UK Health Research Research Articles

The Impact of the COVID-19 Pandemic on the Mental Health and Wellbeing of UK Healthcare Workers

Background: The COVID-19 pandemic has placed healthcare systems and healthcare workers (HCW) under considerable burden. There is an urgent need to understand the psychological impact of the pandemic on UK HCW and identify factors which raise risk of, or protect against, poor mental health during the pandemic. Methods: 2773 UK HCWs completed an online survey between 22nd April and 10th May 2020 which contained validated scales of anxiety, depression, PTSD, and stress, and questions about their roles, workplace, and COVID-19-related factors including COVID-19 preparation and risk management. Using established criteria, respondents were classified as high or low symptomatic on each scale and logistic regressions revealed explanatory models of risk and protective factors for each scale. Change in wellbeing from pre to during COVID-19 was also quantified and symptom severity of key subgroups was compared. Findings: A large proportion of UK HCW reported high levels of mental health symptoms. Wellbeing, particularly of frontline workers (FL), had significantly worsened compared to pre-COVID-19 levels. Specific clusters of factors conferred risk of high symptoms. ‘Fixed’ factors included being female, being FL, pre-existing mental health diagnosis, and experience of stressful/traumatic events. An additional set of controllable factors also significantly increased risk of high symptoms: PPE, workplace preparation, workload, and sufficient COVID-19 training and information. Resilience and sharing stress reduced risk, as did ethics panel support for those making decisions about patient treatment. Allied HCW and especially managers were at risk of high symptoms, particularly PTSD. BAME HCWs were significantly at risk of high PTSD and were more worried than non-BAME about COVID and PPE. Interpretation: Poor mental wellbeing was prevalent in HCW during the UK COVID-19 response. A number of ‘controllable’ factors including reducing perception of preventable risk should be targeted, and protective factors promoted, to reduce the detrimental effect of pandemics on HCW mental health.Funding Statement: The study was unfunded.Declaration of Interests: JG has consulted for Takeda Pharmaceuticals within 3 years of beginning the submitted work. The other authors have nothing to declare.Ethics Approval Statement: The study was reviewed and approved by University of Roehampton ethics committee (REF: PSYCH 20/361) and the UK Health Research Authority.

The Discharge Communication Study: research protocol for a mixed methods study to investigate and triangulate discharge communication experiences of patients, GPs, and hospital professionals, alongside a corresponding discharge letter sample

BackgroundDischarge letters are crucial during care transitions from hospital to home. Research indicates a need for improvement to increase quality of care and decrease adverse outcomes. These letters are often sent from the hospital discharging physician to the referring clinician, typically the patient’s General Practitioner (GP) in the UK, and patients may or may not be copied into them. Relatively little is known about the barriers and enablers to sending patients discharge letters. Hence, the aim of this study was to investigate from GP, hospital professional (HP) and patient perspectives how to improve processes of patients receiving letters and increase quality of discharge letters. The study has a particular focus on the impacts of receiving or not receiving letters on patient experiences and quality of care.MethodsThe setting was a region in the West Midlands of England, UK. The research aimed to recruit a minimum of 30 GPs, 30 patients and 30 HPs in order to capture 90 experiences of discharge communication. Participating GPs initially screened and selected a range of recent discharge letters which they assessed to be successful and unsuccessful exemplars. These letters identified potential participants who were invited to take part: the HP letter writer, GP recipient and patient. Participant viewpoints are collected through interviews, focus groups and surveys and will be “matched” to the discharge letter sample, so forming multiple-perspective “quartet” cases. These “quartets” allow direct comparisons between different discharge experiences within the same communicative event. The methods for analysis draw on techniques from the fields of Applied Linguistics and Health Sciences, including: corpus linguistics; inferential statistics; content analysis.DiscussionThis mixed-methods study is novel in attempting to triangulate views of patients, GPs and HPs in relation to specific discharge letters. Patient and practitioner involvement will inform design decisions and interpretation of findings. Recommendations for improving discharge letters and the process of patients receiving letters will be made, with the intention of informing guidelines on discharge communication. Ethics approval was granted in July 2017 by the UK Health Research Authority. Findings will be disseminated in peer-reviewed journals, reports and newsletters, and presentations.

