The continuing failure to include sex differences in study design and analysis may mean that the evidence base supporting many aspects of medicine is fundamentally flawed, suggests Anita Holdcroft, Reader in Anaesthesia and Honorary Consultant Anaesthetist, Imperial College London and Chelsea and Westminster Hospital, in the Journal of the Royal Society of Medicine recently (2007;100:2-3).

Holdcroft notes that several barriers hinder the recruitment of women into clinical trials. For example, a lack of funding for sex-specific research “in effect maintains women’s lower economic status,” she argues, noting “there is a dearth of gender-based clinical research” in the UK. The resulting lack of sex-specific data compromises evidence-based medicine. For example, the management of coronary heart disease encompasses “well recognized gender differences” in critical care units. Despite this, the UK management guidelines are not sex-specific.

Furthermore, Holdcroft argues that hormonal contraception, required in many studies, poses a barrier to participation. For example, she remarks that almost 10% of protocols allowed no exclusions, such as celibacy or sexual orientation, for contraceptive use. In some cases, women required up to four counter-signatures to confirm contraceptive use.

Four main barriers

In an interview with PharmaTimes Clinical News, Holdcroft identified four main barriers to adequate enrolment of women in studies run by pharmaceutical companies: a lack of awareness about gender medicine; legal and ethical constraints; a reluctance to give women responsibility for their actions on contraception; and study designs that don’t incorporate adequate numbers to analyse gender-specific effects. “The pharmaceutical sector needs to actively recruit women, especially those of childbearing years, and not to impose barriers of contraception (side effects etc) if they can take responsibility to prevent pregnancy,” she added.

In some cases, such as studies of NSAIDs, Holdcroft cites evidence that studies reflect the population in which they are used clinically. In contrast, women comprised 16% of the population enrolled trials for studies assessing statins. However, women account for 45% of those taking statins in clinical practice. Tellingly, a 2005 report commented that eight out of ten prescription drugs withdrawn from the US market were pulled because of issues relating to women’s health.

“In the UK we should seize the opportunity to implement best practices for health care research across genders and to establish gender specific evidence based guidance, Holdcroft concludes. By Mark Greener