Global Perianal Crohn’s Disease 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 Perianal Crohn’s Disease 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.  

Perianal Crohn’s disease (pCD) is a common manifestation of Crohn’s disease (a chronic inflammatory condition of the gastrointestinal tract) occurring in around 18.7% of all patients with CD. Perianal Crohn’s disease represents a diverse array of pathologies, including fistulae, abscesses, strictures, fissures, ulcers, skin tags, haemorrhoids and anal carcinoma (.PDF) as well as regional cutaneous conditions. Perianal fistulae are the most common manifestation of perianal Crohn’s disease.

Medical treatments such as Anti-Tumour Necrosis Factor (Anti-TNF) drugs are effective but have significant relapse rates on cessation, and rates of fistulae closure are modest. A plethora of surgical treatments are available, with a number of promising treatments emerging such as video-assisted anal fistula treatment (VAAFT), Fistula Laser Closure (FiLaC), and recent promising results with mesenchymal stem cells. The long-term efficacy and precise roles of these treatments in the treatment pathway are uncertain. 

Perianal Crohn’s disease is a highly morbid condition. Qualitative research has demonstrated the significant impact on the quality of life of patients with perianal Crohn’s disease, encompassing the burden of the disease and symptoms itself, as well as the burden of treatments. These elements may lead to negative impacts due to emotional consequences, physical restrictions, as well as social and work-related issues. 

No priority setting partnership has been undertaken on the topic of perianal Crohn’s disease. However, in the 2017 PSP to identify the top research priorities in Inflammatory Bowel Disease, the need for further research into perianal Crohn’s disease was identified as the 5th most important priority. A follow up study in 2021 demonstrated that this area was the subject of two non-pharmaceutical sponsored studies and one pharmaceutical sponsored study, with the majority of studies focused elsewhere. 

Perianal Crohn’s requires lifelong treatment and multiple interventions. Options for treatment and their impact on quality of life, efficacy of medical and surgical procedures, and the impact of setons, stomas and proctectomy remain inadequately assessed, and centre around shared decision making. Therefore it is crucial that a collaborative and patient-centred approach is taken in order to prioritise research questions in a field with many unmet needs. 

The purpose of the pCD PSP is to provide an opportunity for healthcare professionals, researchers, patients and carers to collaborate to develop a top 10 list of research priorities in perianal Crohn’s disease. This will be an global  PSP, with international representation  in both the Steering Group and survey respondents. 

Aims, objectives and scope of the PSP

The aim of the international Perianal Crohn’s Disease  PSP is to identify the unanswered questions about Perianal Crohn’s Disease from patient, carer and clinical perspectives and then prioritise those that patients, carers and clinicians agree are the most important for research to address. 

The objectives of the PSP are to:

• work with patients, carers and clinicians internationally to identify uncertainties about aetiology, definitions and classifications, diagnosis and investigations, treatments, post-surgical concerns and all aspects of the patient pathway.
• to agree by consensus a prioritised list of those uncertainties, for research
• to publicise the results of the PSP and process
• to take the results to international research commissioning bodies to be considered for funding.

The scope of the Perianal Crohn’s Disease PSP is defined as: 

• Uncertainties relating to the following aspects of pCD:
  • Aetiology and risk factors
  • Definitions and classification
  • Diagnosis and investigations
  • Treatments, post-surgical concerns and all aspects of the patient pathway.

Stomas are likely to form a key element, and specific issues such as vaginal fistulae and fistulae in the context of extensive perianal disease may also feature.

• Uncertainties relating to both fistulising and non-fistulising conditions, including fistulas, strictures, abscesses, skin tags, fissures, ulcers, and associated regional cutaneous manifestations. Questions regarding related conditions that may result from, or complicate management of perianal Crohn’s disease, such as anorectal carcinoma and haemorrhoids, will also be considered.
• Uncertainties related to pCD in both adult and paediatric populations. As perianal Crohn’s disease is a condition that can affect all ages but is common in young adults and adolescents.