MA20.06 Neutrophil to Lymphocyte Ratio Is an Independent Prognostic Predictor in Thymoma

Thymoma is the most common primary neoplasm of the anterior mediastinum in adults and conventional prognostic factors include Masaoka Stage, WHO histology and completeness of resection. Little is known of preoperative peripheral neutrophil-to-lymphocyte ratio (NLR) as an independent additional discriminator of prognosis. We performed an international multicentre retrospective cohort study (UK Health Research Reference 19/HRA/0440 and EU internal approval reference xxxxxx). We included patients who underwent complete resection for thymoma and data was acquired through patient medical records with follow up data obtained through national database and hospital records. NLR calculated on pre-operation bloods results. From July 1987 to December 2017, 433 patients underwent surgery for thymoma. The majority were male 228(53%) with a mean age (SD) of 55(15) years. The surgical approach was sternotomy in 335 patients (77%), thoracotomy in 23(5%) and VATS in 75(17%). The WHO classification was type A 63(15%), AB 126(29%), B1 98(23%), B2 55(13%) and B3 86(20%) patients. The Masaoka-Koga stage was I in 135(33%) II in 194(47%), III in 54 (13%) and IV in 31(7%) patients. Median (IQR) follow-up time was 86 (30 to 152) months with a 5 and 10-year survival of 88% and 79% respectively. The median NLR was 2.1 (1.5 to 3.1), when split into three groups (NLR < 1.4, NLR between 1.4 and 2.3 and NLR > 2.3), higher NLR was associated with poorer survival (log rank P<0.001) that persisted on Cox regression after adjustment for WHO grade and Masaoka stage with a HR of 1.69 (95% CI 1.20 to 2.39; P=0.002). Pre-operative NLR is a simple, low cost biomarker that can stratify risk of death independent to WHO grade and Masaoka stage in patients undergoing surgery for thymoma.

Rare but heard: using asynchronous virtual focus groups, interviews and roundtable discussions to create a personalised psychological intervention for primary sclerosing cholangitis: a protocol

IntroductionPrimary sclerosing cholangitis (PSC) is a rare and chronic disease characterised by inflammation and fibrosis of the liver’s bile ducts. There is no known cause or cure for the illness,...

'We're passengers sailing in the same ship, but we have our own berths to sleep in': Evaluating patient and public involvement within a regional research programme: An action research project informed by Normalisation Process Theory.

BackgroundPatient and public involvement (PPI) is a requirement for UK health and social care research funding. Evidence for how best to implement PPI in research programmes, such as National Institute for Health Research (NIHR) Collaborations for Applied Health Research and Care (CLAHRCs), remains limited. This paper reports findings from an action research (AR) project called IMPRESS, which aims to strengthen PPI within CLAHRC East of England (EoE). IMPRESS combines AR with Normalisation Process Theory (NPT) to explore PPI within diverse case study projects, identifying actions to implement, test and refine to further embed PPI.MethodsWe purposively selected CLAHRC EoE case study projects for in-depth analysis of PPI using NPT. Data were generated from project PPI documentation, semi-structured qualitative interviews with researchers and PPI contributors and focus groups. Transcripts and documents were subjected to abductive thematic analysis and triangulation within case. Systematic across case comparison of themes was undertaken with findings and implications refined through stakeholder consultation.ResultsWe interviewed 24 researchers and 13 PPI contributors and analysed 28 documents from 10 case studies. Three focus groups were held: two with researchers (n = 4 and n = 6) and one with PPI contributors (n = 5). Findings detail to what extent projects made sense of PPI, bought in to PPI, operationalised PPI and appraised it, thus identifying barriers and enablers to fully embedded PPI.ConclusionCombining NPT with AR allows us to assess the embeddedness of PPI within projects and programme, to inform specific local action and report broader conceptual lessons for PPI knowledge and practice informing the development of an action framework for embedding PPI in research programmes. To embed PPI within similar programmes teams, professionals, disciplines and institutions should be recognised as variably networked into existing PPI support. Further focus and research is needed on sharing PPI learning and supporting innovation in PPI.

