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Policy Research Programme - PRP (35-01-14) Research to support evidence building and the evaluation of the UK Rare Diseases Framework 2021- 2026

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Published: 10 January 2023

Version: 3.0 January 2023

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Timetable and Budget

DescriptionDeadline/Limit
Deadline for Stage 1 Applications 14 February 2023, 1 PM
Notification of outcome of Stage 1 Application April 2023
Deadline for Stage 2 application 06 June 2023, 1 PM
Notification of outcome of Stage 2 Application October-November 2023
Project Start As soon as possible after contracting
Project Duration By the end of 2025
Budget Please refer to budget section

Introduction 

We invite applications for research to evaluate and add to evidence on the United Kingdom (UK) Rare Diseases Framework 2021 – 2026. This is a significant opportunity to inform government policy and build vital evidence for patients and those around them. 

We intend to commission research in three related strands:

Strand 1: Designing high level metrics for a portfolio level evaluation of England’s Rare Diseases Action plans

Strand 2: Measuring time to diagnosis for people with rare diseases

Strand 3: Improving the coordination of care for people living with rare diseases – building the evidence base 

At this first outline application stage you may bid for one, two or three of these strands. These strands are being commissioned together to minimise burdens on the rare diseases community, maximise synergies between projects, and to ensure good value for money. The expert panel which will advise on commissioning this research will be attentive to these factors,  including in feedback to help shape stage two full proposals. This feedback could potentially involve asking bidders at outline stage to collaborate on stage two proposals.  

These strands of research should contribute evidence to determine whether the England’s Rare Diseases Action Plans have helped improve the lives of people living with rare diseases.

Background 

Rare diseases are those which affect fewer than 1 in 2,000 people within the general population. There are more than 7,000 rare diseases, and one in 17 people will be affected by a rare disease at some point in their lives – this equates to approximately 3.5 million people in the UK. People living with rare diseases, and their families, often face a lifetime of complex care leading to a profound impact on their education, financial stability, physical mobility, and mental health. 

DHSC published the UK Rare Diseases Framework in January 2021, outlining a national vision for how the UK will improve the lives of those living with rare diseases. The Framework lists four high-level priorities: (1) helping patients get a final diagnosis faster; (2) increasing awareness of rare diseases among healthcare professionals; (3) better coordination of care; and (4) improving access to specialist care, treatments, and drugs. 

In order to implement this vision, all 4 nations of the UK have committed to developing action plans, detailing how the four priorities of the Framework will be met. England’s first Rare Diseases Action Plan was published in February 2022, setting out 16 specific, measurable actions for the coming year under each of the Framework’s four priority areas, developed together with delivery partners across the health system and representatives of the rare disease community. Action plans for England are due to be published annually during the lifetime of the Framework, reporting on progress against the actions set out in previous action plans, as well as proposing updated and new actions. All the individual actions within England’s 2022 Action Plan are underpinned by a logic model; each will be monitored by our delivery partners and reported on annually over the course of the Framework.

There are two surveys and some pre-existing research addressing aspects of this topic, for example: the 2019 National Conversation on Rare Diseases, which helped to identify the four priorities of the Framework, and Genetic Alliance UK’s Rare Experience 2020 survey, which provided further information of the experiences of people living with rare diseases as broken down against these priorities. The commissioned research however will seek to build on this and, through working with the rare diseases community, establish appropriate metrics to help us: understand the value and influence of the UK Rare Diseases Framework as a whole, and as component parts, understand the specific challenges of time to diagnosis and coordination of care, and inform future Action Plans and DHSC and NHS England policy.

The evidence generated through this research will enable us to enhance our future rare disease policy development including future frameworks.

Research priorities

Research is required to build evidence on and evaluate the United Kingdom (UK) Rare Diseases Framework 2021 – 2026, in three strands as outlined above. Applicants should consider the following overarching policy question throughout their application(s): Has the UK Rare Diseases Framework, delivered through England’s Action Plans, succeeded in improving the lives of people living with rare diseases in England?

