Choosing and evaluating randomisation methods in clinical trials: a qualitative study.

BACKGROUND: There exist many different methods of allocating participants to treatment groups during a randomised controlled trial. Although there is research that explores trial characteristics that are associated with the choice of method, there is still a lot of variety in practice not explained. This study used qualitative methods to explore more deeply the motivations behind researchers' choice of randomisation, and which features of the method they use to evaluate the performance of these methods. METHODS: Data was collected from online focus groups with various stakeholders involved in the randomisation process. Focus groups were recorded and then transcribed verbatim. A thematic analysis was used to analyse the transcripts. RESULTS: Twenty-five participants from twenty clinical trials units across the UK were recruited to take part in one of four focus groups. Four main themes were identified: how randomisation methods are selected; researchers' opinions of the different methods; which features of the method are desirable and ways to measure method features. Most researchers agree that the randomisation method should be selected based on key trial characteristics; however, for many, a unit standard is in place. Opinions of methods were varied with some participants favouring stratified blocks and others favouring minimisation. This was generally due to researchers' perception of the effect these methods had on balance and predictability. Generally, predictability was considered more important than balance as adjustments cannot be made for it; however, most researchers felt that the importance of these two methods was dependent on the design of the study. Balance is usually evaluated by tabulating variables by treatment arm and looking for perceived imbalances, predictability was generally considered much harder to measure, partly due to differing definitions. CONCLUSION: There is a wide variety in practice on how randomisation methods are selected and researcher's opinions on methods. The difference in practice observed when looking at randomisation method selection can be explained by a difference in unit practice, and also by a difference in researchers prioritisation of balance and predictability. The findings of this study show a need for more guidance on randomisation method selection.

Recording harms in randomised controlled trials of behaviour change interventions: a qualitative study of UK clinical trials units and NIHR trial investigators.

BACKGROUND: Harms, also known as adverse events (AEs), are recorded and monitored in randomised controlled trials (RCTs) to ensure participants' safety. Harms are recorded poorly or inconsistently in RCTs of Behaviour Change Interventions (BCI); however, limited guidance exists on how to record harms in BCI trials. This qualitative study explored experiences and perspectives from multi-disciplinary trial experts on recording harms in BCI trials. METHODS: Data were collected through fifteen in-depth semi-structured qualitative interviews and three focus groups with thirty-two participants who work in the delivery and oversight of clinical trials. Participants included multi-disciplinary staff from eight CTUs, Chief investigators, and patient and public representatives. Interviews and focus group recordings were transcribed verbatim and thematic analysis was used to analyse the transcripts. RESULTS: Five themes were identified, namely perception and understanding of harm, proportionate reporting and plausibility, the need for a multi-disciplinary approach, language of BCI harms and complex harms for complex interventions. Participants strongly believed harms should be recorded in BCI trials; however, making decisions on "how and what to record as harms" was difficult. Recording irrelevant harms placed a high burden on trial staff and participants, drained trial resources and was perceived as for little purpose. Participants believed proportionate recording was required that focused on events with a strong plausible link to the intervention. Multi-disciplinary trial team input was essential for identifying and collecting harms; however, this was difficult in practice due to lack of knowledge on harms from BCIs, lack of input or difference in opinion. The medical language of harms was recognised as a poor fit for BCI trial harms but was familiar and established within internal processes. Future guidance on this topic would be welcomed and could include summarised literature. CONCLUSIONS: Recording harms or adverse events in behaviour change intervention trials is complex and challenging; multi-disciplinary experts in trial design and implementation welcome forthcoming guidance on this topic. Issues include the high burden of recording irrelevant harms and use of definitions originally designed for drug trials. Proportionate recording of harms focused on events with a strong plausible link to the intervention and multi-disciplinary team input into decision making are essential.

Current usage of explainer animations in trials: a survey of the UKCRC registered clinical trial units in the UK.

BACKGROUND: Explainer animations are a means to communicate aspects of clinical trials to participants in a more engaging and accessible way. Delivered well these have the potential to enhance recruitment and retention. The range of media technology used to deliver this material is expanding rapidly but is highly fragmented. Usage of explainer animations across the UK is unknown, the aim of this research was to determine current usage across the 52 registered UK Clinical Research Collaboration (UKCRC) Clinical Trials Units (CTUs) to understand the current landscape and any barriers that could be preventing wider uptake of this functionality. METHODS: A survey link was emailed to all UKCRC CTU Directors and Trial Management Leads to ascertain current usage of explainer animations within their CTU. The survey ran between 01 February 2023 and 07 March 2023. RESULTS: Responses were received from 35 CTUs-representing a response rate of 67%. 24 CTUs (69%) reported that they had created/used at least one explainer animation within their unit, although the usage, cost, length and production activities varied among the units. CONCLUSIONS: The survey showed that a high proportion of the UKCRC CTUs have used explainer animations to provide information to participants about clinical studies. For those not using the technology yet, the most common reasons cited were a lack of expertise, lack of resources and costs to produce them. One of the desired outcomes of this project is the creation of a free-to-use library of animations to encourage wider uptake and avoid duplication.

