Guidance

Ethics and approvals

From:
MRC
Published:

1. Introduction

This section provides guidance on the regulations and approvals that may be required for specific types of research.

If your research will involve human participants, their biosamples (tissues) or data, then you should consider and address any relevant ethical issues in your application.

The lists below include some common considerations for research involving people as participants, their biosamples or data. If any of the following are relevant to your research, and you have not already covered these in your application, you should confirm how you intend to address them.

Benefits and risks: you should describe the nature and extent of any benefits likely to come from your research and outline how you will mitigate any risks (such as risks to the safety, dignity, rights or wellbeing of participants, potential participants and staff working on the study).

Consent for research: appropriately informed, voluntary consent is the most common way to recruit human participants into research. You should indicate whether there are specific considerations in relation to consent in your application. Learn more on consent for research.

Information management: your data management plan should describe how you will manage participant confidentiality, data security and any data sharing.

Management of biosamples or biobanks: if you will access biosamples for your research from a biobank, then the biobank should review and confirm the feasibility of your sample access request before submission of your application for funding.

You should also work with local contacts to ensure appropriate transfer and storage arrangements will be provided. Learn more in ‘using human samples’ in section 8.

Patient and public involvement: we encourage you to consider how to involve patients or the public, or both, in developing your research. If you have undertaken preliminary engagement work or have plans for future engagement, you should state these in your application.

Learn more about patient and public involvement.

Ensure research outputs reflect diversity in society: to ensure that research brings fair benefits to all in society, it is important that the participants, proposed analysis and outputs from your research reflect the diversity of the population that you are studying. Learn about MRC’s expectations on embedding diversity in research design.

We have the following expectations when your research involves people as participants, their biosamples or data.

You must comply with all relevant regulatory, policy and ethical requirements. While your research organisation is responsible for ensuring compliance, you have a role to play (for example, in securing the relevant approvals or sponsorship, or both). For further guidance, visit your local research office.

You should comply with relevant MRC policies and guidance. This includes open research policies that promote sharing of data, samples, materials, reagents, code and more.

Your research should not start before the necessary approvals are in place. Approvals do not need to be in place at the time of applying for a grant.

You can find further guidance on requirements that may be relevant to your research below. You can also seek guidance and advice to help you understand specific requirements for your research from the MRC Regulatory Support Centre.

2. Embedding diversity in research design

Your application should meet the requirements of MRC’s embedding diversity in research design policy by embedding consideration of the relevant diversity characteristics in the design and conduct of your research.

This policy is relevant to all studies involving human participants, samples and data, including, but not limited to:

  • clinical studies
  • public health and population-based research
  • observational studies
  • studies using data from people or the use of human biological material (for example, cells and tissues)

Relevant guidance, resources and toolkits are available at embedding diversity in research design and sex in experimental design.

3. Clinical staff

If you intend to employ any clinically trained individuals to undertake research on your grant, and they remain interested in pursuing a clinical career, they must discuss these plans with their postgraduate medical dean or equivalent.

This will ensure that, where appropriate, one year of MRC-funded research counts towards the certificate of completion of their specialist training.

4. Approvals

The types of approvals you will need for your research will depend on your research, what it will involve and where it will take place.

If your research involves human participants, ethical review by a research ethics committee (REC) is the most common approval we require.

Ethical approval may be from your research organisation (for example university REC), or an NHS (or Health and Social Care in Northern Ireland) REC.

To learn when you need NHS REC review, visit do I need NHS REC review?

You may also need approvals from places such as schools or other establishments, depending on the nature of your project.

There are times when you need no REC approval (usually for studies considered low risk). Work with your local research office to understand your local policy.

You should not start any research before the necessary approvals are in place. Approvals do not need to be in place at the time of applying for a grant.

5. Interventional research involving people as participants

If your research involves an intervention or action(s) expected to result in change, such as providing your participants with a drug treatment, a surgery or different surgical technique or approach, altering diet, exercise or some other lifestyle aspect, then we have the following additional expectations:

  • you should consider how to involve people with lived experience in appropriate aspects of your study, considering study design, management, conduct and dissemination
  • trial registration and dissemination
  • you should include adequate information in each application to enable MRC to evaluate any physical or psychological hazard to which participants may be exposed
  • you should specify in each application the number, sex, age range and state of health of the human participants
  • you should indicate whether participants are patients, healthy volunteers or individuals in a control cohort and how you will obtain consent
  • you can pay participants to take part in your research, provided that the payment is to reimburse expense or compensate for time and inconvenience and not at a level that would constitute an inducement to take part

Clinical trials of investigational medicinal products, including advanced therapies

These interventional trials test the safety and or efficacy of medicinal products and include trials of advanced therapies, which are governed by the Clinical Trials Regulations. You can find further guidance on the regulatory requirements of these trials in:

If you are proposing a clinical trial of an investigational medicinal product, you will need to apply for combined review from the NHS REC and MHRA, using a new part of the Integrated Research Application System (IRAS).

