Right from the Start - Including more women in Clinical Trials (Guest blog)

Sex and gender in clinical research and medicines regulation
Attention to sex and gender in biomedical, health and clinical research is an important quality and safety issue. Medicinal products are safer and more effective for everyone when clinical research includes diverse population groups. Historically, women’s health issues have focused on reproductive health, followed by gender issues, such as how societal constructs, e.g. behaviour, socio-economic factors, culture, lifestyles etc. influence biological development and health.

Over the years more scientific knowledge has become available that some treatments work differently in men and women, but the proportion of treatments for which men and women respond differently is yet unknown. As we gain a better understanding of the strong correlation between sex and the incidence, prevalence, symptoms, age at onset and severity of disease as well as the reaction to medicines, it becomes imperative to act upon this knowledge and better target medicines treatment to respective patient population groups.

It has also become apparent that many physiological and pathological functions are influenced by sex-based differences in biology. Recent research on cardiovascular disease, osteoporosis, and depression has identified significant differences among women and men with respect to the distribution of certain diseases. Women and men have different sex- and gender-related risks for developing certain conditions and also may respond to treatment differently. For example: biological differences between males and females can affect how a medicine works in the body. Additionally, patterns of gene expression differ between males and females. This has important implications for health and healthcare.

Yet women are generally under-represented in clinical trials. Ever since the Thalidomide tragedy in the late 1950s there has been a reluctance to include women of childbearing age in clinical trials. “The general assumption prevailed that women did not differ from men except where their reproductive organs were concerned and data obtained from clinical research involving men could simply be extrapolated to women.”[1]

An article in the Nature journal argues that gender inequalities in biomedical research are undermining patient care and the article calls for the “sex bias in basic research and clinical medicine to end.[2]

The new European Clinical Trials Regulation - including different population groups.
The new EU Clinical Trial Regulation No 536/2014 aims to create an environment that is favourable to conducting clinical trials in the EU with the highest standards of ethical and safety protection for participants. The Regulation requires more transparency of clinical trials data, including the population groups for whom the medicines are intended . “Unless otherwise justified in the protocol, the subjects participating in a clinical trial should represent the population groups, for example gender and age groups, that are likely to use the medicinal product investigated in the clinical trial” and “non-inclusion has to be justified. It also contains new rules for including pregnant and breastfeeding women under strict protective measures[3].

The US Food and Drug Administration
The US has been on the forefront of developing policies for including population groups such as women and minorities in biomedical research and clinical studies. Policy drivers have been Congress, the National Institutes of Health (NIH) with its Office of Research on Women’s (ORWH), as well as the Food and Drug Administration (FDA) and its Office of Women’s Health (OWH), which was established by Congressional mandate in 1994.

As far back as 1993 NIH addressed the exclusion of women from biomedical and clinical studies through the NIH Revitalisation Act that called for women and minorities to be included in all human subject research in adequate numbers to allow for valid analyses in phase III clinical trials. NIH explicitly stated that cost was not an acceptable reason for excluding women and minorities. The FDA has its own Office of Women’s Health to protect and support the health of women through policy and science. The OWH advocates for the participation of women in clinical trials and for sex, gender and subpopulation analysis.

Moving from knowledge to practice
Given that the scientific knowledge on sex differences as worked out by the FP7 funded research Eugenmed project[4] is now well known and a more supportive legislative environment in Europe is in force, the time has come to address remaining barriers and move from the description of sex differences to a more systematic approach of implementation into regulatory and clinical practice for the benefit of patients and, ultimately, to improve health and healthcare for all. The European Institute of Women’s Health looks forward to the full implementation of the Clinical Trial Regulation.

Blog post written by Hildrun Sundseth, President EIWH, and Peggy Maguire, Director General, EIWH

* About the European Institute of Women’s Health (EIWH) *
Founded in 1996, the European Institute of Women’s Health (EIWH) is a non-governmental organisation (NGO) that uses an evidence-based approach to advocate for an equitable, sex- and gender-sensitive approach in health policy, research, promotion, treatment and care. The Institute promotes biomedical and socio-economic research that addresses sex and gender-based differences to ensure access to quality treatment and care for women across their lifespan. The EIWH strives to reduce inequities by drawing policymaker’s attention to the obstacles that women in minority, migrant, refugee and socio-economic disadvantaged groups face. The Institute’s activities work to empower individuals to play an active part in their own health management.

For more information, please visit:

[1] Health Canada: Considerations for Inclusion of Women in Clinical Trials and Analysis of Data by Sex - 2013 Guidance Document.
[2] Nature vol 465, issue no 7299, 10 June 2010.
[3] Sex ad Gender in Medicine Regulation
[4] European Gender Medicine Network (EUGenMed), Grant agreement number 602050. A project funded by the European Commission Directorate-General for Research & Innovation.