The Impact of Malnutrition on the Developing Lung and Long-Term Lung Health: A Narrative Review of Global Literature.

Worldwide, over 2 billion children under the age of 5 experience stunting, wasting, or are underweight. Malnutrition contributes to 45% of all deaths in this age group (approximately 3.1 million deaths) [1]. Poverty, food insecurity, suboptimal feeding practices, climate change, and conflict are all contributing factors. Malnutrition causes significant respiratory problems, including increased risk of respiratory infections, impaired lung function, and increased risk of subsequent adult respiratory disease, including asthma, COPD, and lung cancer. Childhood malnutrition not only has serious consequences for children's health but it also has numerous consequences on wellbeing and educational attainment. Childhood malnutrition is a complex and multifaceted problem. However, by understanding and addressing the underlying causes, and investing in prevention and treatment programs, it is possible to maximize children's health and wellbeing on a global scale. This narrative review will focus on the impact of childhood malnutrition on lung development, the consequent respiratory disease, and what actions can be taken to reduce the burden of malnutrition on lung health.

Opening up ideas: an advent calendar for patient and public engagement in clinical trials research.

The involvement of patients and the public in research is now an expectation in research with funders requesting a clear plan of involvement and engagement. In the United Kingdom involvement typically focuses on research prioritisation, design and delivery, in contrast activities that share the results of research or research methods more generally are considered to be engagement. Clinical trials tend to concentrate on involvement activities with less emphasis on engagement. To promote engagement activities in the context of clinical trials we asked people attending the 2022 International Clinical Trials Methodology Conference to share ideas on how we can best engage with patients and the public. Responses were reviewed and 22 themes identified. One suggestion was to create an advent calendar and so these 22 themes plus two from the authors were used as a daily tweet from the 1st to the 24th December 2022. Here we share these ideas and draw comparisons between engagement activities in research and traditions of the Christmas period. The ideas shared are not intended as a definitive list but instead a novel way to start discussions between experts by experience, researchers, health professionals and communities to facilitate co-production of meaningful engagement strategies.

Patient and public involvement and engagement are terms used to describe specific activities that have a variety of goals from information giving through topublic co-production of research. Involvement and engagement are important as they can help reduce waste in research by ensuring that the research is relevant, conducted well and that the results are shared to those that will use them to make decisions about treatments, including patients. In the United Kingdom the term "engagement" usually refers to activities that focus mainly on information giving, for example sharing the results of research or information about how research is done in general. In this commentary we share ideas for engagement activities that were collected from people attending the International Clinical Trials Methodology Conference in 2022. One of the ideas shared was to have an advent calendar and we have used this to draw comparisons between traditions surrounding the Christmas period and engagement of patients and the public. We share 24 different ideas in the form of a printable advent calendar and invite the clinical trials community, including experts by experience, to reflect on these to generate more ideas for meaningful engagement activities so that everyone who will use the results of research has the opportunity to shape, share, and benefit from research.

Core outcome measurement instruments for use in clinical and research settings for adults with post-COVID-19 condition: an international Delphi consensus study.

Post-COVID-19 condition (also known as long COVID) is a new, complex, and poorly understood disorder. A core outcome set (COS) for post-COVID-19 condition in adults has been developed and agreement is now required on the most appropriate measurement instruments for these core outcomes. We conducted an international consensus study involving multidisciplinary experts and people with lived experience of long COVID. The study comprised a literature review to identify measurement instruments for the core outcomes, a three-round online modified Delphi process, and an online consensus meeting to generate a core outcome measurement set (COMS). 594 individuals from 58 countries participated. The number of potential instruments for the 12 core outcomes was reduced from 319 to 19. Consensus was reached for inclusion of the modified Medical Research Council Dyspnoea Scale for respiratory outcomes. Measures for two relevant outcomes from a previously published COS for acute COVID-19 were also included: time until death, for survival, and the Recovery Scale for COVID-19, for recovery. Instruments were suggested for consideration for the remaining nine core outcomes: fatigue or exhaustion, pain, post-exertion symptoms, work or occupational and study changes, and cardiovascular, nervous system, cognitive, mental health, and physical outcomes; however, consensus was not achieved for instruments for these outcomes. The recommended COMS and instruments for consideration provide a foundation for the evaluation of post-COVID-19 condition in adults, which should help to optimise clinical care and accelerate research worldwide. Further assessment of this COMS is warranted as new data emerge on existing and novel measurement instruments.

