Phase I clinical trials represent a critical point in drug development because the investigational medicinal product is being tested in humans for the first time. For this reason, it is essential to evaluate and identify the Maximum Tolerated Dose (MTD) and the safety of the new compound. To mitigate the possible risks associated with drug administration and treatment, the European Competent Authority issued various guidelines to provide provisions and harmonize risk management processes. In the UK and Italy, particular attention should be paid to the Medicines & Healthcare Products Regulatory Agency (MHRA) phase I accreditation scheme and the specific rules set by the Italian Drug Authority through the AIFA Determination no. 809/2015. Both reference documents are based on the concept of quality risk management while conducting phase I clinical studies. Moreover, the AIFA determination outlines specific requirements for those sites that want to conduct non-profit phase I clinical trials. Indeed, the document reports peculiar activities to the \"Clinical Trial Quality Team\", which is a team that should support the clinical site researchers in designing, starting, performing, and closing non-profit phase I studies. In this paper, we provide a general overview of the main European guidelines concerning the management of risks during phase I trials, focusing on the main peculiarities of the schemes and rules set by the MHRA and AIFA.

There is an overall scientific consensus that no new coal mines can be developed, if the Paris Agreement to limit global temperature rises is to be met. Yet in December 2022, following a lengthy Public Inquiry, the UK Government approved the development of Woodhouse Colliery in Cumbria. In doing so, it accepted the claim that the coal mine would be \'zero carbon\' and could even result in lower global emissions overall. As this paper demonstrates, there is no independent evidence to support these claims, whilst a large body of independent evidence comes to the opposite conclusion. This paper uses the example of Woodhouse Colliery to examine the use of evidence and expertise in climate governance processes. It finds that the nature of expertise and evidence is not properly considered, and that there is ambiguity and confusion surrounding the implementation of the UK\'s climate legislation, particularly the Climate Change Act. It also finds that the ways in which the decision-making process solicited and assessed evidence was flawed, promoting a \'false balance\'. This ambiguity and false balance provide scope for developers to argue the case for destructive developments, even while claiming adherence to climate ambitions. The paper concludes by suggesting reforms to governance processes, to provide a more transparent and credible implementation of policies to achieve the UK\'s net zero target. Suggested reforms include clearer rules governing fossil fuel phase-out; greater transparency and better handling of conflicts of interest in decision-making; and devolution of climate responsibilities to local areas.

Citizen science is now commonly employed to collect data on plastic pollution and is recognised as a valuable tool for furthering our understanding of the issue. Few studies, however, use citizen science to gather information on water-borne plastic debris. Here, citizen scientists adopted a globally standardised methodology to sample the sea-surface for small (1-5 mm) floating plastic debris off the Cornish coast (UK). Twenty-eight trawls were conducted along five routes, intersecting two Marine Protected Areas. Of the 509 putative plastic items, fragments were most common (64 %), then line (19 %), foam (7 %), film (6 %), and pellets (4 %). Fourier-transform infrared spectroscopy identified the most common polymer type as polyethylene (31 %), then nylon (12 %), polypropylene (8 %), polyamide (5 %) and polystyrene (3 %). This study provides the first globally comparative baseline of floating plastic debris for the region (mean: 8512 items km-2), whilst contributing to an international dataset aimed at understanding plastic abundance and distribution worldwide.

Early access programs (EAPs) generally refer to patient access to medicines/indications before marketing authorization, possibly extended to price and reimbursement approval. These programs include compassionate use, which is usually covered by pharmaceutical companies, and EAPs reimbursed by third-party payers. This paper aims at comparing EAPs in four European countries (France, Italy, Spain, UK) and providing empirical evidence on EAPs in Italy. The comparative analysis was conducted through a literature review (including scientific and grey literature), complemented by 30-min semi-structured interviews with local experts. The Italian empirical analysis employed data available on the National Medicines Agency website. Although EAPs are very different across countries, they exhibit some common features: (i) eligibility criteria refer to the absence of valid therapeutic alternatives and a presumed favourable risk-benefit profile; (ii) payers do not allocate a pre-determined budget to these programs; (iii) total spending on EAPs is unknown. The French EAPs seem to be the most structured, financed through social insurance, covering pre-marketing, post-marketing and pre-reimbursement phases and providing for data collection. Italy\'s approach to EAPs has been varied, with several programs covered by different payers, including the cohort-based 648 List (for both early access and off-label use), the nominal-based 5% Fund, and Compassionate Use. Most applications to EAPs are from the Antineoplastic and immunomodulating drug class (ATC L). Some 62% of indications in the 648 List are either not under clinical development or have never been approved (pure off-label use). For those subsequently approved, most approved indications coincide with those covered through EAPs. Only the 5% Fund provides data on economic impact (€ 81.2 million in 2021; average cost per patient € 61.5K). Diverse EAPs are a possible source of inequalities in access to medicines across Europe. A harmonization of these programs, though difficult to achieve, could be modelled on the French EAPs and provide key advantages, not least of which a common effort to collect real-world data in parallel with clinical trials and clear separation between EAPs and off-label use programs.