Ionising radiation in human participants

Ionising radiation includes, but is not limited to:

  • X-rays, CT scans, DXA scans
  • radiotherapy (including brachytherapy and therapy using unsealed sources)
  • radionucleotide imaging
  • administration of radioactive substances (for example, nuclear medicine and PET or CT scanning)

Neither MRI nor ultrasound involve ionising radiation.

You have a legal and ethical requirement to justify the use of ionising radiation in your application. Be aware that the Ionising Radiation (Medical Exposure) Regulations (IRMER) relate to any research exposure, not only to those additional to routine clinical care.

Guidance is available on this and other relevant legal frameworks in the HRA website.

Where research involves the administration of radioactive substances, this must also be approved by the Administration of Radioactive Substances Advisory Committee (ARSAC).

All imaging technologies have the potential to uncover previously unknown pathology. You should always consider how likely such a discovery may be and, if appropriate, describe in your application how you would handle such discoveries.

For further guidance see the MRC-Wellcome Trust Framework on the feedback of health-related findings in research.

Testing a medical device or an in vitro diagnostic

Testing a medical device, including software products, may be regulated under the Medical Device Regulations depending on the purpose of the device, commercial intent and whether an exemption applies. Discuss with your sponsor’s office, as local interpretation of the exemption differs.

If you are within scope of the Medical Devices Regulations, you may be conducting a clinical investigation that requires an application to MHRA and NHS REC.

For in vitro diagnostics you may be conducting a performance evaluation, which you will need to register with MHRA.

Learn more about the regulation of medical devices and in vitro diagnostics.

6. Using data and information about people

When your research involves data or information about people, requirements largely depend on whether you will access or use identifiable or anonymised data.

You can find out more about these requirements in using data about people in research.

If you plan to access confidential patient information without consent in England and Wales, you will need section 251 support from the Confidentiality Advisory Group. Scotland and Northern Ireland have equivalent arrangements.

To learn more, visit ‘accessing identifiable information without consent’ in using information about people in health research.

Health data discovery and access

Use the Health Data Research Innovation Gateway to discover what data is available from central NHS providers and others.

Data is not held by Health Data Research UK (HDRUK) but by different organisations. The gateway provides the means to contact some organisations and apply for data access, although for most you will need to apply directly to individual organisations (or data custodians).

See the MRC Health Data Access Toolkit for the approvals you will need. This includes details of the approvals you will need when accessing NHS data from central providers or direct from NHS care organisations.

Accessing data takes time. If there are bespoke linkages and complex approvals, it can take over six months. You should build this into your grant.

If you are accessing identifiable information or collecting data from research participants, consent and confidentiality are very important.

We expect your research organisation to have policies in place to manage confidentiality and the privacy of your participants.

7. Artificial intelligence

If your research involves the development of AI algorithms, you need to take steps to assess and reduce potential bias. You might consider carrying out an AI impact assessment (AIA).

The data used for the development and training of algorithms needs to represent the diversity of the target population as closely as possible. Learn more about AIA from the Ada Lovelace Institute.

8. Using human samples

If you are establishing a new collection of human samples, it is important to seek consent that is both broad in scope and duration to allow for storage and future use.

We recommend two-phase consent, where you ask donors about the initial project, and for storage and future use in other research projects. A research ethics committee should review your consent arrangements.

If you intend to access an existing collection of human samples for your research, for example from a biobank or a collaborator, you should work with them to determine what is required in terms of ethical approval.

You should also speak to your local research office for their policy on human samples and ethical review, as well as about how to manage any transfer of samples.

If parties agree that appropriate consent is in place, and your project does not pose any ethical issues, you may not require REC review.

You can search the UK Clinical Research Collaboration (UKCRC) tissue directory to discover human samples available for use in research.

You should speak to relevant local contacts to discuss storage arrangements and ensure that these can be provided.

Exactly who you should speak to will depend on how your research organisation manages human samples, but this is likely to be your:

  • local lab manager
  • health and safety contact
  • designated individual (if you have one)

If you are based in England, Wales or Northern Ireland, your lab may operate under a Human Tissue Authority research licence (supervised by a designated individual).

If you are based in England, Wales or Northern Ireland and your lab is not covered by a licence, you will need to meet the licensing requirement of the Human Tissue Act 2004 if you intend to ‘store’ relevant material for your research.

