Guidance

Guidance for applications involving animals

From:
MRC
Published:

1. Introduction

We strongly advise you to read the following section carefully before preparing an application to ensure you include all the relevant information required in the appropriate sections of your application. In particular, you should ensure your application clearly justifies the following:

  • research objectives and how the knowledge generated will advance the field
  • the need to use animals and lack of realistic alternatives
  • choice of species of animals to be used
  • type of animal(s), for example, strain, pathogen free, sex, genetically modified or mutant
  • planned experimental design and its justification
  • numbers of animals and frequency of measurements and interventions to be used
  • primary outcomes to be assessed
  • planned statistical analyses

A compelling scientific case is essential for justifying the use of animals in research.

There have been several important initiatives aimed at raising the standard of design and reporting of animal experiments. The ARRIVE guidelines lay out criteria that you should meet in reporting animal studies so that their results and conclusions can be properly evaluated.

These criteria address a range of issues relating to:

  • transparency and validity of experimental design
  • the avoidance or minimisation of bias
  • the adequacy of statistical aspects of the study, including statistical power and appropriate statistical analysis

Our guidance reflects the information we need to allow proper assessment of the scientific strengths and weaknesses of applications for funding involving animal use.

Where following our guidance will require additional resources, for example for animal identification such as ‘microchipping’, increased maintenance charges resulting from the randomisation procedure, or salary costs associated with obtaining statistical support, we recognise this and will support such costs where fully justified in the application.

We also require that you consider sex appropriately in research involving animals, cells and tissues. In applications involving animals, cells and tissues, you should plan to use both sexes unless there is a strong reason for not doing so, which you should detail in the application. See sex in experimental design.

2. Replacement, reduction and refinement of animal experiments

We expect you to have developed your application in accordance with the cross-funder guidance for the use of animals in research, responsibility in the use of animals in bioscience research, and NC3Rs guidelines, primate accommodation, care and use.

Experiments using animals funded by MRC must comply with the Animals (Scientific Procedures) Act 1986 (ASPA), amended 2012 and any further embodiments, in:

  • using the simplest possible, or least sentient, species of animal appropriate
  • ensuring that distress and pain are avoided wherever possible
  • employing an appropriate design and using the minimum number of animals consistent with ensuring that scientific objectives will be met

You can find advice on opportunities and techniques for implementing these principles, including the Experimental Design Assistant (EDA), on the NC3Rs website.

3. Experimental design, avoidance of bias and statistical considerations

There is a wide range of designs and approaches to animal experimentation that are appropriate depending on the objectives of the research application. In all cases, we expect you to provide well justified information in your application concerning the experimental design and its suitability to answering the research questions posed.

While we recognise that there are ethical imperatives to reduce the number of animals used, it is also unethical to conduct a study that, because of its limited size, has inadequate statistical power to robustly answer a research question.

You should therefore provide adequate justification for your choice of design and numbers of animals and interventions. It is important that you give adequate information concerning methodological issues, including (but not restricted to):

  • the avoidance of bias, for example masking (blinding) of observers assessing outcomes to the group allocation in a randomised design
  • how you will carry out randomisation (if used) or why it is not appropriate if you will not use it
  • a clear definition of the experimental unit in the analysis and the implications of that experimental unit (that is, there is a difference between N samples from one animal, as distinct from one sample from each of N animals, or combining samples from multiple animals)
  • a principled justification of the adequacy of the numbers of animals you are including to minimise the likelihood of spurious results due to the play of chance alone
  • where you are using animals in multiple types of experimental approaches in a single application (for example for tissue supply, pilot experiments or more defined preclinical studies) you should provide exemplars for these types of experiment of the sex of the animals you are using, and if you are proposing only a single sex, justification for why the study fits one of the exemption categories outlined by MRC (sex in experimental design)
  • the number of different time points where you will make measurements on each animal
  • a description of the statistical analysis methods that you will use, explaining how they relate to the experimental design and showing that they are appropriate for the types of data that you will collect
  • an indication of the number of independent replications of each experiment you will perform with the objective of minimising the likelihood of spurious nonreplicable results (if you have no plans to independently replicate studies to within the current application, then you will need to justify this)

You will find examples of the level of detail and type of information required in experimental design for animal research: proposal examples.

