Dr Marco Stramba-Badiale is director of the Department of Geriatrics and Cardiovascular Medicine at the IRCCS Istituto Auxologico Italiano in Milan. Stramba-Badiale answered written questions from EurActiv's Henriette Jacobsen.
Why is it dangerous for women's health that only a few women, usually less than 50% of the test persons, take part in drug tests during clinical trials?
Gender differences in the clinical presentation of several diseases have been demonstrated and some therapeutic options may not be equally effective and safe in men and women.
Furthermore, sex differences in pharmacokinetics, pharmacodynamics and physiology may contribute to a different response to drugs in women when compared with men.
Accordingly, preventive and therapeutical interventions should be tested in populations that fairly represent the gender distribution for each specific clinical condition or group at risk.
Why are there not more women recruited into the clinical trials?
One of the reasons of a lower enrolment of women in clinical trials, particularly in the field of cardiovascular diseases, is indeed the lower occurrence of outcomes in females, which may affect the costs of the study.
Another reason may be the lower willingness of women to be enrolled, due to their misperception of risk, particularly of cardiovascular diseases, which are the main cause of death also in women.
An additional explanation might be the difficulties in terms of transportation or support for the follow-up visits which are greater in women than in men.
Is this problem, the lack of gender balance in clinical trials, only related to certain disease sectors or to all?
The lack of gender balance in clinical trials affects almost all medical sectors, but it is particularly relevant in the field of cardiovascular diseases.
Despite an increase in the number and proportion of women enrolled in cardiovascular clinical trials, there is still an under-representation of women.
The EuroHeart study, funded by the European Union and jointly conducted by the European Society of Cardiology and the European Heart Network, has shown that only 33% of trials participants are women. Furthermore, approximately 50% of the trials did not report an analysis of the results by gender.
What can be done in order to get more women recruited into these clinical trials?
Enrolment criteria and follow-up duration should allow the inclusion of women at risk of developing events.
A minimum enrolment for women should be ensured (e.g., maintain open enrolment for women until pre-specified proportion is reached). External barriers to the enrolment of women in clinical trials need to be addressed, and in particular transportation difficulties for follow-up visits.
What makes it possible under the current legislation for companies to get away with not recruiting more women for the clinical trials?
The lack of strict rules by the regulatory agencies on the issue of recruitment of women in clinical trials. There are only suggestions but not requirements for drug or devices companies in the conduct of clinical trials.
The EU's Clinical Trials Directive is up for a review. How should it be updated according to address the issue?
Regulatory agencies are urged to adopt strict rules on the inclusion of women in clinical trials and a systematic gender analysis. The gender balance should become a formal requirement and not only a recommendation for the performance of clinical trials.
Scientific societies, patients’ associations and foundations should cooperate with European institutions, national health care authorities and regulatory agencies to promote scientific research on gender issues in medicine and a larger representation of women in clinical trials.
It appears as if more research has been done by health authorities in the US and Canada than in the EU on this. What is the reason for this?
After the FDA Guidelines on gender issues, released in 1993 and the 1998 regulation in US, there has been a significant increase in the number and proportion of women who participate in clinical trials and some studies have been conducted specifically in females.
The issue of gender balance in clinical research has been raised in Europe only in 2005, when the European Medicines Agency released a document on gender considerations in the conduct of clinical trials, emphasising the importance of a fair representation of women.
In the same year, at the policy conference on Cardiovascular Diseases in Women of the European Society of Cardiology, it was recommended that, based on the specific question addressed, clinical trials enrolling only female patients or clinical trials enrolling a significant proportion of women to allow for pre-specified gender analysis should be conducted.