Strand 1: Designing high level metrics for a portfolio level evaluation of England’s Rare Diseases Action plans

The objective of this stand is to determine whether the actions of the Action Plans are collectively achieving meaningful progress against the four priorities of the Framework, and to evaluate the value of this policy intervention as a whole. To meet these aims we envisage that the research will be in two phases:

Phase 1. Evaluation assessment 

  • The initial phase should identify potential suitable robust metrics, working in collaboration with the rare diseases’ community, which can be used to evaluate progress against the four priorities of the UK Rare Diseases Framework. 

  • Establishing robust metrics for the Framework as a whole (not just for the individual interventions) is crucial to understanding whether the overarching strategy is achieving desired outcomes, and will allow us to develop a robust evidence base.

  • To help identify metrics we have developed logic models which set out anticipated outputs and outcomes for each priority of the Framework, based on the actions in England’s current Action Plan. These will be shared with successful applicants. 

Phase 2. Evaluation 

  • Once suitable metrics have been identified, these could be applied in a mixed methods approach to the questions below (with exa. Examples of the questions this research would enable us to answer are also provided.
  1. Is the time to diagnosis for rare disease patients reducing?
  1. How do people living with rare diseases describe their experience of time to diagnosis?

  2. Are the number of rare diseases tests available (and being used) and numbers of diagnoses increasing?

  3. Are there differences in time to diagnosis for different rare diseases, or across different regions of England?

  4. What are the factors in relation to diagnostic pathways that may have an impact on speed of diagnosis? 

  5. Are there external factors that influence time to diagnosis for people living with rare diseases?

  6. Has the time to diagnosis changed for people with certain categories of rare disease (e.g., those with non-genetic rare conditions)?

    b. Are healthcare professionals more aware of rare diseases?

  1. Has healthcare professionals’ self-reported awareness of rare disease and engagement with resources on rare diseases increased? Do they feel better able to signpost to sources of advice and support for rare diseases? Does this differ across groups of healthcare professionals?

  2. Are the numbers of referrals for specialist care increasing?

  3. Are numbers of referrals for genomic testing increasing? 

  4. Do people living with rare diseases perceive that health care professionals are more aware of rare conditions?

  5. What are the external factors that may influence healthcare professionals’ awareness of rare diseases?

    c. Is care for people living with rare diseases more coordinated?

  1. Do people living with rare diseases and their families/carers report a reduced care burden?

  2. Is the number of successful referrals to secondary/tertiary care increasing?

  3. Do people living with rare diseases report better coordination of care across wider services beyond healthcare (e.g., mental health support, housing, education)?

  4. Do people living with rare diseases feel healthcare professionals are more aware of the need for coordinated care?

  5. What are the external factors that influence how care is coordinated for people living with rare diseases?

     d. Are people living with rare diseases better able to access specialist care, treatment, and drugs?

  1. Is the number of rare disease drugs receiving market authorisation and/or National Institute for Health and Care Excellence (NICE) approval increasing? Is time to decision and market authorisation/NICE approval for these drugs reducing?

  2. Is access at the point of expected delivery of treatments/drugs improving?

  3. Is the geographical distribution of drug access/uptake more equitable?

  4. Do people living with rare diseases report improvements in their experiences of accessing specialist care treatment and drugs?

  5. What are the external factors that influence access to specialist care, treatment and drugs?

    e. What are the critical levers remaining which would bring about the change under the four framework priority areas?

    f. What is the impact of factors relating to inequalities and ethnicity, across these areas of the  framework? 

    Strand 2: Measuring time to diagnosis for people with rare diseases 

To evaluate the impact of rare disease policy on the time to diagnosis, we need an effective method for measuring the length of time between symptoms presenting and conditions being diagnosed. There are currently no robust and routinely used methods for measuring the diagnostic odyssey for rare diseases across the NHS. A 2015 NIHR Policy Innovation Research Unit (PIRU) report considered several potential methods (including the use of clinical databases, rare disease registries and hospital administrative records), suggesting pilot studies for testing these.

This work was developed further in a report by Hay et al 2022 [8] which demonstrated the feasibility of studying the diagnostic odyssey for rare diseases in secondary care using hospital episode statistics (HES) data. This report also highlights challenges in accessing data (particularly in primary care), and granularity of disease coding. These issues will need to be overcome before metrics could be applied at a national population level. In England’s 2022 Rare Diseases Action Plan, we have committed to “explore ways to build on these findings, to monitor the impact of interventions on the length of the diagnostic odyssey.”