In addition, the NC3Rs has developed a free online tool to guide you through the design of your experiments, helping to ensure you use the minimum number of animals consistent with your scientific objectives, methods to reduce subjective bias, and appropriate statistical analysis.

The Experimental Design Assistant will help you build a machine-readable diagram representing your experimental plan, following capture of your methodology, and allows you to generate a PDF report that provides a transparent description of the experimental design in a standardised format.

This tool can assist you in the design of experiments using both sexes of animal, tissue or cell. We encourage you to consider embedding the summary diagram of this tool into your approach, where appropriate.

4. Animal-relevant sections in the UKRI Funding Service

Information about the use of animals will be subject to scrutiny and will carry substantial weight when we assess the scientific strength of your application. Guidance on where you should address each aspect in the application is available below.

You must provide this information for all applications involving animals, regardless of whether we are requesting animal costs as part of the application.

Approach: reproducibility and statistical design

You should detail the scientific case underpinning the choice of animal model and the experimental plans in the approach section (recommended 500 words for reproducibility and statistical design).

You should outline the experimental design, including a justification of the total numbers of animals you are using, their sex, and, where appropriate, the frequency of measurements and interventions required on each animal.

You should outline planned procedures to minimise experimental bias, for example, randomisation protocols and masking (blinding), or explain why such procedures are not appropriate. You do not need to describe each experiment in detail, but you must include sufficient information that reviewers are readily able to understand the experimental plan.

You must provide a properly constructed justification of how you determined the numbers of animals to be used. In general, we expect you to seek professional statistical advice in putting this section together.

In many instances this section will include statistical power calculations based on justifiable and explicit assumptions about the anticipated size of the experimental effects. If you are not giving statistical power calculations, you should provide a principled explanation of the choice of numbers.

You can use power calculations to calculate the minimum sample size so that one can be reasonably likely to detect an effect of a given size, or to calculate the minimum effect size that is likely to be detected in a study using a given sample size.

In general, we will not consider explanations as adequate if you base them solely in terms of ‘usual practice’. You should include an overview of the planned statistical analyses and their relation to the choice of sample size.

You should provide an explanation of how and why the animal species and model you are using can address the scientific objectives and the relevance to human biology. If you are proposing a single sex study, you must give adequate justification why this is necessary.

You should include information on the sources of knockout or transgenic lines and relevant information to demonstrate the verification of lines selected.

You must clearly make the case for how the chosen design will enable you to achieve the stated objectives of the study, with reference to the information on the numbers of animals and planned statistical analyses.

In addition to the usual background and specification of the primary and secondary objectives of the study, or specific hypotheses being tested, you should clearly define the primary and secondary experimental outcomes you will assess, for example cell death, molecular markers, behavioural changes.

You do not need to describe each experiment in detail, but you must include sufficient information that reviewers are readily able to understand the design rationale and make robust judgements on the scientific case.

Research involving the use of animals

You must complete the template document in this section and give details of any procedures categorised as moderate or severe (in accordance with the maximum prospective severity rating in the Home Office licence under which the work will be carried out).

This is so that the assessment of the application can balance the importance of the potential scientific advancement with the welfare of the animals.

You must give sound scientific reasons for the use of animals and explain why there are no realistic alternatives and how the choice of species complies with ASPA. See replacement, reduction and refinement of animal experiments in section 2.

You should include the following information:

  • sound scientific rationale for the use of animals
  • explanation of why there are no realistic non-animal alternatives
  • how the choice of species complies with the Animals (Scientific procedures) Act (1986), for knockout or transgenic lines, briefly including information on your sources and relevant information to demonstrate the verification of lines selected
  • relevant information about the animals you will use (for example species, strain, sex, developmental stage, weight)

We encourage you to provide other ‘supporting information’ regarding experimental design and statistical analyses in the approach section.