Recording harms in randomized controlled trials of behavior change interventions: a scoping review and map of the evidence.

OBJECTIVES: Randomized controlled trials evaluate diverse interventions. This can include medical interventions such as drugs or surgical procedures, or behavior change interventions (BCIs) that aim to change a habit, belief, or attitude to improve health, for example, healthy eating, psychological wellbeing. Harms are often recorded poorly or inconsistently within randomized controlled trials of BCIs. This scoping review aimed to collate and describe literature on categories, definitions, and mechanisms of harms from BCIs; methods of identifying plausible harms; and recommendations for recording harms. STUDY DESIGN AND SETTING: A scoping review was conducted. Three databases (MEDLINE, PsycINFO, and CINAHL) were searched. Reference list checking and citation searching were performed. Articles were included if they discussed (1) interventions that aimed to modify behavior, (2) categories or mechanisms of harms, and (3) methods or recommendations for recording harms. All research designs were included. One reviewer reviewed titles, abstracts, and full texts; queries were checked with another reviewer. Data were extracted and synthesized descriptively by one reviewer and checked by another reviewer. A thematic map was constructed to summarize the review findings. Harms described from specific BCIs were identified, and examples were selected and summarized. RESULTS: The review included 37 articles. Nineteen of 37 articles contributed to a thematic review. Three articles described categories of harms; categories of harm included physical, psychological, group and social interactions, cultural, equity, opportunity cost, environmental, and economic. Seven articles included mechanisms or underlying factors for harms including feelings of failure leading to shame or stigma, and group interventions enabling knowledge exchange on unhealthy behaviors. Twelve articles provided recommendations for recording harms, including taking a proportionate approach by focusing on the most plausible and important harms, collecting different perspectives on whether harms had occurred (eg, caregivers and family members), and using qualitative research methods to identify harms. One article described a three-step method to identify plausible harms from an intervention, and six articles supported aspects of the method. Eighteen of 37 articles contributed to a review which collated harms arising from specific interventions, for example, a peer support intervention in inflammatory bowel disease caused distressing conversations which might lead to anxiety and confrontation with a possible negative future. CONCLUSION: BCIs can cause harm. This review identified categories and proposed mechanisms of harms, as well as methods and recommendations for identifying and recording harms in BCIs for inclusion in forthcoming recommendations.

Can we achieve better trial recruitment by presenting patient information through multimedia? Meta-analysis of 'studies within a trial' (SWATs).

BACKGROUND: People need high-quality information to make decisions about research participation. Providing information in written format alone is conventional but may not be the most effective and acceptable approach. We developed a structure for the presentation of information using multimedia which included generic and trial-specific content. Our aim was to embed 'Studies Within A Trial' (SWATs) across multiple ongoing trials to test whether multimedia presentation of patient information led to better rates of recruitment. METHODS: Five trials included a SWAT and randomised their participants to receive a multimedia presentation alongside standard information, or standard written information alone. We collected data on trial recruitment, acceptance and retention and analysed the pooled results using random effects meta-analysis, with the primary outcome defined as the proportion of participants randomised following an invitation to take part. RESULTS: Five SWATs provided data on the primary outcome of proportion of participants randomised. Multimedia alongside written information results in little or no difference in recruitment rates (pooled odds ratio = 0.96, 95% CI: 0.79 to 1.17, p-value = 0.671, I2 = 0%). There was no effect on any other outcomes. CONCLUSIONS: Multimedia alongside written information did not improve trial recruitment rates. TRIAL REGISTRATION: ISRCTN71952900, ISRCTN 06710391, ISRCTN 17160087, ISRCTN05926847, ISRCTN62869767.

Transient Elastography and Video Recovery Narrative Access to Support Recovery From Alcohol Misuse: Development of a Novel Intervention for Use in Community Alcohol Treatment Services.