The most common way to meet the licensing requirement on unlicensed premises is with NHS or Health and Social Care REC approval (as this provides a legal exemption for licensing).

If you are accessing relevant material from a UK-based biobank that has generic ethical approval, then their approval can extend to you and provide you with a legal exemption for licensing.

If you need a legal exemption for licensing, check whether the biobank provides such ethical approval and whether it places any other conditions on your use of their samples.

There are other licensing exemptions. You can find more in using human samples in research.

If you are accessing samples from a biobank you should attach a ‘letter of support’ or equivalent that confirms that your request is feasible and has been adequately costed. If you need additional storage for your research (for example, a new freezer or off-site storage), you can cost this into your grant.

Using human embryos, admixed embryos or embryonic stem cells and lines

If your research involves embryos or the derivation of embryonic stem cells and lines, then it may be regulated by the Human Fertilisation and Embryology Authority (HFEA).

You can read about HFEA’s requirements for research in section 22 of their code of practice. ‘Licences for research’ details when you need an HFEA research licence.

Learn more about applying for an HFEA research licence.

Xenotransplantation

If your application includes the use of animals containing human material, you must follow the Home Office guidance on the use of human material in animals.

Developing cell and tissue-based therapies

If your research will develop a cell or tissue-based therapy, then human application requirements apply pre-trial stage.

You can learn more about these requirements (procurement, testing, processing, storage, distribution, import and export of tissues and cells) in the Human Tissue Authority’s guidance on human application.

For guidance on the trial stage, see clinical trials of investigational medicinal products, including advanced therapies in section 5.

9. Induced pluripotent stem cells

If your research involves the use of induced pluripotent stem cells (iPSC) you should make a strong case in support of the proposed iPSCs being able to appropriately recapitulate the natural state or diseased condition of interest versus other means of gaining similar insight.

You must adhere to relevant UK regulations and guidelines. For guidance see the code of practice for the use of human stem cell lines.

iPSC collections should ideally be based on well phenotyped cohorts with linked clinical and lifestyle data. Donations should be altruistic, anonymised and traceable.

You must secure appropriate consent for all proposed uses. To futureproof derived lines, you should consider seeking generic consent for a broad range of potential uses, given their pluripotent nature.

Depending on the specific project, you should consider seeking specific consent for areas of particular interest including:

  • genetic analysis of derived cells
  • potential use in animal research, clinical transplantation or reproductive medicine
  • potential commercial applications of cell lines but without donors receiving personal financial benefit
  • the feedback of data from derived cell lines
  • documenting and banking for future reference the tissue source of cells from which the iPSC lines are derived

Derivation and characterisation

This is a fast-moving field with numerous derivation approaches emerging. You should use comparable methods of iPSC generation where possible and provide full details of the reprogramming method.

You should calibrate lines derived using novel methodologies against lines derived using established protocols and ideally human embryonic stem cell lines.

You should characterise lines to establish features including clonal purity, absence of expression of reprogramming factors, self-renewal capacity, genetic stability and pluripotency.

Characterisation should take into account uncertainties regarding the degree of reprogramming and the extent and durability of epigenetic memory.

We note that fully characterising lines may be costly and time consuming. The level of characterisation should be fit for purpose.

Robust quality control systems should be in place to ensure the identity and specification of banked and released cells.

Internationally agreed standards and guidance for stem cell line banking are available from the International Stem Cell Banking Initiative, and you can seek advice through the UK Stem Cell Bank and the European Bank for Induced pluripotent Stem Cells (EBiSC).

You can access existing healthy and disease-relevant lines from the European Collection of Authenticated Cell Cultures (ECACC), the UK Stem Cell Bank or EBiSC.

Access

Collections should detail how access will be provided to third parties in line with MRC policy on data sharing and cohort resource policy.

You should consider material and data transfer agreements (MDTAs), intellectual property licensing and freedom to operate, where appropriate, to ensure the broadest utility of derived lines.

MDTAs should control third-party use and ensure UK guidelines and ethical procedures are followed, for example, in relation to potential use in animals, clinical studies or reproductive science.

You should mandate equivalent standards if you are exporting stem cells for international use.

10. Research in low and middle-income countries

Applications for research involving human participants in lower and middle-income countries may have additional ethical implications that you should consider in developing the research protocol.

We expect any partnership between the UK and research organisations in these countries to be fair and ethical. See UKRI equitable partnerships guidance.

Research involving human participants requires approval from an independent ethics committee in the UK. You should also seek ethical review from an independent ethics committee in any developing country where there are study participants.

If you are struggling to obtain a UK REC review, email: international@mrc.ukri.org.

In the ethics and responsible research and innovation section of the grant application form, you should describe any ethical implications relevant to your application and confirm that these are being addressed.

