Plain English summary Researchers test treatments to ensure these work and are safe. They do this by studying the effects that treatments have on patients by measuring outcomes, such as pain and quality of life. Often research teams measure different outcomes even though each team is studying the same condition. This makes it hard to compare the findings from different studies and it can reduce the accuracy of the treatment advice available to patients. Increasingly, researchers are tackling this problem by developing ‘core outcome sets’. These are lists of outcomes that all researchers working on a given condition should measure in their studies. It is important that patients have a voice in the development of core outcome sets and children and young people are no exception. But their voices have rarely been heard when core outcome sets are developed. Researchers are trying to address this problem and make sure that core outcome sets are developed in ways that are suitable for children and young people. As a first step, we held two international workshops with children and young people to listen to their views. They emphasised the importance of motivating young people to participate in developing core outcome sets, making them feel valued, and making the development process more interactive, enjoyable and convenient. We hope this commentary will encourage researchers to include children and young people when developing core outcome sets and to adapt their methods so these are suitable for young participants. Future research is important to examine whether these adaptations are effective. Abstract Background Different research teams looking at treatments for the same condition often select and measure inconsistent treatment outcomes. This makes it difficult to synthesise the results of different studies, leads to selective outcome reporting and impairs the quality of evidence about treatments. ‘Core outcome sets’ (COS) can help to address these problems. A COS is an agreed, minimum list of outcomes that researchers are encouraged to consistently measure and report in their studies. Including children and young people (CYP) as participants in the development of COS for paediatric conditions ensures that clinically meaningful outcomes are measured and reported. However, few published COS have included CYP as participants. COS developers have described difficulties in recruiting and retaining CYP and there is a lack of guidance on optimising COS methods for them. We aimed to explore CYP’s views on the methods used to develop COS and identify ways to optimise these methods. Main body This commentary summarises discussions during two workshops with approximately 70 CYP (aged 10–18 years old) at the International Children’s Advisory Network Research and Advocacy Summit, 2018. Delegates described what might motivate them to participate in a COS study, including feeling valued, understanding the need for COS and the importance of input from CYP in their development, and financial and other incentives (e.g. certificates of participation). For Delphi surveys, delegates suggested that lists of outcomes should be as brief as possible, and that scoring and feedback methods should be simplified. For consensus meetings, delegates advised preparing CYP in advance, supporting them during meetings (e.g. via mentors) and favoured arrangements whereby CYP could meet separately from parents and other stakeholders. Overall, they wanted COS methods that were convenient, enjoyable and engaging. Conclusion This commentary points to the limitations of the methods currently used to develop COS with CYP. It also points to ways to motivate CYP to participate in COS studies and to enhancements of methods to make participation more engaging for CYP. Pending much needed research on COS methods for CYP, the perspectives offered in the workshops should help teams developing COS in paediatrics and child health.

