgent need for improved regulatory standards. Our results indicate which disease areas deserve particular attention for research funding to facilitate proper regulatory appraisal in the near- to mid-term future.

Zoonoses Anticipation and Preparedness Initiative, stakeholders conference, February 4 & 5, 2021

The Zoonoses Anticipation and Preparedness Initiative (ZAPI) was set up to prepare for future outbreaks and to develop and implement new technologies to accelerate development and manufacturing of vaccines and monoclonal antibodies. To be able to achieve surge capacity, an easy deployment and production at multiple sites is needed. This requires a straightforward manufacturing system with a limited number of steps in upstream and downstream processes, a minimum number of in vitro Quality Control assays, and robust and consistent platforms. Three viruses were selected as prototypes: Middle East Respiratory Syndrome (MERS) coronavirus, Rift Valley fever virus, and Schmallenberg virus. Selected antibodies against the viral surface antigens were manufactured by transient gene expression in Chinese Hamster Ovary (CHO) cells, scaling up to 200 L. For vaccine production, viral antigens were fused to multimeric protein scaffold particles using the SpyCatcher/SpyTag system. In vivo models demonstrated the efficacy of both antibodies and vaccines.The final step in speeding up vaccine (and antibody) development is the regulatory appraisal of new platform technologies. Towards this end, within ZAPI, a Platform Master File (PfMF) was developed, as part of a licensing dossier, to facilitate and accelerate the scientific assessment by avoiding repeated discussion of already accepted platforms. The veterinary PfMF was accepted, whereas the human PfMF is currently under review by the European Medicines Agency, aiming for publication of the guideline by January 2022.

“Regulation, I presume?” said the robot – Towards an iterative regulatory process for robot governance

This article envisions an iterative regulatory process for robot governance. In the article, we argue that what lacks in robot governance is actually a backstep mechanism that can coordinate and align robot and regulatory developers. In order to solve that problem, we present a theoretical model that represents a step forward in the coordination and alignment of robot and regulatory development. Our work builds on previous literature, and explores modes of alignment and iteration towards greater closeness in the nexus between research and development (R&D) and regulatory appraisal and channeling of robotics’ development. To illustrate practical challenges and solutions, we explore different examples of (related) types of communication processes between robot developers and regulatory bodies. These examples help illuminate the lack of formalization of the policymaking process, and the loss of time and resources that the waste of knowledge generated for future robot governance instruments implies. We argue that initiatives that fail to formalize the communication process between different actors and that propose the mere creation of coordinating agencies risk being seriously ineffective. We propose an iterative regulatory process for robot governance, which combines the use of an ex ante robot impact assessment for legal/ethical appraisal, and evaluation settings as data generators, and an ex post legislative evaluation instrument that eases the revision, modification and update of the normative instrument. In all, the model breathes the concept of creating dynamic evidence-based policies that can serve as temporary benchmark for future and/or new uses or robot developments. Our contribution seeks to provide a thoughtful proposal that avoids the current mismatch between existing governmental approaches and what is needed for effective ethical/legal oversight, in the hope that this will inform the policy debate and set the scene for further research.

'Regulation, I Presume?', Said the Robot. Towards an Iterative Regulatory Process for Robot Governance

This project envisions an iterative regulatory process for robot governance. A theoretical model represents a step forward in the coordination and alignment of robot and regulatory development. Our work builds on previous literature, and explores modes of alignment and iteration towards greater closeness in the nexus between research and development (R&D) and regulatory appraisal and channeling of robotics’ development. To illustrate practical challenges and solutions, we explore different examples of (related) types of communication processes between robot developers and regulatory bodies. These examples help illuminate the lack of formalization of the policy making process, and the loss of time and resources that the waste of knowledge generated for future robot governance instruments implies. We argue that initiatives that fail to formalize the communication process between different actors and that propose the mere creation of coordinating agencies risk being seriously ineffective. We propose an iterative regulatory process for robot governance, which combines the use of an ex ante robot impact assessment for legal/ethical appraisal, and evaluation settings as data generators, and an ex post legislative evaluation instrument that eases the revision, modification and update of the normative instrument. In all, the model breathes the concept of creating dynamic evidence-based policies that can serve as temporary benchmark for future and/or new uses or robot developments. Our contribution seeks to provide a thoughtful proposal that avoids the current mismatch between existing governmental approaches and what is needed for effective ethical/legal oversight, in the hope that this will inform the policy debate and set the scene for further research.

