Registry-based randomised controlled trials: conduct, advantages and challenges-a systematic review.

BACKGROUND: Registry-based randomised controlled trials (rRCTs) have been described as pragmatic studies utilising patient data embedded in large-scale registries to facilitate key clinical trial procedures including recruitment, randomisation and the collection of outcome data. Whilst the practice of utilising registries to support the conduct of randomised trials is increasing, the use of the registries within rRCTs is inconsistent. The purpose of this systematic review is to explore the conduct of rRCTs using a patient registry to facilitate trial recruitment and the collection of outcome data, and to discuss the advantages and challenges of rRCTs. METHODS: A systematic search of the literature was conducted using five databases from inception to June 2020: PubMed, Embase (through Ovid), CINAHL, Scopus and the Cochrane Controlled Register of Trials (CENTRAL). The search strategy comprised of MESH terms and key words related to rRCTs. Study selection was performed independently by two reviewers. A risk of bias for each study was completed. A narrative synthesis was conducted. RESULTS: A total 47,862 titles were screened and 24 rRCTs were included. Eleven rRCTs (45.8%) used more than one registry to facilitate trial conduct. Six rRCTs (25%) randomised participants via a specific randomisation module embedded within a registry. Recruitment ranged between 209 to 106,000 participants. Advantages of rRCTs are recruitment efficiency, shorter trial times, cost effectiveness, outcome data completeness, smaller carbon footprint, lower participant burden and the ability to conduct multiple trials from the same registry. Challenges are data collection/management, quality assurance issues and the timing of informed consent. CONCLUSIONS: Optimising the design of rRCTs is dependent on the capabilities of the registry. New registries should be designed and existing registries reviewed to enable the conduct of rRCTs. At all times, data management and quality assurance of all registry data should be given key consideration. We suggest the inclusion of the term 'registry-based' in the title of all rRCT manuscripts and a clear simple breakdown of the registry-based conduct of the trial in the abstract to facilitate indexing in the major databases.

Trial participants' self-reported understanding of randomisation phrases in participation information leaflets can be high, but acceptability of some descriptions is low, especially those linked to gambling and luck.

BACKGROUND: Evidence indicates that trial participants often struggle to understand participant information leaflets (PILs) for clinical trials, including the concept of randomisation. We analysed the language used to describe randomisation in PILs and determine the most understandable and acceptable description through public and participant feedback. METHODS: We collected 280 PILs/informed consent forms and one video animation from clinical research facilities/clinical trial units in Ireland and the UK. We extracted text on how randomisation was described, plus trial characteristics. We conducted content analysis to group the randomisation phrases inductively. We then excluded phrases that appeared more than once or were very similar to others. The final list of randomisation phrases was then presented to an online panel of participants and the public. Panel members were asked to rate each phrase on a 5-point Likert scale in terms of their understanding of the phrase, confidence in their understanding and acceptability of the phrase. RESULTS: Two hundred and eighty PILs and the transcribed text from one video animation represented 229 ongoing or concluded trials. The pragmatic content analysis generated five inductive categories: (1) explanation of why randomisation is required in trials; (2) synonyms for randomisation; (3) comparative randomisation phrases; (4) elaborative phrases for randomisation (5) and phrases that describe the process of randomisation. We had 48 unique phrases, which were shared with 73 participants and members of the public. Phrases that were well understood were not necessarily acceptable. Participants understood, but disliked, comparative phrases that referenced gambling, e.g. toss of a coin, like a lottery, roll of a die. They also disliked phrases that attributed decision-making to computers or automated systems. Participants liked plain language descriptions of what randomisation is and those that did not use comparative phrases. CONCLUSIONS: Potential trial participants are clear on their likes and dislikes when it comes to describing randomisation in PILs. We make five recommendations for practice.

Retention strategies are routinely communicated to potential trial participants but often differ from what was planned in the trial protocol: an analysis of adult participant information leaflets and their corresponding protocols.