Building on the findings of these reports will involve developing methods to utilise routinely collected healthcare data for the whole of the UK, to accurately identify cases, and their diagnosis date (for example, using a specific International Classification of Diseases (ICD)-coded in-patient or day-case admission, or a particular genetic test, where the timing of any of these is known to closely correspond to the diagnosis date for that specific disease).

The research should seek to overcome some of the challenges highlighted by previous work, such as:

  1. The bias introduced by a retrospective approach, which by definition only includes those patients who have already received a diagnosis, potentially leading to an underestimation of the average time to diagnosis.

  2. The heterogeneity of patient data recording systems, and the difficulties of longitudinal follow-up.

  3. Developing methodology applicable across a range of rare diseases with different disease types, ages at onset etc.

  4. Including a focus on how to access and interrogate primary care data, since secondary care data alone are usually too coarse, and are reliant on a secondary care event being recorded.

Based on the recommendations of the report, evaluation of the diagnostic odyssey in secondary care could be undertaken at a national level through access to HES data within the National Congenital Anomalies and Rare Diseases Registration Service (NCARDRS), while linkage to the General Practice Extraction Service (GPES) or Clinical Practice Research Datalink (CPRD) could be investigated to enable evaluation of primary care. 

However, we are aware that there are numerous other potential routes to obtaining this data and are open to considering any approach which effectively addresses the challenge of measuring the diagnostic odyssey for rare diseases in a replicable fashion. 

Broader points to consider when developing new metrics include the distribution of waiting times in each condition, case-control studies to explore what factors may increase the odds of an earlier diagnosis, and impact of health inequalities (including digital exclusion, stigma and cultural competency of healthcare professionals)   on disparities in time to diagnosis. It will also be crucial to capture the views of people with lived experience, to determine their experience of the diagnostic odyssey and the factors they would like to see taken into account when measuring this. 

Outputs of this strand should complement the analysis of time to diagnosis under Strand 1, by providing the metrics needed to support a quantitative analysis of the diagnostic odyssey alongside data on patient experience. Applicants should explain how they would integrate learning across strands 1 and 2 (particularly if bidding for only one strand) .

     Strand 3: Improving the coordination of care for people living with rare diseases – building the evidence base

The third strand should fill evidence gaps relating to how the most effective approaches for care coordination for people living with rare diseases can be operationalised in the NHS.

The NIHR has previously funded the Coordinated Care Of Rare Diseases (CONCORD) study to investigate how services for people with rare diseases are coordinated in the UK, and how people living with rare diseases, and healthcare professionals who treat rare diseases, would like services coordinated. This study published a landmark definition of coordination of care in rare diseases and a taxonomy of care coordination, as well as developing hypothetical models of care coordination, exploring which types of coordination may be appropriate in different situations. CONCORD emphasised that “coordination needs to be …family-centred, holistic (including a patient’s medical, psychosocial, educational and vocational needs), evidence-based, with equal access to coordinated care irrespective of diagnosis, patient circumstances and geographical location.”[5]

The required research would build on the findings of CONCORD, to provide the evidence needed to operationalise improved coordination of care within the NHS in the future. This strand of research should include economic modelling, and/or consider costs and benefits of different care coordination approaches. Research should focus on supporting implementation of improved care coordination in England but would benefit from consideration of approaches across the UK. Research should look at care coordination for both genetic and non-genetic rare conditions, and should ideally include approaches which address policy priority areas, including:

  1. Improving the paediatric to adult transition, 

  2. Integrating psychological and mental health support (for people living with rare diseases and their families) into rare disease clinical care,

  3. Improving access to advice and resources, and peer-to-peer support for people living with rare diseases and their families,

  4. Ensuring robust care pathways post diagnosis, 

  5. Exploring the use of healthcare passports/shared records, and

  6. Identifying opportunities for coordination of care linking healthcare with social care and wider public services (for example education and housing).