BACKGROUND: Mortality from alcohol-related liver disease has risen significantly for 3 decades. Transient elastography (TE) is a noninvasive test providing a numerical marker of liver disease. Preliminary evidence suggests that TE can reduce alcohol consumption. The KLIFAD (does knowledge of liver fibrosis affect high-risk drinking behavior?) study has developed a complex intervention wherein people receiving alcohol treatment are provided with access to TE, accompanied by scripted feedback tailored to their disease state, and access to video narratives describing alcohol misuse recovery after receiving TE. Recovery narratives are included due to preliminary evidence from mental health studies which suggest that access to digital narratives describing recovery from mental health problems can help people affected by mental health problems, including through mechanisms with the potential to be transferable to an alcohol treatment setting, for example, by increasing hope for the future, enabling learning from the experience of others, or promoting help-seeking behaviors. OBJECTIVE: We aimed to develop the KLIFAD intervention to the point that it could be delivered in a feasibility trial and to produce knowledge relevant to clinicians and researchers developing interventions making use of biomarkers of disease. METHODS: In research activity 1, standardized scripted feedback was developed by this study, and then iterated through focus groups with people who had experienced alcohol misuse and TE, and key alcohol workers with experience in delivering TE. We report critical design considerations identified through focus groups, in the form of sensitizing concepts. In research activity 2, a video production guide was coproduced to help produce impactful video-based recovery narratives, and a patient and public involvement (PPI) panel was consulted for recommendations on how best to integrate recovery narratives into an alcohol treatment setting. We report PPI recommendations and an overview of video form and content. RESULTS: Through research activity 1, we learnt that patient feedback has not been standardized in prior use of TE, that receiving a numeric marker can provide an objective target that motivates and rewards recovery, and that key alcohol workers regularly tailor information to their clients. Through research activity 2, we developed a video production guide asking narrators what recovery means to them, what helped their recovery, and what they have learned about recovery. We produced 10 recovery narratives and collected PPI recommendations on maximizing impact and safety. These led to the production of unplanned videos presenting caregiver and clinician perspectives, and a choice to limit narrative availability to alcohol treatment settings, where support is available around distressing content. These choices have been evaluated through a feasibility randomized controlled trial [ISRCTN16922410]. CONCLUSIONS: Providing an objective target that motivates and rewards recovery is a candidate change mechanism for complex interventions integrating biomarkers of disease. Recovery narratives can contain distressing content; intervention developers should attend to safe usage. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1136/bmjopen-2021-054954.

Widening participation - recruitment methods in mental health randomised controlled trials: a qualitative study.

BACKGROUND: Barriers to mental health research participation are well documented including distrust of services and research; and stigma surrounding mental health. They can contribute to a lack of diversity amongst participants in mental health research, which threatens the generalisability of knowledge. Given the recent widespread use of the internet in medical research, this study aimed to explore the perspectives of key partners on the use of online (e.g. social media) and offline (e.g. in-person) recruitment as an approach to improving diversity in mental health randomised controlled trials (RCTs). METHODS: Face-to-face and online interviews/focus groups with researchers working in mental health and Patient and Public Involvement partners in the United Kingdom. Recordings were transcribed and analysed using a combination of inductive and deductive thematic analysis. RESULTS: Three focus groups and three interviews were conducted with a total N = 23 participants. Four overarching themes were identified: (1) recruitment reach; (2) Demographic factors that affect selection of recruitment method; (3) safety of technology, and; (4) practical challenges. Five main factors were identified that affect the choice of recruitment method: age, complexity of mental health problem and stigma, cultural and ethnicity differences and digital divide. The use of online methods was considered more accessible to people who may feel stigmatised by their mental health condition and with a benefit of reaching a wider population. However, a common view amongst participants was that online methods require closer data monitoring for quality of responders, are not fully secure and less trustworthy compared to offline methods that enable participants to build relationships with health providers. Funding, staff time and experience, organisational support, and technical issues such as spam or phishing emails were highlighted as practical challenges facing online recruitment. All participants agreed that using a hybrid approach tailored to the population under study is paramount. CONCLUSIONS: This study highlighted the importance of offering a flexible and multifaceted recruitment approach by integrating online with offline methods to support inclusivity and widening participation in mental health research. The findings will be used to develop considerations for researchers designing RCTs to improve recruitment in mental health research.

Does knowledge of liver fibrosis affect high-risk drinking behaviour (KLIFAD): an open-label pragmatic feasibility randomised controlled trial.

Background: Early identification followed by effective behaviour interventions is pivotal to changing the natural history of alcohol-related liver disease. We examined the feasibility of using transient elastography based advice and alcohol recovery video stories (ARVS) to change drinking behaviour in community alcohol services. Methods: A feasibility randomised control trial (RCT) was conducted in three community alcohol services. Adults 18+ years presenting with a primary alcohol problem were randomised (1:1) to receive either usual care (control group) or usual care and the KLIFAD Intervention, consisting of advice tailored to liver stiffness measure and access to ARVS (intervention group). Data were collected at baseline and six months. To establish definitive trial feasibility, recruitment and retention rates, study procedure safety and extent of effectiveness were measured (Start date: 02.10.2019, End date: 30.11.2022, ISRCTN.com: 16922410). Findings: 382 service users were screened, 184 were randomised (intervention: 93, control: 91), and baseline data were collected for 128 (intervention: 71, control: 59). Six months follow-up data were available in 87 (intervention: 53, control: 34). Intervention compared to the control group had a longer duration of engagement with services (mean difference 8.6 days SD = 18.4), was more likely to complete the allocated treatment program and reduced or stop drinking (54.9% vs 43.9%) and reduce AUDIT category (71.7% vs 61.8%). There were no reported serious adverse reactions, one intervention group participant reported an increase in AUDIT category. Interpretation: Integration of transient elastography in community alcohol services is feasible. It may improve engagement with services, retention in clinical trials and supplement the reduction in self-reported alcohol consumption. A definitive RCT is supported. Funding: National Institute for Health and Care Research (NIHR201146).

