Introduction
The Health Research Authority (HRA) and the Medicines and Healthcare products Regulatory Agency (MHRA) are committed to enabling the highest quality health and social care research which can benefit the whole UK population.
The purpose of the Inclusion and Diversity Plan (the Plan) is to ensure clinical research is designed to include people who could be impacted by the findings, and that people often under-served by research are not overlooked.
This document sets out what you should include in the Plan and how to submit a Plan.
Background
The UK population is made up of a wide range of communities, groups, and individuals from different backgrounds. To ensure that the whole population can benefit from research, there needs to be an understanding of how interventions work on and for different groups of people. Including a range of people in research provides an understanding of the safety and effectiveness of drugs, devices or interventions for an illness or condition across different groups.
It’s known that there are people and communities under-served by research1 who, despite potentially having a higher disease burden for certain diseases compared to the general population, are frequently underrepresented or excluded from research. More needs to be done to include them and support their participation in research.
Developing a Plan will support you, and other members of the research team, to consider how you can do as much as possible to include all those who may be impacted by your research, particularly those from under-served groups. Involving these groups when designing a study will help to make the research more inclusive.
Inclusion of these populations in clinical trials and clinical investigations helps to:
- improve our understanding of a disease and the medical product / intervention under investigation
- ensure that the data generated reflects the diversity of the population expected to use the medical product / intervention
- potentially identify effects on safety or efficacy outcomes that may be associated with or occur more or less frequently within these populations
When is a Plan needed?
Submission of a Plan with an application is not mandatory, however it is encouraged. You should develop a Plan if you’re a sponsor or a researcher planning a clinical trial or clinical investigation. This includes:
- a clinical trial of an investigational medicinal product (CTIMPs)
- a clinical investigation or other study of a medical device
- a combined trial of an investigational medicinal product and an investigational medical device
- any other clinical trial to study a novel intervention or randomised clinical trial to compare interventions in clinical practice.
Observational studies are out of scope for this guidance.
Single studies, multi-phase studies and development programmes
You can submit a Plan for a single study, or you can submit a Plan for the whole product development programme clearly indicating the information that is relevant to the study.
Early phase trials and Healthy Volunteer trials
Inclusivity should be considered from the very first stage of any product development. Sponsors should consider full justification of any population that would be excluded from early phase trials within the context of the overall product development programme.
Submission of a Plan is not mandatory, and we do not expect companies delivering phase 1 trials, on behalf of sponsors, to develop their own Plan. However, if you’re planning an early phase trial, including Healthy Volunteer trials, you can briefly describe and justify the trial population for this study as part of your research ethics application, providing assurance that no group has been unnecessarily excluded.
People and groups to consider in the Plan
Although under-served people and groups are generally considered to be people, communities or groups who are less represented in health research, the communities that constitute these groups may vary depending on the context or study. The NIHR have identified several characteristics common to under-served groups including:
- lower inclusion in research than one would expect from population estimates
- high healthcare burden that is not matched by the volume of research designed for the group
- important differences in how a group responds to or engages with healthcare interventions compared to other groups, with research neglecting to address these factors.
It’s important that the study population reflects the real-world and every effort should be made to include the full range of people who the research is for and about. You should consider:
- how your study population reflects the real-world population
- reaching out to the people and communities who could be impacted by your research
- the effect of your work on minority communities, under-served groups, people who have been identified with health inequalities, people with poor literacy, people from different cultural backgrounds, and people with protected characteristics
- sharing back your findings with under-served groups, to build trust in the effect of their participation in the research process
The HRA and INVOLVE have previously released a briefing explaining the value of public involvement in the design, management, conduct and dissemination of research. Excellent public involvement is essential and has been shown to improve the quality and impact of health and social care research 2, 3, 4. Involving people who your research is for and about in the design stage, will help ensure that your research is accessible to everyone. The four principles for meaningful involvement of patients and the public in health and social care also provides guidance on best practice for public involvement.
The following are examples of groups or factors you should consider when developing a Plan (this is not an exhaustive list). The NIHR-INCLUDE project also provides examples of groups that may be under-served. These lists are to support you in considering who may be under-served. You are not expected to make reference to every group listed in your Plan.
- different ethnic groups
- people living in remote or rural areas
- sex characteristics
- carers
- sexual orientation
- neurodiversity
- language barriers
- people with a learning disability
- level of education
- multiple health conditions
- physical or mobility impairments
- pregnancy
- people belonging to a faith community or belief group
- socioeconomic factors such as employment status, income
- highly mobile communities such as Gypsy, Roma, and Traveller communities, or homelessness
- youngest and oldest age groups such as under 18 and over 75
When considering different people and groups in your Plan, it’s important to consider how different characteristics interact and overlap to create greater disease burden and barriers to inclusion.
Developing an Inclusion and Diversity Plan
Content of the Inclusion and Diversity Plan
The following section gives advice on what you should include in your Plan.
The Plan should detail who could be impacted by the research and demonstrate that you’ve carefully considered and planned for how you’ll involve and include them. There may be instances in which excluding people who will be impacted by the research is necessary for the study. However, you should include the reasons for why you need to exclude them in the Plan.