Lameness is a significant health and welfare issue in farmed animals. This paper uses a governmentality approach, which focuses on how a problem is made governable, to examine an emerging \'ecology of devices\' introduced to intervene in, and attempt to reduce, on-farm incidence of lameness. These devices are associated with advisers who work with farmers on-farm; they enact lameness as a governable entity, are tools to assess the existence of lameness against established norms, and prescribe actions to be taken in response to evidence of lameness. In doing this they subjectify farmers and advisers into seeing and responding to lameness in particular ways. Using concepts of governmentality alongside other perspectives on the power relations and the simplifications and complexities involved in interventions in animal health and farm practice, the paper draws on in-depth research with advisers including vets and other paraprofessionals who work with farmers, and their cows and sheep. It explores how this set of devices introduces particular techniques and practices in lameness management, and produces farmer and adviser subjectivities. It then explores some of the problematics of this mode of governing lameness, including analysis of the limitations and unintended consequences of attempts to simplify lameness management. The paper concludes by arguing that its approach is valuable in analysing ongoing intensification of interventions in farming practices and in understanding the limits of such interventions and the unanticipated divergences from expected conduct.

Introducing legislation that restricts companies from exposing children to marketing of unhealthy food and beverage products is both politically and technically difficult. To advance the literature on the technical design of food marketing legislation, and to support governments around the world with legislative development, we aimed to describe the legislative approach from three governments.
A multiple case study methodology was adopted to describe how three governments approached designing comprehensive food marketing legislation (Chile, Canada and the United Kingdom). A conceptual framework outlining best practice design principles guided our methodological approach to examine how each country designed the technical aspects of their regulatory response, including the regulatory form adopted, the substantive content of the laws, and the implementation and governance mechanisms used. Data from documentary evidence and 15 semi-structured key informant interviews were collected and synthesised using a directed content analysis.
All three countries varied in their legislative design and were therefore considered of variable strength regarding the legislative elements used to protect children from unhealthy food marketing. When compared against the conceptual framework, some elements of best practice design were present, particularly relating to the governance of legislative design and implementation, but the scope of each law (or proposed laws) had limitations. These included: the exclusion of brand marketing; not protecting children up to age 18; focusing solely on child-directed marketing instead of all marketing that children are likely to be exposed to; and not allocating sufficient resources to effectively monitor and enforce the laws. The United Kingdom\'s approach to legislation is the most comprehensive and more likely to meet its regulatory objectives.
Our synthesis and analysis of the technical elements of food marketing laws can support governments around the world as they develop their own food marketing restrictions. An analysis of the three approaches illustrates an evolution in the design of food marketing laws over time, as well as the design strengths offered by a legislative approach. Opportunities remain for strengthening legislative responses to protect children from unhealthy food marketing practices.

The UK\'s fishing industry has contracted considerably since 1972 due to overfishing, increased fuel prices, and implementation of the European Union (EU) Common Fisheries Policy (CFP). Despite this decline affecting the industry at large and the incomes of fishers, some fishers have carried on, or even freshly started or returned to the business. Why have these fishers done so despite the challenges they encounter in the fishing industry? In this article, we investigate why some fishers still choose to fish in the wake of all the EU regulations designed to control overfishing by reducing the size of the industry and discouraging entry by taking measures that affect revenues. Our data are collected through ethnographic research involving participant observation and interviews with fishers in North Shields, England. Based on our findings, we argue that the decision to carry on fishing, or even to return, is predominantly based on so-called intrinsic motivations, rather than on cost-benefit calculations, and stems from three interlinked basic human emotional needs which fishing seems to fulfil: the need to connect (sometimes also defined as the need to relate or belong); the desire for autonomy; and the desire to show competence (and have that competence recognized by relevant others). As such, the findings offer a fresh way to explain fishers\' decisions, based on a deliberated choice, to remain or leave the sector, and to understand and interrogate the challenges confronting present-day fishing both on a local level in the UK and also for Europe at large.