BACKGROUND: Retaining participants in randomised controlled trials (RCTs) is challenging and trial teams are often required to use strategies to ensure retention or improve it. Other than monetary incentives, there is no requirement to disclose the use of retention strategies to the participant. Additionally, not all retention strategies are developed at the planning stage, i.e. post-funding during protocol development, but some protocols include strategies for participant retention as retention is considered and planned for early in the trial planning stage. It is yet unknown if these plans are communicated in the corresponding participant information leaflets (PILs). The purpose of our study was to determine if PILs communicate plans to promote participant retention and, if so, are these outlined in the corresponding trial protocol. METHODS: Ninety-two adult PILs and their 90 corresponding protocols from Clinical Trial Units (CTUs) in the UK were analysed. Directed (deductive) content analysis was used to analyse the participant retention text from the PILs. Data were presented using a narrative summary and frequencies where appropriate. RESULTS: Plans to promote participant retention were communicated in 81.5% (n = 75/92) of PILs. Fifty-seven percent (n = 43/75) of PILs communicated plans to use "combined strategies" to promote participant retention. The most common individual retention strategy was telling the participants that data collection for the trial would be scheduled during routine care visits (16%; n = 12/75 PILs). The importance of retention and the impact that missing or deleted data (deleting data collected prior to withdrawal) has on the ability to answer the research question were explained in 6.5% (n = 6/92) and 5.4% (n = 5/92) of PILs respectively. Out of the 59 PILs and 58 matching protocols that both communicated plans to use strategies to promote participant retention, 18.6% (n = 11/59) communicated the same information, the remaining 81.4% (n = 48/59) of PILs either only partially communicated (45.8%; n = 27/59) the same information or did not communicate the same information (35.6%; n = 21/59) as the protocol with regard to the retention strategy(ies). CONCLUSION: Retention strategies are frequently communicated to potential trial participants in PILs; however, the information provided often differs from the content in the corresponding protocol. Participant retention considerations are best done at the planning stage of the trial and we encourage trial teams to be consistent in the communication of these strategies in both the protocol and PIL.

Codesign and Launch of 'On the Ball': An Inclusive Community-Based 'Testicular Awareness' Campaign.

INTRODUCTION: Increased awareness of testicular diseases can lead to early diagnosis. Evidence suggests that men's awareness of testicular diseases is low, with many expressing their willingness to delay help-seeking for symptoms of concern. The risk of testicular diseases is higher in gender and sexual minority groups. In this study, we discuss the codesign, refinement and launch of 'On the Ball', an inclusive community-based 'testicular awareness' campaign. METHODS: The World Café participatory research methodology was used. Individuals from Lesbian, Gay, Bisexual, Transgender and Queer+ friendly organisations, testicular cancer survivors, policymakers, media/marketing experts and graphic designers were recruited. Participants were handed a brief for 'On the Ball', which was designed based on feedback from a previous World Café workshop. They were assigned to three tables. Participants rotated tables at random for three 20-min rounds of conversations. Each table had a facilitator who focussed on one element of the campaign brief. Data were collected using audio recorders and in writing and were analysed thematically. RESULTS: Thirteen individuals participated in the workshop. The following themes emerged from the data: (i) campaign identity, (ii) campaign delivery and (iii) campaign impact. Participants recommended enhancements to the campaign logo, slogan, social media posts and poster. They suggested delivering the campaign online via social media and offline using various print and broadcast media. Participants recommended targeting areas with a large number of men such as workplaces. To help measure the impact of the campaign, participants proposed capturing social media analytics and tracking statistics relating to testicular diseases. Recommendations were used to refine the 'On the Ball' campaign and launch it in a university. In total, 411 students engaged with the various elements of the campaign during the soft launch. CONCLUSIONS: 'On the Ball' campaign visuals ought to be inclusive. Online and offline campaign delivery is warranted to reach out to a wider cohort. Campaign impact can be captured using social media analytics as well as measuring clinical outcomes relating to testicular diseases. Future research is needed to implement the campaign online and offline, explore its impact and evaluate its feasibility, acceptability, cost and effect on promoting testicular awareness. PATIENT OR PUBLIC CONTRIBUTION: The 'On the Ball' campaign was codesigned and refined with members of Lesbian, Gay, Bisexual, Transgender and Queer+ friendly organisations, testicular cancer survivors, health policymakers, media and marketing experts and graphic designers using the World Café participatory research methodology.