Developing an online, searchable database to systematically map and organise current literature on retention research (ORRCA2).

BACKGROUND: Addressing recruitment and retention challenges in trials is a key priority for methods research, but navigating the literature is difficult and time-consuming. In 2016, ORRCA (www.orrca.org.uk) launched a free, searchable database of recruitment research that has been widely accessed and used to support the update of systematic reviews and the selection of recruitment strategies for clinical trials. ORRCA2 aims to create a similar database to map the growing volume and importance of retention research. METHODS: Searches of Medline (Ovid), CINAHL, PsycINFO, Scopus, Web of Science Core Collection and the Cochrane Library, restricted to English language and publications up to the end of 2017. Hand searches of key systematic reviews were undertaken and randomised evaluations of recruitment interventions within the ORRCA database on 1 October 2020 were also reviewed for any secondary retention outcomes. Records were screened by title and abstract before obtaining the full text of potentially relevant articles. Studies reporting or evaluating strategies, methods and study designs to improve retention within healthcare research were eligible. Case reports describing retention challenges or successes and studies evaluating participant reported reasons for withdrawal or losses were also included. Studies assessing adherence to treatments, attendance at appointments outside of research and statistical analysis methods for missing data were excluded. Eligible articles were categorised into one of the following evidence types: randomised evaluations, non-randomised evaluations, application of retention strategies without evaluation and observations of factors affecting retention. Articles were also mapped against a retention domain framework. Additional data were extracted on research outcomes, methods and host study context. RESULTS: Of the 72,904 abstracts screened, 4,364 full texts were obtained, and 1,167 articles were eligible. Of these, 165 (14%) were randomised evaluations, 99 (8%) non-randomised evaluations, 319 (27%) strategies without evaluation and 584 (50%) observations of factors affecting retention. Eighty-four percent (n = 979) of studies assessed the numbers of participants retained, 27% (n = 317) assessed demographic differences between retained and lost participants, while only 4% (n = 44) assessed the cost of retention strategies. The most frequently reported domains within the 165 studies categorised as 'randomised evaluations of retention strategies' were participant monetary incentives (32%), participant reminders and prompts (30%), questionnaire design (30%) and data collection location and method (26%). CONCLUSION: ORRCA2 builds on the success of ORRCA extending the database to organise the growing volume of retention research. Less than 15% of articles were randomised evaluations of retention strategies. Mapping of the literature highlights several areas for future research such as the role of research sites, clinical staff and study design in enhancing retention. Future studies should also include cost-benefit analysis of retention strategies.

Identifying a core outcome set for pulmonary sarcoidosis research - the Foundation for Sarcoidosis Research - Sarcoidosis Clinical OUtcomes Taskforce (SCOUT).

Background: Pulmonary sarcoidosis is a rare granulomatous disease of unknown aetiology. Heterogeneity in the outcomes measured in trials of treatment for pulmonary sarcoidosis has impacted on the ability to systematically compare findings, contributing to research inefficiency. The FSR-SCOUT study has aimed to address this heterogeneity by developing a core outcome set that represents a patient and health professional consensus on the most important outcomes to measure in future research for the treatment of pulmonary sarcoidosis. Research design and methods: systematic review of trial registries, narrative synthesis of published qualitative literature on the patient experience and results of a patient survey contributed to the development of a comprehensive list of outcomes that were rated in a two round online Delphi survey. The Delphi survey was completed by patients/carers and health professionals and the results discussed and ratified at an online consensus meeting. Results: 259 patients/carers and 51 health professionals completed both rounds of the Delphi survey. A pre-agreed definition of consensus was applied and the results discussed at an online consensus meeting attended by 17 patients and 7 health professionals). Fifteen outcomes, across five domains (physiological/clinical, treatment, resource use, quality of life, and death), reached the definition of consensus and were included in the core outcome set. Conclusions: The core outcome set represents a patient and health professional consensus on the most important outcomes for pulmonary sarcoidosis research. The use of the core outcome set in future trials, and efforts to validate its components, will enhance the relevance of trials to stakeholders and will increase the opportunity for the research to contribute to evidence synthesis.

Scout - sarcoidosis outcomes taskforce. A systematic review of outcomes to inform the development of a core outcome set for pulmonary sarcoidosis.

