International trials can be challenging to operationalise due to incompatibilities between country-specific policies and infrastructures. The aim of this systematic review was to identify the operational complexities of conducting international trials and identify potential solutions for overcoming them.

Systematic review.

Medline, Embase and Health Management Information Consortium were searched from 2006 to 30 January 2023.

All studies reporting operational challenges (eg, site selection, trial management, intervention management, data management) of conducting international trials were included.

Search results were independently screened by at least two reviewers and data were extracted into a proforma.

38 studies (35 RCTs, 2 reports and 1 qualitative study) fulfilled the inclusion criteria. The median sample size was 1202 (IQR 332–4056) and median number of sites was 40 (IQR 13–78). 88.6% of studies had an academic sponsor and 80% were funded through government sources. Operational complexities were particularly reported during trial set-up due to lack of harmonisation in regulatory approvals and in relation to sponsorship structure, with associated budgetary impacts. Additional challenges included site selection, staff training, lengthy contract negotiations, site monitoring, communication, trial oversight, recruitment, data management, drug procurement and distribution, pharmacy involvement and biospecimen processing and transport.

International collaborative trials are valuable in cases where recruitment may be difficult, diversifying participation and applicability. However, multiple operational and regulatory challenges are encountered when implementing a trial in multiple countries. Careful planning and communication between trials units and investigators, with an emphasis on establishing adequately resourced cross-border sponsorship structures and regulatory approvals, may help to overcome these barriers and realise the benefits of the approach.

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Clinical practice guideline (CPG) developers conduct systematic summaries of research evidence, providing them great capacity and ability to identify research priorities. We systematically analysed the reporting form and content of research priorities in CPGs related to knee osteoarthritis (KOA) to provide a valuable reference for guideline developers and clinicians.

A methodological literature analysis was done and the characteristics of the reporting form and the content of the research priorities identified in KOA CPGs were summarised.

Six databases (PubMed, Embase, China National Knowledge Infrastructure, VIP Database for Chinese Technical Periodicals, Wanfang and Chinese Biomedical Literature Database) were searched for CPGs published from 1 January 2017 to 4 December 2022. The official websites of 40 authoritative orthopaedic societies, rheumatology societies and guideline development organisations were additionally searched.

We included all KOA CPGs published in English or Chinese from 1 January 2017 that included at least one recommendation for KOA. We excluded duplicate publications, older versions of CPGs as well as guidance documents for guideline development.

Reviewers worked in pairs and independently screened and extracted the data. Descriptive statistics were used, and absolute frequencies and proportions of related items were calculated.

187 research priorities reported in 41 KOA CPGs were identified. 24 CPGs reported research priorities, of which 17 (41.5%) presented overall research priorities for the entire guideline rather than for specific recommendations. 110 (58.8%) research priorities were put forward due to lack of evidence. Meanwhile, more than 70% of the research priorities reflected the P (population) and I (intervention) structural elements, with 135 (72.2%) and 146 (78.1%), respectively. More than half of the research priorities (118, 63.8%) revolved around evaluating the efficacy of interventions. Research priorities primarily focused on physical activity (32, 17.3%), physical therapy (30, 16.2%), surgical therapy (27, 14.6%) and pharmacological treatment (26, 14.1%).

Research priorities reported in KOA CPGs mainly focused on evaluating non-pharmacological interventions. There exists considerable room for improvement for a comprehensive and standardised generation and reporting of research priorities in KOA CPGs.

The COVID-19 pandemic accelerated changes to clinical research methodology, with clinical studies being carried out via online/remote means. This mixed-methods study aimed to identify which digital tools are currently used across all stages of clinical research by stakeholders in clinical, health and social care research and investigate their experience using digital tools.

Two online surveys followed by semistructured interviews were conducted. Interviews were audiorecorded, transcribed and analysed thematically.

To explore the digital tools used since the pandemic, survey participants (researchers and related staff (n=41), research and development staff (n=25)), needed to have worked on clinical, health or social care research studies over the past 2 years (2020–2022) in an employing organisation based in the West Midlands region of England (due to funding from a regional clinical research network (CRN)). Survey participants had the opportunity to participate in an online qualitative interview to explore their experiences of digital tools in greater depth (n=8).