To improve coordination of care it is vital to understand patient experiences and what current and best practice look like. Research proposals need to demonstrate an approach to working collaboratively with the rare diseases’ community, and with the NHS, to identify evidence needs and learn from examples of best practice.  

We acknowledge the difficulties of conducting research in this area and expect applications to reflect these challenges. Applicants should also reflect on the ethical issues associated with this topic and provide details on how all participants might be supported.

New Guidance on Health Inequalities data collection within NIHR PRP Research: 

Health Inequalities is a high priority area within the Department of Health and Social Care and the NIHR and is often present in a majority of funded projects. We are now assessing all NIHR research proposals in relation to health inequalities. We are asking applicants to identify in their application whether or not there is a health inequalities component or theme and how this research hopes to impact health inequalities. We are also asking researchers to collect relevant data, if appropriate for the research. Our goal is to collect information on health inequalities in research and data relating to the main outcome(s) of the proposed research. Please clearly identify in this section whether or not your application has a health inequalities component or relevance to health inequalities and detail the core set of health inequalities breakdowns that will be reported; if none please explain why. We understand that research projects have different methodologies and focus on different populations, so please explain what data will be collected and reported for the methodology you plan to use. If a health inequalities component is not included, please explain why this does not fit within your proposed research. This should only be a few sentences.

For quantitative research we would ideally like researchers to provide one-way breakdowns of their main outcome(s) by the following equity-relevant variables: age, sex, gender, disability, region, 5 ONS Ethnic groups, and the 5 IMD quintile groups. If more detailed cross tabulations are appropriate, please include these. This table should be submitted to NIHR PRP at the end of the project. Due to data limitations, judgement calls may be necessary about which breakdowns to report and whether to merge categories to increase counts in particular cells; we ask you to make these judgement calls yourself, bearing in mind our data curation aim of enabling future evidence synthesis work in pooling results from different studies. Details and an example table can be found in Appendix A.

For qualitative research projects, this can be purely descriptive statistics giving the number of observations against the various variables. Further details about this new request can be found in Appendix A.

A recording of the Health Inequalities in NIHR PRP Research Q&A Event which was held on 19 September 2022 is available to view on Youtube, this may be useful to refer to as it provides additional information.

Scope for research 

For strand 1, applications should focus on the overarching need to build the evidence base and evaluate whether actions outlined in the England Rare Diseases Action Plans are achieving meaningful progress against the aims of the UK Framework. Research is not required to cover the Action Plans of the Devolved Administrations. However, indicating how approaches could be adopted across the devolved nations would be welcomed, if applicable.

Similar for strand 2, there is a need to build an evidential understanding on measuring time to diagnosis now and in the future. The metrics developed will need to be replicable, though will not be required to be replicated within this application. Time to diagnosis will likely be a metric for on-going policy development and activity. The methodology should be appropriate for England, but any indication of applicability to the devolved nations would be welcomed. 

The third strand on effective approaches to improving coordination of care. The effectiveness should be based on evidence gathered regarding the application of appropriate interventions. Recommendations for future activity/intervention or elements that should or should not be taken forward can be included, but only where appropriately supported by evidence. 

Technical requirements / Expertise required 

Alongside having the required technical expertise outlined in the above sections, applicants should also ensure they articulate in their application their expertise with working either with the rare disease community or with similar communities.

Outputs 

Applicants are asked to consider the timing and nature of deliverables in their proposals. Policymakers will need research evidence to meet key policy decisions and timescales, so resource needs to be flexible to meet these needs. A meeting to discuss policy needs with DHSC officials will be convened as a matter of priority following contracting. 

Outputs should include: 

  1. Interim reports and updates as agreed at project scoping and to meet policymaking timelines.

  2. Draft publishable reports of interim findings at key milestones (including at the end of each calendar year, for publications of updates to the action plans) and a final publishable report, with an executive and lay summary. These outputs include:

  1. for strand 1, a final report assessing the implementation of the Framework

  2. for stands 2 and 3, an appropriate output to provide the NHS for proposed operationalising

     c. Other summative outputs (such as policy briefings) may be required to disseminate the findings across the range of stakeholders (including for NHS commissioning and patient representatives).

     d. A presentation of findings to DHSC colleagues and key stakeholders from other government departments and arms-length bodies.

