Exploring the feasibility of theory synthesis:A worked example in the field of health related risk-taking

AbstractThe idea of synthesising theory is receiving attention within public health as part of a drive to design theoretically informed interventions. Theory synthesis is not a new idea, however, having been debated by sociologists for several decades. We consider the various methodological approaches to theory synthesis and test the feasibility of one such approach by synthesising a small number of sociological theories relevant to health related risk-taking. The synthesis consisted of three stages: (i) synthesis preparation, wherein parts of relevant theories were extracted and summarised; (ii) synthesis which involved comparing theories for points of convergence and divergence and bringing together those points that converge; and (iii) synthesis refinement whereby the synthesis was interrogated for further theoretical insights. Our synthesis suggests that serious and sustained risk-taking is associated with social isolation, liminality and a person's position in relation to the dominant social group. We reflect upon the methodological and philosophical issues raised by the practice of theory synthesis, concluding that it has the potential to reinvigorate theory and make it more robust and accessible for practical application

What do young people think about their school-based sex and relationship education?:A qualitative synthesis of young people’s views and experiences

OBJECTIVES: Although sex and relationship education (SRE) represents a key strand in policies to safeguard young people and improve their sexual health, it currently lacks statutory status, government guidance is outdated and a third of UK schools has poor-quality SRE. We aimed to investigate whether current provision meets young people's needs. DESIGN: Synthesis of qualitative studies of young people's views of their school-based SRE. SETTING: Eligible studies originated from the UK, Ireland, the USA, Australia, New Zealand, Canada, Japan, Iran, Brazil and Sweden. PARTICIPANTS: Studies of students aged 4–19 in full-time education, young adults ≤19 (not necessarily in full-time education) or adults ≤25 if recalling their experiences of school-based SRE. RESULTS: –69 publications were identified, with 55 remaining after quality appraisal (representing 48 studies). The synthesis found that although sex is a potent and potentially embarrassing topic, schools appear reluctant to acknowledge this and attempt to teach SRE in the same way as other subjects. Young people report feeling vulnerable in SRE, with young men anxious to conceal sexual ignorance and young women risking sexual harassment if they participate. Schools appear to have difficulty accepting that some young people are sexually active, leading to SRE that is out of touch with many young people's lives. Young people report that SRE can be negative, gendered and heterosexist. They expressed dislike of their own teachers delivering SRE due to blurred boundaries, lack of anonymity, embarrassment and poor training. CONCLUSIONS: SRE should be ‘sex-positive’ and delivered by experts who maintain clear boundaries with students. Schools should acknowledge that sex is a special subject with unique challenges, as well as the fact and range of young people's sexual activity, otherwise young people will continue to disengage from SRE and opportunities for safeguarding and improving their sexual health will be reduced

What is best practice in sex and relationship education? A synthesis of evidence, including stakeholders' views.

OBJECTIVES: Sex and relationship education (SRE) is regarded as vital to improving young people's sexual health, but a third of schools in England lacks good SRE and government guidance is outdated. We aimed to identify what makes SRE programmes effective, acceptable, sustainable and capable of faithful implementation. DESIGN: This is a synthesis of findings from five research packages that we conducted (practitioner interviews, case study investigation, National Survey of Sexual Attitudes and Lifestyles, review of reviews and qualitative synthesis). We also gained feedback on our research from stakeholder consultations. SETTINGS: Primary research and stakeholder consultations were conducted in the UK. Secondary research draws on studies worldwide. RESULTS: Our findings indicate that school-based SRE and school-linked sexual health services can be effective at improving sexual health. We found professional consensus that good programmes start in primary school. Professionals and young people agreed that good programmes are age-appropriate, interactive and take place in a safe environment. Some young women reported preferring single-sex classes, but young men appeared to want mixed classes. Young people and professionals agreed that SRE should take a 'life skills' approach and not focus on abstinence. Young people advocated a 'sex-positive' approach but reported this was lacking. Young people and professionals agreed that SRE should discuss risks, but young people indicated that approaches to risk need revising. Professionals felt teachers should be involved in SRE delivery, but many young people reported disliking having their teachers deliver SRE and we found that key messages could become lost when interpreted by teachers. The divergence between young people and professionals was echoed by stakeholders. We developed criteria for best practice based on the evidence. CONCLUSIONS: We identified key features of effective and acceptable SRE. Our best practice criteria can be used to evaluate existing programmes, contribute to the development of new programmes and inform consultations around statutory SRE