Six themes were identified in the qualitative interviews: ‘definition of a digital tool in clinical research’; ‘impact of the COVID-19 pandemic’; ‘perceived benefits/drawbacks of digital tools’; ‘selection of a digital tool’; ‘barriers and overcoming barriers’ and ‘future digital tool use’. The context of each theme is discussed, based on the interview results.

Findings demonstrate how digital tools are becoming embedded in clinical research, as well as the breadth of tools used across different research stages. The majority of participants viewed the tools positively, noting their ability to enhance research efficiency. Several considerations were highlighted; concerns about digital exclusion; need for collaboration with digital expertise/clinical staff, research on tool effectiveness and recommendations to aid future tool selection. There is a need for the development of resources to help optimise the selection and use of appropriate digital tools for clinical research staff and participants.

To explore the importance of, and barriers to achieving, diversity in early-phase clinical trials.

Qualitative interviews analysed using thematic analysis.

Five professionals (clinical researchers and methodologists) and three patient and public representatives (those with experience of early-phase clinical trials and/or those from ethnic minority backgrounds) were interviewed between June and August 2022. Participants were identified via their institutional web page, existing contacts or social media (eg, X, formerly known as Twitter).

Professionals viewed that diversity is not currently considered in all early-phase clinical trials but felt that it should always be taken into account. Such trials are primarily undertaken at a small number of centres, thus limiting the populations they can access. Referrals from clinicians based in the community may increase diversity; however, those referred are often not from underserved groups. Referrals may be hindered by the extra resources required to approach and recruit underserved groups and participants often having to undertake ‘self-driven’ referrals. Patient and public representatives stated that diversity is important in research staff and that potential participants should be informed of the need for diversity. Those from underserved groups may require clarification regarding the potential harms of a treatment, even if these are unknown. Education may improve awareness and perception of early-phase clinical trials. We provide 14 recommendations to improve diversity in early-phase clinical trials.

Diversity should be considered in all early-phase trials. Consideration is required regarding the extent of diversity and how it is addressed. The increased resources needed to recruit those from underserved groups may warrant funders to increase the funds to support the recruitment of such participants. The potential harms and societal benefits of the research should be presented to potential participants in a balanced but accurate way to increase transparency.

Our main objective is to assess the inter-reviewer reliability (IRR) reported in published systematic literature reviews (SLRs). Our secondary objective is to determine the expected IRR by authors of SLRs for both human and machine-assisted reviews.

We performed a review of SLRs of randomised controlled trials using the PubMed and Embase databases. Data were extracted on IRR by means of Cohen’s kappa score of abstract/title screening, full-text screening and data extraction in combination with review team size, items screened and the quality of the review was assessed with the A MeaSurement Tool to Assess systematic Reviews 2. In addition, we performed a survey of authors of SLRs on their expectations of machine learning automation and human performed IRR in SLRs.

After removal of duplicates, 836 articles were screened for abstract, and 413 were screened full text. In total, 45 eligible articles were included. The average Cohen’s kappa score reported was 0.82 (SD=0.11, n=12) for abstract screening, 0.77 (SD=0.18, n=14) for full-text screening, 0.86 (SD=0.07, n=15) for the whole screening process and 0.88 (SD=0.08, n=16) for data extraction. No association was observed between the IRR reported and review team size, items screened and quality of the SLR. The survey (n=37) showed overlapping expected Cohen’s kappa values ranging between approximately 0.6–0.9 for either human or machine learning-assisted SLRs. No trend was observed between reviewer experience and expected IRR. Authors expect a higher-than-average IRR for machine learning-assisted SLR compared with human based SLR in both screening and data extraction.

Currently, it is not common to report on IRR in the scientific literature for either human and machine learning-assisted SLRs. This mixed-methods review gives first guidance on the human IRR benchmark, which could be used as a minimal threshold for IRR in machine learning-assisted SLRs.

CRD42023386706.

Randomised controlled trials (RCTs) inform healthcare decisions. It is now apparent that some published RCTs contain false data and some appear to have been entirely fabricated. Systematic reviews are performed to identify and synthesise all RCTs that have been conducted on a given topic. While it is usual to assess methodological features of the RCTs in the process of undertaking a systematic review, it is not usual to consider whether the RCTs contain false data. Studies containing false data therefore go unnoticed and contribute to systematic review conclusions. The INveStigating ProblEmatic Clinical Trials in Systematic Reviews (INSPECT-SR) project will develop a tool to assess the trustworthiness of RCTs in systematic reviews of healthcare-related interventions.

