5. Ethics and approvals
- 5.1 Clinical staff
- 5.2 Human participants in research
- 5.2.1 Regulations and guidance
- 5.2.2 Research involving human participants in lower and middle income countries (LMICs)
- 5.2.3 Use of human tissue
- 5.2.4 Xenotransplantation
- 5.2.5 Use of radioactive medicinal products in humans
- 5.2.6 Genetic modification
- 5.3 Dangerous pathogens
- 5.4 Controlled drugs
- 5.5 Development of software as part of a grant
- 5.6 Bioterrorism and biomedical research
- 5.7 Induced Pluripotent Stem Cell (iPSC) resources
It is important that any clinically-trained individuals who intend to be employed through the grant to undertake research, and who remain interested in pursuing clinical careers, discuss their plans with their postgraduate medical dean, or equivalent, to ensure that where appropriate, one year of MRC-funded research counts towards the Certificate of Completion of Specialist Training.
5.2.1 Regulations and guidance
The MRC expects all work involving human participants to be undertaken in accordance with its policies and guidance.
- Research regulation and ethics – MRC position (2005)
- MRC Guidelines for Management of Global Health Trials (2017)
- Good Research Practice: Principles and Guidelines (2012)
- Human Tissue and Biological Samples for Use in Medical Research (2001): Operational and Ethical Guidelines (2015)
- Human material derived from the nervous system (2003)
- Medical Research Involving Children (2004)
- Medical research involving adults who cannot consent (2007)
- Personal Information in Medical Research (2000)
- Research Involving Human Participants in Developing Societies (2004)
- Framework on the feedback of health-related findings in research (2014)
All these publications can be accessed in the publications section of our website.
Adequate information should be included in each proposal to enable the MRC to evaluate any physical or psychological hazard to which participants may be exposed. Each proposal should specify the number, sex, age range and state of health of the human participants. Applicants will also need to indicate how informed consent will be obtained and whether the participants are, for example, patients, healthy volunteers or individuals in a control cohort.
Payments to healthy volunteers participating in research are allowable, provided that the payment is to reimburse expense or compensate for time and inconvenience, and is not at a level that would constitute an inducement for people to take part in studies.
Independent ethics committee approval is required for research that involves human participants (whether patients or healthy volunteers); their data and/or tissues. There may be cases where this review must be made by an NHS Research Ethics Committee (NHS REC). For further guidance on when NHS REC approval is required please see go to the Determine which review body approvals are required pages of the Health Research Authority (HRA) website. Proportionate review is also available for studies which present minimal risk or burden to participants.
If the study is testing the safety or efficacy of a medicinal product, it is likely that this will fall under the scope of the UK Medicines for Human Use (Clinical Trials) Regulations 2004, regulated by Medicines and Healthcare products Regulatory Agency (MHRA). More information on the types of studies that fall under these Regulations and practical help on implementing the requirements (including the requirements of a Clinical Trial Authorisation (CTA) application) can be found on the Clinical Trials Toolkit. Guidance on risk-proportionate approaches to the management and monitoring of clinical trials is provided in the MRC/DH/MHRA Joint Project document (see Appendix 2). For details of the risk-adapted approach to Clinical Trial Authorisations, please see Submitting a Notification for a trial on the MHRA website.
For investigations that involve NHS patients, their data, tissues or NHS resources; NHS R&D management permission is required from all relevant NHS organisations for research. For further guidance please the MRC Data and Tissues Tool Kit.
If the investigation is to take place within an organisation such as a factory, school or service establishment, applicants may be asked to provide evidence of relevant approval(s) from the appropriate authorities.
Approval(s) for the research detailed in an MRC grant proposal must be granted by the appropriate bodies before any work can commence. Institutions, applicants and grant holders have absolute responsibility for ensuring that the necessary approvals are granted for the research considered by the MRC and that no research requiring approvals is initiated until they are in place.
The MRC reserves the right to refuse to make an award on ethical grounds alone, even if the agreement of an independent ethics committee has been obtained.
Applicants must ensure that the appropriate approval(s) are in place before that aspect of the research can start with the MRC.
