Searching for Alternatives

Searching for Replacements

Accessing information on opportunities and approaches that help replace animals in research is essential for scientific, legal and ethical reasons. It can prevent unnecessary duplication of studies, improve experimental design, and ensure that existing and new alternative methods are used as widely as possible.

Below are the basic principles of searching to help people find and identify information relevant to their specific area of interest. Please see the complete guide for more detailed advice on terminology, appropriate strategies, and available resources for efficiently conducting online searches. You may also find our Replacement Checklist tool helpful for assessing whether your searches for Replacements have been completed and reported robustly. We support individuals and organisations with Replacement tools and training.

There are five basic steps in a comprehensive search:

Formulating a focused research question
Identifying appropriate databases and other sources of information
Transforming the research question into a search strategy
Collecting output and identifying potentially relevant papers
Saving and reporting searches

1) Formulating a Focused Research Question

The value of any research lies in the nature of its benefits, its beneficiaries, the likelihood that (any) benefit may arise from it, and the timeframe during which this benefit might accrue. Framing the research in terms of its benefits is necessary when applying for funding, for ethical review, when submitting a manuscript for publication, and when exploring opportunities to avoid the use of animals.

It is important to consider who the beneficiaries of the research would be. How might they input into its design to optimise its impact?

The main components of the research question determine the structure and the sequence of any search. That means carefully identifying these components is key. Within applied research, a specific research question generally contains the following components:

Intervention/exposure.
Disease of interest/health problem.
Target/host biological system in which the problem arises.
Outcome measures.

A well-formulated research question could then be: ‘What is the effect of [intervention/exposure] on [outcome measures] in [target/host biological system in which the problem arises] for [disease of interest/health problem]?’

In basic or fundamental research, the search strategy remains the same. However, the building blocks for the research question may be a bit different. Other types of search components may be relevant when formulating a specific research question in fundamental science, but the translation of the research question into a search strategy is similar.

2) Identifying appropriate databases and other sources of information

Because there is no single complete source of information for animal replacement, a thorough exploration of ways to avoid animal use will involve searching multiple sources of information:

Librarians can help identify databases and training opportunities.
Bibliographic databases will hold information invisible to common search engines like Google.
Online communities and forums are useful for specialist advice.
Webinars and conferences share up to date scientific infomation.
Social media platforms like Bluesky and LinkedIn enable networking with relevant experts.
Contact organisations like Replacing Animal Research, InterNICHE and NC3Rs. Please see Norecopa’s global map of 3R centres and networks.

Online platforms and search engines

Search engines such as Google, can be useful in finding relevant information, networks, communities and databases, but are limited by what is visible to them, and are biased by search engine optimisation and commercial sponsorship.

Using appropriate search terms can identify useful ‘grey literature’ like pre-registered protocols, pre-prints of papers, reports from research commission by governmental bodies or NGOs, policy literature, newsletters, government documents, white papers or similar.

Searching social media platforms using suitable key terms (and hashtags where appropriate) may also help in finding suitable conference presentations, webinars, pre-recorded research updates and public engagement materials from academic and other research institutions and networks, biotech firms, and 3Rs and advocacy organisations.

‘Grey literature’, including preprints of protocols or approaches from other fields:

Online community discussion forums, social media, and other networks are used to seek advice or assistance from others.
Directly contacting those with expertise or experience (e.g. 3Rs Centres, 1R organisations, or specialist subject networks and learned societies).

Bibliographic databases

Because they require subscription or registration, some scientific information is invisible to web search engines. However, they enable a much deeper search of existing techniques and approaches, many of which have been peer reviewed.

A regularly updated A to Z list of databases can be found on the Norecopa website.

New AI tools such as the Biomedical models Hub developed in the EU and launched in November 2025, are also helpful to use alongside traditional database searches.

3) Transforming the research question into a search strategy

Creating a search strategy for a specific database depends upon specific search terms, the search capabilities of the database and the indexing system it uses.

Subject-Specific Terms

The four components of the research question: intervention/exposure; disease of interest/health problem; target/host/biological system in which the problem arises; and any outcome measures, should be used to generate suitable subject-specific search terms. One of the easiest ways to do this is to identify a set of core papers. A good place to start is by looking through some relevant reviews.