Factors influencing smartwatch use and comfort with health data sharing: a sequential mixed-method study protocol.

INTRODUCTION: Smartwatches have become ubiquitous for tracking health metrics. These data sets hold substantial potential for enhancing healthcare and public health initiatives; it may be used to track chronic health conditions, detect previously undiagnosed health conditions and better understand public health trends. By first understanding the factors influencing one's continuous use of the device, it will be advantageous to assess factors that may influence a person's willingness to share their individual data sets. This study seeks to comprehensively understand the factors influencing the continued use of these devices and people's willingness to share the health data they generate. METHODS AND ANALYSIS: A two-section online survey of smartwatch users over the age of 18 will be conducted (n ≥200). The first section, based on the expectation-confirmation model, will assess factors influencing continued use of smartwatches while the second section will assess willingness to share the health data generated from these devices. Survey data will be analysed descriptively and based on structural equation modelling.Subsequently, six focus groups will be conducted to further understand the issues raised in the survey. Each focus group (n=6) will consist of three smartwatch users: a general practitioner, a public health specialist and an IT specialist. Young smartwatch users (aged 18-44) will be included in three of the focus groups and middle-aged smartwatch users (aged 45-64) will be included in the other three groups. This is to enhance comparison of opinions based on age groups. Data from the focus groups will be analysed using the microinterlocutor approach and an executive summary.After the focus group, participants will complete a brief survey to indicate any changes in their opinions resulting from the discussion. ETHICS AND DISSEMINATION: The results of this study will be disseminated through publication in a peer-reviewed journal, and all associated data will be deposited in a relevant, publicly accessible data repository to ensure transparency and facilitate future research endeavours.This study was approved by the Social Research Ethic Committee (SREC), University College Cork-SREC/SOM/21062023/2.

When describing harms and benefits to potential trial participants, participant information leaflets are inadequate.

BACKGROUND: Providing informed consent for trials requires providing trial participants with comprehensive information about the trial, including information about potential risks and benefits. It is required by the ethical principle of respecting patient autonomy. Our study examines the variation in the way information about potential trial benefits and harms is shared in participant information leaflets (PILs). METHODS: A total of 214 PILs and informed consent forms from clinical trials units (CTUs) and Clinical Research Facilities (CRFs) in Ireland and the UK were assessed by two authors independently, to check the extent to which they adhered to seven recently developed principles. Discrepancies were resolved by a third. RESULTS: Usage of the seven principles varied widely between PILs regardless of the intended recipient or trial type. None of the PILs used more than four principles, and some (4%) used none. Twenty-seven per cent of PILs presented information about all known potential harms, whereas 45% presented information on all known potential benefits. Some PILs did not provide any potential harms or potential benefits (8%). There was variation in the information contained in adult and children PILs and across disease areas. CONCLUSION: Significant variation exists in how potential trial benefits and harms are described to potential trial participants in PILs in our sample. Usage of the seven principles of good practice will promote consistency, ensure informed ethical decision-making and invoke trust and transparency. In the long term, a standardised PIL template is needed.

Analysis of core outcome set reporting in coronary intervention trials.

