Ensuring Medical Research Accounts for Sex and Gender: The MESSAGE Project

Authors: Marina Politis, The George Institute for Global Health UK and Newcastle University; Alice Witt, The George Institute for Global Health UK; Kate Womersley, The George Institute for Global Health UK, Imperial College London and NHS Lothian | Editors: Romina Garcia de leon, Janielle Richards (Blog Co-Coordinators) | Expert Reviewer: Dr. Liisa Galea

Published: December 13th, 2024

From the girl who doesn’t receive an ADHD diagnosis, but instead is labelled an anxious daydreamer, to the trans woman who faces dire outcomes following a heart attack and is not counted by clinical trials, to the man with depression who is less likely to reach out for help, neglecting sex and gender negatively harms us all. 

Why Sex and Gender Matter in Research

What springs to mind when asked about the factors influencing our health? Socioeconomic status, lifestyle factors such as smoking or alcohol use, and genetic risk are all variables that are ingrained in the public’s, clinicians’ and researchers’ consciousness as crucial considerations. Sex and gender, despite being fundamental to us all, remain neglected across medical research, with over five times more male than female cells and animals used in preclinical research and only 20% of participants being women in phase I clinical trials.

The MESSAGE Project 

Enter the MESSAGE (Medical Science Sex & Gender Equity) project, a UK initiative aiming to ensure that biomedical and healthcare researchers incorporate sex and gender considerations at every stage of their research project. Unlike sex and gender policies that have been designed and implemented by individual funders in the US and Canada, MESSAGE brings together the wider UK research sector – from government organizations to charitable funders to ensure change doesn’t happen in silos. 

As a sector, MESSAGE stakeholders have created a policy framework, designed as a template, that can be adopted as is or adapted based on the individual needs of research funders to enable tangible action across the research pipeline. Adoption of policies based on this framework will mean that any researcher applying for funding will need to state in their application how they plan to account for sex and gender dimensions.  This would bring sex and gender dimensions to the forefront of researchers’ thinking right from the outset of the study design. 

The Policy Lab Process

The MESSAGE project has been structured around four Policy Labs and consists of collaborative workshops which bring together diverse stakeholders to tackle the specific challenges related to integrating sex and gender considerations into research. The first Policy Lab focused on: articulating a vision for sex and gender policy change, emphasizing a lack of awareness about the relevance of sex and gender in medical research, recruitment challenges and the challenges surrounding inflammatory public and political discourse, for example inappropriately essentializing sex. Subsequent labs focused on refining the policy framework, implementation strategies and developing a five-year roadmap for sector-wide change.

The MESSAGE Policy Framework

The MESSAGE policy framework requires researchers to justify four key aspects to account for sex and gender: sex and/or gender characteristics, target distribution of participants in terms of sex/gender, strategies for recruitment and retention and the sex and/or gender distribution in secondary data from original datasets. Researchers must also detail any planned sex/gender disaggregated analyses or justify their absence. Researchers are not expected to have sample sizes powered for statistically significant results for each sex or gender group, but they should consider how sex and gender may impact study outcomes and report on these dimensions transparently. 

The policy also aims to address gaps in medical evidence regarding trans, non-binary, and intersex individuals, encouraging their inclusion and outlining recruitment strategies. Reporting data, even in small numbers, can facilitate meta-analyses and novel conclusions. 

International Collaboration & Global Standards

MESSAGE is not working in isolation, and is informed by a precedent of robust sex and gender policies set by other nations, notably the Canadian Institutes for Health Research (CIHR) (2010), the National Institute for Health (NIH) in the United States (2016) and countries in the European Union under Horizon (2016). 

These policies are not merely documents resigned to paper as recent evaluations demonstrate that sex and gender policies are a critical first step to enacting change. A 10-year evaluation of the effect of the CIHR policy on proposed studies for research funding found a four-fold increase in the number of studies accounting for sex, and a three-fold increase in studies accounting for gender. Even here, it is important to highlight that when analysis moved beyond mandatory boxes, which is where we may see tokenism, to published abstracts, only a small 2% mention sex or gender, with no huge increase in reporting of sex or gender in Canadian funded research and the same is true of NIH funding. Evidently, more work is needed in this space.

A Call to Action

All of us, whatever role we have in the research pipeline – bench scientist, trialist, statistician, person with lived experience, participant, clinician – can change the norms surrounding sex and gender considerations in our work. From funders, who can update funding application systems to reflect sex and gender principles to leaders in higher education who can reflect on the research culture they create and  embed sex and gender principles into curricula. Researchers can also critically review literature, interpret the research they read and incorporate sex and gender considerations into their own projects from initial methodology to final reporting.

As MESSAGE concludes its first project, the resulting policy framework sets a new standard for medical research, ensuring that sex and gender considerations are no longer an afterthought but a core component of scientific inquiry.