Cross-Ownership: A Device for Management Entrenchment?

By artificially inflating capital and creating own shares, cross-ownership can be a key device for managerial entrenchment. This paper proposes a game-theoretical method to measure the extent of shareholder expropriation through cross-ownership. By properly accounting for cross-ownership linkages, we show how managers can seize indirect voting rights, and so insulate their firms from outside control. Significant examples of cross-ownership are found not only in civil law countries, but also in the U.S. mutual fund industry. We apply our method to Germany’s Allianz Group. This paper paves the way to better regulatory appraisal of management entrenchment through cross-ownership.

An Ethical Framework for Evaluating Experimental Technology.

How are we to appraise new technological developments that may bring revolutionary social changes? Currently this is often done by trying to predict or anticipate social consequences and to use these as a basis for moral and regulatory appraisal. Such an approach can, however, not deal with the uncertainties and unknowns that are inherent in social changes induced by technological development. An alternative approach is proposed that conceives of the introduction of new technologies into society as a social experiment. An ethical framework for the acceptability of such experiments is developed based on the bioethical principles for experiments with human subjects: non-maleficence, beneficence, respect for autonomy, and justice. This provides a handle for the moral and regulatory assessment of new technologies and their impact on society.

TO MEASURE IS TO KNOW: THE QUANTIFICATION OF REGULATION

In recent debates and policies on regulation the quantification of effects – in terms of numbers, figures and costs – plays an ever more important role. Whatever the underlying cause for this quantification trend may be, it does allow countries to share information on (the effects of) regulation in ways that were unfathomable before. This paper looks into this regulatory quantification trend and assesses it. The paper discusses the way in which jurisdictions all around the world, perhaps triggered by regulatory competition, are adopting each other's regulatory appraisal practices at an extraordinary pace, in most cases in order to enable policy makers to gather more and better information about the possible effects of regulation. In this process – particularly in OECD countries – these jurisdictions don't just copy each other's quantification methods but to a certain extent also each other's institutional arrangements. One of these effects in any case is that regulators will be able to take decisions on the basis of better information and be more able to weigh up the content of alternative solutions. It can make the regulatory process better informed and more inclusive as well. There are serious downsides to quantification as well, as the conclusion of the article argues: quantification may make the regulatory more exclusive as well, make the debate during the regulatory process too one sided. It may be abused to fence off an open debate on alternatives, and it does not help to dampen the ambitions of regulators in thinking that every problem can be solved by regulatory intervention; it rather more seems to feed this ambition.

Public Safety Appraisal for Siting Marine Liquefied Natural Gas Terminals in California

AbstractMultifarious proposals for siting, design, construction, and operation of onshore and offshore liquefied natural gas (LNG) import terminals in California have recently undergone a rigorous federal and state regulatory appraisal. The regulations call for compliance with various environmental, public safety, and security mandates encoded in legal statutes. Public safety from the hazards of a large-scale LNG spill over water, during LNG tanker transit or marine terminal operation, emerged as the dominant concern for the affected local communities. To address their apprehension, extensive modeling of potentially perilous beyond design basis spill scenarios, ensuing from natural, accidental, and malevolent intentional events was conducted. It entailed finite element modeling for vessel collision with diverse LNG tanker types and applying computational fluid dynamics to predict the extent of LNG spread over water, atmospheric dispersion of vapor cloud, and the consequences of ignition. The objective was...

Coming to grips with scientific ignorance in the governance of endocrine disrupting chemicals and nanoparticles

• We argue that ignorance places new technology experts in irreducible double binds. • Adequately addressing double binds require phronesis, or practical wisdom. • Being phronimos, a person who can do phronesis, involves synthetic phronesic skill. • Phronesic skill is deeply related to the human capacity of pattern recognition. • Phronesis enables a new operationalization of the precautionary principle. New technologies are characterized by various forms of incertitude that challenge both scientific expertise and regulatory action. In this paper, we argue that these incertitudes place experts in irreducible double bind situations, which may end in paralysis. Double binds emerge when primary injunctions are contradicted by secondary injunctions at a different logical level, which affects the interpretation of the primary injunction. Adequately addressing the challenges posed by new technologies requires phronesis, or pragmatic, context-dependent and action-oriented knowledge grounded in value deliberation. Using endocrine disruptors and carbon nanotubes as empirical examples, we argue that in relation to new technologies involving various kinds of incertitude, being phronimos—the person who can do phronesis—involves synthetically and simultaneously enacting parts of the three interrelated domains of knowledge, ethics and institutions, also across different logical levels. The special kind of experience-based phronesic skill that required in the regulatory appraisal of new technologies is thus fundamentally related to the human capacity of pattern recognition. Finally, we argue that being aware of and making full use of practical wisdom thus conceptualized enables a new operationalization of the precautionary principle.