5.2.2 Research involving human participants in lower and middle income countries (LMICs)
Applications involving research with human participants in lower and middle income countries (LMICs) may have additional ethical implications that should be considered in developing the research protocol. Any partnership between the UK and LMIC research organisations is expected to be fair and ethical (see J Dodson. (2017) Building Partnerships of Equals. UK Collaborative on Development Science).
Research involving human participants requires approval from an independent ethics committee in the UK; ethical review should also be sought from an independent ethics committee in any LMIC in which there are study participants.
In the ‘ethical implications’ section of the application form, applicants should describe any ethical implications relevant to their proposal and confirm that these are being addressed. The following is a list of ethical considerations that might arise when designing and conducting research in LMICs. If any of these are relevant to the research and not discussed elsewhere in the proposal, then confirm these issues are being addressed. It is not necessary to make a statement about issues that are not relevant to the proposal.
- Research approvals: Applicants should confirm that they have sought or are seeking appropriate ethics review and any other relevant approvals, in the UK and in any other countries involved. For further information about the requirements for ethics review, please see Research Involving Human Participants in Developing Societies (Specific consideration 7).
- Vulnerable groups: Applicants 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, individuals lacking capacity, or disadvantaged by poverty or gender.
- Informed consent: Applicants should indicate if there are specific considerations in relation to consent influencing their 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: Applicants should state whether, in the design of the research, they 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/or ancillary care.
- Information Management: Describe how participant confidentiality and data security will be managed, including transfer outside the LMIC or sharing data in a registry. All relevant information formats should be considered, including conversations, medical consultations, written data, images, sample analyses, and research outputs. Research data management should be described in the Data Management Plan, however specific issues can also be highlighted in the ‘ethical implications’ section of the application form.
- Management of biosamples/biobanks: If a proposal involves the collection or use of biosamples, then applicants should confirm that they will comply with local LMIC (and/or UK) codes of practice or legal requirements. For example, this may influence arrangements for transfer of biosamples outside the LMIC for analysis.
- Adverse impacts of the research: Applicants should consider the wider impact of the research, negative as well as positive, on participants and communities and state how this will be managed. 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 / Community engagement (PCE in the LMIC): Applicants are encouraged to involve community and patient advocate groups in designing and conducting the research to increase the acceptability of the study and its findings. If preliminary engagement work has been undertaken or there are plans for future engagement, this should be stated. If all public engagement activities have taken (or will take) place only in the UK, then applicants should demonstrate that these are relevant to the LMIC participant population and that consideration has been given to capacity-building in LMICs.
5.2.3 Use of human tissue
Applicants whose proposed research involves the use of human tissue and/or use of human tissue to treat patients as specified in the relevant legislation must confirm in their proposal that they will comply with the appropriate legislation and follow the relevant Codes of Practice issued by the Human Tissue Authority (HTA).
For further guidance please see the MRC Data and Tissues Tool Kit – Which approvals are needed? and HTA licence.
Applicants whose proposed research involves the use of human foetal tissue, or non-foetal products of conception, (eg amniotic fluids, umbilical cord, placenta or membranes) should follow the guidance set out in relevant Codes of Practice issued by the HTA (in particular see paragraphs 157-161 in the Code of Practice on Consent).
Research involving gametes and embryos is subject to regulation by the Human Fertilisation and Embryology Authority (HFEA) and researchers must ensure that they adhere to the relevant guidance. For further details please see the MRC Data and Tissues Tool Kit – HFEA licence.
Cell lines and embryonic stem cell lines fall within the regulatory remit of the HTA by virtue of the Human Tissue (Quality and Safety for Human Application) Regulations 2007, which regulates the processing, storage and distribution of stem cell lines for human application. Both the HFEA and the MHRA also have a regulatory remit in respect of cell lines and embryonic stem cell lines. A position statement on regulating human embryonic stem cell lines has been issued by the HTA, HFEA and MHRA which provides guidance on the relevant regulatory remits. More information on the regulatory routes for conducting human stem cell research in the UK can be found on the UK Stem Cell Tool Kit.
A letter of support must be attached to the application if human tissue will be sourced from a public or collaborator’s resource eg brain bank (even if from the PI’s RO), or from a separate RO.