Developing guidance for a risk-proportionate approach to blinding statisticians within clinical trials: a mixed methods study.

BACKGROUND: Existing guidelines recommend statisticians remain blinded to treatment allocation prior to the final analysis and that any interim analyses should be conducted by a separate team from the one undertaking the final analysis. However, there remains substantial variation in practice between UK Clinical Trials Units (CTUs) when it comes to blinding statisticians. Therefore, the aim of this study was to develop guidance to advise CTUs on a risk-proportionate approach to blinding statisticians within clinical trials. METHODS: This study employed a mixed methods approach involving three stages: (I) a quantitative study using a cohort of 200 studies (from a major UK funder published between 2016 and 2020) to assess the impact of blinding statisticians on the proportion of trials reporting a statistically significant finding for the primary outcome(s); (II) a qualitative study using focus groups to determine the perspectives of key stakeholders on the practice of blinding trial statisticians; and (III) combining the results of stages I and II, along with a stakeholder meeting, to develop guidance for UK CTUs. RESULTS: After screening abstracts, 179 trials were included for review. The results of the primary analysis showed no evidence that involvement of an unblinded trial statistician was associated with the likelihood of statistically significant findings being reported, odds ratio (OR) 1.02 (95% confidence interval (CI) 0.49 to 2.13). Six focus groups were conducted, with 37 participants. The triangulation between stages I and II resulted in developing 40 provisional statements. These were rated independently by the stakeholder group prior to the meeting. Ten statements reached agreement with no agreement on 30 statements. At the meeting, various factors were identified that could influence the decision of blinding the statistician, including timing, study design, types of intervention and practicalities. Guidance including 21 recommendations/considerations was developed alongside a Risk Assessment Tool to provide CTUs with a framework for assessing the risks associated with blinding/not blinding statisticians and for identifying appropriate mitigation strategies. CONCLUSIONS: This is the first study to develop a guidance document to enhance the understanding of blinding statisticians and to provide a framework for the decision-making process. The key finding was that the decision to blind statisticians should be based on the benefits and risks associated with a particular trial.

Mental health in clinically referred children and young people before and during the Covid-19 pandemic.

The Covid-19 pandemic and mitigation approaches, including lockdowns and school closures, are thought to have negatively impacted children and young people's (CYP) mental health. However, the impact for clinically referred CYP is less clear. We investigated differences in the mental health of CYP referred to specialist Child and Adolescent Mental Health Services (CAMHS) before and since the onset of the pandemic. Using baseline data (self- and parent- completed Mood and Feelings Questionnaire and Strengths and Difficulties Questionnaire) from an ongoing RCT (STADIA; ISRCTN: 15748675) in England involving 5-17-year-olds with emotional difficulties recently referred to CAMHS (non-urgent referrals), with repeated cross-sectional comparisons of CYP (n = 1028) recruited during 5 different time  periods: (1) Before schools were closed (Group 1 (pre-pandemic); n = 308; 27.08.2019-20.03.2020). (2) Early pandemic period until schools fully re-opened, which included the first national lockdown, its easing and the summer holidays (Group 2 (in-pandemic); n = 183; 21.03.2020-31.08.2020). (3) The following school-term-schools fully re-opened and remained open, including during the second national lockdown (Group 3 (in-pandemic); n = 204; 01.09.2020-18.12.2020). (4) Schools closed as part of the third national lockdown (Group 4 (in-pandemic); n = 101; 05.01.2021-07.03.2021). (5) Schools re-opened and remained open, until the school summer holidays (Group 5 (in-pandemic); n = 232; 08.03.2021-16.07.2021). Most CYP scored above cutoff for emotional problems and depression, with three-quarters meeting criteria for a probable disorder ('caseness'). The groups did not differ on parent-rated mental health measures. However, self-rated emotional problems, depression, functional impairment and caseness appeared to be higher amongst participants recruited in the two periods following school re-openings. In particular, functional impairment and caseness were greater in Group 5 compared with Group 2. Although symptom severity or impairment did not change in the initial pandemic period, self-reported difficulties were greater during the periods after schools re-opened. This suggests possible greater stresses in the adjustment to re-starting school following recurrent lockdowns and school closures.

The Journeying through Dementia psychosocial intervention versus usual care study: a single-blind, parallel group, phase 3 trial.