Among friends:A qualitative exploration of the role of peers in young people's alcohol use using Bourdieu’s concepts of habitus, field and capital

Drinking is viewed by young people as a predominantly social activity which provides an opportunity for entertainment and bonding with friends. Using Bourdieu's concepts of habitus, field and capital, this article explores young people's attitudes and beliefs around alcohol use, influences on behaviour, and the role of peers, with a view to informing the development of preventive interventions. Semi-structured interviews were conducted with 28 young people aged 18–20 in the south west of England. We describe how friends were integral in drinking experiences, and drinking with friends was equated with fun and enjoyment. In this way, the desire for social and symbolic capital appeared to be a key motivator for adolescent drinking. Critically, however, wider cultural norms played the predominant role in shaping behaviour, via the internalisation of widely accepted practice and the subsequent externalisation of norms through the habitus. Applying Bourdieu's theory suggests that population-level interventions that regulate alcohol consumption, and thus disrupt the field, are likely to facilitate behaviour change among young people by driving a response in habitus

Retrospective harm benefit analysis of pre-clinical animal research for six treatment interventions

The harm benefit analysis (HBA) is the cornerstone of animal research regulation and is considered to be a key ethical safeguard for animals. The HBA involves weighing the anticipated benefits of animal research against its predicted harms to animals but there are doubts about how objective and accountable this process is.i. To explore the harms to animals involved in pre-clinical animal studies and to assess these against the benefits for humans accruing from these studies; ii. To test the feasibility of conducting this type of retrospective HBA.Data on harms were systematically extracted from a sample of pre-clinical animal studies whose clinical relevance had already been investigated by comparing systematic reviews of the animal studies with systematic reviews of human studies for the same interventions (antifibrinolytics for haemorrhage, bisphosphonates for osteoporosis, corticosteroids for brain injury, Tirilazad for stroke, antenatal corticosteroids for neonatal respiratory distress and thrombolytics for stroke). Clinical relevance was also explored in terms of current clinical practice. Harms were categorised for severity using an expert panel. The quality of the research and its impact were considered. Bateson's Cube was used to conduct the HBA.The most common assessment of animal harms by the expert panel was 'severe'. Reported use of analgesia was rare and some animals (including most neonates) endured significant procedures with no, or only light, anaesthesia reported. Some animals suffered iatrogenic harms. Many were kept alive for long periods post-experimentally but only 1% of studies reported post-operative care. A third of studies reported that some animals died prior to endpoints. All the studies were of poor quality. Having weighed the actual harms to animals against the actual clinical benefits accruing from these studies, and taking into account the quality of the research and its impact, less than 7% of the studies were permissible according to Bateson's Cube: only the moderate bisphosphonate studies appeared to minimise harms to animals whilst being associated with benefit for humans.This is the first time the accountability of the HBA has been systematically explored across a range of pre-clinical animal studies. The regulatory systems in place when these studies were conducted failed to safeguard animals from severe suffering or to ensure that only beneficial, scientifically rigorous research was conducted. Our findings indicate a pressing need to: i. review regulations, particularly those that permit animals to suffer severe harms; ii. reform the processes of prospectively assessing pre-clinical animal studies to make them fit for purpose; and iii. systematically evaluate the benefits of pre-clinical animal research to permit a more realistic assessment of its likely future benefits

