Epidermolysis Bullosa PSP protocol

Purpose of the PSP and background

The purpose of this protocol is to clearly set out the aims, objectives and commitments of the Epidermolysis Bullosa (EB) Priority Setting Partnership (PSP) in line with James Lind Alliance (JLA) principles. The Protocol is a JLA requirement and will be published on the PSP’s page of the JLA website. The Steering Group will review the Protocol regularly and any updated version will be sent to the JLA.

The JLA is a non-profit making initiative, established in 2004. It brings patients, carers and clinicians together in PSPs. These PSPs identify and prioritise the evidence uncertainties, or ‘unanswered questions’, that they agree are the most important for research in their topic area. Traditionally PSPs have focused on uncertainties about the effects of treatments, but some PSPs have chosen to broaden their scope beyond that. The aim of a PSP is to help ensure that those who fund health research are aware of what really matters to patients, carers and clinicians. The National Institute for Health and Care Research (NIHR) coordinates the infrastructure of the JLA to oversee the processes for PSPs, based at the NIHR Coordinating Centre (NIHRCC), University of Southampton.

Epidermolysis bullosa (EB) is an incredibly painful genetic skin blistering condition. It causes the skin to blister and tear at the slightest touch. With skin as fragile as a butterfly’s wings, it’s often referred to as ‘butterfly skin’. EB can affect the hands and feet only, or in the most severe cases, any part of the body, including blistering on the eyes and internal organs. People living with EB live in constant, debilitating pain and, in severe cases, it can be fatal.

A previous study with JLA in 2012 looked at the priorities for people living with Dystrophic EB and did successfully help shape the research strategy for DEB. But other main sub types of EB were not included in the study, and we wish to replicate the success of the DEB PSP to include all four main EB sub-types. Treatments and care have advanced to various degrees since the last PSP and therefore now is a good time to understand current priorities for all EB types to help prioritise research questions.

This is a UK-led PSP, and DEBRA UK has a membership of around 3,500 members who are directly affected by EB, as well clinicians/professionals working with the EB community, who we will engage in this work. But we will also seek global input through our networks and links with other DEBRAs, and organisations supporting people with EB, around the world.

Aims, objectives and scope of the PSP

The aim of the EB PSP is to identify the unanswered questions, from EB patients, carers of those with EB and clinicians, about all four main sub-types of EB – EB Simplex, Dystrophic EB, Junctional EB and Kindler EB. The most important questions for research to address will then be identified and prioritised.

The objectives of the PSP are to:

• work with EB patients, carers of those living with EB, and clinicians to identify uncertainties about care and treatments for the EB community, with care being defined as ways to manage the symptoms of EB. The UK healthcare system is included within this scope, but we will not be conducting a comparison of international healthcare systems involved in the delivery of EB care.
• to agree by consensus a prioritised list of those uncertainties, for research to address
• to publicise the results of the PSP and its process
• to take the results to research commissioning bodies to be considered for funding.

The scope of the EB PSP is defined as:

• To include people of all ages living with the four sub-types of EB – Simplex, Dystrophic, Junctional and Kindler.
• The PSP will be developed and initiated in the UK with opportunities for representation from global communities, via DEBRA organisations from around the world, being included throughout the project.
• The PSP will aim to assess and understand the similarities and differences in research priorities across the 4 main EB sub-types, and will remain open to understanding how these differences are incorporated into the final priorities.
• To identify the research priorities across the 4 main EB types.
• People living with EB Simplex are currently underrepresented in research and publications but constitute c75% of the EB population. This study will consciously communicate and engage representation from this group, as well as other under-served populations as defined by the steering group in order to ensure that this PSP focuses on all four main types of EB.

The scope of this project may be refined through early discussion in the steering group.

The PSP will exclude from its scope questions about:

• While it is believed that the research uncertainties from the global populations will be similar, but not yet evidenced, the local healthcare service needs may not have similarities in priorities due to the disparities of local care/support available. Therefore non-UK healthcare service needs will not be included in the study.
• Epidermolysis Bullosa Acquisita will not be within the scope of this PSP, because this conditions presents in a similar way to other EB types, the underlying cause of EBA is different to other EB types and therefore research priorities may differ.

The Steering Group is responsible for discussing what implications the scope of the PSP will have for the evidence-checking stage of the process. Resources and expertise will be put in place to do this evidence checking.