Background Previous research has identified the need for a randomised controlled trial (RCT) evaluating the most appropriate corticosteroid induction regimen to be used for children and young people (CYP) with juvenile idiopathic arthritis (JIA) (1). A recent qualitative study found that parents and CYP understood trial concepts and were able to identify potential flaws in a proposed RCT. This confirms the need to involve parents and CYP in co-designing RCTs to best meet the needs of future trial participants (2). Objectives To co-design components of an RCT of corticosteroid regimens with CYP and parents living with JIA. Methods A focus group was conducted with CYP with JIA and parents as part of a wider consensus and discussion group meeting within the Steroid Induction Regimen for Juvenile Idiopathic Arthritis (SIRJIA) study in December 2018. The discussion focused on two components of the RCT design: i) Discussing the most appropriate treatment protocols; and ii) Addressing practicalities associated with an RCT. Results Two RCT protocol options, chosen through an online survey by a clear majority out of a possible eight protocols, were discussed and critiqued: i) Protocol A (intravenous vs intraarticular corticosteroid delivery); and ii) Protocol B (intravenous vs intraarticular vs intramuscular vs oral corticosteroid delivery). Several issues pertaining to both protocols were raised, related to the influence of age and past experience, routes of administration and concerns over randomisation. Participants emphasised the importance of clinicians/researchers discussing all of the potential risks with them. Participants also wanted enough information to make an informed choice. Participants emphasised the usefulness of combining trial visits with regular follow-up appointments to minimise the burden of taking part in an RCT and had a preference for their usual hospital being the site they visited. Some participants remarked that videos could be a useful way of conveying information beyond traditional participant information sheets. Some also felt that awareness of research opportunities is not equally accessible to them either, depending on where they lived in the country. Participants would want to be kept regularly updated about the progress of the RCT and felt that incentives were a good way of keeping people engaged, although some were trepidatious to hear negative treatment results. With regards to dissemination, participants felt that study results should be readily available to them in an accessible format, should they wish to view them. Conclusion CYP and parents have a considerable amount of knowledge and experience which can shape the design of RCTs. With adequate support, complex concepts such as treatment protocols can be discussed and critiqued. Involving CYP and parents at the design stage of an RCT has been shown to eliminate some potential challenges in the future. References [1] Deepak, et al. (2017). Literature review on the use of corticosteroids in juvenile idiopathic arthritis (JIA). Rheumatology 56(Suppl7). [2] Sherratt FC, et al. (2018). Protective parents and permissive children: what qualitative interviews with parents and children can tell us about the feasibility of juvenile idiopathic arthritis trials. Pediatric Rheumatology 16:76. Acknowledgement This activity was funded as part of the SIRJIA study, funded by the NIHR Health Technology Assessment Programme (14/167/01). The funders did not have a role in the design, collection, analysis, or interpretation of the data. Disclosure of Interests Simon Stones Consultant for: SS has provided consultancy services to Envision Pharma Group, though this is not related to the contents of this abstract., Speakers bureau: SS has undertaken speaking engagements for Actelion, eyeforpharma, Four Health, Janssen and Roche, though these are not related to the contents of this abstract., Heather Bagley: None declared, Frances Sherratt: None declared, Louise Roper: None declared, Eileen Baildam Consultant for: EB has received one paid consultancy for Pfizer in the last 12 months, but this was not related to this study.

Background Juvenile idiopathic arthritis (JIA) is an umbrella term for seven relapsing-remitting inflammatory conditions in children and young people (CYP). Early, intensive treatment can prevent long-term damage; however, established drugs exhibit a delayed response, prompting the need for rapid-onset treatment in the form of corticosteroids. Given a lack of consensus as to which corticosteroid induction regimen should be used for CYP with JIA, a feasibility trial of different regimens is needed. Objectives The aim was to achieve consensus among CYP, families, and healthcare professionals (HCPs) about the primary outcome measures and protocol components to include in a prospective feasibility study. Methods A modified Nominal Group Technique was used to achieve consensus on the most appropriate primary outcome measure to be included in a prospective feasibility study, in addition to other protocol components such as inclusion/exclusion criteria. Fifteen participants participated in the process, including a combination of CYP with JIA, families (n=9) and HCPs (n=6). Results In the first vote, participants agreed that ‘Juvenile Arthritis Disease Activity Score (JADAS)’ and ‘Physician Global Assessment Score’ were most meaningful. During sub-group discussions, the need for a composite score which captured the voice of CYP and families was emphasised. In the second vote, ‘JADAS’ and the ‘JIA Core Set’ were identified as the most important. Further discussions led to the results of the third vote, agreeing ‘JADAS’ as the primary outcome measure of choice being measured at 6 weeks after commencement of treatment. The majority of HCPs, CYP and families voted for all JIA sub-types to be included in a prospective feasibility study, with some queries about the inclusion of systemic JIA given its unique presentation. Participants also identified the need for more frequent data collection time points to capture the rapid onset of corticosteroid action, while CYP and families opted for accessible mechanisms for participation, such as digital follow-up strategies. Conclusion It is feasible to include CYP, families and HCPs in synthesising complex concepts to agree by consensus the design components of clinical research. The primary outcome measure for inclusion in a prospective feasibility study of corticosteroid regimens in CYP with JIA was co-prioritised, with CYP and families taking a leading role in the ultimate selection of an appropriate outcome measure and other study protocol components. Using consensus methods with CYP, families and HCPs is a systematic and rigorous way in which to select outcome measures that are both meaningful and relevant to everyone involved in the care and treatment of CYP with JIA. References [1] Sherratt F, et al. Family perspectives on the feasibility of a corticosteroid induction regimen trial in juvenile idiopathic arthritis. In: International Clinical Trials Methodology Conference: 2017; Liverpool, UK: Trials; 2017 Acknowledgement This consensus meeting was funded as part of the SIRJIA study, funded by the NIHR Health Technology Assessment Programme (14/167/01). The funders did not have a role in the design, collection, analysis, or interpretation of the data Disclosure of Interests Simon Stones Consultant for: SS has provided consultancy services to Envision Pharma Group, though this is not related to the contents of this abstract., Speakers bureau: SS has undertaken speaking engagements for Actelion, eyeforpharma, Four Health, Janssen and Roche, though these are not related to the contents of this abstract., Heather Bagley: None declared, Ashley Jones: None declared, Flora McErlane: None declared, Tracy Moitt: None declared, Gloria Nkhoma: None declared, Frances Sherratt: None declared, Bridget Young: None declared, Michael Beresford: None declared, Eileen Baildam Consultant for: EB has received one paid consultancy for Pfizer in the last 12 months, but this was not related to this study.