Physical Frailty and Sarcopenia (PF&S), an unmet medical need deserving integrated scientific and regulatory appraisal

Physical Frailty and Sarcopenia (PF&S), an unmet medical need deserving integrated scientific and regulatory appraisal

To Measure Is to Know: The Quantification of Regulation

In recent debates and policies on regulation the quantification of effects – in terms of numbers, figures and costs – plays an ever more important role. Whatever the underlying cause for this quantification trend may be, it does allow countries to share information on (the effects of) regulation in ways that were unfathomable before. This paper looks into this regulatory quantification trend and assesses it. The paper discusses the way in which jurisdictions all around the world, perhaps triggered by regulatory competition, are adopting each other’s regulatory appraisal practices at an extraordinary pace, in most cases in order to enable policy makers to gather more and better information about the possible effects of regulation. In this process – particularly in OECD countries – these jurisdictions don’t just copy each other’s quantification methods but to a certain extent also each other’s institutional arrangements. One of these effects in any case is that regulators will be able to take decisions on the basis of better information and be more able to weigh up the content of alternative solutions. It can make the regulatory process better informed and more inclusive as well. There are serious downsides to quantification as well, as the conclusion of the paper argues: quantification may make the regulatory more exclusive as well, make the debate during the regulatory process to one sided. It may be abused to fence off an open debate on alternatives, and it does not help to dampen the ambitions of regulators in thinking that every problem can be solved by regulatory intervention; it rather more seems to feed this ambition.

ECONOMIC RATIONALES, LEARNING, AND REGULATORY POLICY INSTRUMENTS

European governments have adopted policy instruments for regulatory appraisal, oversight, ex‐post evaluation, and simplification in the context of the so‐called ‘smart regulation agenda’. In this article we compare the two most important instruments, that is, regulatory impact assessment (RIA) and the standard cost model (SCM). We answer the following questions: What are the economic rationales that, at least in principle, should make the SCM and RIA work? What are the learning models that, yet again in principle, allow the two instruments to produce effects? The RIA economic rationale is grounded in welfare economics. The SCM economics is rudimentary: one can hardly make an economic case for the SCM. With regard to learning models, RIA draws on rational‐synoptic models, whilst the SCM is inspired by experience‐based learning. We then discuss economic rationales and learning models jointly, thus explaining the different implementation patterns of the two instruments and exposing the ambiguities in the relationship among instruments, ideas, and behavioural change.

Regulatory Compliance for Marine LNG Import Terminals in California

California’s projected natural gas demand, coupled with the reality of moribund supply basins, has prompted plans for the import of liquefied natural gas (LNG). Several project applications for the siting, design, construction, and operation of onshore and offshore LNG import terminals have recently undergone a rigorous federal and state regulatory appraisal. The environmental, public safety, and security mandates encoded in current legal statutes were the dominant compliance issues. Addressing compliance required comprehensive risk assessment with extensive modeling of the potentially perilous scenarios, including natural and malevolent intentional hazards for LNG tanker movements and marine terminal operations. The objective was to evaluate the effect of adverse consequences on public and property not associated with LNG terminal. On the basis of this evaluation experience, the principal federal and state laws, regulations, standards and concerns, and jurisdictional and technical conflicts relevant to environmental, public safety, and security compliance for a marine LNG import terminal are outlined. This will benefit others planning similar ventures in California or elsewhere.

Linking Emissions Trading Schemes: An Assessment with Regard to Environmental Integrity

This paper critically assesses the potential for linkage of emissions trading schemes (ETS) designed to curb greenhouse gases. Based on current negotiations in order to link domestic schemes, we highlight the institutional barriers that exist due to different design options. Among these barriers, we highlight the potential negative effects on environmental integrity that arise from linking a rate-based system with an absolute system. Our results therefore suggest that increasing interests in linking ETS shall not be exempt from careful regulatory appraisal ex ante. Besides, we raise new questions by demonstrating how the linking process has an impact on agents' choices of technology and pollution levels.