BACKGROUND: This paper will focus on outcome reporting within percutaneous coronary intervention (PCI) trials. A core outcome set (COS) is a standardised set of outcomes that are recommended to be reported in every clinical trial. Using a COS can help to ensure that all relevant outcomes are consistently reported across clinical trials. In 2018, the European Society of Cardiology outlined the only COS published for PCI trials. METHODS: We searched the literature for all randomised controlled trials published between 2014 and 2022. PCI trials included were late-phase trials and must investigate coronary intervention. The primary outcome was the proportion of trials that reported all of the COS-defined outcomes within their publication as either a primary, secondary or safety endpoint. The secondary outcomes included; the number of primary outcomes reported per study, the proportion of studies which use patient and public involvement (PPI) during trial design, outcome variability and outcome consistency. RESULTS: 9580 trials were screened and 115 studies met inclusion/exclusion criteria. Our study demonstrated that 55% (34/62) of PCI trials used a COS when it was available, compared with 40% (21/53) before the availability of a PCI COS set, p=0.121. Fewer primary outcomes were reported after the implementation of the COS, 2 compared with 2.3, p=0.014. There was no difference in the use of PPI between either group. There was a higher level of variability in outcomes reported before the availability of the COS, while the consistency of outcome reporting remained similar. CONCLUSION: The use of a COS in PCI trials is low. This study provides evidence that there still is a lack of awareness of the COS among those who design clinical trials. We also presented the inconsistency and heterogenicity in reporting clinical trial outcomes. Finally, there was a clear lack of PPI utilisation in PCI trials.

How, and why, science and health researchers read scientific (IMRAD) papers.

OBJECTIVES: The purpose of our study was to determine the order in which science and health researchers read scientific papers, their reasons for doing so and the perceived difficulty and perceived importance of each section. STUDY DESIGN AND SETTING: An online survey open to science and health academics and researchers distributed via existing research networks, X (formerly Twitter), and LinkedIn. RESULTS: Almost 90% of respondents self-declared to be experienced in reading research papers. 98.6% of the sample read the abstract first because it provides an overview of the paper and facilitates a decision on continuing to read on or not. Seventy-five percent perceived it to be the easiest to read and 62.4% perceived it to be very important (highest rank on a 5-point Likert scale). The majority of respondents did not read a paper in the IMRAD (Introduction, Methods, Results And Discussion) format. Perceived difficulty and perceived importance influenced reading order. CONCLUSION: Science and health researchers do not typically read scientific and health research papers in IMRAD format. The more important a respondent perceives a section to be, the more likely they are to read it. The easier a section is perceived, the more likely it will be read. We present recommendations to those teaching the skill of writing scientific papers and reports.

Investigating the characteristics of health-related data collection tools used in randomised controlled trials in low-income and middle-income countries: protocol for a systematic review.

INTRODUCTION: Health-related data collection tools, including digital ones, have become more prevalent across clinical studies in the last number of years. However, using digital data collection tools in low-income and middle-income countries presents unique challenges. In this review, we aim to provide an overview of the data collection tools currently being used in randomised controlled trials (RCTs) conducted in low-resource settings and evaluate the tools based on the characteristics outlined in the modified Mobile Survey Tool framework. These include functionality, reliability, usability, efficiency, maintainability, portability, effectiveness, cost-benefit, satisfaction, freedom from risk and context coverage. This evidence may provide a guide to selecting a suitable data collection tool for researchers planning to conduct research in low-income and middle-income countries for future studies. METHODS AND ANALYSIS: Searches will be conducted in four electronic databases: PubMed, CINAHL, Web of Science and EMBASE. For inclusion, studies must be a RCT, mention a health-related data collection tool and conducted in a low- and middle-income country. Only studies with available full-text and written in English will be included. The search was restricted to studies published between January 2005 and June 2023. This systematic review will use the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) tool. Two review authors will screen the titles and abstracts of search results independently for inclusion. In the initial screening process, the full-text articles will be retrieved if the abstract contains limited information about the study. Disagreements will be resolved through discussion. If the disagreement cannot be resolved, a third author (JO'D) will adjudicate. The study selection process will be outlined in a PRISMA flow-diagram. Data will be analysed using a narrative synthesis approach. The included studies and their outcomes will be presented in a table. ETHICS AND DISSEMINATION: Formal ethical approval is not required as primary data will not be collected in this study. The findings from this systematic review will be published in a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42023405738.

