European expert recommendations on clinical investigation and evaluation of high-risk medical devices for children.

Several high-risk medical devices for children have become unavailable in the European Union (EU), since requirements and costs for device certification increased markedly due to the EU Medical Device Regulation. The EU-funded CORE-MD project held a workshop in January 2023 with experts from various child health specialties, representatives of European paediatric associations, a regulatory authority and the European Commission Directorate General Health and Food Safety. A virtual follow-up meeting took place in March 2023. We developed recommendations for investigation of high-risk medical devices for children building on participants' expertise and results of a scoping review of clinical trials on high-risk medical devices in children. Approaches for evaluating and certifying high-risk medical devices for market introduction are proposed.

Publication Categories in Toxicologic Pathology.

Toxicologic Pathology is the official journal of the Society of Toxicologic Pathology (STP), the British Society of Toxicological Pathology, and the European STP (ESTP). Toxicologic Pathology publishes articles related to topics in various aspects of toxicologic pathology such as anatomic pathology, clinical pathology, experimental pathology, and biomarker research. Publications include society-endorsed Best Practice/Position and Points to Consider publications and ESTP Expert Workshop articles that are relevant to toxicologic pathology and scientific regulatory processes, Opinion articles under the banner of the STP Toxicologic Pathology Forum, Original Articles, Review Articles (unsolicited/contributed, mini, and invited), Brief Communications, Letters to the Editor, Meeting Reports, and Book Reviews. This article provides details on the various publication categories in Toxicologic Pathology and will serve as a reference for authors and readers.

Defining Elimination of Genital Warts-A Modified Delphi Study.

Background: Substantial declines in genital warts (GW) have been observed in countries with quadrivalent HPV vaccination programmes, with Australia showing the highest reductions due to early commencement and high vaccination coverage. There is a real potential to achieve GW elimination; however, no GW elimination definition exists. Taking Australia as a case study, we aimed to reach expert consensus on a proposed GW elimination definition using a modified Delphi process. Method: We used modelling and epidemiological data to estimate the expected number of new GW cases, from pre-vaccination (baseline) in 2006 to the year 2060 in Australian heterosexuals, men who have sex with men (MSM), and newly arrived international travellers and migrants. We used these data and the literature, to develop a questionnaire containing ten elimination-related items, each with 9-point Likert scales (1-strongly disagree; 9-strongly agree). The survey was completed by 18 experts who participated in a full day face-to-face modified Delphi study, in which individuals and then small groups discussed and scored each item. The process was repeated online for items where consensus (≥70% agreement) was not initially achieved. Median and coefficient of variation (COV) were used to describe the central tendency and variability of responses, respectively. Findings: There was a 95% participation rate in the face-to-face session, and 84% response rate in the final online round. The median item score ranged between 7.0 and 9.0 and the COV was ≤0.30 on all items. Consensus was reached that at ≥80% HPV vaccination coverage, GW will be eliminated as a public health problem in Australia by 2060. During this time period there will be a 95% reduction in population-level incidence compared with baseline, equivalent to <1 GW case per 10,000 population. The reductions will occur most rapidly in Australian heterosexuals, with 73%, 90% and 97% relative reductions by years 2021, 2030 and 2060, respectively. The proportion of new GW cases attributable to importation will increase from 3.6% in 2006 to ~49% in 2060. Interpretation: Our results indicate that the vaccination programme will minimise new GW cases in the Australian population, but importation of cases will continue. This is the first study to define GW elimination at a national level. The framework developed could be used to define GW elimination in other countries, with thresholds particularly valuable for vaccination programme impact evaluation. Funding: LK supported through an Australian Government Research Training Programme Scholarship; unconditional funding from Seqirus to support the Delphi Workshop.

Consensus workshops on the development of an ADHD medication management protocol using QbTest: developing a clinical trial protocol with multidisciplinary stakeholders.