Reviews are useful to identify key papers and authors, and older references can be followed forward in time to identify articles which have cited them. Relevant words can then be extracted from the full texts of the core papers, including any keywords supplied by the authors.

Consider:

The field of interest: cardiology, pharmacology, neurology.
The biological systems or anatomical structures that are studied.
Any biological or disease processes involved.
Any cell types, molecules, agents of interest or relevance to the study.

Keywords hinting at Replacement:

It’s important to remember that there is no single clear labelling system for replacement approaches. Authors of scientific publications and databases rarely use the terms ‘alternatives’, ‘NATs’, ‘NAMs’, or ‘replacement’ in tags, titles, abstracts, or keywords.

Subject-specific terms need to be combined with terms that hint at non-animal approaches, such as:

Co-culture	Biopsy	Organoid	Microfluidic
Spheroid	Explant	Organ-on-a-chip	In silico
Microphysiological	(in) vitro	Non-animal	Machine learning
Equivalent	assay	3D	Ex-vivo

Optimising a Search

If the first search retrieves too many and/or irrelevant documents, the search filter can be focused by using narrower terms, for example searching on “organoids” instead of “in vitro”.

Use parentheses and operators like AND, OR and NOT to construct complex search filters or ‘strings’, that include keywords covering the entire search.

AND and OR are Boolean operators. OR combines synonyms, abbreviations and related terms on a similar concept. The results of a search will increase as OR is used to combine more terms together. ‘OR is more’.

AND is used to combine different concepts and to retrieve results where all the concepts are present. AND is sometimes automatic for two or more search terms, depending on the database. AND makes the search more specific and reduces the number of results.

Keeping notes on which search term combinations are being used at each stage is helpful. Copying and saving the search filters created means they can be used again in future, and the search can be reported to others. (See Reporting searches below.)

WE HAVE CREATED A STEP-BY-STEP EXAMPLE OF SEARCHING FOR REPLACEMENTS FOR ANIMALS IN MULTIPLE SCLEROSIS RESEARCH

SEARCHING FOR REPLACEMENTS FOR ANIMALS IN MULTIPLE SCLEROSIS RESEARCH

4) Collecting output and identifying potentially relevant papers

Having performed the subject-specific search, full copies of relevant articles should be obtained and appraised to see if it they’re appropriate and usable. If any are found to be irrelevant, then note down the criteria used to exclude them and how many papers were excluded under each criterion.

Both peer-reviewed research articles and those referred to as ‘grey literature’ should be critically appraised for their relevance and rigour. Alongside the critical academic assessment of the quality of a study (see Applying critical and reflective thinking in academic and professional contexts: science perspective), including various factors like the importance of the research question, the design and methodology of a study, the validity of the results and their usefulness (application or relevance), the legitimacy of the conclusions, and any potential conflicts of interest, whether and how the approach might inform a replacement approach must also be considered.

When assessing the output of searches for replacement opportunities, it’s important to remember that all models have limitations.

No individual model mimics every aspect of the real-life situation.

Models are used as a proxy that allows the control of certain parameters and variables that enable measurement and observation. Because of this, extrapolation from them comes with caveats. This must be acknowledged when comparing the results of searches for alternatives to current animal ‘model’ use.

Useful questions to ask are:

Does any of the retrieved information cover the minimum elements of what is needed?
Can they replace part of the work?
Is it possible to adapt or optimize protocols to make them more applicable?
What resources would be needed to do this?

Remember that 1:1 replacement is rare, but a combination of approaches may collectively answer the same question.

5) Saving and reporting searches

To evidence the systematic and robust nature of a search for replacement, it is important to save and report the search strategy and outcome.

A report could take the form of supplementary information to a scientific paper, an internal report to an AWERB/AWB/Animal Ethics Committee, a blog or social media post, or other format that enables open sharing of information.

Please use our Replacement Checklist to ensure that all opportunities to replace animal use have been explored and demonstrated.

Why is it important? Because disseminating Replacement information helps other researchers search effectively, and prevents duplicated effort.

Download your searching for replacements guide