How do trial teams plan for retention during the design stage of the trial? A scoping review.

BACKGROUND: Retention to trials is important to ensure the results of the trial are valid and reliable. The SPIRIT guidelines (18b) require "plans to promote participant retention and complete follow-up, including list of any outcome data to be collected for participants who discontinue or deviate from intervention protocols" be included in trial protocols. It is unknown how often protocols report this retention information. The purpose of our scoping review is to establish if, and how, trial teams report plans for retention during the design stage of the trial. MATERIALS AND METHODS: A scoping review with searches in key databases (PubMed, Scopus, EMBASE, CINAHL (EBSCO), and Web of Science from 2014 to 2019 inclusive) to identify randomised controlled trial protocols. We produced descriptive statistics on the characteristics of the trial protocols and also on those adhering to SPIRIT item 18b. A narrative synthesis of the retention strategies was also conducted. RESULTS: Eight-hundred and twenty-four protocols met our inclusion criteria. RCTs (n = 722) and pilot and feasibility trial protocols (n = 102) reported using the SPIRIT guidelines during protocol development 35% and 34.3% of the time respectively. Of these protocols, only 9.5% and 11.4% respectively reported all aspects of SPIRIT item 18b "plans to promote participant retention and to complete follow-up, including list of any outcome data for participants who discontinue or deviate from intervention protocols". Of the RCT protocols, 36.8% included proactive "plans to promote participant retention" regardless of whether they reported using SPIRIT guidelines or not. Most protocols planned "combined strategies" (48.1%). Of these, the joint most commonly reported were "reminders and data collection location and method" and "reminders and monetary incentives". The most popular individual retention strategy was "reminders" (14.7%) followed by "monetary incentives- conditional" (10.2%). Of the pilot and feasibility protocols, 40.2% included proactive "plans to promote participant retention" with the use of "combined strategies" being most frequent (46.3%). The use of "monetary incentives - conditional" (22%) was the most popular individual reported retention strategy. CONCLUSION: There is a lack of reporting of plans to promote participant retention in trial protocols. Proactive planning of retention strategies during the trial design stage is preferable to the reactive implementation of retention strategies. Prospective retention planning and clear communication in protocols may inform more suitable choice, costing and implementation of retention strategies and improve transparency in trial conduct.

Determining clinical perspectives and strategies for improving enrollment of minoritized communities in prostate cancer clinical trials.

BACKGROUND: Black men and other minoritized populations have represented 4-5% or less of participants in most practice-informing clinical trials. This study sought to assess the knowledge, attitudes, and practices of clinicians around equity and inclusion in prostate cancer clinical trial initiatives in the United States. METHODS: An anonymous, web-based questionnaire was administered via REDCap (Research Electronic Data Capture) with questions focused on inclusivity of minoritized populations with respect to race and ethnicity in prostate cancer clinical trials research. The survey link was distributed across the United States via several professional organizations, prostate cancer groups, and social media. Responses were analyzed both quantitatively (descriptive statistics) and qualitatively (thematic analysis). RESULTS: Overall, 131 respondents completed the survey (70% self-identified as White, 17% as Asian, and 6% as Black). Most respondents practiced in an urban setting (89%). Of those who engaged in outreach with minoritized communities during the trial design process, 69% observed improved enrollment of minoritized populations. However, 18% of respondents noted that outreach alone does not overcome existing structural barriers to participation in clinical trials. Thematic analysis identified four key areas to address for improving equity: structural, health system, trial-/study-specific, and relationship-/engagement-related factors. CONCLUSION: Study participants demonstrated a knowledge of the importance of improving equity in prostate cancer clinical trials research. Designing trials that reduce issues associated with access and improving community outreach were emphasized as key focus areas for reducing health disparities in prostate cancer clinical trials research.