Abstract Background Previous research has identified the need for a randomised controlled trial (RCT) evaluating the most appropriate corticosteroid induction regimen to be used for children and young people (CYP) with juvenile idiopathic arthritis (JIA). A recent qualitative study found that parents and CYP understood trial concepts and were able to identify potential flaws in a proposed RCT. This confirms the need to involve parents and CYP in co-designing RCTs to best meet the needs of future trial participants. We aimed to co-design components of an RCT of corticosteroid regimens with CYP and parents living with JIA. Methods A focus group was conducted with CYP with JIA and parents as part of a wider consensus and discussion group meeting within the Steroid Induction Regimen for Juvenile Idiopathic Arthritis (SIRJIA) study in December 2018. The discussion focused on two components of the RCT design: i) Discussing the most appropriate treatment protocols; and ii) Addressing practicalities associated with an RCT. Results Two RCT protocol options, chosen through an online survey by a clear majority out of a possible eight protocols, were discussed and critiqued: i) Protocol A (intravenous vs intraarticular corticosteroid delivery); and ii) Protocol B (intravenous vs intraarticular vs intramuscular vs oral corticosteroid delivery). Several issues pertaining to both protocols were raised, related to the influence of age and past experience, routes of administration and concerns over randomisation. Participants emphasised the importance of clinicians/researchers discussing all of the potential risks with them. Participants also wanted enough information to make an informed choice. Participants emphasised the usefulness of combining trial visits with regular follow-up appointments to minimise the burden of taking part in an RCT and had a preference for their usual hospital being the site they visited. Some participants remarked that videos could be a useful way of conveying information beyond traditional participant information sheets. Some also felt that awareness of research opportunities is not equally accessible to them either, depending on where they lived in the country. Participants would want to be kept regularly updated about the progress of the RCT and felt that incentives were a good way of keeping people engaged, although some were apprehensive about hearing negative treatment results. With regards to dissemination, participants felt that study results should be readily available to them in an accessible format, should they wish to view them. Conclusion CYP and parents have a considerable amount of knowledge and experience which can shape the design of RCTs. With adequate support, complex concepts such as treatment protocols can be discussed and critiqued. Involving CYP and parents at the design stage of an RCT has been shown to eliminate some potential challenges in the future. Conflicts of Interest The authors declare no conflicts of interest.