BACKGROUND: Clinical trials evaluating different management strategies for pulmonary sarcoidosis may measure different outcomes. This heterogeneity in outcomes can lead to waste in research due to the inability to compare and combine data. Core outcome sets (COS) have the potential to address this issue and here we describe a systematic review of outcomes as the first step in the development of a COS for pulmonary sarcoidosis research. METHODS: A search of clinical trial registries for phase II, III and IV trials of pulmonary sarcoidosis was undertaken along with a rapid review of the patient perspective literature. Each study was screened for eligibility and outcomes extracted verbatim from the registry entry or publication then reviewed, grouped and categorised using the COMET taxonomy. RESULTS: 36 trial registry entries and 6 studies on patients' perspective of pulmonary sarcoidosis were included reporting 56 and 82 unique outcomes respectively across 23 domains. The most frequently reported outcome domain was "respiratory, thoracic and mediastinal outcomes". However, the patients' perspective literature identified outcomes in the "personal circumstances" and "societal/carer burden" domains that were not reported in any of the included trial registrations. CONCLUSIONS: Using both clinical trial registry data and published literature on patients' perspective has allowed rapid review of outcomes measured and reported in pulmonary sarcoidosis research. The use of multiple sources has led to the development of a comprehensive list of outcomes that represents the first step in the development of a COS for use in future pulmonary sarcoidosis research.

Can harmonisation of outcomes bridge the translation gap for pre-clinical research? A systematic review of outcomes measured in mouse models of type 2 diabetes.

BACKGROUND: In pre-clinical research, systematic reviews have the potential to mitigate translational challenges by facilitating understanding of how pre-clinical studies can inform future clinical research. Yet their conduct is encumbered by heterogeneity in the outcomes measured and reported, and those outcomes may not always relate to the most clinically important outcomes. We aimed to systematically review outcomes measured and reported in pre-clinical in vivo studies of pharmacological interventions to treat high blood glucose in mouse models of type 2 diabetes. METHODS: A systematic review of pre-clinical in vivo studies of pharmacological interventions aimed at addressing elevated blood glucose in mouse models of type 2 diabetes was completed. Studies were screened for eligibility and outcomes extracted from the included studies. The outcomes were recorded verbatim and classified into outcome domains using an existing outcome taxonomy. Outcomes were also compared to those identified in a systematic review of registered phase 3/4 clinical trials for glucose lowering interventions in people with type 2 diabetes. RESULTS: Review of 280 included studies identified 532 unique outcomes across 19 domains. No single outcome, or domain, was measured in all studies and only 132 (21%) had also been measured in registered phase 3/4 clinical trials. A core outcome set, representing the minimum that should be measured and reported, developed for type 2 diabetes effectiveness clinical trials includes 18 core outcomes, of these 12 (71%) outcomes were measured and reported in one or more of the included pre-clinical studies. CONCLUSIONS: There is heterogeneity of outcomes reported in pre-clinical research. Harmonisation of outcomes across the research pathway using a core outcome set may facilitate interpretation, evidence synthesis and translational success, and may contribute to the refinement of the use of animals in research. Systematic review registration: The study was prospectively registered on the PROSPERO Database, registration number CRD42018106831.

Development of a core outcome set for use in routine orthodontic clinical trials.

INTRODUCTION: A diverse range of outcomes is used in orthodontic research with a focus on measuring outcomes important to clinicians and little consistency in outcome selection and measurement. We aimed to develop a core outcome set for use in clinical trials of orthodontic treatment not involving cleft or orthognathic patient groups. METHODS: A list of outcomes measured in previous orthodontic research was identified through a scoping literature review. Additional outcomes of importance to patients were obtained using qualitative interviews and focus groups with adolescents aged 10-16 years. Rating of outcomes was carried out in a 2-round electronic Delphi process involving health care professionals and patients using a 9-point scale. A face-to-face meeting was subsequently held with stakeholders to discuss the results before refining the core outcome set. RESULTS: After triangulation, a final list of 34 outcomes grouped under 10 domains was obtained for rating in the e-Delphi surveys. Fifteen outcomes were voted "in" after the second Delphi round involving 274 participants with a further outcome being included after the consensus meeting. These were subsequently refined into a final set of 7 core outcomes, including the impact of self-perceived esthetics, alignment and/or occlusion, skeletal relationship, stability, patient-related adherence, breakages, and adverse effects on teeth or teeth-supporting structures. CONCLUSIONS: A bespoke orthodontic core outcome set encompassing both clinician- and patient-focused outcomes was developed. Incorporating this is the first step into providing a more holistic assessment of the impact of treatment while allowing for meaningful comparisons and synthesis of results from individual trials.