Promoting 'testicular awareness': Co-design of an inclusive campaign using the World Café Methodology.

INTRODUCTION: Testicular cancer is the most common cancer in men aged 15-44 years in many countries. Most men with testicular cancer present with a lump. Testicular symptoms are more likely to occur secondary to benign diseases like epididymo-orchitis, a common sexually transmitted infection. Gender and sexual minorities are at an increased risk of testicular diseases and health disparities. The aim of this study was to co-design an inclusive community-based campaign to promote testicular awareness. METHODS: This study uses the World Café methodology. Participation was sought from Lesbian, Gay, Bisexual, Transgender and Queer+ friendly organisations, testicular cancer survivors, health policy makers, media and marketing experts and graphic designers. Participants engaged in three rounds of conversations to co-design the campaign. Data were collected using drawing sheets, artefact cards, sticky notes, coloured markers and a voice recorder. Deductive thematic analysis was conducted. RESULTS: Seventeen individuals participated in the study. Six themes emerged from the analysis as follows: (i) online communication; (ii) offline communication; (iii) behavioural targeting and education; (iv) campaign frequency and reach; (v) demographic segmentation; and (vi) campaign identity. The use of social media for campaign delivery featured strongly in all conversations. Participants also recommended offline communication using posters and radio/television advertisements to scale up the campaign and achieve wider reach. Advertisements to overcome embarrassment surrounding testicular health were particularly recommended. Participants emphasised that campaign delivery must be dynamic whilst ensuring that the health-promoting messages are not diluted or lost. They stressed the importance of being inclusive and tailoring the campaign to different age groups, gender identities and sexual orientations. CONCLUSIONS: Study recommendations will be used to design and deliver the campaign. Future research will be needed to evaluate the feasibility, acceptability, cost and effect of the campaign on promoting testicular awareness and early detection of testicular diseases. PATIENT OR PUBLIC CONTRIBUTION: A participatory research approach was used to co-design the campaign with members of Lesbian, Gay, Bisexual, Transgender and Queer+ (LGBTQ+) friendly organisations, LGBTQ+ student bodies, LGBTQ+ staff networks, LGBTQ+ sports clubs, men's health organisations, testicular cancer survivors, health policy makers, media and marketing experts and graphic designers.

Underrecording and underreporting of participant ethnicity in clinical trials is persistent and is a threat to inclusivity and generalizability.

OBJECTIVES: People from ethnic minority groups are underserved by randomized trials, and poor representation of these groups reduces generalizability of results. There is no guidance on which ethnicity categories are appropriate for use in trials and thus inconsistency exists. The purpose of this study is to establish, in a large sample of trials, if participant ethnicity is recorded, how it is obtained (categories used), and if its reporting varies from its recording. STUDY DESIGN AND SETTING: We reviewed trial documentation for 407 randomized controlled trials published in the UK National Institute of Health Research library from 2016 to 2021. We extracted data on the recording (if it was recorded and the categories used) and reporting (if the categories remained the same as those obtained, or not) of ethnicity for each trial along with demographics. In the analysis we categorized the manner of recording and reporting of ethnicity in the trials according to UK Census ethnicity categories. RESULTS: Ethnicity was recorded in 67.3% (n = 274) of trials. The location in the trial report where ethnicity was recorded was available for 42% (n = 116) of trials. The details on how ethnicity was collected (predefined categories or self-defined) was available for 54/274 (20%) of trials and details on the specifics of the categories recorded was available for 44 (16%) trials. Of the 44, 6 of those did not go on to report on ethnicity in the trial report. Of the remaining 38, only 13 reported ethnicity exactly as it had been recorded. Taken as a whole from the 407 trial reports examined 9.3% (38/407) of trials demonstrated exactly how they both recorded, and reported, ethnicity. Authors made reference to whom results were relevant in terms of ethnicity in 80/407 (19.7%). CONCLUSION: Ethnicity is underrecorded and underreported in clinical trials. This is a threat to the generalizability of the findings and needs to be improved.