The INSPECT-SR tool will be developed using expert consensus in combination with empirical evidence, over five stages: (1) a survey of experts to assemble a comprehensive list of checks for detecting problematic RCTs, (2) an evaluation of the feasibility and impact of applying the checks to systematic reviews, (3) a Delphi survey to determine which of the checks are supported by expert consensus, culminating in, (4) a consensus meeting to select checks to be included in a draft tool and to determine its format and (5) prospective testing of the draft tool in the production of new health systematic reviews, to allow refinement based on user feedback. We anticipate that the INSPECT-SR tool will help researchers to identify problematic studies and will help patients by protecting them from the influence of false data on their healthcare.

The University of Manchester ethics decision tool was used, and this returned the result that ethical approval was not required for this project (30 September 2022), which incorporates secondary research and surveys of professionals about subjects relating to their expertise. Informed consent will be obtained from all survey participants. All results will be published as open-access articles. The final tool will be made freely available.

Community-based participatory research (CBPR) is a collaborative research approach that equally engages researchers and community stakeholders throughout all steps of the research process to facilitate social change and increase research relevance. Community advisory boards (CABs) are a CBPR tool in which individuals with lived experience and community organisations are integrated into the research process and ensure the work aligns with community priorities. We seek to (1) explore the best practices for the recruitment and engagement of people with lived experiences on CABs and (2) identify the scope of literature on minimising power dynamics between organisations and community members with lived experience who work on CABs together.

This scoping review will follow the Arksey and O’Malley methodological framework, informed by Levac et al, and will be reported using a PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) diagram. Detailed and robust search strategies have been developed for Embase, Medline and PsychINFO. Grey literature references and reference lists of included articles published between 1 January 1990 and 30 March 2023 will be considered. Two reviewers will independently screen references in two successive stages of title/abstract and full-text screening. Conflicts will be decided by consensus or a third reviewer. Thematic analysis will be applied in three phases: open coding, axial coding and abstraction. Extracted data will be recorded and presented in a tabular format and/or graphical summaries, with a descriptive overview discussing how the research findings relate to the research questions. At this time, a preliminary search of peer-reviewed and grey literature has been conducted. Search results for peer-reviewed literature have been uploaded to Covidence for review and appraisal for relevance.

Formal ethics approval is not required for this review. Review findings will inform ongoing and future CBPR community advisory board dynamics.

The protocol has been registered prospectively on the Open Science Framework (https://doi.org/10.17605/OSF.IO/QF5D3)

The process of transitioning young people from children’s or adolescents’ health services into adults’ services is a crucial time in the lives and health of young people and has been reported to be disjointed rather than a process of preparation in which they are involved. Such transitions not only fail to meet the needs of young people and families at this time of significant change, but they may also result in a deterioration in health, or disengagement with services, which can have deleterious long-term consequences. Despite the wealth of literature on this topic, there has yet to be a focus on what works for whom, in what circumstances, how and why, in relation to all young people transitioning from children’s into adults’ services, which this realist synthesis aims to address.

This realist synthesis will be undertaken in six stages: (1) the scope of the review will be defined; (2) initial programme theories (IPTs) developed; (3) evidence searched; (4) selection and appraisal; (5) data extraction and synthesis; and (6) finally, refine/confirm programme theory. A theory-driven, iterative approach using the ‘On Your Own Feet Ahead’ theoretical framework, will be combined with an evidence search including a review of national transition policy documents, supplemented by citation tracking, snowballing and stakeholder feedback to develop IPTs. Searches of EMBASE, EMCARE, Medline, CINAHL, Cochrane Library, Web of Science, Scopus, APA PsycINFO and AMED will be conducted from 2014 to present, supplemented with grey literature, free-text searching (title, abstract and keywords) and citation tracking. Data selection will be based on relevance and rigour and extracted and synthesised iteratively with the aim of identifying and exploring causal links between contexts, mechanisms and outcomes. Results will be reported according to the Realist And Meta-narrative Evidence Syntheses: Evolving Standards Quality and Publication Standards.

This realist synthesis forms part of the National Transition Evaluation Study, which has received ethical and regulatory approval (IRAS ID: 313576). Results will be disseminated through peer-review publication, conference presentations and working with healthcare organisations, stakeholder groups and charities.

NCT05867745.

CRD42023388985.