Designing and using incentives to support recruitment and retention in clinical trials: a scoping review and a checklist for design.

BACKGROUND: Recruitment and retention of participants are both critical for the success of trials, yet both remain significant problems. The use of incentives to target participants and trial staff has been proposed as one solution. The effects of incentives are complex and depend upon how they are designed, but these complexities are often overlooked. In this paper, we used a scoping review to 'map' the literature, with two aims: to develop a checklist on the design and use of incentives to support recruitment and retention in trials; and to identify key research topics for the future. METHODS: The scoping review drew on the existing economic theory of incentives and a structured review of the literature on the use of incentives in three healthcare settings: trials, pay for performance, and health behaviour change. We identified the design issues that need to be considered when introducing an incentive scheme to improve recruitment and retention in trials. We then reviewed both the theoretical and empirical evidence relating to each of these design issues. We synthesised the findings into a checklist to guide the design of interventions using incentives. RESULTS: The issues to consider when designing an incentive system were summarised into an eight-question checklist. The checklist covers: the current incentives and barriers operating in the system; who the incentive should be directed towards; what the incentive should be linked to; the form of incentive; the incentive size; the structure of the incentive system; the timing and frequency of incentive payouts; and the potential unintended consequences. We concluded the section on each design aspect by highlighting the gaps in the current evidence base. CONCLUSIONS: Our findings highlight how complex the design of incentive systems can be, and how crucial each design choice is to overall effectiveness. The most appropriate design choice will differ according to context, and we have aimed to provide context-specific advice. Whilst all design issues warrant further research, evidence is most needed on incentives directed at recruiters, optimal incentive size, and testing of different incentive structures, particularly exploring repeat arrangements with recruiters.

Incorporating patients' perspectives into the initial stages of core outcome set development: a rapid review of qualitative studies of type 2 diabetes.

Conducting systematic reviews of qualitative studies to incorporate patient perspectives within the early stages of core outcome set (COS) development can be resource intensive. We aimed to identify an expedited approach to be used as part of the wider COS development process. Specifically, we undertook a rapid review of qualitative studies of patients' views and experiences of type 2 diabetes. We searched MEDLINE from inception to June 2017 to identify studies reporting qualitative empirical findings of perspectives of people with type 2 diabetes. Qualitative methodological filters were used to minimize irrelevant references. Drawing on content analysis, data synthesis involved identifying text in eligible studies relevant to outcomes of type 2 diabetes and interpreting and categorizing this according to the 38 core domains of the Core Outcome Measures in Effectiveness Trials taxonomy. Of 146 studies screened, 26 were included. Four hundred and fifty-eight outcomes were derived from the included studies. In comparison to the outcomes extracted from clinical trials, more life impact outcomes were derived from the qualitative studies, but fewer physiological/clinical outcomes. Outcomes relating to 'mortality/survival' and 'role functioning' were more prevalent in studies conducted in low/middle-income countries. This rapid review and synthesis of qualitative studies identified outcomes that had not previously been identified by a systematic review of clinical trials. It also identified differences in the types of outcomes given prominence to in the clinical trials and qualitative literatures. Incorporating qualitative evidence on patient perspectives from the outset of the COS development process can help to ensure outcomes that matter to patients are not overlooked. Our method provides a pragmatic and resource-efficient way to do this. For those developing international COS, our method has potential for incorporating the perspectives of patients from diverse countries in the early stages of COS development.

Selecting Core Outcomes for Randomised Effectiveness trials In Type 2 diabetes (SCORE-IT): a patient and healthcare professional consensus on a core outcome set for type 2 diabetes.

Objectives: Heterogeneity in outcomes measured across trials of glucose-lowering interventions for people with type 2 diabetes impacts on the ability to compare findings and may mean that the results have little importance to healthcare professionals and the patients that they care for. The SCORE-IT study (Selecting Core Outcomes for Randomised Effectiveness trials In Type 2 diabetes) has addressed this issue by establishing consensus on the most important outcomes for non-surgical interventions for hyperglycemia in type 2 diabetes. Research design and methods: A comprehensive list of outcomes was developed from registered clinical trials, online patient resources, qualitative literature and long-term studies in the field. This list was then scored in a two-round online Delphi survey completed by healthcare professionals, people with type 2 diabetes, researchers in the field and healthcare policymakers. The results of this online Delphi were discussed and ratified at a face-to-face consensus meeting. Results: 173 people completed both rounds of the online survey (116 people with type 2 diabetes, 37 healthcare professionals, 14 researchers and 6 policymakers), 20 of these attended the consensus meeting (13 people with type 2 diabetes and 7 healthcare professionals). Consensus was reached on 18 core outcomes across five domains, which include outcomes related to diabetes care, quality of life and long-term diabetes-related complications. Conclusions: Implementation of the core outcome set in future trials will ensure that outcomes of importance to all stakeholders are measured and reported, enhancing the relevance of trial findings and facilitating the comparison of results across trials.

