Purpose of the PSP and background
The purpose of this protocol is to clearly set out the aims, objectives, and commitments of the Sickle Cell Genomics 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.
Genomics England, through a new initiative Diverse Data, is embarking on a partnership with Sickle Cell Society to explore how genomics can bring research and clinical benefit to Sickle Cell patients. Sickle Cell is the most common rare disease known; however research and funding has been lacking over the decades, leading to many patients being neglected in terms of knowledge, support and treatments available to them and their clinicians. This has been evidenced through the No one’s listening report published by the Sickle Cell Society in 2021. Despite the genetic cause of Sickle Cell being known for many decades, many specialists have limited understanding of the mechanisms behind the wide variability in disease progression across their patients. For this reason, genomics is seen as a potentially highly useful tool to provide these deeper insights into how different variations in DNA could be contributing to this. There is currently an increased interest in generating genomic data on Sickle Cell, making this a timely opportunity to understand the priorities of patients and healthcare professionals. We have therefore embarked on a PSP in order to outline the priority areas for patients and healthcare professionals.
Aims, objectives and scope of the PSP
The aim of the Sickle Cell Genomics PSP is to identify the unanswered questions about the variations, predictability and treatment options of Sickle Cell from patient, carer and clinical perspectives and then prioritise those that patients, carers and clinicians agree are the most important for research to address. We also recognise that new genomic technologies are transforming research and how this is applied to healthcare. On this basis we are including key questions around the approaches taken in research that aims to generate genomic data and evidence.
This work also aims to better understand the level of knowledge from patients, carers and health care professionals regarding Genomics and Sickle Cell and to provide education and information around this topic.
The objectives of the PSP are to:
- Increase visibility of Sickle Cell, and the potential for genomics to better understand the condition
- Work with patients, carers, carriers and healthcare professionals to identify uncertainties about the relationship between Sickle Cell and Genomics for example, how Sickle Cell progresses in individuals, new treatment developments and links between severity and risk, and understand the uncertainties in the practices used in this field of research.
- To agree by consensus a prioritised list of those uncertainties, for future research
- To publicise the results of the PSP and process
- To take the results to research commissioning bodies to be considered for funding.
The scope of the Sickle Cell Genomics PSP is defined as:
- To identify the role genomics must play in better understanding Sickle Cell and how research can bring the best outcomes to patients.
- We define people affected by Sickle Cell as adults and children with any Sickle Cell genotype including those who carry one copy of the genetic change also referred to as carriers/trait.
- Our focus is on the UK population, but we will not exclude survey responses from those who live outside of the UK. We will note the locations of the people completing the survey.
The PSP will exclude from its scope questions about:
- NHS services and care pathways
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 Sickle Cell Genomics PSP will be led and managed by a Steering Group involving the following:
Patient and carer representative/s
Hazel Attua – London/Essex
Natasha Gordon Douglas - South
Samuel Chuku - Midlands
Oleander - Hackney and City support group Solace
Clinical representative/s
Dianne Addei – NHS Inequalities
Santoshi Patel – North Mids Nurse
Olushola Shoyemi – GSTT Nurse
Kate Gardner - Adult Consultant, Genomics
Joe Sharif - Adult Consultant
Amanda Hogan - NHS Screening (Nurse)
Joan Walters - Nurse/ Senior lecturer
Information specialists
Anna Hood
Michelle Peter
Fred Piel
Project coordinators
John James, Sickle Cell Society, Marie Nugent, Genomics England & Rashae Peart, Sickle Cell Society
James Lind Alliance Adviser and Chair of the Steering Group
Suzannah Kinsella, JLA
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 Sickle Cell or who are a Sickle Cell carrier
- Carers of people who have Sickle Cell
- Health and social care professionals - with experience of Sickle Cell
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.
We are not looking at other haemoglobinopathies for this PSP.
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 Sickle Cell Genomics 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 Sickle Cell Genomics PSP will carry out a series of workshops to inform the design of an open-ended survey to gather uncertainties from patients, carers and healthcare professionals.
A period of 12 months will be given to complete this exercise (which may be revised by the Steering Group if required).
The Sickle Cell Genomics PSP recognises that the following groups may require additional consideration. We intend to reach Sickle Cell patient communities across England. Equally, we aim to engage with specialists in treating Sickle Cell. We recognise that outside of London these groups and specialists can be much less visible, fewer in number and more remote.
The Steering Group will use the following methods to reach the target groups:
- Engage Sickle Cell patients in workshops (mix online and face to face)
- Engage Sickle Cell health professionals and supporters in workshops (mix online and face to face)
- Create survey capturing evidence uncertainties/ open questions
- Use survey and literature review to identify key focus areas for further explorations
- Create survey to refine list of uncertainties to bring to steering group
- Steering group agrees Top 10
- Publish findings and methods
Existing sources of evidence uncertainties may also be searched. Including but not limited to The ‘No one’s listening’ report, Sickle Cell World Assessment Survey, Novartis, Picker Europe UK Survey 2016.
Evidence will also be gained in the form of research recommendations from systematic reviews and clinical guidelines. Alongside academic research papers that indicate opportunities for genomics in understanding disease progression. Including the variability and predictability of Sickle Cell.
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 Information Specialists; Fred Piel, Michelle Peter and Anna Hood, 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 Fred Piel. 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 Fred Piel. 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 Sickle Cell Genomics. 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.
- 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.
- 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 John James and Marie Nugent.
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 Sickle Cell Genomics PSP Steering Group agreed the content and direction of this Protocol on 13th May 2024.