Juvenile idiopathic arthritis (JIA) is an umbrella term for seven relapsing-remitting inflammatory conditions in children and young people (CYP). Early, intensive treatment can prevent long-term damage; however, established drugs exhibit a delayed response, prompting the need for rapid-onset treatment in the form of corticosteroids. Given a lack of consensus as to which corticosteroid induction regimen should be used for CYP with JIA, a feasibility trial of different regimens is needed. The aim was to achieve consensus among CYP, families, and healthcare professionals (HCPs) about the primary outcome measures and protocol components to include in a prospective feasibility study. A modified Nominal Group Technique was used to achieve consensus on the most appropriate primary outcome measure to be included in a prospective feasibility study, in addition to other protocol components such as inclusion/exclusion criteria. Fifteen participants participated in the process, including a combination of CYP with JIA, families (n = 9) and HCPs (n = 6). In the first vote, participants agreed that Juvenile Arthritis Disease Activity Score (JADAS) and Physician Global Assessment Score were most meaningful. During sub-group discussions, the need for a composite score which captured the voice of CYP and families was emphasised. In the second vote, JADAS and the JIA Core Set were identified as the most important. Further discussions led to the results of the third vote, agreeing JADAS as the primary outcome measure of choice being measured at 6 weeks after commencement of treatment. The majority of HCPs, CYP and families voted for all JIA sub-types to be included in a prospective feasibility study, with some queries about the inclusion of systemic JIA given its unique presentation. Participants also identified the need for more frequent data collection time points to capture the rapid onset of corticosteroid action, while CYP and families opted for accessible mechanisms for participation, such as digital follow-up strategies. It is feasible to include CYP, families and HCPs in synthesising complex concepts to agree by consensus the design components of clinical research. The primary outcome measure for inclusion in a prospective feasibility study of corticosteroid regimens in CYP with JIA was co-prioritised, with CYP and families taking a leading role in the ultimate selection of an appropriate outcome measure and other study protocol components. Using consensus methods with CYP, families and HCPs is a systematic and rigorous way in which to select outcome measures that are both meaningful and relevant to everyone involved in the care and treatment of CYP with JIA. The authors declare no conflicts of interest.

Background Core outcome sets (COS) are being developed in many clinical areas to increase the quality and comparability of clinical trial results as well as to ensure their relevance for patients. A COS represents an agreed standardized set of outcomes that describes the minimum that should be consistently reported in all clinical trials of a defined area. It comprises a core domain set (defining what core outcomes should be measured) and a core measurement set (defining measurement/assessment instruments for each core domain). For pressure ulcer prevention trials a COS is lacking. The great heterogeneity of reported outcomes in this field indicates the need for a COS. Methods/design The first part of this project aims to develop a core domain set by following established methods, which incorporates four steps: (1) definition of the scope, (2) conducting a scoping review, (3) organizing facilitated workshops with service users, (4) performing Delphi surveys and establishing consensus in a face-to-face meeting with different stakeholders. Discussion After achieving consensus on the core domain set, further work will be undertaken to determine a corresponding core measurement set. This will lead to better pressure ulcer prevention research in the future. There are a number of methodological challenges in the field of COS development. To meet these challenges and to ensure a high-quality COS, the OUTPUTS project affiliates to current standards and works in close collaboration with international experts and with existing international service user groups. Trial registration The OUTPUTs project is registered in the COMET database: ( http://www.comet-initiative.org/studies/details/283 ). Registered on 2015.

The selection of appropriate outcomes is crucial when designing clinical trials in order to compare the effects of different interventions directly. For the findings to influence policy and practice, the outcomes need to be relevant and important to key stakeholders including patients and the public, health care professionals and others making decisions about health care. It is now widely acknowledged that insufficient attention has been paid to the choice of outcomes measured in clinical trials. Researchers are increasingly addressing this issue through the development and use of a core outcome set, an agreed standardised collection of outcomes which should be measured and reported, as a minimum, in all trials for a specific clinical area.Accumulating work in this area has identified the need for guidance on the development, implementation, evaluation and updating of core outcome sets. This Handbook, developed by the COMET Initiative, brings together current thinking and methodological research regarding those issues. We recommend a four-step process to develop a core outcome set. The aim is to update the contents of the Handbook as further research is identified.