The following is a list of ethical considerations that might arise when designing and conducting research in lower and middle-income countries.

If any of these are relevant to your research and not discussed elsewhere, you should confirm how you will address these issues. You do not need to make a statement about issues that are not relevant to the application.

Research approvals

You should confirm that you will seek appropriate ethics review, and any other relevant approvals, in the UK and in any other countries involved. No research should start until these approvals are in place. They do not need to be in place at the time of applying for a grant.

Vulnerable groups

You should state whether any participants will be from vulnerable groups, justify their involvement and briefly clarify how the study design takes account of their needs.

Examples of vulnerable groups might include children, prisoners, victims of violence, military conscripts, and individuals lacking capacity or disadvantaged by poverty or gender.

Informed consent

You should indicate if there are specific considerations in relation to consent influencing the proposal, for example, providing information to participants whose language has no written form, or seeking consent from community leaders as well as participants when this is expected.

Managing participant care

You should state whether, in the design of the research, you have considered the risks of any intervention, the standard of care to be offered to participants (including controls) during the research, continuing care after the research ends and ancillary care.

Information management

Describe how you will manage participant confidentiality and data security, including transfer outside the developing country or sharing of data in a registry.

You should consider all relevant information formats, including conversations, medical consultations, written data, images, sample analyses and research outputs.

You should describe research data management in the data management pan. However, you can also highlight specific issues in the ‘ethical implications’ section of the application form.

Management of biosamples and biobanks

If your application involves the collection or use of biosamples, then you should confirm you will comply with relevant local or UK codes of practice or legal requirements.

For example, this may influence arrangements for transfer of biosamples outside the developing country for analysis

Adverse impacts of the research

You should consider the wider impact of the research, negative as well as positive, on participants and communities and state how you will manage this.

For example, this may include engagement with local stakeholders to ensure that the outputs of the research are used to benefit the local population and reduce inequity or discrimination.

Public and community engagement in the developing countries

We encourage you to involve community and patient advocate groups in designing and conducting the research to increase the acceptability of the study and its findings.

If you have undertaken preliminary engagement work or there are plans for future engagement, you should state this.

If all public engagement activities have taken (or will take) place only in the UK, then you should demonstrate that these are relevant to the participant population in the developing country and that you have considered capacity-building in developing countries.

11. Health and Safety

Genetic modification

The Genetically Modified Organisms (Contained Use) Regulations 2014 require laboratories that intend to carry out genetic modification to assess the risks of all activities and make sure that any necessary controls are in place.

Genetically modified organisms (GMOs) may be plants, animals or (most commonly) microorganisms (including bacteria, viruses, parasites and fungi). Humans are not regarded as GMOs under this legislation.

Further information about the legislation and relevant approvals required is available on the Health and Safety Executive website.

Dangerous pathogens

Research organisations proposing to accommodate projects that will involve the use of dangerous pathogens must comply with the safeguards recommended by the Advisory Committee on Dangerous Pathogens (ACDP).

Read ACDP publications on guidance and regulation.

12. Controlled drugs

If your research requires the use of drugs controlled under the Misuse of Drugs Act, 1971, and its subsequent amendments, you must seek a Home Office licence directly through the host institution’s normal channels.

You should refer to the Psychoactive Substances Act: guidance for researchers to ensure you comply with the Psychoactive Substances Act 2016.

13. Development of software as part of a grant

In accordance with government policy on open source software (OSS), if your research aims to produce software outputs you must specify a proposed software exploitation route in the case for support.

When the project is completed, the software should be exploited either commercially, within an academic community or as OSS.

Further information on OSS can be found on the Open Source Initiative website.

Note: the policy on exploiting research and development software does not apply to software developed in the areas of defence, national security or law enforcement. Neither does it apply to software developed by trading funds.

Visit developing healthcare products if you are developing an app or other software with a medical purpose. These may be medical devices.

14. Research misuse and biosecurity

Some biomedical research, while having potential to greatly benefit society, carries the risk that the research outcomes or technologies used in research could be deliberately misused or unintentionally result in harm (for example, certain gain-of-function studies with the potential to enhance the pathogenicity or transmissibility of pathogens).

UKRI is committed to ensuring that applications for funding consider and manage these types of risks appropriately.

Refer to MRC’s policy statement on managing the risks of research misuse for more information.

You must identify risks associated with the unethical use of your proposed research and other biosecurity implications of your study and detail how you will mitigate them. Considerations may include, for example:

  • measures for safe and secure access to the project data, information or outcomes
  • access to research infrastructure or certain technologies

When collaborating internationally, you should ensure that you apply UKRI trusted research and innovation principles.

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