Requirements on integration of sex in experimental design
We want to fund the best quality medical research, which is relevant to and benefits all. Beating cancer means beating it for everyone.
But cancer is complex and affects people in different ways. So where possible, we want the research we fund to be generalisable to build a better understanding of the full range of biological differences in patient populations and determine the impact of these differences on cancer and cancer treatments.
Sex is one key biological variable that may influence cancer biology, but its full role in cancer and cancer treatments is understudied. Through our new requirements for the inclusion of sex in experimental design, the design, analysis and reporting of our funded research experiments will help to build evidence around the role biological sex plays in cancer.
What changes are we making?
We now require male and female sexes to be used in the design of experiments described in all funding applications to us that involve animals, human and animal tissues, and cells. However, exceptions, to permit single sex experiments, may be granted, particularly if you have a strong scientifically-based justification. See the full requirements below for examples of exceptions.
Under the new requirements, all relevant applications should include information about the sex of the animals to be used in experiments, as well as the sex of studied tissues and cells. If you don’t know the sex of the cells and tissues you use, you should plan to determine this as part of your research.
Using the same or only modest increases in sample size, you can often convert a randomised single-sex experiment analysed by student’s t-test into an experiment including males and females with multi-factorial statistical analysis. We’ve shared resources to help you do this below. Examples of the design of in vivo experiments can equally be applied to studies involving cells or tissues. These experimental design considerations should be incorporated into your future research proposals.
We’ll roll out these new expectations gradually across our funding portfolio and they will continue to evolve as we gain insights from the peer review process during our upcoming grant review rounds.
There will be no retrospective application of this requirement to existing awards or previously submitted applications, but we encourage all of our researchers to consider how to incorporate these principles where practical and explore ways to make their discoveries more generalisable.
What do these new requirements mean for research?
1. Design studies that take sex into account or explain why it isn't included
2. Experiment using male and female samples and record as sex-based data
3. Analyse sex-based data and the interactions between all variables
4. Share methods and results from any sex-based experiments
We encourage you to share all research outputs – including where possible those that show negative results (e.g., where biological sex has no impact on findings). This can help all researchers better understand the overall effect of different biological factors and support the development of future hypotheses and study designs.
What are the new requirements in full?
We’re aligning our requirements with the Medical Research Council’s (MRC) guidance and their definitions of sex and gender for consistency across the UK research network.
Use of both male and female sexes will be the default
Both male and female sexes of animals, or tissues or cells should be incorporated into each experiment. There is no requirement to ‘balance’ or use equal numbers of the sexes, although, where possible, equal numbers will support the best statistical power to examine the sex variable. The new requirement does not apply to the use of immortalised cell lines.
Exceptions for single-sex studies with justification
We may still fund single-sex studies where there is strong justification in the research proposal for doing so.
Cases where the use of a single sex may be appropriate include:
- single sex biological mechanisms or diseases (for example, ovarian cancer)
- research into the mechanisms of purely molecular interactions (for example, when investigating protein-protein interactions)
- where there are acutely scarce resources (for example, human tissue samples of rare cancers)
- where costs would be excessive (for example, several times higher than a single sex study)
Other reasons for conducting research in a single sex will be considered as part of the peer review process. These may include scientific, logistical or ethical considerations and should have robust justification.
Please note in most cases female variability will not be sufficient as a justification for using only one sex. We will not accept as a justification that prior work has been performed in only one sex or that there is a lack of evidence of sex having an effect.
What additional support and resources are available?
Contact us
We want to hear from you if you have any questions, comments or concerns about these new requirements and their impact on your research. We also want to hear about any great examples of research already integrating sex in experimental design, both where sex does and doesn’t show an effect.