Choosing important health outcomes for comparative effectiveness research: 4th annual update to a systematic review of core outcome sets for research.

BACKGROUND: The Core Outcome Measures in Effectiveness Trials (COMET) database is a publically available, searchable repository of published and ongoing core outcome set (COS) studies. An annual systematic review update is carried out to maintain the currency of database content. METHODS: The methods used in the fourth update of the systematic review followed the same approach used in the original review and previous updates. Studies were eligible for inclusion if they reported the development of a COS, regardless of any restrictions by age, health condition or setting. Searches were carried out in March 2018 to identify studies that had been published or indexed between January 2017 and the end of December 2017. RESULTS: Forty-eight new studies, describing the development of 56 COS, were included. There has been an increase in the number of studies clearly specifying the scope of the COS in terms of the population (n = 43, 90%) and intervention (n = 48, 100%) characteristics. Public participation has continued to rise with over half (n = 27, 56%) of studies in the current review including input from members of the public. The rate of inclusion of all stakeholder groups has increased, in particular participation from non-clinical research experts has risen from 32% (mean average in previous reviews) to 62% (n = 29). Input from participants located in Australasia (n = 17; 41%), Asia (n = 18; 44%), South America (n = 13; 32%) and Africa (n = 7; 17%) have all increased since the previous reviews. CONCLUSION: This update included a pronounced increase in the number of new COS identified compared to the previous three updates. There was an improvement in the reporting of the scope, stakeholder participants and methods used. Furthermore, there has been an increase in participation from Australasia, Asia, South America and Africa. These advancements are reflective of the efforts made in recent years to raise awareness about the need for COS development and uptake, as well as developments in COS methodology.

Development of an online resource for recruitment research in clinical trials to organise and map current literature.

BACKGROUND: Recruiting the target number of participants within the pre-specified time frame agreed with funders remains a common challenge in the completion of a successful clinical trial and addressing this is an important methodological priority. While there is growing research around recruitment, navigating this literature to support an evidence-based approach remains difficult. The Online resource for Recruitment Research in Clinical triAls project aims to create an online searchable database of recruitment research to improve access to existing evidence and to identify gaps for future research. METHODS: MEDLINE (Ovid), Scopus, Cochrane Database of Systematic Reviews and Cochrane Methodology Register, Science Citation Index Expanded and Social Sciences Citation Index within the ISI Web of Science and Education Resources Information Center were searched in January 2015. Search strategy results were screened by title and abstract, and full text obtained for potentially eligible articles. Studies reporting or evaluating strategies, interventions or methods used to recruit patients were included along with case reports and studies exploring reasons for patient participation or non-participation. Eligible articles were categorised as systematic reviews, nested randomised controlled trials and other designs evaluating the effects of recruitment strategies (Level 1); studies that report the use of recruitment strategies without an evaluation of impact (Level 2); or articles reporting factors affecting recruitment without presenting a particular recruitment strategy (Level 3). Articles were also assigned to 1, or more, of 42 predefined recruitment domains grouped under 6 categories. RESULTS: More than 60,000 records were retrieved by the search, resulting in 56,030 unique titles and abstracts for screening, with a further 23 found through hand searches. A total of 4570 full text articles were checked; 2804 were eligible. Six percent of the included articles evaluated the effectiveness of a recruitment strategy (Level 1), with most of these assessing aspects of participant information, either its method of delivery (33%) or its content and format (28%). DISCUSSION: Recruitment to clinical trials remains a common challenge and an important area for future research. The online resource for Recruitment Research in Clinical triAls project provides a searchable, online database of research relevant to recruitment. The project has identified the need for researchers to evaluate their recruitment strategies to improve the evidence base and broaden the narrow focus of existing research to help meet the complex challenges faced by those recruiting to clinical trials.

Selecting Core Outcomes for Randomised Effectiveness trials In Type 2 Diabetes (SCORE-IT): study protocol for the development of a core outcome set.