Many people with Parkinson’s (PwP) are not given the opportunity or do not have adequate access to participate in clinical research. To address this, we have codeveloped with users an online platform that connects PwP to clinical studies in their local area. It enables site staff to communicate with potential participants and aims to increase the participation of the Parkinson’s community in research. This protocol outlines the mixed methods study protocol for the usability testing of the platform.

We will seek user input to finalise the platform’s design, which will then be deployed in a limited launch for beta testing. The beta version will be used as a recruitment tool for up to three studies with multiple UK sites. Usability data will be collected from the three intended user groups: PwP, care partners acting on their behalf and site study coordinators. Usability questionnaires and website analytics will be used to capture user experience quantitatively, and a purposive sample of users will be invited to provide further feedback via semistructured interviews. Quantitative data will be analysed using descriptive statistics, and a thematic analysis undertaken for interview data. Data from this study will inform future platform iterations.

Ethical approval was obtained from the University of Plymouth (3291; 3 May 2022). We will share our findings via a ‘Latest News’ section within the platform, presentations, conference meetings and national PwP networks.

Antimicrobial resistant (AMR) infections are a major public health problem and the burden on population level is not yet clear. We developed a method to calculate the excess burden of resistance which uses country-specific parameter estimates and surveillance data to compare the mortality and morbidity due to resistant infection against a counterfactual (the expected burden if infection was antimicrobial susceptible). We illustrate this approach by estimating the excess burden for AMR (defined as having tested positive for extended-spectrum beta-lactamases) urinary tract infections (UTIs) caused by E. coli in the Netherlands in 2018, which has a relatively low prevalence of AMR E. coli, and in Italy in 2016, which has a relatively high prevalence.

Excess burden was estimated using the incidence-based disability-adjusted life-years (DALYs) measure. Incidence of AMR E. coli UTI in the Netherlands was derived from ISIS-AR, a national surveillance system that includes tested healthcare and community isolates, and the incidence in Italy was estimated using data reported in the literature. A systematic literature review was conducted to find country-specific parameter estimates for disability duration, risks of progression to bacteraemia and mortality.

The annual excess burden of AMR E. coli UTI was estimated at 3.89 and 99.27 DALY/100 0000 population and 39 and 2786 excess deaths for the Netherlands and Italy, respectively.

For the first time, we use country-specific and pathogen-specific parameters to estimate the excess burden of resistant infections. Given the large difference in excess burden due to resistance estimated for Italy and for the Netherlands, we emphasise the importance of using country-specific parameters describing the incidence and disease progression following AMR and susceptible infections that are pathogen specific, and unfortunately currently difficult to locate.

This study aimed to understand the role of surgical Trainee Research Collaboratives (TRCs) in conducting randomised controlled trials and identify strategies to enhance trainee engagement in trials.

This is a mixed methods study. We used observation of TRC meetings, semi-structured interviews and an online survey to explore trainees’ motivations for engagement in trials and TRCs, including barriers and facilitators. Interviews were analysed thematically, alongside observation field notes. Survey responses were analysed using descriptive statistics. Strategies to enhance TRCs were developed at a workshop by 13 trial methodologists, surgical trainees, consultants and research nurses.

This study was conducted within a secondary care setting in the UK.

The survey was sent to registered UK surgical trainees. TRC members and linked stakeholders across surgical specialties and UK regions were purposefully sampled for interviews.

We observed 5 TRC meetings, conducted 32 semi-structured interviews and analysed 73 survey responses. TRCs can mobilise trainees thus gaining wider access to patients. Trainees engaged with TRCs to improve patient care, surgical evidence and to help progress their careers. Trainees valued the TRC infrastructure, research expertise and mentoring. Challenges for trainees included clinical and other priorities, limited time and confidence, and recognition, especially by authorship. Key TRC strategies were consultant support, initial simple rapid studies, transparency of involvement and recognition for trainees (including authorship policies) and working with Clinical Trials Units and research nurses. A 6 min digital story on YouTube disseminated these strategies.

Trainee surgeons are mostly motivated to engage with trials and TRCs. Trainee engagement in TRCs can be enhanced through building relationships with key stakeholders, maximising multi-disciplinary working and offering training and career development opportunities.

External control arms (ECAs) provide useful comparisons in clinical trials when randomised control arms are limited or not feasible. We conducted a systematic review to summarise applications of ECAs in trials of immune-mediated inflammatory diseases (IMIDs).