The list of materials considered to be ‘relevant material’ under the Human Tissue Act 2004 can be found here.
Applicants must therefore seek relevant approval(s) and confirm in their proposal that they will follow the DH guidance and, if applicable, comply with the ATMP regulations. For further guidance please see the MRC Experimental Medicine Tool Kit – Xenotransplantation.
5.2.5 Use of radioactive medicinal products in humans
Applicants, whose proposed research requires the administration of radioactive medicinal products (including in- vivo neutron activation analysis in humans), should follow the guidance issued by the Administration of Radioactive Substances Advisory Committee (ARSAC) and seek the relevant approval(s) as appropriate. Please note that ARSAC is currently moving to a more integrated process with the Health Research Authority (HRA) that will remove the requirement for additional ‘research certificate’ applications. For further details please see the HRA website.
5.2.6 Genetic modification
The Genetically Modified Organisms (Contained Use) Regulations 2000 (GMO (CU)) as amended by the Genetically Modified Organisms (Contained Use) (Amendment) Regulations in 2002, 2005 and 2010 require laboratories that intend to carry out genetic modification to assess the risks of all activities and make sure that any necessary controls are put in place. Further information about the legislation and relevant approval(s) required is available on the Health and Safety Executive (HSE) website.
Institutions/departments proposing to accommodate projects involving the use of dangerous pathogens must comply with the safeguards recommended by the Advisory Committee on Dangerous Pathogens in their reports: Biological Agents; the principles, design and operation of containment in a level 4 facility (2006) and Biological Agents; managing the risks in laboratories and healthcare premises (2005).
Applicants whose proposed research requires the use of drugs controlled under the Misuse of Drugs Act, 1971, and its subsequent amendments, must seek a Home Office licence directly through the host institution’s normal channels.
In accordance with Government policy on Open Source Software (OSS), applicants whose proposed research aims to produce software outputs 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 at www.opensource.org
The MRC is aware that in light of global events, biomedical research that involves the use of potentially harmful pathogens and toxins has come under increased scrutiny, and that there are heightened concerns that the misuse of this research could increase the potential threat of bioterrorist attacks. Applicants are asked to take note of MRC's policy statement when preparing proposals.
Applicants whose proposed research involves the use of induced Pluripotent Stem Cells (iPSC) 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.
Relevant UK regulations and guidelines must be adhered to. For guidance see the Code of Practice for the use of Human Stem Cell lines (PDF, 487KB).
iPSC collections should ideally be based on well phenotyped cohorts with linked clinical and lifestyle data. Donations should be altruistic, anonymised and traceable. Appropriate consent must be secured for all proposed uses. To future proof derived lines, consideration should be given to seeking generic consent for a broad range of potential uses, given their pluripotent nature.
Depending on the specific project, consideration should be given to ensuring specific consent is sought for areas of particular interest including:
- Genetic analysis of derived cells
- Potential use in animal research, clinical transplantation or reproductive medicine; and
- Potential commercial applications of cell lines but without donors receiving personal financial benefit
- Consideration should also be given to the feedback of data from derived cell lines.
- The tissue source of cells from which the iPSC lines are derived should be documented and ideally banked for future reference.
Derivation and characterization
This is a fast moving field with numerous derivation approaches in use emerging. Comparable methods of iPSC generation should be used where possible, with full details of the reprogramming method provided.
Lines derived using novel methodologies should be calibrated against lines derived using established protocols and ideally human embryonic stem cell lines. Lines should be characterised 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.
It is noted that fully characterizing lines may be costly and time consuming. The level of characterisation should be fit for purpose. Robust quality control systems should be put 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 through the International Stem Cell Banking Initiative, and advice can be sought through MRC-funded resources such as the UK Stem Cell Bank and Human iPSC Initiative.
Collections should detail how access will be provided to third parties in line with MRC policy on data sharing (PDF, 108KB) and cohort resource policy.
Material and Data Transfer Agreements (MDTAs), IP Licensing and Freedom to Operate should be considered, 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. Equivalent standards should be mandated if exported for overseas use.