The guidance below provides more detail about the information required in the approach for applications requesting the use of animals. A summary of where to put all required information regarding the use of animals in your application is in section 8 under justification of animal use.

Conducting research with animals overseas

If your project involves the use of animals overseas you must provide a statement in the ‘conducting research with animals overseas’ section of the application that confirms:

  • all named applicants will adhere to all relevant national and local regulatory systems in the UK and internationally
  • the research will be conducted in accordance with the guidelines laid out in the NC3Rs responsibility in the use of animals in bioscience research document and the work carried out to UK welfare standards
  • before starting the proposed research work, you will obtain appropriate approvals from institutional or central animal ethics committees for the experimental protocols you will adopt in your projects; we may expect successful applications to provide copies of these permissions before we release funding
  • details on where the animal research will take place (UK or international) and through which funder you are seeking resources

If the research involves the use of animals (rodents, rabbits, sheep, goats, pigs, cattle xenopus) overseas, rather than in the UK, you should also complete the appropriate additional questions on the use of [species] overseas’ form, and upload to the ‘Conducting research with animals overseas’ section of the application.

Resources and costs

You may request the costs of both the animals themselves and their maintenance.

If you are planning to use animals purchased from commercial suppliers, you should, wherever possible, use UK suppliers to minimise the risk of suffering during transport. For cats, dogs and primates, you must use Home Office-approved suppliers.

If you are contracting out animal research or proposing to undertake any animal experiments as part of collaborative programmes outside the UK, please see the section below on ‘Ethical and welfare standards and review’.

If you are planning research using rhesus macaques you should obtain animals from the MRC Centre for Macaques, which will advise on costs. You should contact the centre at the earliest opportunity and ensure you inform them in the event of a successfully funded application.

Justification of resources

You should give detailed justification of the animal costs you are requesting. Where experiments involve genetically altered animals, you may include examples of the breeding strategies in the justification to support the total number of animals you are requesting. You should not include any experimental or statistical details in this section.

5. Ethical and welfare standards and review

You must ensure that you follow best practice in relation to animal husbandry and welfare. Where the work you propose is not covered by an existing project licence under ASPA, you should put your application to the local Animal Welfare and Ethical Review Body for review before submission and ensure that you address any ethical and welfare issues raised.

You should be aware that the NC3Rs will be involved in the review of any MRC applications proposing to use non-human primates, cats, dogs or equines, providing advice specifically on the 3Rs and animal welfare.

If you are contracting out animal research or proposing to undertake any animal experiments as part of collaborative programmes outside the UK, you must conduct these experiments in a way that conforms to the legal and ethical practices in that country, as well as to the standards (including animal welfare) required in the UK.

Where standards are different, the more rigorous guidelines will apply. We strongly advise you to view the Choosing contractors for animal research: expectations of the major UK public funders presentation produced by the NC3Rs, which sets out our requirements and other major funding bodies’ requirements on standards of animal welfare and study design, including for preclinical studies at contract research organisations.

6. Home Office licences

You are responsible for ensuring that the appropriate Home Office licences are obtained. This will include the requirement that the local ethical review process approves the research application.

You do not have to obtain Home Office licences (or amendments to existing licences) before you submit the application. However, if we award a grant, you must have the necessary licences in place before any animal experimentation begins.

7. Mouse strains

We encourage the archiving and sharing of genetically altered mouse strains as a means of both reducing and refining animal use. We support a central repository of mouse strains, the MRC Mouse Frozen Embryo and Sperm Archive (FESA) at MRC Harwell.

FESA aims to:

  • ensure that valuable mouse strains are safeguarded
  • reduce the need to maintain colonies of live mice for long periods of time
  • capitalise fully on the significant investment in engineering strains

You must fully justify any need for the repeated creation of pre-existing genetically modified mouse strains. If you are planning to produce genetically modified mouse strain(s), you should investigate whether suitable strains are available via FESA or elsewhere before requesting resources for creating new strains.

If you are planning on creating new genetically altered mouse strains as part of your work, you should actively consider archiving and sharing these strains via FESA. When archiving and sharing of genetically modified mice is not possible, clearly state the reasons for this in your application.