Clinical research nurse predictions of trial failure, recruitment and retention: a case for their early inclusion in trial design.

BACKGROUND: Clinical research nurses are a key part of the clinical trial team but typically get involved later in the trial, usually during recruitment. The purpose of our study was to establish if CRNs who read the trial protocol can predict the performance of the trial. METHODS: We randomly selected 18 trial protocols with three statuses, terminated, withdrawn, and completed, from ClinicalTrials.gov, between 2014 and 2018 inclusive. We gave the protocols to five CRNs, asked them to make a judgement and provide a reason for that judgement (via a 12-item questionnaire) on the status of the trial (terminated, withdrawn or completed), if the trial met its recruitment target, if it recruited on time, and if it retained its participants. We also asked if it was likely a CRN was involved in the design of the trial. The CRNs were blinded to the study outcomes, did not receive any training on how to read a protocol and were prohibited from using/abstained from using the internet while completing the task. RESULTS: Twenty-three questionnaires on 23 trial protocols (18 different trials) were completed by 5 CRNs. The CRNs correctly predicted the trial status 48%, 95% CI: 29-67% (11/23) of the time; successful/unsuccessful recruitment 74%, 95% CI: 54-87% (17/23) of the time; on-time recruitment 70%, 95% CI: 49-84% (16/23) of the time; and participant retention 52%, 95% CI: 33-71% (12/23). CRNs identified 100% (sensitivity) of sites that hit their target and 63%, 95% CI: 36-84% (specificity) of sites that missed their target. CONCLUSIONS: CRNs are very good judges of trial recruitment and site performance issues and are a vital part of the clinical trial team. Taken with the ESP (Estimating Site Performance) study, we have made a strong case for broadening the trial team at the trial design stage. Early engagement of a broad skillset can potentially offset problems of recruitment, retention and trial failure.

Trial lay summaries were not fit for purpose.

BACKGROUND AND OBJECTIVES: To establish if trial lay summaries are suitable for lay readers. METHODS: A random sample of 60 randomized controlled trial (RCT) reports (15%) from the National Institute for Health and Care Research (NIHR) Journals Library, UK, were selected from 407 available ones. We extracted the lay summary and determined the readability using the previously validated Flesch Reading Ease Score (FRES), Flesch-Kincaid Grade Level (FKGL), Simplified Measure of Gobbledegook (SMOG), Gunning Fog (GF), Coleman-Liau Index (CLI), and Automated Readability Index (ARI) readability scales. This provided us with a reading age. We also assessed the compatibility of the lay summaries with the Plain English UK Guidelines and the National Adult Literacy Agency Guidelines, Ireland. RESULTS: No lay summary met the recommended reading age for health care information of 11-12 years. None of them were considered "easy" to read, in fact over 85% were considered "difficult" to read. CONCLUSION: The lay summary is a key document for disseminating trial results to a broad population who may not necessarily have the medical or technical jargon to read a trial report. Its importance cannot be overstated. Assessing readability in conjunction with plain language guidelines is relatively easy and therefore an immediate change to practice is feasible. However, since specific skills are required to write lay summaries that meet the required standards, it is important that the need for such expertise is recognized and supported by research funders.

Physical and mental illness comorbidity among individuals with frequent self-harm episodes: A mixed-methods study.

