Mitochondrial 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 Mitochondrial Diseases 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 – www.nihr.ac.uk) coordinates the infrastructure of the JLA to oversee the processes for PSPs, based at the NIHR Evaluation, Trials and Studies Coordinating Centre (NETSCC), University of Southampton.

Having being involved in other successful rare disease PSPs, that focussed on groups of related conditions, Genetic Alliance UK applied for and was granted funding by Wellcome Trust for a new rare disease PSP. In November 2017, Genetic Alliance UK put a call out to their members for expressions of interest in participating in the PSP. Members’ responses determined the topic of the PSP. Following discussion with those interested, it was agreed that the focus of this PSP would be rare primary mitochondrial diseases. This area had a number of committed patient groups representing related conditions, as well as interest and capacity from within the medical community.

Aims, objectives and scope of the PSP

The aim of the Mitochondrial Diseases PSP is to identify the unanswered questions about rare, primary, mitochondrial diseases 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 to identify uncertainties about:
  
  o the natural history of these diseases, ie how they start and change over time
  o the genetics and causes
  o care, treatment and management, including supplements, alternative medicine and psychological support.
• 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 research commissioning bodies to be considered for funding.

The scope of the Mitochondrial Diseases PSP is defined as:

• primary mitochondrial disease*
• affected adults and children of all ages, and their families/carers
• natural history of the conditions;
• care, treatment and management including supplements, alternative medicine and psychological support

The PSP will exclude from its scope questions about:

• non-primary mitochondrial disease
• diagnosis

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.

* Primary mitochondrial disease refers to a group of disorders caused by mutations in DNA that lead to disturbances of mitochondrial structure and function.

The Steering Group

The Steering Group membership includes patients and carers and clinicians, as individuals or representatives from a relevant group.

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

Patient and carer representative/s:

• Jenny Sharpe, Muscular Dystrophy UK
• Lindsay Weaver, Metabolic Support UK
• Russell Wheeler, LHON Society
• Lyndsey Butterworth, The Lily Foundation
• Amy Hunter, Genetic Alliance UK

Clinical representative/s:

• Catherine Feeney, Nurse Consultant, Highly Specialised Service for Rare Mitochondrial Disease, Newcastle
• Rhys Thomas, Honorary Consultant Neurologist, Wellcome Trust Centre for Mitochondrial Research, Newcastle
• Marcela Votruba, Honorary Consultant Ophthalmologist, The University Hospital of Wales, Cardiff
• Jo Lowndes, Senior Genetic Counsellor, Oxford Centre for Genomic Medicine
• Sarah Holmes, Clinical Specialist Physiotherapist, National Hospital for Neurology and Neurosurgery, London
• Shamima Rahman, Consultant Metabolic Paediatrician, UCL Great Ormond Street Institute of Child Health
• Tracey Graves, Consultant Neurologist, Hinchingbrooke and Addenbrooke’s Hospitals

Project coordinator:

Amy Hunter, Genetic Alliance UK

James Lind Alliance Adviser and Chair of the Steering Group:

Sheela Upadhyaya, 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 mitochondrial diseases
• carers of people who have mitochondrial diseases
• health and social care professionals - with experience of mitochondrial diseases.

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 at www.jla.nihr.ac.uk 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 Mitochondrial Diseases 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 faceto-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 Mitochondrial Diseases PSP will carry out a consultation to gather uncertainties from patients, carers and clinicians. A period of three months will be given to complete this exercise (which may be revised by the Steering Group if required).

The Mitochondrial Diseases PSP recognises that the following groups may require additional consideration, and discussions are ongoing about how to engage them effectively and consistently:

• children and young people affected;
• those for whom English is not their first language;

The Steering Group will use the following methods to reach the target audiences

• Online surveys
• Downloadable pdf surveys (with postage paid return address to project coordinator, or for Steering Group members to input
• answers online on behalf of respondents)
• Presentations and group sessions at patient meetings
• Pending additional funding: bilingual awareness raising, bilingual staff to facilitate survey completion and workshops.

Existing sources of evidence uncertainties may also be searched. Genetic Alliance UK will use inhouse expertise to guide the Steering Group on the PSP search strategy. This will be developed after the initial survey goes live.

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 Kristina Staley 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 Steering Group with support from Kristina Staley. 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 Kristina Staley. 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 mitochondrial diseases. 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 involve the whole Steering Group and be led by Genetic Alliance 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 Mitochondrial Diseases PSP Steering Group agreed the content and direction of this Protocol on 19/02/2019.