Systematic review with an appraisal of ECA source quality rated across five domains (data collection, study populations, outcome definitions, reliability and comprehensiveness of the dataset, and other potential limitations) as high, low or unclear quality.

Embase, Medline and Cochrane Central Register of Controlled Trial were searched through to 12 September 2023.

Eligible studies were single-arm or randomised controlled trials (RCTs) of inflammatory bowel disease, pouchitis, rheumatoid arthritis, juvenile idiopathic arthritis, ankylosing spondylitis, psoriatic arthritis, psoriasis and atopic dermatitis in which an ECA was used as the comparator.

Two authors independently screened the search results in duplicate. The characteristics of included studies, external data source(s), outcomes and statistical methods were recorded, and the quality of the ECA data source was assessed by two independent authors.

Forty-three studies met the inclusion criteria (inflammatory bowel disease: 16, pouchitis: 1, rheumatoid arthritis: 12, juvenile idiopathic arthritis: 1, ankylosing spondylitis: 5, psoriasis: 3, multiple indications: 4). The majority of these trials were single-arm (33/43) and enrolled adult patients (34/43). All included studies used a historical control rather than a contemporaneous ECA. In RCTs, ECAs were most often derived from the placebo arm of another RCT (6/10). In single-arm trials, historical case series were the most common ECA source (19/33). Most studies (31/43) did not employ a statistical approach to generate the ECA from historical data.

Standardised ECA methodology and reporting conventions are lacking for IMIDs trials. The establishment of ECA reporting guidelines may enhance the rigour and transparency of future research.

Adverse events are a major cause of patient harm in the hospitalised setting. Low-income and middle-income countries account for a disproportionate share of the global burden of adverse events. However, patient safety research is still centred around high-income countries and high-resource health systems. The methods and data produced from these efforts are ill-suited to low-income and middle-income systems due to the social and technical differences between these settings. We aim to use our pilot-tested, locally developed methodology to estimate the frequency and characteristics of adverse events in hospitalised patients in a lower-middle-income country to inform patient safety policies and initiatives.

This multi-centre study will employ a two-step chart review methodology to identify adverse events in a representative sample of patients admitted at five hospitals between 1 January 2019 and 31 December 2019. The first step will include assessing patient files against a list of triggers to detect adverse events and the second step will involve an in-depth review of the events to capture pertinent characteristics. The triggers have been adapted from validated tools used in other studies. The reviewing team will be trained on the use of research tools and operational definitions to ensure that data are collected uniformly. The main outcome of interest is the rate at which adverse events occur in hospitalised patients. Further analysis will look to identify and quantify associations between the main outcome of interest and a variety of variables such as patient age and gender using tests of independence and regression techniques.

This study protocol has been approved by the Ethics Review Committee at Aga Khan University (Reference number: 2023-6324-24566). The findings of this study will be published in a peer-reviewed journal and disseminated to the public through national and international conferences, workshops, websites and social media.

This study aims to assess sample selection bias in mobile phone survey estimates of fertility and under-5 mortality.

With data from the Demographic and Health Surveys, we use logistic regressions to identify sociodemographic correlates of mobile phone ownership and access, and Poisson regressions to estimate the association between mobile phone ownership (or access) and fertility and under-5 mortality estimates. We evaluate the potential reasons why estimates by mobile phone ownership differ using a set of behavioural characteristics.

34 low-income and middle-income countries, mostly in sub-Saharan Africa.

534 536 women between the ages of 15 and 49.

Under-5 mortality rate (U5MR) and total fertility rate (TFR).

Mobile phone ownership ranges from 23.6% in Burundi to 96.7% in Armenia. The median TFR ratio and U5MR ratio between the non-owners and the owners of a mobile phone are 1.48 and 1.29, respectively. Fertility and mortality rates would be biased downwards if estimates are only based on women who own or have access to mobile phones. Estimates of U5MR can be adjusted through poststratification using age, educational level, area of residence, wealth and marital status as weights. However, estimates of TFR remain biased even after adjusting for these covariates. This difference is associated with behavioural factors (eg, contraceptive use) that are not captured by the poststratification variables, but for which there are also differences between mobile phone owners and non-owners.

Mobile phone surveys need to collect data on sociodemographic background characteristics to be able to weight and adjust mortality estimates ex post facto. Fertility estimates from mobile phone surveys will be biased unless further research uncovers the mechanisms driving the bias.