Incorporating new approach methodologies into regulatory nonclinical pharmaceutical safety assessment

New approach methodologies (NAMs) based on human biology enabletheassessment of adverse biological effects of pharmaceuticals and other chemicals. Currently,however, it is unclear how NAMsshould be usedduring drug development to improve human safety evaluation. A series of 5 workshops with 13 international experts (regulators, preclinical scientists and NAMs developers) were conducted to identify feasible NAMsand to discuss how to exploit them in specific safety assessmentcontexts. Participants generated four‘maps’of how NAMs can be exploited in the safety assessment ofthe liver, respiratory, cardiovascular,and central nervous systems. Each map showsrelevant end points measured, tools used (e.g.,cells, assays, platforms), and highlights gaps where furtherdevelopment and validation of NAMs remainsnecessary. Each map addresses the fundamental scientific requirements for the safety assessment of that organ system, providing users with guidance on the selection of appropriate NAMs. In addition to generating the maps, participants offered suggestions for encouraging greater NAM adoption within drug development and their inclusion in regulatory guidelines. A specific recommendation was that pharmaceutical companies should be more transparent about how they use NAMs in-house. As well as giving guidance for the fourorgan systems, the maps providea template that could be used for additional organ safety testing contexts.Moreover, their conversion to an interactive format would enable users to drill down to the detail necessary to answer specific scientific and regulatory questions. 1IntroductionExtensive nonclinical safety studies are undertaken on new pharmaceuticals prior to and alongside clinical trials. Their purpose is to identify and understand the toxic effects of thecompoundin order to determine whether its anticipated benefit versusrisk profile justifies clinical evaluation and, if so, to inform the design and monitoring of clinical studies. The nonclinical safety studies are mandated by regulatory guidelines and include a variety of safety pharmacologyand toxicology investigations.Safety pharmacology studies aimto determinewhether pharmaceuticalscause on-or off-target effects on biological processes which can affect the function of critical organ systems (e.g.,cardiovascular, respiratory, gastrointestinal,and central nervous systems)and to assess potency, which is needed to assess safety margins versushuman clinical drug exposure. Safety pharmacology studiesalso help informthe selectionof follow-on investigations that can aid human risk assessmentand may provide insight into mechanismswhich underlie any effectsthat arise in humans.Multiple leading pharmaceutical companies (e.g.,AstraZeneca, GlaxoSmithKline, Novartis,and Pfizer) have outlined the advantages provided by in vitrosafety pharmacological profiling, including early identification of off-target interactionsandthe prediction ofclinical side effects that may be missed in animalstudies, and have highlighted that these studies enable much more cost-effective and rapid profiling of large numbers of compounds than animal procedures (Bowes et al., 2012).Toxicology studies evaluate systemic organ toxicities, behavioraleffects, reproductive and developmental toxicology, genetic toxicology,eye irritancy and dermal sensitization. They include single and repeat dose studies in rodent and non-rodentanimal species, which identify target organs, assessseverity andreversibility,and define dose-response and no observed adverse effect levels. These are critical parameters which are essential for regulatory decision-makingon whether the compound can be progressed into clinical trials and if so, estimation ofa suitable starting dose,maximum dose, dose escalation regime,andany non-standard clinical safety monitoringthat may be needed.Toxicity observedinnonclinical animal safety studies is an important cause of the high attrition rate of candidate drugs prior to clinicaltrials that occurs inmultiple pharmaceutical companies(Cook et al., 2014).However, many drugs cause clinically serious adverseeffects in humans which are not detectedin animals(Bailey et al., 2015). For example, human drug induced liver injury(DILI),which is not detected in animal safety studies,is animportant cause of attrition late in clinical development, failed licensing and/or of restrictive drug labelling(Watkins, 2011). Attrition due to toxicity observed in animals and/or in humans isanimportant cause of the high failure rate of clinical drug development(Cook et al., 2014; Watkins, 2011; Thomas et al., 2021).New approach methodologies (NAMs)includemethods which predict and evaluate biological processes by which pharmaceuticals may elicit desirable pharmacological effects and/or may cause undesirable toxicity. Many different types of NAMs have been described. Theseinclude simple in vitrocell-based tests, more complex organotypic or microphysiologicalsystems (MPS)/organ-on-a-chipdevices,and whole human tissuesmaintained ex vivo. Interpretation ofthe invivorelevance of the data providedby these methods is complementedbycomputational toolswhichsimulate and predict in vivodrug disposition and kinetics, in particular physiologically based pharmacokinetic (PBPK) models. Accurate in vitroto in vivoextrapolation isfurther aided by human low-dose testing and microdosing studies (phase 0 testing), which provide precise data on systemic human drug exposure and kineticsin vivo