Science, precaution, and practice

b The precautionary principle has become an increasingly prominent theme in the debate over technological risk, raising many questions over its implications for policy making. A key issue is the relationship between precautionary and more traditional so-called science-based approaches to decision-making, such as cost-benefit and risk analyses. Some fear that a precautionary approach— unlike risk assessment—is too ambiguous and impractical to serve as a basis for real decision-making, and that it is somehow antagonistic to science and may even stifle technological innovation. This article first examines some of the key issues affecting the relationship between science and precaution. Far from being in tension, these two concepts are actually consistent and even mutually reinforcing. A more useful distinction is found to lie between the narrow risk assessments of many regulatory apprais- als and the broader precautionary approaches to hazard reduction and policy- making under conditions of scientific uncertainty, complexity, and high deci- sion stakes. This article identifies a series of key features characterizing a precautionary approach to regulatory appraisal. It cites a recent European Environment Agency (EEA) study that provides examples of how some of these key features could have improved past decision-making on risk. 1 Finally, it illustrates a method that addresses these issues and delivers an approach to regulatory appraisal that is both precautionary and scientifically robust.

Science, precaution, and practice.

b The precautionary principle has become an increasingly prominent theme in the debate over technological risk, raising many questions over its implications for policy making. A key issue is the relationship between precautionary and more traditional so-called science-based approaches to decision-making, such as cost-benefit and risk analyses. Some fear that a precautionary approach— unlike risk assessment—is too ambiguous and impractical to serve as a basis for real decision-making, and that it is somehow antagonistic to science and may even stifle technological innovation. This article first examines some of the key issues affecting the relationship between science and precaution. Far from being in tension, these two concepts are actually consistent and even mutually reinforcing. A more useful distinction is found to lie between the narrow risk assessments of many regulatory apprais- als and the broader precautionary approaches to hazard reduction and policy- making under conditions of scientific uncertainty, complexity, and high deci- sion stakes. This article identifies a series of key features characterizing a precautionary approach to regulatory appraisal. It cites a recent European Environment Agency (EEA) study that provides examples of how some of these key features could have improved past decision-making on risk. 1 Finally, it illustrates a method that addresses these issues and delivers an approach to regulatory appraisal that is both precautionary and scientifically robust.

A Novel Approach to the Appraisal of Technological Risk: A Multicriteria Mapping Study of a Genetically Modified Crop

The recent controversy over genetically modified (GM) foods amply demonstrates the general difficulties encountered in the social appraisal of technological risk. Existing procedures for regulatory appraisal neglect many possible forms of impact and routinely exclude important cultural and social dimensions of risk. A narrow, expert, ‘science-based’ approach is now widely acknowledged to be insufficient. There is a need for new approaches that are more broadly based, transparent, pluralistic and ready to acknowledge uncertainty as well as being practically feasible and robust. The authors investigate the potential for a novel ‘multicriteria mapping’ (MCM) method as one such possible tool. Drawing on a variety of perspectives in the current UK debate, a range of agricultural strategies for the production of oilseed rape, including both GM and non-GM options were explored in this MCM pilot exercise. The results demonstrate the general feasibility and positive potential of this type of approach, with specific findings providing modest insights for policymaking in this difficult area.

Precautionary approaches to the appraisal of risk: a case study of a genetically modified crop.

There are strong scientific reasons for holding the broader scope of precautionary approaches to be more consistent with the scientific foundations of rational choice and probability theory than are conventional narrow risk-assessment techniques. The imperatives both of science and precaution can be seen to pull in the same direction. The regulatory appraisal of risk should become more systematic and broader in scope. In particular, a set of criteria can be developed concerning the need for greater humility, completeness, transparency, and participation in regulatory appraisal, with specific attention to the comparison of different options (including mixtures of options), the consideration of benefits and justifications, and the systematic "mapping" of the ways in which different framing assumptions lead to different pictures of performance. A case study of a pilot exercise applying a multi-criteria mapping method to the regulatory appraisal of a genetically modified crop is reported. The results are more complete than orthodox risk assessment, in that they embody consideration of an unlimited array of issues and include consideration of a wide range of different strategic alternatives to the use of GM technologies. It is concluded that conventional regulatory appraisal might be adapted to better address the imperatives of both science and precaution.