BACKGROUND: Type 2 diabetes is characterised by abnormal glucose metabolism, and treatment is aimed at normalising glycaemia. Outcomes measured in clinical trials should be meaningful to patients, health care professionals and researchers, yet there is heterogeneity in the outcomes used across trials of glucose-lowering interventions. This inconsistency affects the ability to compare findings and may mean that the results have little importance to health care professionals and the patients for whom they care. The SCORE-IT study aims to develop a core outcome set (COS) for use in all trials of glucose-lowering interventions for people with type 2 diabetes. METHODS/DESIGN: This study will involve three key stages in the development of a COS: (1) A list of outcomes will be identified from multiple sources, specifically registered clinical trials, online patient resources, the qualitative literature and landmark studies identified by a Study Steering Committee. (2) The list of outcomes will be scored by multiple stakeholder groups in a two-round online international Delphi survey. (3) The results of the online Delphi will be summarised and discussed at a face-to-face consensus meeting with representation from all stakeholder groups. DISCUSSION: The SCORE-IT study aims to develop an internationally relevant set of core outcomes for use in future trials of glucose-lowering interventions for type 2 diabetes. The use of a COS will improve the consistency of outcomes, allowing results of studies to be compared and combined and for new effective treatments to made available more quickly. TRIAL REGISTRATION: The COS study, of which this is a part, is registered in the Core Outcome Measures in Effectiveness Trials (COMET) database, http://www.comet-initiative.org/studies/details/956 . Registered January 2017.

SCORE-IT (Selecting Core Outcomes for Randomised Effectiveness trials In Type 2 diabetes): a systematic review of registered trials.

BACKGROUND: Outcomes measured in clinical trials should be meaningful to patients, healthcare professionals and researchers, yet there is heterogeneity in the outcomes used across trials. This inconsistency impacts on the ability to compare findings and may mean that the results have little importance to healthcare professionals and the patients that they care for. The aim of the present study is to review the outcomes used in registered trials of therapies for type 2 diabetes mellitus as the first step in the development of a core outcome set for effectiveness trials in type 2 diabetes. METHODS: A systematic review of clinicaltrials.gov entries was completed for randomised, open (actively recruiting or in follow-up period), phase 3 and 4 trials of type 2 diabetes mellitus in adults. Trials of the treatment of diabetes complications, co-morbidities, prevention and surgery were excluded. Each trial was screened for eligibility and outcomes extracted from the primary and secondary outcomes data fields and free text study information. The outcomes were recorded verbatim and classified into core outcome domains according to the COMET taxonomy. RESULTS: A total of 354 trial registrations were reviewed for eligibility and 138 trials included. In total, 1444 outcomes were extracted with a median of eight outcomes per trial (range = 1-60). Outcomes were categorised into 30 different outcome domains according to the COMET taxonomy, but no single domain or outcome was measured in 100% of trials. The majority of trials (88%) included outcomes in the 'metabolism and nutrition' domain, such as lipids and lipoproteins (21%), HbA1c (18%), hypoglycaemia (14%), fasting plasma/blood glucose (11%), glycaemic variability (8%), postprandial response (8%) and insulin sensitivity (5%). Only 10% of trials included one or more patient reported outcomes; of these, 29% included the Diabetes Treatment Satisfaction Questionnaire. CONCLUSIONS: There is marked heterogeneity in the outcomes measured in registered therapeutic intervention trials for type 2 diabetes. The use of an agreed set of core outcomes will improve the consistency of reporting in clinical trials for type 2 diabetes. TRIAL REGISTRATION: The core outcome set study, of which this is a part, is registered in the COMET database, http://www.comet-initiative.org/studies/details/956 . Registered on 24 January 2017.

A cohort examination to establish reporting of the remit and function of Trial Steering Committees in randomised controlled trials.