Evidence-based intervention to reduce avoidable hospital admissions in care home residents (the Better Health in Residents in Care Homes (BHiRCH) study): protocol for a pilot cluster randomised trial

IntroductionAcute hospital admission is distressing for care home residents. Ambulatory care sensitive conditions, such as respiratory and urinary tract infections, are conditions that can cause unplanned hospital admission but may...

Manual therapy for chronic migraine: a pragmatic randomised controlled trial study protocol

IntroductionChronic migraine is a largely refractory condition affecting between 1 and 2.2% of the overall population worldwide, with females more affected than males. There are also high health and socioeconomic costs associated both for the individual and society. The mainstay of chronic migraine management is pharmacological, but the options available have limited efficacy and there are often unwanted side effects. There is some evidence for manual therapy as a treatment option for migraine, but its effectiveness for chronic migraine is unknown. Therefore, we have designed a pragmatic randomised control trial to investigate whether adding manual therapy to the tertiary specialist treatment of chronic migraine improves patient-reported outcomes.MethodsA pragmatic, randomised controlled trial in a hospital tertiary headache clinic. Participants will be randomised into one of two groups: treatment as usual or treatment as usual plus manual therapy. The primary outcome measure will be a change in the Headache Impact Test score. Secondary outcomes will also be measured over the 12-week study period including changes in headache frequency, migraine specific quality of life and reductions in relevant medicine consumption. The manual therapy group will have five treatment sessions each lasting 30 min. The recruitment target of 64 participants will allow power at 80% with p = 0.05 using minimal clinical difference for Headache Impact Test of 3.7 and includes provision for a 10% dropout rate. Recruitment will take place between August 2018 and February 2019. The results will form part of a doctoral study and be published in peer-reviewed journals and presented at national/international conferences.DiscussionCurrent pharmacological approaches have limited effects in the management of chronic migraine and there is a requirement to improve treatment options and reduce the health and economic burden of the condition. Manual therapy has been shown to be effective in other chronic pain conditions as well as other primary headaches. This study will explore the effectiveness of manual therapy as an adjunctive approach to the management of chronic migraine.Trial registrationThe trial has received a favourable opinion from the UK Health Research Authority (IRAS 228901) and is registered at ClinicalTrials.gov.number NCT03395457. Registered 1st March 2018.

The burden of proof: The process of involving young people in research.

Patient and public involvement in research includes non‐academics working with researchers, on activities from consultative tasks, to joint working, and on user‐led initiatives. Health and social care funding bodies require involvement in research projects. A current debate focuses on a perceived lack of empirical “proof” to demonstrate the impact of involvement upon the quality of research. It is also argued that the working relationships between researchers and those becoming involved need to be understood more fully. These areas are beginning to be reported upon but there are few studies of young people involved in health research. This study describes the experiences of adult academics and young people, working together on a large‐scale, UK health research programme. Using qualitative interview and focus group methods, the aim was to explore participants’ perceptions about the process and outcomes of their work together. The importance of cyclical, dynamic and flexible approaches is suggested. Enablers include having clear mechanisms for negotiation and facilitation, stakeholders having a vision of “the art of the possible,” and centrally, opportunities for face‐to‐face working. What is needed is a continuing discourse about the challenges and benefits of working with young people, as distinct from younger children and adults, understanding the value of this work, without young people having to somehow “prove” themselves. Involvement relies on complex social processes. This work supports the view that an improved understanding of how key processes are enabled, as well as what involvement achieves, is now needed.

