Most early research into cardiovascular disease was conducted on men, and women continue to be under-represented, making up only 25% of participants across thirty-one landmark trials for congestive heart failure between 1987 and 2012.30 Women represent 55% of HIV-positive adults in the developing world,31 and in parts of Africa and the Caribbean women aged five to twenty-four are up to six times more likely to be HIV-positive than young men of the same age.32 We also know that women experience different clinical symptoms and complications due to HIV, and yet a 2016 review of the inclusion of women in US HIV research found that women made up only 19.2% of participants in antiretroviral studies, 38.1% in vaccination studies and 11.1% in studies to find a cure.33
Because of their routine exclusion from clinical trials we lack solid data on how to treat pregnant women for pretty much anything. We may not know how a disease will take hold or what the likely outcome may be, although the WHO warns that many diseases can have ‘particularly serious consequences for pregnant women, or can harm the foetus’.34 Some strains of influenza virus (including the 2009 H1N1 swine flu virus) have ‘particularly severe symptoms during pregnancy’. There is also evidence that SARS can be more severe during pregnancy. It is of course understandable that a pregnant woman may be reluctant to take part in medical research, but this doesn’t mean that we have to just throw our hands up in the air and accept that we know nothing: we should be routinely and systematically tracking, recording and collating pregnant-women’s health outcomes. But we aren’t – not even during pandemics: during the 2002-4 SARS outbreak in China, pregnant-women’s health outcomes were not systemically tracked and ‘consequently’, the WHO points out, ‘it was not possible to fully characterize the course and outcome of SARS during pregnancy’.35 Another gender data gap that could have been so easily avoided, and information that will be lacking for when the next pandemic hits.
Like the failure to include women in anatomy textbooks, the failure to include women in medical trials is a historical problem that has its roots in seeing the male body as the default human body, but this traditional bias was radically enhanced in the 1970s, to the great detriment of women’s health, following one of the biggest medical scandals of the twentieth century.36
In 1960 doctors began prescribing thalidomide to pregnant women who suffered from morning sickness. The drug, which had been available as a mild over-the-counter sedative in many countries since the late 1950s, was considered safe because its developers ‘could not find a dose high enough to kill a rat’.37 But while it didn’t kill rats, it did affect foetal development (something that in fact the manufacturers knew as early as 1959).38 Before the drug was taken off the market in 1962, over 10,000 children had been born around the world with thalidomide-related disabilities.39 In the wake of the scandal, the US Food and Drug Administration (FDA) issued guidelines in 1977 excluding women of childbearing potential from drug trials. This exclusion went unquestioned.40 The acceptance of the male norm went unquestioned.
The male norm continues to go unquestioned by many today, with some researchers continuing to insist, in the face of all the evidence, that biological sex doesn’t matter. One public-health researcher revealed that she had received the following feedback on two different grant applications: ‘I wish you’d stop with all this sex stuff and get back to science’, and ‘I’ve been in this field for 20 years and this [biological difference] doesn’t matter’.41 It isn’t just anonymous notes, either. A 2014 op-ed published in the journal Scientific American complained that including both sexes in experiments was a waste of resources;42 in 2015 an op-ed in the official scientific journal of the US National Academy of Sciences insisted that ‘focusing on preclinical sex differences will not address women’s and men’s health disparities’.43
Alongside insisting that sex differences don’t matter, some researchers advocate against the inclusion of women in research on the basis that while biological sex may matter, the lack of comparable data arising from the historical data gap makes including women inadvisable (talk about adding insult to injury).44 Female bodies (both the human and animal variety) are, it is argued, too complex, too variable,45 too costly to be tested on. Integrating sex and gender into research is seen as ‘burdensome’.46 It is seen as possible for there to be ‘too much gender’,47 and for its exclusion to be acceptable on the basis of ‘simplification’48 – in which case it’s worth noting that recent studies on mice have actually shown greater variability in males on a number of markers.49 So who’s too complicated now?
Beyond the argument that women’s bodies, with their fluctuating, ‘atypical’ hormones, are simply inconvenient research vessels, researchers also defend their failure to include women in trials by claiming that women are harder to recruit. And it is certainly true that, due to women’s care-giving responsibilities they have less leisure time and may find it harder to make, for example, clinic appointments during the school run. However, this is an argument for adapting trial schedules to women, rather than simply excluding them, and in any case, it is possible to find women if you really want to. While reviews of FDA-mandated medical product trials found that women made up only 18% of participants in trials for endovascular occlusion devices (used if your foetal blood vessel hasn’t closed of its own accord)50 and 32% of participants in studies on coronary stents (which, incidentally, are another device where women have worse outcomes than men),51 women represented 90% and 92% of participants in facial wrinkle correction trials and dental device trials, respectively.
A more novel approach to addressing the problem of female under-representation in medical research is simply to claim that there is no problem, and women are represented just fine, thank you very much. In February 2018 a paper was published in the British Journal of Pharmacology entitled ‘Gender differences in clinical registration trials: is there a real problem?’52 Following ‘cross sectional, structured research into publicly available registration dossiers of Food and Drug Administration (FDA)-approved drugs that are prescribed frequently’, the all-male-authored paper concluded that, no, the problem was not ‘real’.
Leaving aside any philosophical debate over what an unreal problem might be, the authors’ conclusions are baffling. For a start, data was available for only 28% of the drug trials, so we have no way of knowing how representative the sample is. In the data researchers were able to access, the number of female participants in over a quarter of trials did not match the proportion of women in the US affected by the disease the drug was supposed to treat. Furthermore, the study did not address trials for generic drugs, which represent 80% of prescriptions in the United States.53 The FDA describes a generic drug as ‘a medication created to be the same as an already marketed brand-name drug’ and they are sold after the patent for the original branded drug runs out. Drugs trials for generic drugs are much less rigorous than original trials, having only to demonstrate equal bioavailability, and they are conducted ‘almost exclusively’ in young adult males.54 This matters because even with the same active ingredient, different inactive ingredients and different fabrication technology can affect a drug’s potency.55 And sure enough, in 2002 the FDA’s Center for Drug Evaluation and Research showed ‘statistically significant differences between men and women in bioequivalence for most generic drugs compared with reference drugs’.56