BACKGROUND: The DAMOCLES project established a widely used Data Monitoring Committee (DMC) Charter for randomised controlled trials (RCTs). Typically, within the UK, the DMC is advisory and recommends to another executive body; the Trial Steering Committee (TSC). Despite the executive role of the TSC, the CONSORT Statement does not explicitly require reporting of TSC activity, although is included as an example of good reporting. A lack of guidance on TSC reporting can impact transparency of trial oversight, ultimately leading to a misunderstanding regarding role and, subsequently, further variation in practice. This review aimed to establish reporting practice of TSC involvement in RCTs, and thus make recommendations for reporting. METHODS: A cohort examination identifying reporting practice was undertaken. The cohort comprised RCTs published in three leading medical journals (the British Medical Journal, The Lancet and the New England Journal of Medicine) within 6 months in 2012 and the full NIHR HTA Monograph series. Details of TSC constitution and impact were extracted from main publications and published supplements. RESULTS: Of 415 publications, 264 were eligible. These were typical in terms of trial design. Variations in reporting between journals and monographs was notable. TSC presence was identified in approximately half of trials (n = 144), of which 109 worked alongside a DMC. No publications justified not convening a TSC. When reported, the role of the committee and examples of impact in design, conduct and analysis were summarised. CONCLUSIONS: We present the first review of reporting TSC activity in the published academic literature. An absence of reporting standards with regards to TSC constitution, activity and impact on trial conduct was identified which can influence transparency of reporting trial oversight. Consistent reporting is vital for the benefits and impact of the TSC role to be understood to support adoption of this oversight structure and reduce global variations in practice.

A patient and public involvement (PPI) toolkit for meaningful and flexible involvement in clinical trials - a work in progress.

PLAIN LANGUAGE SUMMARY: Funders of research are increasingly requiring researchers to involve patients and the public in their research. Patient and public involvement (PPI) in research can potentially help researchers make sure that the design of their research is relevant, that it is participant friendly and ethically sound. Using and sharing PPI resources can benefit those involved in undertaking PPI, but existing PPI resources are not used consistently and this can lead to duplication of effort. This paper describes how we are developing a toolkit to support clinical trials teams in a clinical trials unit. The toolkit will provide a key 'off the shelf' resource to support trial teams with limited resources, in undertaking PPI. Key activities in further developing and maintaining the toolkit are to: ● listen to the views and experience of both research teams and patient and public contributors who use the tools; ● modify the tools based on our experience of using them; ● identify the need for future tools; ● update the toolkit based on any newly identified resources that come to light; ● raise awareness of the toolkit and ● work in collaboration with others to either develop or test out PPI resources in order to reduce duplication of work in PPI. ABSTRACT: Background Patient and public involvement (PPI) in research is increasingly a funder requirement due to the potential benefits in the design of relevant, participant friendly, ethically sound research. The use and sharing of resources can benefit PPI, but available resources are not consistently used leading to duplication of effort. This paper describes a developing toolkit to support clinical trials teams to undertake effective and meaningful PPI. Methods The first phase in developing the toolkit was to describe which PPI activities should be considered in the pathway of a clinical trial and at what stage these activities should take place. This pathway was informed through review of the type and timing of PPI activities within trials coordinated by the Clinical Trials Research Centre and previously described areas of potential PPI impact in trials. In the second phase, key websites around PPI and identification of resources opportunistically, e.g. in conversation with other trialists or social media, were used to identify resources. Tools were developed where gaps existed. Results A flowchart was developed describing PPI activities that should be considered in the clinical trial pathway and the point at which these activities should happen. Three toolkit domains were identified: planning PPI; supporting PPI; recording and evaluating PPI. Four main activities and corresponding tools were identified under the planning for PPI: developing a plan; identifying patient and public contributors; allocating appropriate costs; and managing expectations. In supporting PPI, tools were developed to review participant information sheets. These tools, which require a summary of potential trial participant characteristics and circumstances help to clarify requirements and expectations of PPI review. For recording and evaluating PPI, the planned PPI interventions should be monitored in terms of impact, and a tool to monitor public contributor experience is in development. Conclusions This toolkit provides a developing 'off the shelf' resource to support trial teams with limited resources in undertaking PPI. Key activities in further developing and maintaining the toolkit are to: listen to the views and experience of both research teams and public contributors using the tools, to identify the need for future tools, to modify tools based on experience of their use; to update the toolkit based on any newly identified resources that come to light; to raise awareness of the toolkit and to work in collaboration with others to both develop and test out PPI resources in order to reduce duplication of work in PPI.

Exploring the role and function of trial steering committees: results of an expert panel meeting.