Please refer to the stand alone document on the NIHR website for more information on output requirements.

Budget and duration 

The overall budget for all three strands is up to £850,000, with an expected budget range of £200,000 - £400,000 per individual strand, depending on the project. 

Costings can include up to 100% full economic costing (FEC) but should exclude output VAT. Applicants are advised that value for money is one of the key criteria that peer reviewers and commissioning panel members will assess applications against.

At this stage, we would expect the research to complete by December 2025 depending on the strand, to provide detailed and useful insights for policy development. Our expected duration for each research stage is as follows:

  • Strand 1: The first phase (evaluation assessment) is to begin in 2023, with the second phase (evaluation) taking place between 2024 – 2025

    It is expected that appropriate interim findings will be available throughout the duration of the project and to incorporate into the next five-year Framework (development expected in 2025). The final report should be published soon after the expiry of the Framework in 2026. 

  • Strand 2: Preliminary results are to be reported in 2025.

    It is expected that the initial research proposal will be reported in the 2024 Action Plan (publishing in February 2024). The final report should be published soon after the expiry of the Framework in 2026.

  • Strand 3: Preliminary results are to be reported in 2025.

    It is expected that the initial research proposal will be reported in the 2024 Action Plan (February 2024). The final report should be published soon after the expiry of the Framework in 2026.

Interim reports in a form suitable for busy policymakers will be expected throughout. We would like the research to commence as soon as possible after notification of successful outcome and applications will be favoured where research can commence on, or soon after, issue of contract.

Management arrangements

A research advisory group including, but not limited to, representatives of DHSC, NHS England, other stakeholders,  patient representatives, and the successful applicants for the research should be established. The advisory group will provide guidance, meeting regularly over the lifetime of the research. The successful applicants should be prepared to review research objectives with the advisory group, and to share emerging findings on an ongoing basis. They will be expected to:

  1. Provide regular feedback on progress

  2. Produce timely reports to the advisory group

  3. Produce a final report for sign off

Research contractors will be expected to work with nominated officials in DHSC, its partners and the NIHR. Key documents including, for example, research protocols, research instruments, reports and publications must be provided to DHSC in draft form allowing sufficient time for review.

Involvement of the rare diseases community will be vital across all three strands of research.  Applicants should describe how the issue of PPI will be addressed throughout the research process.

Applicants are required to detail what active involvement is planned, how it will be facilitated, how it will benefit the research and the rationale for their approach. This should be considered in conjunction with the need to ensure independence and objectivity across the research design, collection and analysis given the immense (political/stakeholder) interest.

PPI needs to be undertaken in a manner that acknowledges that some people may need additional support, or to acquire new knowledge or skills to enable them to become involved effectively (see INVOLVE publications for guides for researchers). Applicants should therefore provide information on arrangements for training and support. In addition, applicants should note that a budget line for the costs of PPI is included in the finance form and is carefully scrutinised by the Committee.

Applications that do not have active involvement from the rare disease community are unlikely to be successful. 

References and key documents

  1. Department of Health and Social Care (2021) UK Rare Diseases Framework. [Accessed November 2022]
  2. Department of Health and Social Care (2022) England Rare Diseases Action Plan 2022. [Accessed November 2022]
  3. Black N, Martineau F, Manacorda T (2015) Rare diseases Final report.pdf. [Accessed November 2022]
  4. Hay E, Elmslie E, Lanyon P, Cole T (2021) The Diagnostic Odyssey in rare diseases; a Task and Finish Group report for the Department of Health and Social Care. [Accessed November 2022]
  5. Walton H, Hudson E, Simpson A, Ramsay AIG, Kai J, Morris S, Sutcliffe, Fulop (2020) Defining Coordinated Care for People with Rare Conditions: A Scoping Review. [Accessed November 2022]
  6. Walton H, Simpson A, Ramsay AIG, et al (2022) Developing a taxonomy of care coordination for people living with rare conditions: a qualitative study. [Accessed November 2022]
  7. Walton H, Simpson A, Ramsay AIG, et al (2022) Development of models of care coordination for rare conditions: a qualitative study. [Accessed November 2022]