NOX2 Derived Superoxide Induces Pro-Tumoral p16INK4a Driven Senescence in the AML Bone Marrow Microenvironment

BackgroundAcute myeloid leukaemia (AML) is an age-related disease that is highly dependent on the bone marrow (BM) microenvironment. Senescence is the irreversible arrest of cell proliferation and is associated with the senescence associated secretary phenotype (SASP). The senescent phenotype has been associated with pro-tumoral changes that support proliferation and survival of malignant cells. Because AML is an age-related disease and highly dependent on the BM microenvironment, which naturally becomes senescent with age, we hypothesized, and subsequently tested the idea, that AML not only favors a senescent microenvironment but might actively shape a senescent microenvironment to promote tumor proliferation and survival.MethodsPrimary AML and bone marrow stroma was isolated from bone marrow samples obtained from patients following informed consent and non-malignant CD34+ cells were isolated from cord blood following informed consent. All primary tissue was used under approval from the UK Health Research Authority. NSG, p16-3MR(Demaria et al. 2014 Cell Development) and wildtype C57Bl/6 animals were used and experiments were conducted with approval from the UK Home Office and University of East Anglia Animal Welfare and Ethical Review Board. Primary AML and non-malignant human CD34+ cells were engrafted into NSG mice (AML-NSG and hu-NSG). Bone marrow stromal cells (BMSCs) were isolated by cell sorting for mouse CD45-, Ter119-, CD31-, CD105+, CD140a+. Syngeneic AML cells were generated from lineage negative cells transduced with the oncogene MN1. Senescence was determined by p16, p21 mRNA expression, SASP expression (IL-6 and MIP3a), senescence associated β-Galactosidase activity and using themonomeric red fluorescent protein (mRFP) component of the p16-3MR mouse model. Oxidative stress and superoxide levels were measured using 2‘,7‘-dichlorofluorescein (DCF) fluorescence and the Amplex Red assay. NOX-2 in AML was inhibited by RNAi.ResultsFirst, we isolated and analysed BMSC from AML-NSG and hu-NSG. Using real-time PCR we detected high expression of p16 and p21 in the BMSC isolated from AML-NSG but not hu-NSG. Moreover, we detected high mouse IL-6 and MIP3a cytokine levels from serum isolated from AML-NSG but not hu-NSG. MN1 engrafted into the p16-3MR model induced mRFP expression in the BMSC population. This shows that in both a xenograft and syngeneic model of AML the BMSC population becomes senescent. Using the p16-3MR model we selectively depleted senescent BMSC via the viral thymidine kinase death switch. Treatment of p16-3MR mice engrafted with MN1 with ganciclovir reduced tumour volume and prolonged animal survival. Since hydrogen peroxide has been shown to induce senescence we hypothesised that NOX2 derived superoxide from AML drives the BMSC senescence. BMSCs isolated from the MN1 engrafted p16-3MR model isolated BMSC show increased DCF fluorescence and isolated BM shows elevated superoxide compared to BMSC and BM isolated from control mice. NOX2 knock down resulted in significant reduction in BM derived superoxide and BMSC DCF fluorescence and this resulted in a reduced BMSC senescent phenotype.ConclusionHere we show that in AML, NOX2 derived superoxide induces a p16INK4a drivensenescent phenotype in the BMSC. Moreover, we find that this process forms a fundamental part of the pro-tumoral pathophysiology of the disease. The senescent bone marrow microenvironment may therefore present new treatment targets in AML. DisclosuresNo relevant conflicts of interest to declare.

Cross-sectional analysis of UK research studies in 2015: results from a scoping project with the UK Health Research Authority

ObjectivesTo determine whether data on research studies held by the UK Health Research Authority (HRA) could be summarised automatically with minimal manual intervention. There are numerous initiatives to reduce research...

The Sri Lankan community of descent in the UK: a neglected population in demographic and health research

ABSTRACTThe Sri Lankan diaspora population is substantially neglected in UK demographic and health research and not captured in census and survey ethnic group questions, though 127,242 Sri Lankan-born migrants were enumerated in England and Wales in 2011. Important intersections are reported between the period of arrival of these migrants, the purpose behind their movement, and related population characteristics, with 47% having arrived during 2001–2011. Between 1984 and 2004 around 50,000 asylum applications were made by Sri Lankan Tamils. Sri Lankan migrants generally display more favourable circumstances on key socio-economic variables than do other diaspora populations from South Asia. These include generic health status and mortality. This may be attributable to the ‘healthy migrant’ effect, given the community’s recent migration, though the application of its effect to this population requires caution as a significant proportion came to Britain as asylum-seekers (forced migration) rather than as self-selecting migrants. A more advantageous socio-economic profile may also have contributed.