BACKGROUND: The independent oversight of clinical trials, which is recommended by the Medical Research Council (MRC) Guidelines for Good Clinical Practice, is typically provided by an independent advisory Data Monitoring Committee (DMC) and an independent executive committee, to whom the DMC makes recommendations. The detailed roles and function of this executive committee, known as the Trial Steering Committee (TSC), have not previously been studied or reviewed since those originally proposed by the MRC in 1998. METHODS: An expert panel (n = 7) was convened comprising statisticians, clinicians and trial methodologists with prior TSC experience. Twelve questions about the role and responsibilities of the TSC were discussed by the panel at two full-day meetings. Each meeting was transcribed in full and the discussions were summarised. RESULTS: The expert panel reached agreement on the role of the TSC, to which it was accountable, the membership, the definition of independence, and the experience and training needed. The management of ethical issues, difficult/complex situations and issues the TSC should not ask the DMC to make recommendations on were more difficult to discuss without specific examples, but support existed for further work to help share issues and to provide appropriate training for TSC members. Additional topics discussed, which had not been identified by previous work relating to the DMCs but were pertinent to the role of the TSC, included the following: review of data sharing requests, indemnity, lifespan of the TSC, general TSC administration, and the roles of both the Funder and the Sponsor. CONCLUSIONS: This paper presents recommendations that will contribute to the revision and update of the MRC TSC terms of reference. Uncertainty remains in some areas due to the absence of real-life examples; future guidance on these issues would benefit from a repository of case studies. Notably, the role of a patient and public involvement (PPI) contributor was not discussed, and further work is warranted to explore the role of a PPI contributor in independent trial oversight.

The Importance of Integration of Stakeholder Views in Core Outcome Set Development: Otitis Media with Effusion in Children with Cleft Palate.

BACKGROUND: Approximately 75% of children with cleft palate (CP) have Otitis Media with Effusion (OME) histories. Evidence for the effective management of OME in these children is lacking. The inconsistency in outcome measurement in previous studies has led to a call for the development of a Core Outcome Set (COS). Despite the increase in the number of published COS, involvement of patients in the COS development process, and methods to integrate the views of patients and health professionals, to date have been limited. METHODS AND FINDINGS: A list of outcomes measured in previous research was identified through reviewing the literature. Opinion on the importance of each of these outcomes was then sought from key stakeholders: Ear, Nose and Throat (ENT) surgeons, audiologists, cleft surgeons, speech and language therapists, specialist cleft nurses, psychologists, parents and children. The opinion of health professionals was sought in a three round Delphi survey where participants were asked to score each outcome using a bespoke online system. Parents and children were also asked to score outcomes in a survey and provided an in-depth insight into having OME through semi-structured interviews. The results of the Delphi survey, interviews and parent/patient survey were brought together in a final consensus meeting with representation from all stakeholders. A final set of eleven outcomes reached the definition of "consensus in" to form the recommended COS: hearing; chronic otitis media (COM); OME; receptive language skills; speech development; psycho social development; acute otitis media (AOM); cholesteatoma; side effects of treatment; listening skills; otalgia. CONCLUSIONS: We have produced a recommendation about the outcomes that should be measured, as a minimum, in studies of the management of OME in children with CP. The development process included input from key stakeholders and used novel methodology to integrate the opinion of healthcare professionals, parents and children.

Trial Steering Committees in randomised controlled trials: A survey of registered clinical trials units to establish current practice and experiences.

BACKGROUND: The Medical Research Council Guidelines for Good Clinical Practice outlines a three-committee trial oversight structure--the day-to-day Trial Management Group, the Data Monitoring Committee and the Trial Steering Committee. In this model, the Trial Steering Committee is the executive committee that oversees the trial and considers the recommendations from the Data Monitoring Committee. There is yet to be in-depth consideration establishing the Trial Steering Committee's role and functionality. METHODS: A survey to establish Trial Steering Committee's current practices, role and the use and opinion on the Medical Research Council guidelines was undertaken within UK Clinical Research Collaborative registered Clinical Trials Units. RESULTS: Completed surveys were obtained from 38 of 47 fully and partially registered Units. Individual items in the survey were analysed and reported spanning current Trial Steering Committee practices including its role, requirement and experience required for membership; methods to identify members; and meeting frequency. Terms (a document describing the committee's remit, objectives and functionality) were obtained and analysed from 21 of 33 Units with documents in place at their Unit. A total of 20 responders suggested aspects of the current Medical Research Council Guidelines that need improvement. CONCLUSION: We present the first survey reporting on practices within UK Clinical Research Collaborative registered Clinical Trials Units on the experience and remits of Trial Steering Committees. We have identified a widespread adoption of Medical Research Council Guidelines for Trial Steering Committees in the United Kingdom, but limitations in this existing provision have been identified that need to be addressed.