Health experts urge greater gender balance in clinical trials

Female patient and male doctor.jpg

Too few women are taking part in clinical tests to develop new drugs, putting their lives at risk as women's bodies react differently to medicines, health experts said ahead of International Women's Day.

Cardiovascular disease causes 40% of all deaths in the EU but has traditionally been regarded as a male disease, keeping women largely out of clinical trials to develop new drugs.

Yet cardiovascular disease is also the leading cause of death among women and this one-size-fits-all approach is putting women's health at risk, according to experts.

Marco Stramba-Badiale, director of the Department of Geriatrics and Cardiovascular Medicine at IRCCS Istituto Auxologico Italiano in Milan, said regulatory agencies should 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," Stramba-Badiale told EURACTIV.

"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," Stramba-Badiale added.

A revision of the EU's Clinical Trials Directive is under review by the European Parliament and the Council.

A thorough gender mainstreaming approach in the directive can contribute to achieving more female participation, said Sascha Marschang, policy coordinator for Health Systems at the European Public Health Alliance (EPHA).

"Women should be included in all phases of clinical trials. The gender, age and race dimensions must be considered in clinical trial design and implementation. To me, there’s very little doubt that women should be included in the investigation, recruitment and implementation of clinical trials," Marschang told EURACTIV.

No sub-population

The European Institute of Women’s Health (EIWH) supports those calls, saying clinical studies should systematically assess the effects of medicines among men and women.

"The EIWH holds the view that it is important to ensure that men and women are enrolled in clinical trials at all stages of drug development in order to define the risks and benefits associated with drug therapy for both male and female patients," the organisation said.

Since for women, physiological changes and hormonal levels during childbearing years and menopause may affect the efficacy and safety of a drug, the influence of these parameters should be studied during drug development, according to EIWH.

"For a long time, scientists referred to women as a sub-population when in fact women make up over half of the world’s population," EIWH stated.

Marschang said there this has to be addressed through a change in "mentalities".

"From a public health perspective, it is unacceptable that one half of the population is underrepresented in clinical trials when, on the top of that, they have a longer life expectancy than men and consume more medicines," EPHA's policy coordinator.  

"It is precisely because of these sex or gender differences that we need to know how medicines affect women and men at different stages of their lives. The barriers need to be tackled," Marschang said.

A leading cause of death

Cardiovascular disease kills 43% in women and 36% in men in the EU, according to a study jointly conducted by the European Society of Cardiology and the European Heart Network.

Coronary heart disease by itself is the most common cause of death in the EU, responsible for more than 681,000 deaths annually. Some 14% of women and 15% of men die from coronary disease but women are much more likely to die within a year of having had a heart attack, Stramba-Badiale said.

The Italian physician says stroke is the second most common cause of death in women and affects more women than men. And although cardiovascular disease has declined over the last 40 years, this decline has been smaller for women. New cases for women are rising, he said, and due to their greater longevity, the CVD burden can be said to have shifted gradually onto women.

The EuroHeart study also showed that only 33% of trials participants are women and that approximately half of the trials did not report an analysis of the results by gender.

Stramba-Badiale said one reason behind women's lower enrolment in cardiovasular disease tests may be due to their "misperception of risk" of cardiovascular diseases, which he said are the main cause of death also in women.

Sascha Marschang, policy coordinator at the European Public Health Alliance (EPHA), an NGO, told EURACTIV:

"Despite some advances toward greater inclusion, women continue to populate many clinical trials in insufficient numbers proportionate with the prevalence of certain diseases in women. This means that women's healthcare is compromised by a lack of sex-specific information about dosing and particular uses of drugs that women will nonetheless take." 

"It is recognised that gender differences affect the health of women and men. There is a clear difference in the incidence, treatment responses and prognosis of various diseases, like certain cancers, heart disease, Alzheimer's and depression. For instance, there are physiological and hormonal differences between men and women that have a potentially significant impact on the efficacy of a medicine and women's tolerance for them. Ensuring adequate representation of women and other population groups in clinical trials is essential to understand why certain medicines elicit different responses from them, and in what contexts," Marschang added.

The European Institute of Women’s Health (EIWH) stated:

“The misguided assumption that findings from research studies conducted on men applies equally to women has underserved women far too long. Women and older people of both sexes have rightly been called ‘the understudied majority’. This has to stop. The one-size-fits-all approach for patients will not succeed in helping to reduce the chronic disease burden. The increasing life years gained by women need to be flanked by a rigorous approach aiming to increase healthy life years. Increasing healthy life years by 2% is an important aspirational goal of the EU 2020 strategy.”

Frans Van de Werf, chairman of The European Society of Cardiology (ESC), has likewise called for mandatory gender balance and an update where one investigator will no longer be required to carry out the lion's share of the work, a factor that has put many investigators off getting involved in clinical trials:

"We hope revisions will stem the decline in the number of investigator-led clinical trials that has occurred in the last few years," Van de Werf said.

The European Commission proposed new rules in July 2012 to make it easier for drug companies and researchers to carry out cross-border clinical trials, in a bid to cut costs and red tape.

>> Read: Brussels seeks to simplify rules on clinical trials

The EU's Clinical Trials Directive was implemented in 2004 with a view to improving research standards and protecting patients. 

But those rules have been criticised by researchers who say costs and red tape has increased without bringing any major benefit to patients, researchers or industry

  • 2013: European Parliament and Council to examine new rules on clinical trials.

European Commission


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