Background: Research has indicated an increased risk of self-harm repetition and suicide among individuals with frequent self-harm episodes. Co-occurring physical and mental illness further increases the risk of self-harm and suicide. However, the association between this co-occurrence and frequent self-harm episodes is not well understood. The objectives of the study were (a) to examine the sociodemographic and clinical profile of individuals with frequent self-harm (regardless of suicidal intent) episodes and, (b) the association between physical and mental illness comorbidity, self-harm repetition, highly lethal self-harm methods, and suicide intent. Methods: The study included consecutive patients with five or more self-harm presentations to Emergency Departments across three general hospitals in the Republic of Ireland. The study included file reviews (n = 183) and semi-structured interviews (n = 36). Multivariate logistic regression models and independent samples t-tests were used to test the association between the sociodemographic and physical and mental disorders comorbidity on highly lethal self-harm methods and suicidal intent, respectively. Thematic analysis was applied to identify themes related to physical and mental illness comorbidity and frequent self-harm repetition. Findings: The majority of individuals with frequent self-harm episodes were female (59.6%), single (56.1%), and unemployed (57.4%). The predominant current self-harm method was drug overdose (60%). Almost 90% of the participants had history of a mental or behavioral disorder, and 56.8% had recent physical illness. The most common psychiatric diagnoses were alcohol use disorders (51.1%), borderline personality disorder (44.0%), and major depressive disorder (37.8%). Male gender (OR = 2.89) and alcohol abuse (OR = 2.64) predicted the risk of a highly lethal self-harm method. Suicide intent was significantly higher among those with a diagnosis of major depressive disorder (t = 2.43; p = 0.020). Major qualitative themes were (a) the functional meaning of self-harm (b) self-harm comorbidity (c) family psychiatric history and (d) contacts with mental health services. Participants described experiencing an uncontrollable self-harm urge, and self-harm was referred to as a way to get relief from emotional pain or self-punishment to cope with anger and stressors. Conclusion: Physical and mental illness comorbidity was high among individuals with frequent self-harm episodes. Male gender and alcohol abuse were associated with highly lethal self-harm methods. The mental and physical illness comorbidity of individuals with frequent self-harm episodes should be addressed via a biopsychosocial assessment and subsequent indicated treatment interventions.

Patient and Public Involvement (PPI) in outcome selection in breast cancer and nephrology trials.

We recently reported that according to patients and healthcare professionals in breast cancer and nephrology trials, teams conducting the trials got their choice of primary outcome wrong (72% of the time) more often than they got it right (28% of the time). A Patient and Public Involvement (PPI) representative, co-author of this letter, asked (on Twitter) whether PPI contributors had been involved in the design of the original trials and by extension the outcome selection. The purpose of this study was to answer this question.

How do trial teams plan for retention during the design stage of the trial? A scoping review protocol.

BACKGROUND: Retention remains a major challenge for many clinical trials. The SPIRIT guidelines state the following information on retention should be included in the trial protocol "Plans to promote participant retention and complete follow-up, including list of any outcome data to be collected for participants who discontinue or deviate from intervention protocols". This guidance shows the importance of planning retention methods and handling missing data as this can impact how the results of the trial are interpreted. The most recent Cochrane review of strategies to improve retention in clinical trials highlighted that some trials implemented multiple retention strategies and we questioned whether the use of multiple strategies was planned at the design stage and included in the protocol or are strategies implemented when retention becomes an issue within the trial. The purpose of our scoping review is to establish if and how trial teams prepare for retention at the design phase of clinical trials. METHODS AND ANALYSIS: We will follow the methodological framework and guidelines for scoping reviews outlined by the Joanna Briggs Institute. We will search MEDLINE/PubMed, Scopus, EMBASE, CINAHL (EBSCO), and Web of Science. A comprehensive search strategy for PubMed was developed in collaboration with an experienced research librarian. We will include protocols for phase 2, 3, and 4 RCTs as well as pilot and feasibility studies. The screening process will involve two reviewers. EM will independently screen all titles and abstracts. FS will screen 10% of the overall search output, and where necessary full protocol texts will be screened to determine eligibility. We will randomly sample eligible protocols to ensure the protocols represent a variety of trial and intervention types. Data will be extracted from each protocol and the results will be synthesised. The analysis will be qualitative using a narrative summary and descriptive statistics where appropriate. DISCUSSION: The scoping review will help trial methodologists better understand if retention strategies are planned for during the design stage of the trial contributing to the PRioRiTy II unanswered question "How should people who run trials plan for retention during their funding application and creation of the trial (protocol development)?".