BACKGROUND: There is an urgent clinical need for evidence-based psychosocial interventions for people with mild dementia. We aimed to determine the clinical benefits and cost-effectiveness of Journeying through Dementia (JtD), an intervention designed to promote wellbeing and independence in people with mild dementia. METHODS: We did a single-blind, parallel group, individually randomised, phase 3 trial at 13 National Health Service sites across England. People with mild dementia (Mini-Mental State Examination score of ≥18) who lived in the community were eligible for inclusion. Patients were centrally randomly assigned (1:1) to receive the JtD intervention plus standard care (JtD group) or standard care only (standard care group). Randomisation was stratified by study site. The JtD intervention included 12 group and four one-to-one sessions, delivered in the community at each site. The primary endpoint was Dementia Related Quality of Life (DEMQOL) 8 months after randomisation, assessed according to the intention-to-treat principle. Only outcome assessors were masked to group assignment. A cost-effectiveness analysis reported cost per quality-adjusted life-year (QALY) from a UK NHS and social care perspective. The study is registered with ISRCTN, ISRCTN17993825. FINDINGS: Between Nov 30, 2016, and Aug 31, 2018, 1183 patients were screened for inclusion, of whom 480 (41%) participants were randomly assigned: 241 (50%) to the JtD group and 239 (50%) to the standard care group. Intervention adherence was very good: 165 (68%) of 241 participants in the JtD group attended at least ten of the 16 sessions. Mean DEMQOL scores at 8 months were 93·3 (SD 13·0) for the JtD group and 91·9 (SD 14·6) for the control group. Difference in means was 0·9 (95% CI -1·2 to 3·0; p=0·38) after adjustment for covariates, lower than that identified as clinically meaningful. Incremental cost per QALY ranged from £88 000 to -£205 000, suggesting that JtD was not cost-effective. Unrelated serious adverse events were reported by 40 (17%) patients in the JtD group and 35 (15%) patients in the standard care group. INTERPRETATION: In common with other studies, the JtD intervention was not proven effective. However, this complex trial successfully recruited and retained people with dementia without necessarily involving carers. Additionally, people with dementia were actively involved as participants and study advisers throughout. More research into methods of measuring small, meaningful changes in this population is needed. Questions remain regarding how services can match the complex, diverse, and individual needs of people with mild dementia, and how interventions to meet such needs can be delivered at scale. FUNDING: UK National Institute of Health Research Health Technology Assessment Programme.

Embedding patient and public involvement in dementia research: Reflections from experiences during the 'Journeying through Dementia' randomised controlled trial.

BACKGROUND: The involvement of people with a diagnosis of dementia in patient and public involvement and engagement (PPIE) in research is an emerging field in the delivery of studies. Researchers need to understand and use the learning derived from various projects so that this growing body of knowledge can be applied in future research. OBJECTIVE: To embed PPIE throughout a randomised controlled trial of a psychosocial intervention called Journeying through Dementia. We identify and discuss the approaches to involvement that worked well and those where improvements were indicated. DESIGN: The Guidance for Reporting Involvement of Patients and the Public Short Form (GRIPP2-SF) is used to describe and critically appraise the approaches taken and the impact of PPIE involvement upon study processes, the study team and those people with dementia and their supporters who acted as advisors. FINDINGS: The involvement of people with a diagnosis of dementia and supporters as study advisors improved the accessibility and relevance of the research for people living with dementia. It also highlighted issues that researchers may have otherwise overlooked. Successful engagement of people with dementia and their supporters in the study was associated with staff skills and particularly use of techniques to scaffold meaningful involvement, as well as participants' memory and cognitive capacity. However, embedding robust and meaningful involvement processes required significant time and resources. DISCUSSION: We propose that certain research processes need to be adapted to be accessible and appropriate for people living with dementia. Recruitment of PPIE advisors needs to reflect population diversity. There also needs to be greater parity of voice between people with lived experience of dementia and researchers. These steps will increase the impact of PPIE in research and improve the experience for those who volunteer to be PPIE advisors.

Blinding of study statisticians in clinical trials: a qualitative study in UK clinical trials units.

BACKGROUND: Blinding is an established approach in clinical trials which aims to minimise the risk of performance and detection bias. There is little empirical evidence to guide UK clinical trials units (CTUs) about the practice of blinding statisticians. Guidelines recommend that statisticians remain blinded to allocation prior to the final analysis. As these guidelines are not based on empirical evidence, this study undertook a qualitative investigation relating to when and how statisticians should be blinded in clinical trials. METHODS: Data were collected through online focus groups with various stakeholders who work in the delivery and oversight of clinical trials. Recordings of the focus groups were transcribed verbatim and thematic analysis was used to analyse the transcripts. RESULTS: Thirty-seven participants from 19 CTUs participated in one of six focus groups. Four main themes were identified, namely statistical models of work, factors affecting the decision to blind statisticians, benefits of blinding/not blinding statisticians and practicalities. Factors influencing the decision to blind the statistician included available resources, study design and types of intervention and outcomes and analysis. Although blinding of the statistician is perceived as a desirable mitigation against bias, there was uncertainty about the extent to which an unblinded statistician might impart bias. Instead, in most cases, the insight that the statistician offers was deemed more important to delivery of a trial than the risk of bias they may introduce if unblinded. Blinding of statisticians was only considered achievable with the appropriate resource and staffing, which were not always available. In many cases, a standard approach to blinding was therefore considered unrealistic and impractical; hence the need for a proportionate risk assessment approach identifying possible mitigations. CONCLUSIONS: There was wide variation in practice between UK CTUs regarding the blinding of trial statisticians. A risk assessment approach would enable CTUs to identify risks associated with unblinded statisticians conducting the final analysis and alternative mitigation strategies. The findings of this study will be used to design guidance and a tool to support this risk assessment process.