Your Plan should clearly show that you’ve considered potential under-served groups in the trial design. It’s recommended you start developing the Plan at the point of study design, and that it’s continuously revisited and reviewed.
Overview of the disease/condition
Question 1: Who is affected by the disease or condition being studied?
Purpose
- To understand who is affected by the disease or condition and where there are gaps in data.
- To understand what is/isn’t known about how different groups are impacted by the disease/condition.
Information you should consider including when you answer this question
Provide a short summary of who is affected by the disease/condition.
Describe the current understanding of any similarities and/or differences in the disease or condition under study across different population groups. Reference any data/evidence you used to provide this description.
When considering this question, you should consider under-served groups and how they may potentially be impacted by the disease/condition differently. Under-served groups are generally considered to be groups who are less represented in health research. However, the communities that constitute these groups may vary depending on the context or study. The Plan should show consideration of the under-served groups that are relevant to your study.
Where epidemiological data is available it should be used to support study design (question 2) and recruitment goals (question 3). Where UK specific data is not available, global epidemiological data may be used.
Study design
Question 2: Do the aims/design of the research mean that the findings will be generalisable to all identified in question 1? If this is not the case, please explain why
Purpose
- To understand who could be impacted by the product or intervention that’s being developed or investigated.
- To have a clear justification of which population groups identified in point 1 above, including under-served groups, will be included or excluded from the study population.
- To understand how study design including study population, endpoints, and geographical locations will have an effect on generating data relevant for those who could be impacted by the product or intervention.
- To consider how the study design will give adequate (generalisable) evidence on the safety or effectiveness of the product or intervention.
- To consider if and when to disaggregate the data.
Information you should consider including when you answer this question
Outline and describe the reasons for choosing the population groups to include in your study.
Where applicable, provide information on:
- study design, study population (including study eligibility criteria), study endpoints, the expected geographic location(s) of the study and how this may help to recruit population groups including under-served groups
- any findings from previous clinical pharmacology studies (PK/PD data, pharmacogenomics) or other investigations that may demonstrate a different effect on different populations where this is available
- any findings that demonstrate a potential difference in perception or acceptability of the intervention in different populations
- if the data will be disaggregated
- how the study will support the product’s safety, performance, effectiveness and, if a drug, dosage in a future marketing or licensing submission or prescribing practice
When answering this question, you should show you’ve considered any differences between the population identified in Question 1 and the study population. You should avoid providing a general overview of the study when answering this question.
You should give the rationale for any inclusion/exclusion criteria (and other aspects of the study) that will, or may, influence inclusion or exclusion of under-served groups. However, it’s important that the inclusion criteria are supported by a positive risk/benefit assessment.
If you don’t have any data about how the product or intervention may perform differently between different population groups, recruitment should reflect the epidemiology of the disease. In other words, the study population should be similar to the disease population.
You should include any plans you have to collect and analyse data that will explore potential differences in safety and effectiveness across population groups, particularly under-served groups you have identified in your response to Question 1.
Demographic data collection
Researchers and sponsors should collect demographic data of participants to support transparency and understanding in relation to the safety and efficacy of the intervention in different groups. This will also support the building of an evidence base. We recognise that how categories are defined can vary according to country or different settings. In the absence of agreed international categories, researchers and sponsors should clearly outline how they have defined demographic categories in their study.
Study goals
Question 3: What are your recruitment goals?
Purpose
- Consider what goals can be set to recruit the proposed population groups, particularly under-served groups.
- Decide whether increased recruitment of a population is required for you to identify differences and meet your goals.
Information you should consider including when you answer this question
Specify the approximate number of people you are aiming to recruit from the population groups outlined in question 2.
Outline and provide the rationale for planned recruitment of participants based on the information provided in Question 2.
For this question you should specify the goals for the recruitment of participants, particularly under-served groups. You should base these on the epidemiology of the disease and/or information that may influence outcomes across under-served populations that you identified in Question 2. You should aim to set informed goals that are realistic and achievable.
If it’s a multinational study your Plan should state the overarching study wide recruitment goals and explain how the UK study will contribute to them.
In some cases, increased (meaning greater than the population percentage) recruitment of certain populations may be needed to reveal potentially important differences.
You’re encouraged to use various data sources (for example published literature and real-world data) to set recruitment goals. In certain situations, it may be challenging to set a recruitment goal based on the epidemiology of the disease due to the limited availability of relevant data regarding the disease and patient characteristics. If this is not possible, it may be appropriate to set the recruitment goals based on the demographic characteristics in the overall population with the disease or condition.
You should outline any potential challenges for the study in recruiting under-served populations. This should support the development of a plan of action to recruit and retain the proposed study population (to be answered in Question 4).
Goals should be taken into consideration when selecting study location(s).
Plan of action
Question 4: What is your plan to recruit and retain the proposed study population?
Purpose
- To consider how in practice you’ll recruit and retain the proposed population groups, including under-served groups.
- To consider if additional recruitment and retention strategies are required to support inclusion and access.
- To consider what to do if planned recruitment and retention goals are not met.