BACKGROUND: The study design and protocol that underpin a randomised controlled trial (RCT) are critical for the ultimate success of the trial. Although RCTs are considered the gold standard for research, there are multiple threats to their validity such as participant recruitment and retention, identifying a meaningful change, and non-adherence to the protocol. For clinical RCTs, involving patients and clinicians in protocol design provides the opportunity to develop research protocols that are meaningful to their target audience and may help overcome some of the inherent threats in conducting RCTs. However, the majority of protocols do not describe the methodology underpinning their development, limiting the amount of learned experience shared between research groups. METHOD: With the purpose of reporting a collaborative approach towards developing a protocol, we present the findings from three sequential workshops that were conducted with the aim of developing a protocol to investigate the feasibility of adding a computerised test of attention, impulsivity and activity (QbTest) to medication management of children and young people with Attention deficit hyperactivity disorder (ADHD). Based on previous qualitative interviews with clinicians and families, each workshop prioritised topics for focused discussion. Information from the workshops was fed back to the participants for reflection in advance of the next workshop. RESULTS: The workshops involved 21 multi-disciplinary ADHD experts, including clinicians, patient and public involvement (PPI) members, parents of young people with ADHD and researchers. The consensus workshops addressed key research issues such as: the most relevant outcome measures/ resource drivers; methods and time points for data collection; and the clinical protocol for utilising the QbTest, including when best to use this within the medication management process. The resulting protocol details a feasibility RCT design describing these factors. CONCLUSION: Protocols which are co-developed may help overcome some of the risks associated with RCT completion (e.g. recruitment, retention, protocol adherence) and help prioritise outcomes of greater relevance to the populations under study. The methodology has potential value for researchers and organisations developing clinical guidelines, and offers insights into the valuable impact of PPI upon trial design. TRIAL REGISTRATION: Clinicaltrials.gov NCT03368573, 11th December 2017 (retrospectively registered).

Developing conceptual models that link multiple ecosystem services to ecological research to aid management and policy, the UK marine example.

Our understanding of ecological processes that lead to ecosystem services is still evolving but ecological research aims to understand the linkages between the ecosystem and services. These linkages can affect trade-offs between different ecosystem services. Understanding these linkages, by considering multiple ecosystem services simultaneously supports management of the environment and sustainable use of resources. The UK marine environment is relatively data rich, yet the links between ecosystem and several ecosystem services and linkages between services are poorly described. A workshop with 35 marine scientists was used to create a conceptual model that links ecosystem components and key processes to four services they provide and to highlight trade-offs between them. The model was subsequently further developed to include pressures and mitigating management measures. The models are discussed in terms of their application to marine data to facilitate evidence-based marine management and their usefulness to communicate management measures with managers and stakeholders.

Advancing Risk Analysis for Nanoscale Materials: Report from an International Workshop on the Role of Alternative Testing Strategies for Advancement.

The Society for Risk Analysis (SRA) has a history of bringing thought leadership to topics of emerging risk. In September 2014, the SRA Emerging Nanoscale Materials Specialty Group convened an international workshop to examine the use of alternative testing strategies (ATS) for manufactured nanomaterials (NM) from a risk analysis perspective. Experts in NM environmental health and safety, human health, ecotoxicology, regulatory compliance, risk analysis, and ATS evaluated and discussed the state of the science for in vitro and other alternatives to traditional toxicology testing for NM. Based on this review, experts recommended immediate and near-term actions that would advance ATS use in NM risk assessment. Three focal areas-human health, ecological health, and exposure considerations-shaped deliberations about information needs, priorities, and the next steps required to increase confidence in and use of ATS in NM risk assessment. The deliberations revealed that ATS are now being used for screening, and that, in the near term, ATS could be developed for use in read-across or categorization decision making within certain regulatory frameworks. Participants recognized that leadership is required from within the scientific community to address basic challenges, including standardizing materials, protocols, techniques and reporting, and designing experiments relevant to real-world conditions, as well as coordination and sharing of large-scale collaborations and data. Experts agreed that it will be critical to include experimental parameters that can support the development of adverse outcome pathways. Numerous other insightful ideas for investment in ATS emerged throughout the discussions and are further highlighted in this article.

MORECare research methods guidance development: recommendations for ethical issues in palliative and end-of-life care research.

BACKGROUND: There is little guidance on the particular ethical concerns that research raises with a palliative care population. AIM: To present the process and outcomes of a workshop and consensus exercise on agreed best practice to accommodate ethical issues in research on palliative care. DESIGN: Consultation workshop using the MORECare Transparent Expert Consultation approach. Prior to workshops, participants were sent overviews of ethical issues in palliative care. Following the workshop, nominal group techniques were used to produce candidate recommendations. These were rated online by participating experts. Descriptive statistics were used to analyse agreement and consensus. Narrative comments were collated. SETTING/PARTICIPANTS: Experts in ethical issues and palliative care research were invited to the Cicely Saunders Institute in London. They included senior researchers, service providers, commissioners, researchers, members of ethics committees and policy makers. RESULTS: The workshop comprised 28 participants. A total of 16 recommendations were developed. There was high agreement on the issue of research participation and high to moderate agreement on applications to research ethics committees. The recommendations on obtaining and maintaining consent from patients and families were the most contentious. Nine recommendations were refined on the basis of the comments from the online consultation. CONCLUSIONS: The culture surrounding palliative care research needs to change by fostering collaborative approaches between all those involved in the research process. Changes to the legal framework governing the research process are required to enhance the ethical conduct of research in palliative care. The recommendations are relevant to all areas of research involving vulnerable adults.