Measuring health-related quality of life of care home residents, comparison of self-report with staff proxy responses for EQ-5D-5L and HowRu: protocol for assessing proxy reliability in care home outcome testing

IntroductionResearch into interventions to improve health and well-being for older people living in care homes is increasingly common. Health-related quality of life (HRQoL) is frequently used as an outcome measure,...

Abstract 4970: Mitochondrial trafficking in the bone marrow microenvironment promotes bioenergetic flexibility in multiple myeloma

Abstract Multiple myeloma (MM) is an incurable malignancy of terminally differentiated plasma cells which is highly dependent on the bone marrow microenvironment (BMM). MM tumor survival, proliferation and drug resistance is reliant on ATP production however the mechanisms by which the malignant cells generate ATP are poorly defined. In this study, we investigate the contributions of oxidative phosphorylation and aerobic glycolysis to tumor cell ATP generation within BMM. Furthermore, we address whether ATP generation within tumor cells is enabled by the transfer of mitochondria from the non-malignant stromal cells of the BMM to the malignant plasma cell. Bone marrow was obtained from patients under approval from the UK Health Research Authority. In-vivo experiments were performed with local Animal Welfare and Ethical Review Board approval and under license from the UK Home Office. Using Seahorse extracellular flux analysis we show that primary MM cells have high baseline rates of mitochondrial respiration compared to MM cell lines. Furthermore, mitochondrial respiration rates increased ex-vivo after co-culture with non-malignant bone marrow stromal cells (BMSC). We engrafted the malignant MM1S cell line into NSG mice and examined the mitochondrial respiration rate from isolated tumor cells compared to MM1S cells cultured in-vitro. We found increased rates of mitochondrial respiration in MM1S cells isolated from mouse BM. To determine whether the increase in tumor oxidative phosphorylation observed in the presence of micro-environment cells was a result of mitochondrial transfer from BMSC to MM, we used three methods. Firstly we stained BMSC with the mitochondrial stain MitoTracker Green and cultured these with primary MM cells. Using a combination of flow cytometry and confocal microscopy we detected MitoTracker fluorescence in the MM cells after co-culture, showing that the stained mitochondria are transferred from BMSC to MM cells in-vitro. Secondly, mitochondrial transfer was directly observed between BMSC and MM cells, visualized by the acquisition of a mCherry labeled mitochondrial protein we transfected into BMSC. Finally, using a human MM cell line engrafted into an NSG mouse xenograft model, we detected murine mitochondrial DNA in sorted human MM1S and U266 tumor cells post-transplant. Through fixed cell confocal microscopy we found that mitochondria move through tunnelling nanotubes (TNTs), and inhibition of TNT formation by treatment with cytochalasin B resulted in reduced mitochondrial transfer and tumor cell oxidative phosphorylation. Here we show that MM cellular metabolism favors oxidative phosphorylation over glycolysis, in the setting of the BMM. This is due to mitochondrial transfer occurring between non-malignant BMSC and malignant plasma cells. This process is necessary for optimum tumor growth in-vivo and forms part of the malignant phenotype of MM. Citation Format: Christopher R. Marlein, Rachel E. Piddock, Charlotte Hellmich, Lyubov Zaitseva, Martin J. Auger, Kristian M. Bowles, Stuart A. Rushworth. Mitochondrial trafficking in the bone marrow microenvironment promotes bioenergetic flexibility in multiple myeloma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4970.

PARENTS 2 study protocol: pilot of Parents’ Active Role and ENgagement in the review of Their Stillbirth/perinatal death

BackgroundThe perinatal mortality review meeting that takes place within the hospital following a stillbirth or neonatal death enables clinicians to learn vital lessons to improve care for women and their...