Requirements for physical distancing as a result of COVID-19 and the need to reduce the risk of infection prompted policy supporting rapid roll out of video consulting across the four nations of the UK-England, Northern Ireland, Scotland and Wales. Drawing on three studies of the accelerated implementation and uptake of video consulting across the four nations, we present a comparative and interpretive policy analysis of the spread and scale-up of video consulting during the pandemic. Data include interviews with 59 national level stakeholders, 55 health and social care staff and 30 patients, 20 national documents, responses to a UK-wide survey of NHS staff and analysis of routine activity data. Sampling ensured variations in geography, clinical context and adoption progress across the combined dataset. Comparative analysis was guided by theory on policy implementation and crisis management. The pandemic provided a \"burning platform\" prompting UK-wide policy supporting the use of video consulting in health care as a critical means of managing the risk of infection and a standard mode of provision. This policy push facilitated interest in video consulting across the UK. There was, however, marked variation in how this was put into practice across the four nations. Pre-existing infrastructure, policies and incentives for video consulting in Scotland, combined with a collaborative system-level approach, a program dedicated to developing video-based services and resourcing and supporting staff to deliver them enabled widespread buy-in and rapid spread. In England, Wales and Northern Ireland, pre-existing support for digital health (e.g., hardware, incentives) and virtual care, combined with reduced regulation and \"light touch\" procurement managed to override some (but by no means all) cultural barriers and professional resistance to implementing digital change. In Northern Ireland and Wales, limited infrastructure muted spread. In all three countries, significant effort at system level to develop, review and run video consulting programs enabled a substantial number of providers to change their practice, albeit variably across settings. Across all four nations ongoing uncertainty, potential restructuring and tightening of regulations, along with difficulties inherent in addressing inequalities in digital access, raise questions about the longer-term sustainability of changes to-date.

A range of approaches have been developed to support natural resource management. One such approach, stakeholder analysis, involves the use of a range of tools to identify and assess stakeholder interests and influence. Comprehensive empirical stakeholder analysis, however, can be time consuming and resource intensive. Approaches therefore frequently rely on the researcher\'s personal interpretation rather than empirical analysis. To address this limitation, a web content-based method (WCM) is proposed. Innovative and user-friendly, this empirical method comprises stakeholder information and the use of keywords in a content analysis of preselected stakeholder webpages, demonstrated here, through UK forestry, as an illustrative example. In this study, the application of WCM provides a comprehensive overview of the multitude of stakeholders in UK forestry and in the various goods and services they provide: Stakeholders\' primary interests were in the provisioning services of timber and fuel wood; the cultural services of education and recreation; and to a lesser extent, the regulating services of climate and water regulation. While not without limitations, this systematic method provides an effective tool to support researchers, industry, and non-governmental organisations in different fields and countries, to undertake stakeholder analysis, especially in the case of small-scale studies in complex contexts and where resources are limited.

This article examines the Drink Free Days (DFD) campaign run by Public Health England and the industry funded alcohol education charity, Drinkaware, in eight English regions in 2018-2019. More specifically, it examines uses, and usefulness, of the campaign to the alcohol producers which fund Drinkaware. It draws on 36 semi-structured interviews with policy actors and a framing analysis of industry social media accounts and news coverage of the campaign. Industry-associated bodies such as Drinkaware have been identified as key components of alcohol industry strategies to influence policy and shape the regulatory contexts in which they operate in three ways. First, funding such bodies forms part of corporate social responsibility programmes which allow companies to position themselves as legitimate policy actors and \'part of the solution\' to alcohol related harms. Second, reliance on industry funding incentivises governments to co-operate with industry actors and provides leverage in policy debates. Third, their programmes absorb policy bandwidth and deflect from more effective, evidence based interventions (e.g. on pricing and advertising) which affect industry sales and profits. This is particularly effective if the perception of independence from the industry is created. The analysis presented below suggests that the DFD was not used explicitly by the industry actors for public relations purposes. However, it was useful to their broader strategic aims. It reinforced the position of Drinkaware as a key policy actor and promoted the particular, industry-favoured understanding of alcohol harms and their solutions which it promotes. This is in keeping with the previous insights from international research literature on corporate political activity in health harming industries which finds that policy influence is often subtle, indirect and designed to embed organisations within the policy architecture. It suggests that government agencies should proceed with great caution in entering into such partnerships with industry associated bodies.