The Steering Group

The Steering Group includes membership of EB patients and carers of those living with EB and clinicians, as individuals or representatives from a relevant group.

The EB PSP will be led and managed by a Steering Group involving the following:

Patient and carer representative/s

• Ella Turner
• Hazel Nugent
• Isha Arilal
• Jatinder Harchowal (also Chief Pharmacist, UCLH NHS Foundation Trust)
• Katie White (also Tissue Viability Nurse)
• Maryam Ahmadi
• Paul Cotton (also podiatrist)
• Rebecca Knight
• Ryan Hultman, DEBRA Canada
• Sarah Dixon
• Stefan Edwards

Clinical representative/s

• Ajoy Bardhan (Honorary Consultant Dermatologist, Solihull Hospital and Clinical Lecturer, University of Birmingham)
• Anna Martinez (Paediatric Dermatologist and Honorary Associate Professor at Great Ormond Street Hospital)
• Finola Sheehan (EB Clinical Nurse Specialist, Great Ormond Street Hospital)
• Irene Lara-Corrales (Associate Professor of Paediatrics at the University of Toronto and a staff physician in Paediatric Dermatology at the Hospital for Sick Children in Toronto, Canada)

EB PSP Project Team

• Amy Price (Synergy Healthcare Research and EB PSP Information specialist)
• Caroline Magee (James Lind Alliance Adviser and Chair of the Steering Group)
• Charlotte Sugden Heron (Synergy Healthcare Research and EB PSP Information specialist)
• Claire Mather (DEBRA UK and EB PSP Lead)
• Sagair Hussan (DEBRA UK)
• Sophie Jones (DEBRA UK and EB PSP Coordinator)

The Steering Group will agree the resources, including time and expertise that they will be able to contribute to each stage of the process, with input and advice from the JLA.

Partners

Organisations and individuals will be invited to be involved with the PSP as partners. Partners are organisations or groups who will commit to supporting the PSP, promoting the process and encouraging their represented groups or members to participate. Organisations which can reach and advocate for these groups will be invited to become involved in the PSP. Partners represent the following groups:

• people who have EB
• carers of people who have EB
• health and social care professionals - with experience of EB

Exclusion criteria

Some organisations may be judged by the JLA or the Steering Group to have conflicts of interest. These may be perceived to potentially cause unacceptable bias as a member of the Steering Group. As this is likely to affect the ultimate findings of the PSP, those organisations will not be invited to participate. It is possible, however, that interested parties may participate in a purely observational capacity when the Steering Group considers it may be helpful.

The methods the PSP will use

This section describes a schedule of proposed steps through which the PSP aims to meet its objectives. The process is iterative and dependent on the active participation and contribution of different groups. The methods used in any step will be agreed through consultation between the Steering Group members, guided by the PSP’s aims and objectives. More details of the method are in the Guidebook section of the JLA website where examples of the work of other JLA PSPs can be seen.

Step 1: Identification and invitation of potential partners

Potential partner organisations will be identified through a process of peer knowledge and consultation, through the Steering Group members’ networks. Potential partners will be contacted and informed of the establishment and aims of the EB PSP.

Step 2: Awareness raising

PSPs will need to raise awareness of their proposed activity among their patient, carer and clinician communities, in order to secure support and participation. Depending on budget, this may be done by a face-to-face meeting, or there may be other ways in which the process can be launched, e.g. via social media. It may be carried out as part of steps 1 and/or 3. The Steering Group should advise on when to do this. Awareness raising has several key objectives:

• to present the proposed plan for the PSP
• to generate support for the process
• to encourage participation in the process
• to initiate discussion, answer questions and address concerns.

Step 3: Identifying evidence uncertainties

The EB PSP will carry out a consultation to gather uncertainties from patients, carers and clinicians. A period of 1 month will be given to complete this exercise (which may be revised by the Steering Group if required).

The EB PSP recognises that the following groups may require additional consideration:

• Previously underserved populations – young people affected by EB, minority ethnic groups, people from lower-socioeconomic groups
• A good balance of people representing all types of EB, as previous work focused on Dystrophic EB.