The PSP will likely exclude from its scope:

• Questions relating to development of pCD due to monogenic disease
• Questions that explore localised or nation-specific issues related to health-care infrastructure will be considered out of scope. 

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 patients and carers and clinicians, as individuals or representatives from a relevant group. 

The Perianal Crohn’s Disease PSP will be led and managed by a mix of clinicians (medical, nursing, radiological and surgical), specialist nurses, researchers, carers, patient experts and representatives, with expertise from professional or lived experience of perianal Crohn’s Disease. The Steering Group will be composed of members from a number of countries from North and South America, Europe and Asia, to ensure adequate geographic representation. 

The details of the steering group membership will be confirmed following discussion with the JLA representative. 

Project Leads

Professor Ailsa Hart – Gastroenterology, St Mark’s Hospital

Mr Phil Tozer – Colorectal Surgery, St Mark’s Hospital

Patient representatives

Tom Hough

Dr Sarah Markham

Amira Abbas

Sameer Mannick

Kartheeswaran Selvaraj

Clinical representative/s

Dr Parakkal Deepak, Gastroenterology, Washington University in St Louis, USA

Professor Jeff McCurdy, Gastroenterology, Ottawa, Canada

Professor Shaji Sebastian, Gastroenterology, Hull, York, UK

Dr Phillip Lung, Radiology, St Marks Hospital, UK

Professor Jaap Stoker, Radiology, Amsterdam UMC, Netherlands

Dr Christianne Buskens, Colorectal Surgery, Amsterdam UMC, Netherlands

Lisa Younge, Nurse Consultant, St Marks Hospital, UK,

Denise Robinson, Clinical Nurse Manager, St Mark’s Hospital, UK

Dr Paolo Kotze, Colorectal Surgery, Catholic University of Parana, Brazil

Dr Amir Radmard, Radiology, Tehran University of Medical Sciences, Iran

Dr Harjeet Singh, GI Surgery, PGIMER, India

Partner organisation representative

Dr Yarunessa Khan, Crohn’s and Colitis UK

Data analysis team

Luke Hanna

Shivani Joshi

Eathar Shakweh

Easan Anand

Project coordinator

Mr Theo Pelly, Research Fellow, Fistula Research Unit, St Mark’s Hospital

James Lind Alliance Adviser and Chair of the Steering Group

Dr Jonathan Gower, James Lind Alliance

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 perianal Crohn’s disease
• carers of people who have had perianal Crohn’s disease
• health and social care professionals - with experience of perianal Crohn’s disease

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 Perianal Crohn’s Disease 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 Perianal Crohn’s Disease PSP will carry out a consultation to gather uncertainties from patients, carers and clinicians.  A period of 4 months will be given to complete this exercise (which may be revised by the Steering Group if required). 

The Perianal Crohn’s Disease PSP recognises that  including the following groups in the PSP may require additional consideration to ensure their involvement in the uncertainty-gathering exercise. 

• Children and adolescents with Crohn’s disease, and their parents/carers.
• Patients less able to travel due to their conditions.

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

The steering group will utilise clinician, researcher and patient networks such as the international Treatment Optimisation and Classification of Perianal Crohn’s Disease (TOpCLASS) consortium and Crohn’s and Colitis UK, as well as other organisations in order to ensure that a representative sample of key stakeholders are reached. The survey will be translated as required for international distribution. The survey will be distributed in both paper and online forms across a number of different avenues, including social media, to ensure that children and adolescents are represented. Funding will be allocated to allow for patients and their parents/carers to accompany them to the relevant workshops if required.

Existing sources of evidence uncertainties may also be searched.

Step 4: Refining questions and uncertainties

The consultation process will produce ‘raw’ questions and comments indicating patients’, carers’ and clinicians’ areas of uncertainty.  These raw questions will be categorised and refined by data analysis team and Steering Group members 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 the data analysis team.  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 the data analysis team.  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 Perianal Crohn’s Disease.  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 Perianal Crohn’s Disease. 

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 the JLA Coordinating Team. 

Agreement of the Steering Group

The Perianal Crohn’s Disease PSP Steering Group agreed the content and direction of this Protocol on September 30th 2024.