STAndardised DIagnostic Assessment for children and young people with emotional difficulties (STADIA): protocol for a multicentre randomised controlled trial.

INTRODUCTION: Emotional disorders (such as anxiety and depression) are associated with considerable distress and impairment in day-to-day function for affected children and young people and for their families. Effective evidence-based interventions are available but require appropriate identification of difficulties to enable timely access to services. Standardised diagnostic assessment (SDA) tools may aid in the detection of emotional disorders, but there is limited evidence on the utility of SDA tools in routine care and equipoise among professionals about their clinical value. METHODS AND ANALYSIS: A multicentre, two-arm, parallel group randomised controlled trial, with embedded qualitative and health economic components. Participants will be randomised in a 1:1 ratio to either the Development and Well-Being Assessment SDA tool as an adjunct to usual clinical care, or usual care only. A total of 1210 participants (children and young people referred to outpatient, specialist Child and Adolescent Mental Health Services with emotional difficulties and their parent/carers) will be recruited from at least 6 sites in England. The primary outcome is a clinician-made diagnosis about the presence of an emotional disorder within 12 months of randomisation. Secondary outcomes include referral acceptance, diagnosis and treatment of emotional disorders, symptoms of emotional difficulties and comorbid disorders and associated functional impairment. ETHICS AND DISSEMINATION: The study received favourable opinion from the South Birmingham Research Ethics Committee (Ref. 19/WM/0133). Results of this trial will be reported to the funder and published in full in the Health Technology Assessment (HTA) Journal series and also submitted for publication in a peer reviewed journal. TRIAL REGISTRATION NUMBER: ISRCTN15748675; Pre-results.

An intervention to promote self-management, independence and self-efficacy in people with early-stage dementia: the Journeying through Dementia RCT.

BACKGROUND: There are few effective interventions for dementia. AIM: To determine the clinical effectiveness and cost-effectiveness of an intervention to promote self-management, independence and self-efficacy in people with early-stage dementia. OBJECTIVES: To undertake a randomised controlled trial of the Journeying through Dementia intervention compared with usual care, conduct an internal pilot testing feasibility, assess intervention delivery fidelity and undertake a qualitative exploration of participants' experiences. DESIGN: A pragmatic two-arm individually randomised trial analysed by intention to treat. PARTICIPANTS: A total of 480 people diagnosed with mild dementia, with capacity to make informed decisions, living in the community and not participating in other studies, and 350 supporters whom they identified, from 13 locations in England, took part. INTERVENTION: Those randomised to the Journeying through Dementia intervention (n = 241) were invited to take part in 12 weekly facilitated groups and four one-to-one sessions delivered in the community by secondary care staff, in addition to their usual care. The control group (n = 239) received usual care. Usual care included drug treatment, needs assessment and referral to appropriate services. Usual care at each site was recorded. MAIN OUTCOME MEASURES: The primary outcome was Dementia-Related Quality of Life score at 8 months post randomisation, with higher scores representing higher quality of life. Secondary outcomes included resource use, psychological well-being, self-management, instrumental activities of daily living and health-related quality of life. RANDOMISATION AND BLINDING: Participants were randomised in a 1 : 1 ratio. Staff conducting outcome assessments were blinded. DATA SOURCES: Outcome measures were administered in participants' homes at baseline and at 8 and 12 months post randomisation. Interviews were conducted with participants, participating carers and interventionalists. RESULTS: The mean Dementia-Related Quality of Life score at 8 months was 93.3 (standard deviation 13.0) in the intervention arm (n = 191) and 91.9 (standard deviation 14.6) in the control arm (n = 197), with a difference in means of 0.9 (95% confidence interval -1.2 to 3.0; p = 0.380) after adjustment for covariates. This effect size (0.9) was less than the 4 points defined as clinically meaningful. For other outcomes, a difference was found only for Diener's Flourishing Scale (adjusted mean difference 1.2, 95% confidence interval 0.1 to 2.3), in favour of the intervention (i.e. in a positive direction). The Journeying through Dementia intervention cost £608 more than usual care (95% confidence interval £105 to £1179) and had negligible difference in quality-adjusted life-years (-0.003, 95% confidence interval -0.044 to 0.038). Therefore, the Journeying through Dementia intervention had a mean incremental cost per quality-adjusted life-year of -£202,857 (95% confidence interval -£534,733 to £483,739); however, there is considerable uncertainty around this. Assessed fidelity was good. Interviewed participants described receiving some benefit and a minority benefited greatly. However, negative aspects were also raised by a minority. Seventeen per cent of participants in the intervention arm and 15% of participants in the control arm experienced at least one serious adverse event. None of the serious adverse events were classified as related to the intervention. LIMITATIONS: Study limitations include recruitment of an active population, delivery challenges and limitations of existing outcome measures. CONCLUSIONS: The Journeying through Dementia programme is not clinically effective, is unlikely to be cost-effective and cannot be recommended in its existing format. FUTURE WORK: Research should focus on the creation of new outcome measures to assess well-being in dementia and on using elements of the intervention, such as enabling enactment in the community. TRIAL REGISTRATION: This trial is registered as ISRCTN17993825. FUNDING: This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 26, No. 24. See the NIHR Journals Library website for further project information.