Incorporating new approach methodologies into regulatory nonclinical pharmaceutical safety assessment

© 2023 The Author(s). ALTEX. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY), https://creativecommons.org/licenses/by/4.0/New approach methodologies (NAMs) based on human biology enable the assessment of adverse biological effects of pharmaceuticals and other chemicals. Currently, however, it is unclear how NAMs should be used during drug development to improve human safety evaluation. A series of 5 workshops with 13 international experts (regulators, preclinical scientists, and NAMs developers) was conducted to identify feasible NAMs and to discuss how to exploit them in specific safety assessment contexts. Participants generated four “maps” of how NAMs can be exploited in the safety assessment of the liver, respiratory, cardiovascular, and central nervous systems. Each map shows relevant endpoints measured and tools used (e.g., cells, assays, platforms), and highlights gaps where further development and validation of NAMs remains necessary. Each map addresses the fundamental scientific requirements for the safety assessment of that organ system, providing users with guidance on the selection of appropriate NAMs. In addition to generating the maps, participants offered suggestions for encouraging greater NAM adoption within drug development and their inclusion in regulatory guidelines. A specific recommendation was that pharmaceutical companies should be more transparent about how they use NAMs in-house. As well as giving guidance for the four organ systems, the maps provide a template that could be used for additional organ safety testing contexts. Moreover, their conversion to an interactive format would enable users to drill down to the detail necessary to answer specific scientific and regulatory questions.Peer reviewe

Developing a collaborative agenda for humanities and social scientific research on laboratory animal science and welfare.

Improving laboratory animal science and welfare requires both new scientific research and insights from enquiry in the humanities and social sciences. Whilst scientific research provides evidence to replace, reduce and refine procedures involving laboratory animals (the ‘3Rs’), work in the humanities and social sciences can help understand the social, economic and cultural processes that enhance or impede humane ways of knowing and working with laboratory animals. However, communication across these disciplinary perspectives is currently limited, and they frame questions, generate results, engage users, and seek to influence policy in different ways. To facilitate dialogue and future research at this interface, we convened an interdisciplinary group of 45 life scientists, social scientists, humanities scholars, non-governmental organisations and policy-makers to generate a collaborative research agenda. This drew on other agenda-setting exercises in science policy, using a collaborative and deliberative approach for the identification of research priorities. Participants were recruited from across the community, invited to submit research questions and vote on their priorities. They then met at an interactive workshop in the UK, discussed all 136 questions submitted, and collectively defined the 30 most important issues for the group. The output is a collaborative future agenda for research in the humanities and social sciences on laboratory animal science and welfare. The questions indicate a demand for new research in the humanities and social sciences to inform emerging discussions and priorities on the governance and practice of laboratory animal research, including around: international harmonisation, openness and public engagement, ‘cultures of care’, harm-benefit analysis and the future of the 3Rs. The process underlines the value of interdisciplinary exchange for improving mutual understanding of different research cultures and identifies ways of enhancing the effectiveness of future research at the interface between the humanities, social sciences, science and science policy