BackgroundDespite increasing international interest, there is a lack of evidence about the most efficient, effective and acceptable ways to implement patient and public involvement (PPI) in clinical trials. ObjectiveTo identify the priorities of UK PPI stakeholders for methodological research to help resolve uncertainties about PPI in clinical trials. DesignA modified Delphi process including a two round online survey and a stakeholder consensus meeting. ParticipantsIn total, 237 people registered of whom 219 (92%) completed the first round. One hundred and eighty-seven of 219 (85%) completed the second; 25 stakeholders attended the consensus meeting. ResultsRound 1 of the survey comprised 36 topics; 42 topics were considered in round 2 and at the consensus meeting. Approximately 96% of meeting participants rated the top three topics as equally important. These were as follows: developing strong and productive working relationships between researchers and PPI contributors; exploring PPI practices in selecting trial outcomes of importance to patients; and a systematic review of PPI activity to improve the accessibility and usefulness of trial information (eg participant information sheets) for participants. ConclusionsThe prioritized methodological research topics indicate important areas of uncertainty about PPI in trials. Addressing these uncertainties will be critical to enhancing PPI. Our findings should be used in the planning and funding of PPI in clinical trials to help focus research efforts and minimize waste.

This commentary article describes three interactive workshops that explored how patients can contribute to decisions about what outcomes are measured in clinical trials across the world. Outcomes like quality of life, side-effects and pain are used in trials to measure whether a treatment is effective. Here, we outline how research groups are increasingly coming together to develop ‘core outcomes sets’ for particular conditions. Core outcome sets are lists of agreed outcomes. Their use will help in identifying which treatments are effective by enabling people to compare the findings of different clinical trials in the same condition. Currently, it is often very difficult to make these comparisons because different studies often measure different outcomes. Delegates attending the workshops included patients, clinicians and researchers. They discussed ways of making core outcome set development more meaningful and accessible for patients, and ensuring that they have a genuine say in the development process. This article summarises these discussions and concludes by identifying three distinctive challenges in securing patient input to core outcome set development: the process and objectives can seem far removed from the immediate concerns of patients, difficulties can arise in securing patient input on an international scale, and difficulties can also arise in bringing multiple stakeholder groups together to achieve consensus. While patient participation, involvement and engagement in core outcome set development can draw on lessons from other research areas, these distinctive challenges point to the need for distinctive solutions to enable meaningful patient input to core outcome set development.

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.

Patient and public involvement (PPI) in research involves the active contribution of members of the public in research studies and within research organisations. PPI is important in ensuring the relevance and quality of general health care research. Funders often now request evidence of prior and future planned PPI in health research. The impact of PPI on various aspects of study development and delivery has been described, from study design through to the dissemination and implementation of study findings. Research, however suggests that PPI is inconsistent in terms of levels of engagement, quality and reporting. Within clinical trials variations in intentions and plans for PPI and the experience and impact of such involvement have been identified. Additionally resources to support PPI in clinical trials are often not used in practice. The University of Liverpool Clinical Trials Research Centre PPI working group decided to design a web based toolkit designed to support the PPI activities in clinical trials. The toolkit will signpost chief investigators and trial teams to a range of tools. The tools are designed to facilitate meaningful and effective PPI at all stages of a clinical trial. The development of the toolkit involves: • Describing the PPI pathway through a clinical trial • Identifying existing internal and external resources to support PPI • Identifying additional required resources • Evaluating the use the resources • Disseminating information about the use and impact of the resources and making improvements and modifications to them based on our experience. The results of developing this toolkit will be presented.

Patient and public involvement (PPI) in research involves the active contribution of members of the public in research studies and within research organisations. PPI is important in ensuring the relevance and quality of general health care research. Funders often now request evidence of prior and future planned PPI in health research. The University of Liverpool Clinical Trials Research Centre recently appointed a part time Patient and Public Involvement Co-ordinator. In order to inform the development of a PPI strategy for the Unit, the Co-ordinator is conducting a mapping and gapping exercise to identify where, when and how previous and current trials involve Public Research Partners (PRPs) and where there is potential to increase and improve such involvement. This analysis will seek to: • Map the amount, type and stages of PPI taking place in existing trials in the Unit, including Research Network involvement • Describe current processes for recruiting, training, support and funding of Public Research Partners in the CTRC • Identify current mechanisms for evaluating and documenting the impact of PPI in trials run by the CTRC • Indicate current gaps in PPI within the CTRC and propose recommendations to address these gaps. The facilitator will conduct semi structured interviews with trial co-ordinators and will review PPI plans of trials being run by the unit to examine both involvement in the research application process and to examine what was planned in terms of PPI at the outset. The results from this mapping and gapping exercise will be presented.