There are few services proven effective for people with mild dementia. We therefore explored the potential benefit of a programme called Journeying through Dementia. The content, devised in partnership with people living with dementia, aims to help affected individuals to live well and participate in life. The programme involves meeting in groups of about eight every week for 12 weeks. Each person also has four face-to-face meetings with a staff member. Carers are invited to 3 of the 12 group meetings to all individual meetings if the participant wanted this involvement. A total of 480 people with dementia and 350 carers from 13 locations in England took part. Just over half of the participants were randomly allocated to the new programme, whereas the others were not. This allowed us to compare the groups. We were interested in whether or not attending the Journeying through Dementia programme improved participants' quality of life. The results showed that it did not. We also measured participants' mood, self-management skills, positive attitudes and ability with daily living skills. Only one measure of positive psychology suggested even a small benefit. There was no difference between groups in the remaining measures. Although some individual participants described being more confident, enjoying social contact, trying new activities, feeling valued and having increased independence, overall, the programme is unlikely to be worth implementing. Certain aspects of the programme are worth implementing.

The implementation of Journeying through Dementia: Strategies to run a successful pragmatic multicenter trial of a complex intervention.

OBJECTIVE: A key challenge in delivering pragmatic trials of complex interventions is effective implementation within the study period and beyond. We describe a trial of an intervention to improve quality of life in mild dementia (Journeying through Dementia), describe some of the challenges raised in terms of implementation, and illustrate the methods used to ensure effective implementation. METHOD: The intervention was delivered by staff within local services and supervised by more experienced clinicians within those services in order to test the intervention in real-world settings and establish the potential for future embedding into practice. Researchers delivered training sessions for all facilitators and supervisors, met at regular intervals with intervention supervisors, and provided feedback on summaries of intervention sessions created by facilitators. We conducted a thematic analysis of the content of meetings and written correspondence between the researchers and intervention supervisors regarding implementation issues. RESULTS: Key themes relating to difficulties with implementation were: staff absences and staff leaving posts; participant lack of engagement with intervention; difficulties with delivery of supervision; difficult group dynamics; lack of time to deliver the intervention; and lack of adherence to the intervention and its ethos. CONCLUSION: We provide guidance for researchers involved in the trialing of other complex interventions in how these challenges might be overcome. These include: recruiting additional staff to deliver the intervention; having clear protocols in place for managing staff absences; using supervision to problem solve participant attendance at intervention sessions and difficult group dynamics; monitoring staff engagement in supervision and addressing problems with engagement with staff and managers when this occurs; giving staff ring-fenced time to deliver the intervention and engage in supervision; and regular monitoring and feedback in relation to the content of the intervention to ensure that it is consistent with ethos and content of the intervention manual.

Does knowledge of liver fibrosis affect high-risk drinking behaviour (KLIFAD)? protocol for a feasibility randomised controlled trial.

INTRODUCTION: Heavy drinkers in contact with alcohol services do not routinely have access to testing to establish the severity of potential liver disease. Transient elastography by FibroScan can provide this information. A recent systematic review suggested providing feedback to patients based on markers of liver injury can be an effective way to reduce harmful alcohol intake. This randomised control trial (RCT) aims to establish the feasibility of conducting a larger national trial to test the effectiveness of FibroScan advice and Alcohol Recovery Video Stories (ARVS) in changing high-risk drinking behaviour in community alcohol services common to UK practice. METHODS AND ANALYSIS: This feasibility trial consists of three work packages (WP). WP1: To draft a standardised script for FibroScan operators to deliver liver disease-specific advice to eligible participants having FibroScan. WP2: To create a video library of ARVS for use in the feasibility RCT (WP3). WP3: To test the feasibility of the trial design, including the FibroScan script and video stories developed in WP1 and WP2 in a one-to-one individual randomised trial in community alcohol services. Semi-structured interviews will be conducted at 6 months follow-up for qualitative evaluation. Outcomes will be measures of the feasibility of conducting a larger RCT. These outcomes will relate to: participant recruitment and follow-up, intervention delivery, including the use of the Knowledge of LIver Fibrosis Affects Drinking trial FibroScan scripts and videos, clinical outcomes, and the acceptability and experience of the intervention and trial-related procedures. Data analysis will primarily be descriptive to address the feasibility aims of the trial. All proposed analyses will be documented in a Statistical Analysis Plan. ETHICS AND DISSEMINATION: This trial received favourable ethical approval from the West of Scotland Research Ethics Service (WoSRES) on 20 January 2021, REC reference: 20/WS/0179. Results will be submitted for publication to a peer-reviewed journal. TRIAL REGISTRATION NUMBER: ISRCTN16922410.