A National Initiative in Data Science for Health: An Evaluation of the UK Farr Institute

Objective: To evaluate the extent to which the inter-institutional, inter-disciplinary mobilisation of data and skills in the Farr Institute contributed to establishing the emerging field of data science for health in the UK. Design and Outcome measures: We evaluated evidence of six domains characterising a new field of science: defining central scientific challenges, demonstrating how the central challenges might be solved, creating novel interactions among groups of scientists, training new types of experts, re-organising universities, demonstrating impacts in society. We carried out citation, network and time trend analyses of publications, and a narrative review of infrastructure, methods and tools. Setting Four UK centres in London, North England, Scotland and Wales (23 university partners), 2013-2018. Population Subsets of the UK’s 65 million population with health records accessible for research. The Farr Institute published a research corpus around a central scientific challenge, demonstrating insights from electronic health record (EHR) and administrative data at each stage of the translational cycle in 593 papers with at least one Farr Institute author affiliation on PubMed. Sample sizes showed some evidence of increase but remained less than 10% of the UK population in primary care-hospital care linked studies. The Farr Institute established the first four ISO27001 certified trusted research environments in the UK, and approved more than 1000 approved research users, published on 102 unique EHR and administrative data sources and established open platforms for the scalable re-use of EHR phenotyping (>70 diseases, CALIBER). The co-author publication network expanded from 944 unique co-authors (based on 67 publications in the first 30 months) to 3839 unique co-authors (545 papers in the final 30 months). 4/5 Centres established 27 new faculty (tenured) positions, 3 new university institutes, and 3 new master’s courses, training >400 people at master’s, short-course and leadership level and 48 PhD students. There were over 2300 citations for the 10 most cited papers and Farr research informed eight practice-changing clinical guidelines and policies relevant to the health of millions of UK citizens. Conclusion: The Farr Institute played a major role in establishing and growing the field of data science for health in the UK, with some initial evidence of benefits for health and healthcare. The Farr Institute has now expanded into Health Data Research UK but a key challenge is to network such activities internationally. What is already known: • National research initiatives in data science for health are under way in several countries seeking to harness insights from electronic health record (EHR) and administrative data at regional and national scale for patient and public benefit. • One approach to grow this emerging field, adopted by the UK, is to establish a dedicated national research institute, the Farr Institute. • We do not know how effective such initiatives are: multi-centre, inter-disciplinary research initiatives are common, but there is a lack of research evaluating such initiatives (in general) and national research institutes (in particular). • The Farr Institute ran from 2013 until 2018 when its larger-scale successor, Health Data Research UK, was established. What this study adds: • We provide a framework of six domains relevant for evaluating new inter-institutional, inter-disciplinary initiatives seeking to establish and grow an emerging field of science: defining central scientific challenges, demonstrating how the central challenges might be solved, creating novel interactions among groups of scientists, training new types of experts, re-organising universities, demonstrating impacts in society. • We show that the Farr Institute created new activities in and across each of the six domains for developing a distinctive research field. • The Farr Institute demonstrated the ability of multiple UK health research funders and multiple universities to partner in mobilising data, methodology and expertise across disciplines, organisations and information governance domains, resulting in a larger scale of research and improved methodology. • We have demonstrated globally relevant challenges and opportunities for developing data science for health across institutional and disciplinary barriers, consistent with the need for big investigation not simply big data.

Using comprehensive geriatric assessment for quality improvements in healthcare of older people in UK care homes: protocol for realist review within Proactive Healthcare of Older People in Care Homes (PEACH) study

IntroductionCare home residents are relatively high users of healthcare resources and may have complex needs. Comprehensive geriatric assessment (CGA) may benefit care home residents and improve efficiency of care delivery....

Involving the public in mental health and learning disability research: Can we, should we, do we?