Appendix A: Further Detail on the New Guidance on Health Inequalities data collection within NIHR PRP Research:

Health Inequalities is a high priority area within the Department of Health and Social Care and the NIHR and is often present in a majority of funded projects. We are now assessing all NIHR research proposals in relation to health inequalities. We are asking applicants to identify in their application whether or not there is a health inequalities component or theme and how this research hopes to impact health inequalities. We are also asking researchers to collect relevant data related to health inequalities, if appropriate for the research. Collecting specific information about health inequalities in research submitted to the programme will allow for categorisation of health inequalities research, curation of data to aid future health inequalities research and enable policymakers to better understand the implications of health inequalities within their policy areas. This is a new request from the NIHR PRP and we will be continuing to monitor queries and adapt the process as needed. If you have any feedback on this new request, please contact us at prp@nihr.ac.uk.

Our goal is to facilitate more widespread and consistent reporting of health inequality breakdown data relating to the primary outcomes of NIHR funded research. We would ideally like researchers to focus on the following equity-relevant variables: age, sex, gender, disability, region*, 5 ONS Ethnic groups**, and the 5 IMD quintile groups. These variables are considered an ideal, but we understand that these are subject to change depending on the sample population and specific research question.

For qualitative research projects, this can be purely baseline characteristics of the participants, for example, the number of participants in each ethnic group.

For quantitative research projects, if there are multiple outcomes/effects with your stakeholders, select a small number of main outcomes as appropriate to report equity breakdowns. We will not be prescriptive about the number of the outcomes, as it will depend on the number of study design types and the nature of the project aims. We are asking for one way cross tabulations of each primary outcome by these equity-relevant variables, if appropriate for your research, together with the number of observations in each cell. If more detailed cross tabulations are appropriate for your proposed research, please include these as well. This request applies to both primary data collection studies and secondary analysis of routine data, and to causal inference studies as well as descriptive studies; however, if this is not possible due to data limitations then please explain. Due to sample size and other data limitations there may be difficult scientific and/or data security*** judgement calls to make about which breakdowns to report and whether to merge categories to increase counts in particular cells; we ask you to make these judgments yourself, bearing in mind our data curation aim of enabling future evidence synthesis work in pooling results from different studies. We also ask that researchers report breakdowns for the unadjusted as well as adjusted outcomes/effects, as appropriate.

We understand that research projects may employ different methodologies, and focus on different populations. Please explain how the variables and data collection methods chosen are appropriate to the methodologies used.

We ask that you please clearly identify in the research plan section of the application whether your application has a health inequalities component or not and detail the core set of health inequality breakdown data that will be collected, if applicable. Submission of the data collection will be a condition of the final report for all research with relevant methodologies regardless of whether the research has a health inequalities component that will need to be submitted to NIHR PRP when the grant has finished. This should only take a few sentences within the research plan section.

* Table below uses the nine regions in England, further regions can be used if using the UK as the study population. Please report region breakdown for large samples in nationally representative descriptive studies. There is no need to report this for small sample studies, for sub-national studies, or for quasi-experimental studies where it would require time-consuming re-estimation.
** White, Mixed/ Multiple ethnic groups, Asian/ Asian British, Black/ African/ Caribbean/ Black British, Other ethnic group. If the sample size is small then it is fine to report only some of the requested equity breakdowns and to merge some of the sub-groups as appropriate.
*** For guidance on how to handle data security concerns in reporting of sensitive data please see ONS guidance.

Example data table for submission at the end of the funded research project

(N.B. If there is more than one main outcome then you will require more tables and if you adjust your outcome then you will need two tables for the adjusted outcome and unadjusted outcome. For other methodologies, variable vs number of observations may be more appropriate to record participant data). This table is for an example only. It does not contain sub variables and does not illustrate any preference for certain variables, as these will be dependent on the proposed research.

VariableOutcome (an appropriate average for this subgroup, usually the mean)Number of observationsAdditional information about variation if appropriate, e.g. range, standard deviation
Age - - -
Sex - - -
Gender - - -
Disability - - -
Ethnic Group - - -
IMD Group - - -
Region - - -