The Steering Group will use the following methods to reach the target groups:

• Creative online solutions to surveys (Instagram polls etc).
• Targeted communications to DEBRA UK communities
• Partnership working with DEBRAs worldwide in reaching these underserved communities
• Surveys will be designing in English, but explore options for the survey designs to be easy to translate into other languages

Existing sources of evidence uncertainties may also be searched, including existing clinical guidelines for EB that reference research recommendations, the DEBRA UK EB Insights study, EB community surveys, feedback from professionals working with EB, published EB research papers and work conducted by eg. DEBRAs that has not been published. It has to be noted that there is little published data which heightens the need for the EB PSP.

Step 4: Refining questions and uncertainties

The consultation process will produce ‘raw’ questions and comments indicating EB patients’, carers’ of those living with EB and clinicians’ areas of uncertainty. These raw questions will be categorised and refined by Synergy Healthcare into summary questions which are clear, addressable by research, and understandable to all. Similar or duplicate questions will be combined where appropriate. Out-of-scope and ‘answered’ submissions will be compiled separately. The Steering Group will have oversight of this process to ensure that the raw data is being interpreted appropriately and that the summary questions are being worded in a way that is understandable to all audiences. The JLA Adviser will observe to ensure accountability and transparency.

This will result in a long list of in-scope summary questions. These are not research questions and to try and word them as such may make them too technical for a non-research audience. They will be framed as researchable questions that capture the themes and topics that people have suggested.

The summary questions will then be checked against evidence to determine whether they have already been answered by research. This will be done by Synergy Healthcare. The PSP will complete the JLA Question Verification Form, which clearly describes the process used to verify the uncertainty of the questions, before starting prioritisation. The Question Verification Form includes details of the types and sources of evidence used to check uncertainty. The Question Verification Form should be published on the JLA website as soon as it has been agreed to enable researchers and other stakeholders to understand how the PSP has decided that its questions are unanswered, and any limitations of this.

Questions that are not adequately addressed by previous research will be collated and recorded on a standard JLA template by Synergy Healthcare. This will show the checking undertaken to make sure that the uncertainties have not already been answered. The data should be submitted to the JLA for publication on its website on completion of the priority setting exercise, taking into account any changes made at the final workshop, in order to ensure that PSP results are publicly available.

The Steering Group will also consider how it will deal with submitted questions that have been answered, and questions that are out of scope.

Step 5: Prioritisation – interim and final stages

The aim of the final stage of the priority setting process is to prioritise through consensus the identified uncertainties about EB. This will involve input from patients, carers and clinicians. The JLA encourages PSPs to involve as wide a range of people as possible, including those who did and did not contribute to the first consultation. There are usually two stages of prioritisation.

1. Interim prioritisation is the stage where the long list of questions is reduced to a shorter list that can be taken to the final priority setting workshop. This is aimed at a wide audience, and is done using similar methods to the first consultation. With the JLA’s guidance, the Steering Group will agree the method and consider how best to reach and engage patients, carers and clinicians in the process. The most highly ranked questions (around 25) will be taken to a final priority setting workshop. Where the interim prioritisation does not produce a clear ranking or cut off point, the Steering Group will decide which questions are taken forwards to the final prioritisation.
   
   
2. The final priority setting stage is generally a one-day workshop facilitated by the JLA. With guidance from the JLA and input from the Steering Group, up to 30 patients, carers and clinicians will be recruited to participate in a day of discussion and ranking, to determine the top 10 questions for research. All participants will declare their interests. The Steering Group will advise on any adaptations needed to ensure that the process is inclusive and accessible.

Dissemination of results

The Steering Group will identify audiences with which it wants to engage when disseminating the results of the priority setting process, such as researchers, funders and the patient and clinical communities. They will need to determine how best to communicate the results and who will take responsibility for this. Previous PSPs’ outputs have included academic papers, lay reports, infographics, conference presentations and videos for social media.

It should be noted that the priorities are not worded as research questions. The Steering Group should discuss how they will work with researchers and funders to establish how to address the priorities and to work out what the research questions are that will address the issues that people have prioritised. The dissemination of the results of the PSP will be led by Claire Mather and Dr Sagair Hussain from DEBRA UK.

The JLA encourages PSPs to report back about any activities that have come about because of the PSP, including funded research. Please send any details to jla@soton.ac.uk.

Agreement of the Steering Group

The Epidermolysis Bullosa PSP Steering Group agreed the content and direction of this Protocol on 22/04/24.