Introduction Patient and public involvement (PPI) is integral to UK health research guidance; however, implementation is inconsistent. There is little research into the attitudes of NHS health researchers towards PPI. Aim This study explored the attitude of researchers working in mental health and learning disability services in the UK towards PPI in health research. Method Using a qualitative methodology, semi-structured interviews were conducted with a purposive sample of eight researchers. A framework approach was used in the analysis to generate themes and core concepts. Results Participants valued the perspective PPI could bring to research, but frustration with tokenistic approaches to involvement work was also evident. Some cultural and attitudinal barriers to integrating PPI across the whole research process were identified. Discussion Despite clear guidelines and established service user involvement, challenges still exist in the integration of PPI in mental health and learning disability research in the UK. Implications for practice Guidelines on PPI may not be enough to prompt changes in research practice. Leaders and researchers need to support attitudinal and cultural changes where required, to ensure the full potential of PPI in mental health and learning disability services research is realized. Relevance statement Findings suggest that despite clear guidelines and a history of service user involvement, there are still challenges to the integration of PPI in mental health and learning disability research in the UK. For countries where PPI guidelines are being developed, attention needs to be paid to cultural factors in the research community to win "hearts and minds" and support the effective integration of PPI across the whole research process.

Research ethics committee decision-making in relation to an efficient neonatal trial

ObjectiveRandomised controlled trials, a gold-standard approach to reduce uncertainties in clinical practice, are growing in cost and are often slow to recruit. We determined whether methodological approaches to facilitate large,...

PPI in the PLEASANT trial: involving children with asthma and their parents in designing an intervention for a randomised controlled trial based within primary care

PPI is a key feature of UK health research policy, and is often a requirement of funding from the National Institute for Health Research. There are few detailed accounts of PPI in the design and conduct of clinical trials in the PPI literature for researchers to learn from. We held PPI consultation events to determine whether the proposed intervention for the trial was acceptable to children with asthma and their parents, and to ascertain whether enhancements should be made. Two PPI consultation events were held with children with asthma and their parents, prior to the research commencing. Detailed field notes were taken by the research team at each consultation event. Findings At the first consultation event, parents and children endorsed the trial's rationale, made suggestions to the wording of the trial intervention letter, and made recommendations about to whom the letter should be sent out. At the second consultation event, parents discussed the timing of the intervention, commented on the lay summary of the Research Ethics Application, and were invited to join the trial's steering committee, while the children selected a logo for the study. PPI has resulted in enhancements to the PLEASANT study's intervention. A further PPI consultation event is scheduled for the end of the trial, in order for children with asthma and their parents to contribute to the trial's dissemination strategy.

The DiReCT study - improving recruitment into clinical trials: a mixed methods study investigating the ethical acceptability, feasibility and recruitment yield of the cohort multiple randomised controlled trials design.

BackgroundThe ‘cohort multiple Randomised Controlled Trial’ (cmRCT) design has been proposed as a potential solution to poor recruitment into clinical trials. The design randomly selects participants eligible for experimental treatments from a pre-enrolled cohort of patients, recruiting participants to multiple trials from a single cohort. Controls remain unaware of their participation in specific trials.MethodsWe undertook a mixed methods study to determine the ethical acceptability, the proportion of patients in a routine service consenting to cohort participation, the proportion of these who would consent to being hypothetically randomly selected to receive new treatments, and the views of clinicians on the acceptability of the design. We submitted our cmRCT design for ethical review and recruited participants from people with anxiety and depression attending a community mental health service of twenty-one clinicians. We recorded the proportion of patients who were offered participation in the DiReCT study and the proportion that consented to researcher contact, medical record sharing, and who accepted to be randomly allocated to active treatment procedures in future hypothetical unspecified clinical trials. We used a thematic framework analysis to analyse clinician interviews.ResultsWe obtained a favourable ethical opinion from the UK Health Research Authority. Clinicians approached 131/752 (17%) potentially eligible participants for consent. Of these 131, 84 (64%) initially consented to be contacted by a researcher and all but one consented to being randomised into future trials. We confirmed consent for 71 (54%) of participants approached by clinicians, of whom 69 (53%) consented to being randomised into hypothetical future trials, 9% (69/752) of all potentially eligible patients. The interviewed clinicians described issues impacting on their ability to recruit participants in terms of clinical concerns for patient wellbeing, work pressure, their views of both general research and the specific DiReCT study, and how they viewed patients’ responses to being offered participation in the study.ConclusionsThe cmRCT system offers the potential to improve the recruitment into clinical trials and is acceptable ethically and to many patients. Overcoming the multiple factors driving the difficulties clinicians experience in patient recruitment is likely to require the application of significant implementation science-informed effort.