Promoting Independence in Dementia (PRIDE): A Feasibility Randomized Controlled Trial.

BACKGROUND: There is a need for interventions to foster and maintain independence for people with dementia to support community living, improve morale, and reduce stigma. We investigated a social intervention to promote living well and enhance independence for people with mild dementia. METHODS: In this two arm parallel group, feasibility RCT at six sites in England, participants were randomized (1:1) to the PRIDE intervention (encompassing social, physical, and cognitive domains supported by a facilitator over three sessions) compared to usual care only. The main objective was to determine the feasibility of a main trial with respect to measures of recruitment, retention, and adherence to the intervention. RESULTS: During a 7-month period, 402 people were invited to the trial, 148 were screened (37%, 95% confidence interval (CI)=32-42%), 137 were eligible at pre-consent, 94 consented to the trial (69% of those eligible, 95% CI=60-76%), and 92 were randomized (46 to each group). Of those allocated to the intervention, 42 (91%) received at least one of three intervention sessions. Outcome assessment follow-up visits were completed for 73 participants at 6 months (79%, 95% CI=70-87%), and this was similar for both groups. CONCLUSION: A large multi-center trial of the PRIDE intervention in community-dwelling people with mild dementia is feasible using systematic recruitment strategies. The intervention was successfully delivered and well received by participants. Findings from this study will be used to refine the design and processes for a definitive RCT. TRIAL REGISTRATION: ISRCTN, ISRCTN11288961, registered on 23 October 2018.

Assessing fidelity of a community based psychosocial intervention for people with mild dementia within a large randomised controlled trial.

BACKGROUND: Understanding intervention delivery as intended, particularly in complex interventions, should be underpinned by good quality fidelity assessment. We present the findings from a fidelity assessment embedded as part of a trial of a complex community-based psychosocial intervention, Journeying through Dementia (JtD). The intervention was designed to equip individuals with the knowledge and skills to successfully self-manage, maintain independence, and live well with dementia and involves both group and individual sessions. The methodological challenges of developing a conceptual framework for fidelity assessment and creating and applying purposely designed measures derived from this framework are discussed to inform future studies. METHODS: A conceptual fidelity framework was created out of core components of the intervention (including the intervention manual and training for delivery), associated trial protocols and pre-defined fidelity standards and criteria against which intervention delivery and receipt could be measured. Fidelity data collection tools were designed and piloted for reliability and usability. Data collection in four selected sites (fidelity sites) was via non-participatory observations of the group aspect of the intervention, attendance registers and interventionist (facilitator and supervisor) self-report. RESULTS: Interventionists from all four fidelity sites attended intervention training. The majority of group participants at the four sites (71%) received the therapeutic dose of 10 out of 16 sessions. Weekly group meeting attendance (including at 'out of venue' sessions) was excellent at 80%. Additionally, all but one individual session was attended by the participants who completed the intervention. It proved feasible to create tools derived from the fidelity framework to assess in-venue group aspects of this complex intervention. Results of fidelity assessment of the observed groups were good with substantial inter-rater reliability between researchers KAPPA 0.68 95% CI (0.58-0.78). Self-report by interventionists concurred with researcher assessments. CONCLUSIONS: There was good fidelity to training and delivery of the group aspect of the intervention at four sites. However, the methodological challenges of assessing all aspects of this complex intervention could not be overcome due to practicalities, assessment methods and ethical considerations. Questions remain regarding how we can assess fidelity in community-based complex interventions without impacting upon intervention or trial delivery. TRIAL REGISTRATION: ISRCTN17993825 .

Journeying through Dementia Randomised Controlled Trial of a Psychosocial Intervention for People Living with Early Dementia: Embedded Qualitative Study with Participants, Carers and Interventionists.

OBJECTIVE: To identify the barriers and facilitators to the implementation of a complex psychosocial intervention though a study exploring the experiences of participants, carers and interventionists during a trial. METHODS: Individual semi-structured interviews were conducted with participants, their carers, and interventionists from a sample of recruiting sites that took part in the Journeying through Dementia randomized controlled trial (RCT). Interview data were transcribed and analysed using framework analysis. Co-researcher data analysis workshops were also conducted to explore researcher interpretations of the data through the lens of those with lived experience of dementia. Triangulation enabled comparison of findings from the interviews with findings from the co-researcher workshops. RESULTS: Three main themes emerged from the interview data: being prepared; intervention engagement; and participation and outcomes from engagement. From these themes, a number of factors that can moderate delivery and receipt of the intervention as intended were identified. These were context and environment; readiness, training, skills and competencies of the workforce; identifying meaningful participation and relationships. CONCLUSION: This study highlighted that the observed benefit of the intervention was nuanced for each individual. Mechanisms of change were influenced by a range of individual, social and contextual factors. Future research should therefore consider how best to identify and measure the multifaceted interplay of mechanisms of change in complex interventions. TRIAL REGISTRATION: ISRCTN17993825.