Cancer-drug studies fail to reflect true incidence of disease in the population.
Women are under-represented in cancer studies, according to a survey of clinical research published today. The finding suggests that women are not getting fair access to experimental drugs, the authors believe, and that the effectiveness of some treatments, which can work differently in women than men, may not be fully understood.
Reshma Jagsi, an oncologist at the University of Michigan Medical School who led the survey, is a clinician who specializes in breast cancer. In her field, almost 100% of study participants are women. But she wondered if clinical trials for other types of cancer had a fair proportion of women — that is, the same proportion of women that succumbs to that type of cancer.
In a sample of hundreds of studies, including more than half a million participants, Jagsi and her colleagues found that 75% of the studies under-represented women according to this standard. Out of studies on seven different cancer types, six under-represented women, often by as much as a third. For instance, 45% of lung-cancer diagnoses are in women, but only an average of 31% of lung-cancer study participants were women. The results are published in the journal Cancer1.
Sheri Berenbaum, a member of the US Institute of Medicine's committee on understanding the biological implications of gender differences, says she is "troubled" by the results. "Unequal representation raises a question about differential selection from the population," notes Berenbaum, who is also a professor of psychology at Pennsylvania State University in University Park.
The US National Institutes of Health (NIH) instigated an act in 1993 that noted the importance of including high enough numbers of women to enable independent gender-linked results to be analysed. It is not clear from Jagsi's study whether that condition is being met, but she notes that the proportionality standard she applied is often less strict than the analysis criteria used for some of these studies. "It has been [more than] 15 years [since the act] and we're still seeing a persistent problem," says Jagsi. Previous work has shown deficits in female representation as measured against the NIH standard, though with some improvement over time (see 'The NIH improves its record on women in trials').
The study by Jagsi and her colleagues also shows that studies using government funding do include higher numbers of women participants — 41%, compared with 37% for studies not receiving government funding. So perhaps the NIH act — although vague — may be having some effect, she says.
Differences in male and female physiology can affect drug responses. For example, the anti-cancer drug erlotinib (Tarceva) has been found to work better in women than in men. But such differences are often poorly studied. "We've all been so subconsciously exposed to this male medical model, where the anatomy textbook shows you the male, and there's one chapter on the female," says Jagsi. "She's presented as a variant on the standard."
The reasons for the under-representation aren't clear. Women of child-bearing age who might become pregnant during a trial are often considered a vulnerable group, Jagsi says, and so are excluded from some studies. But it's important to have data from this group too, she notes. "By protecting them from research, we're excluding them." Jagsi adds that exclusion could also mean that these women don't have equal access to new drugs that might save their lives.
Previous studies have suggested that it might be harder for women with childcare responsibilities to take the time to participate in a trial — something that matches Jagsi's own experience. "I had a patient who added up the cost of hiring a babysitter and paying for the fuel and coming in and paying for parking, and said 'it is just too much for me to afford'," says Jagsi. It could also be that men and women react differently to presentations of risk–benefit analysis, she adds.
Jagsi says that more research is needed to unpick the reasons for under-representation, and to address the problem. One solution might be to make it more common to include compensation for expenses in clinical trials, so that such costs as childcare can be covered.
Similar problems with under-representation can affect paediatrics: many drugs have been tested entirely on adults, leaving issues of dosing, side effects and efficacy of those drugs in children unstudied.
Jagsi, R. et al. Cancer advance online publication doi:10.1002/cncr.24366 (2009).