Email: fesa@har.mrc.ac.uk

8. Justification of animal use

If your application involves multiple experiments, for example a pilot study, tissue supply or treatment comparison, you should include the level of detail below for each type of experiment.

Experimental approach

You should include the following details of the experimental approach under ‘approach’:

  • the number of experimental and control groups
  • the total number of animals you will use in each experiment
  • the number of animals in each experimental group
  • the number of times you will measure each animal
  • the number of independent replications of each experiment indicated
  • any steps you will take to minimise the effects of bias when allocating animals to treatment (example randomisation procedure) and when assessing results, for example masking (blinding)

For guidance see ‘Reproducibility and statistical design’ in the application section of the main guidance for applicants and in section 4 above.

Sample size

You should include the following details of the sample size under ‘approach’:

  • an explanation of how you arrived at the number of animals, including power calculations if appropriate or other supporting information to demonstrate that the findings will be robust
  • details of any statistical advice sought/available

For guidance see ‘Reproducibility and statistical design’ in the application section of the main guidance for applicants and in section 4 above.

Planned statistical analyses

You should include the following details of the planned statistical analyses under ‘approach’:

  • an overview of the planned statistical analyses in relation to the choice of sample size
  • details of any statistical advice available

For guidance see ‘Reproducibility and statistical design’ in the application section of the main guidance for applicants and in section 4 above.

Objectives and experimental outcomes

You should include the following details of the objectives and experimental outcomes under ‘approach’:

  • the primary and any secondary objectives of the study, or specific hypotheses you are testing
  • the primary and secondary experimental outcomes you are assessing (for example cell death, molecular markers, behavioural changes)

For guidance see ‘Reproducibility and statistical design’ in the application section of the main guidance for applicants and in section 4 above.

Justification of the choice of species and model

You should include the following details of the justification of the choice of species and model under ‘approach’:

  • an explanation of how and why the animal species and model you will use can address the scientific objectives and the relevance to human biology
  • relevant information about the animals you will use (for example, species, strain, sex, developmental stage, weight)

For guidance see ‘Reproducibility and statistical design’ in the application section of the main guidance for applicants and in section 4 above.

Justification of the experimental design and statistical framework

Under ‘approach’ you should include a scientific justification of why the numbers of animals you will use, the experimental design you have chosen, and planned statistical analyses are appropriate to meet the objectives of your study.

For guidance see ‘Reproducibility and statistical design’ in the application section of the main guidance for applicants and in section 4 above.

Procedure severity

You should include the following details of procedure severity under ‘research involving the use of animals’:

  • confirmation of the use of animals (this should be ticked as ‘yes’ even if you are not requesting animal costs as part of the proposal or application)
  • details of any procedures categorised as moderate or severe in accordance with the maximum prospective severity rating in the Home Office licence under which you will carry out the work

For guidance see ‘Research involving the use of animals’ in section 4 above.

The need to use animals and the choice of species

You should include the following details of the need to use animals and the choice of species under ‘research involving the use of animals’:

  • a sound scientific reason for the use of animals and an explanation why there are no realistic non-animal alternatives
  • an explanation of how your choice of species complies with ASPA
  • relevant information about the animals you will use (for example, species, strain, sex, developmental stage, weight)

For guidance see ‘Research involving the use of animals’ in section 4 above and ‘Replacement, reduction, and refinement of animal experiments’ in section 2 above.

Overseas animal research

Under ‘conducting research with animals overseas’ you should include confirmation that research will be conducted in accordance with welfare standards consistent with those in the UK.

For guidance see ‘Conducting research with animals overseas’ in section 4 above.

Funding requested and explanation of funding requested

You should include the following details of funding requested and explanation of funding requested under ‘resources and cost: justification of resources ’:

  • the total number of animals you are requesting and the associated purchase and upkeep costs
  • overview of how you reached the figure for animal costs

You should not include experimental or statistical details in this section. However, you may include a breeding plan to demonstrate how you determined the total number of animals requested.

For guidance see ‘Resources and costs’ in section 4 above.

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