- To ensure ongoing review of the plan, and action is taken when goals are not met.
Information you should consider including when you answer this question
Describe in detail the operational measure(s) that will be implemented to recruit and retain participants, especially those from under-served groups in your study.
Describe specific study recruitment and retention strategies, including but not limited to:
- study location and access
- patient and public involvement, community engagement and/or outreach activities
- reducing burdens on participants through study design/conduct
Describe metrics to ensure that recruitment and retention goals are achieved and specify what you’ll do during the study if planned goals are not met.
Outline how you’ll monitor the success in achieving your recruitment and retention goals.
Outline how you’ll disaggregate the data according to your Plan and report on your findings.
We recognise the current lack of evidence for effective strategies to recruit and retain under-served groups. However, if you are planning any actions to help earn trust and maintain long term relationships with under-served communities, you should document these in your Plan.
Revisiting and reviewing Plans
A Plan is not intended to be a static document. As your study makes progress, you should monitor the success in achieving your recruitment and retention goals (as you outline in question 4 of the Plan). You may need to try new strategies. It’s good practice to have clear documentation about any changes or updates to a Plan.
We encourage you to share information about what strategies supported you to achieve your goals, those that proved ineffective and any other learnings. This will improve the evidence base relating to effective strategies to recruit and retain different population groups.
Monitoring and reporting
The implementation of Plans will not be monitored. However, we recommend you revisit, review, and update the Plan throughout the study and retain documentation.
Submitting an Inclusion and Diversity Plan
Is it mandatory to submit a Plan?
No, submission of the Plan is not mandatory but we encourage you to do so.
How do you submit a Plan for review?
If you’re a sponsor or researcher and are planning a CTIMP, or a combination trial of an investigational medicinal product and a medical device, you can submit a Plan with your combined review service application in the new part of IRAS.
If you’re planning any other type of clinical trial (including a medical device) or clinical investigation, you can submit via the standard part of IRAS and include your Plan as a supporting document.
You can submit relevant information you have provided to other regulators or funding organisations as part of your plan.
How will the Plan be used?
Research Ethics Committees (RECs) will use the information in the Plan to inform their understanding of the overall application and support discussions in the REC meeting. You can also discuss your Plan if it needs scientific input, via scientific advice meetings with the MHRA.
The Plan is not a submission document that will be directly assessed as part of the clinical trial application. Therefore, it is not considered to be a document which forms part of Clinical Trial Approval application, for the purposes of the UK Medicines for Human Use (Clinical Trials) Regulations 2004 (as amended) nor the Medical Device Regulations 2002 or EU Medical Device Regulation (EU) 2017/745.
We will be piloting submission of a Plan as part of an application with a small number of studies in 2025. For the purpose of this pilot, the MHRA GCP inspectors won’t be inspecting how the contents of the Plan were decided, how the Plan was written and approved or adherence to the Plan. However, if aspects of the Plan are covered in other documents included in the CTA such as the protocol, then that aspect may be subject to review on inspection by the MHRA.
Could failure to submit a Plan, or the content included in a Plan, result in an application being rejected?
No, failure to submit a Plan will not result in an application being rejected. The REC will use the information provided in the Plan to inform their understanding of the overall application. If what’s contained in the Plan leads to questions about the study design, the REC will ask you about it.
However, an application would not be given an unfavourable opinion based on the information contained in the Plan.
If changes are made after review, do you need to resubmit the Plan?
No, you do not need to resubmit the Plan. However, it’s good practice to document any changes or updates to the Plan and retain records.
Will HRA be collecting information provided in Plans to monitor diversity in clinical trials?
No, information provided in Plans will not be collected for the purpose of monitoring the trial or the overall diversity of participants in clinical trials. However, the HRA may explore this in the future.
Will studies that have already received approval from HRA need to submit a Plan?
No, studies that have already received approval will not need to submit a Plan.
If information relevant to the Plan has already been submitted in IRAS, should it be repeated in the Plan?
It is intended that the Plan will prompt thinking about the research in a way that will draw out information which supports the information already provided in IRAS. However, you can reference relevant sections of the IRAS application if it is relevant to the Plan and avoids duplication.
References
1) Bodicoat DH, Routen AC, Willis A and others (2021) ‘Promoting inclusion in clinical trials-a rapid review of the literature and recommendations for action’ Trials 4(22) (viewed on 28 May 2024)
2) Lauzon-Schnittka J, Audette-Chapdelaine S, Boutin D and others (2022) ‘The experience of patient partners in research: a qualitative systematic review and thematic synthesis’ Research Involvement and Engagement 8(55) (viewed on 28 May 2024)
3) Forsythe LP, Carman KL, Szydlowski V and others (2019) ‘Patient Engagement In Research: Early Findings From The Patient-Centered Outcomes Research Institute’ Health Affairs 38(3) (viewed on 28 May 2024)
4) Crocker JC, Ricci-Cabello I, Parker A, and others (2018) ‘Impact of patient and public involvement on enrolment and retention in clinical trials: systematic review and meta-analysis’ British Medical Journal 363 (viewed on 28 May 2024)