Hysteria, Valium and Clinical Trials
An in-depth analysis of the under-representation of women in clinical trials and its effects on modern medicine
What's Changed?
-Addyi
The lack of women in clinical trials still occurs in modern medicine. To illustrate, Addyi is a good example. Addyi (flibanserin), was designed to treat sexual dysfunction in women (the first of its kind), and a trial recently looked at its drug-alcohol interaction. The issue is that 23/25 of the participants were men, despite the drug solely being marketed towards women. (Harrison, 2015). It is well known that women become more intoxicated than men when drinking the same amount of alcohol. Women’s generally smaller body size results in higher blood concentrations after ethanol administration, and their higher body-fat content, and lower body-water volume additionally contribute to increased blood alcohol concentrations. In addition, the gastric mucosa of women secretes less alcohol dehydrogenase than that of men, resulting in slower metabolism of alcohol. (Merkatz et al., 1993, p293). Therefore, it is likely that the study is not generalisable to women due to the vast sex differences. The company responsible, Sprout Pharmaceuticals, issued a statement regarding the drug stating they planned to conduct additional studies on the drug alcohol interaction after the drug goes on sale (the results of which were published in 2019). The statement also noted that with similar medications it is advised to avoid alcohol, hence, “women are capable of weighing the risks and benefits of these medications and making an appropriate treatment decision in consultation with their doctors,” and “they should be afforded the same trust with Addyi.” While this is true this is not the issue here and it is almost as if because the research design was questioned, the company backlashed at women, bringing into question whether women can make their own medical decisions. It may be that there were significant barriers to engagement as a result of the long standing historical discrimination towards women in medicine. However, trial coordinators should ensure women predominate in clinical trials where the target population is exclusively women and especially in trials with an interaction with known sex differences.
Skeletal structure of Flibanserin (Addyi).
Final Thoughts
As mentioned, there can be significant barriers to engagement resulting in an unrepresentative sample of participants. For ethnic minorities, this is normally the time consuming nature of the study combined with the lack of compensation received and the fact that these individuals are usually of a lower socio-economic standing. For women there is a lack of trust due to the longstanding historical discrimination. This persistent bias in healthcare has led to women not being taken seriously and frequently being dismissed or labelled as hysterical if they have reasonable concerns. Thus, they are left not wanting to participate in studies if this is how they are going to be treated. Little has been done to challenge these inequalities and the- primarily- unconscious biases in healthcare.
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Other groups experience similar difficulties within healthcare and have routinely been underrepresented in clinical trials. Individuals are often discriminated against based on their race, class, body size and age, as well as other factors, and despite the fact that this site focuses on the issues faced by women, it does not deny that these groups experience similar grievances. This could easily be the topic of other papers. It is also of note that while sex as a biological variable in medicine is being explored more frequently, research into how sex differences apply to transgender populations is almost non-existent. This is an avenue for future research.
Barriers and
Discrimination
‘Along with religion and politics, medicine has historically played an integral role in policing and controlling women’.
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Jackson, 2019, p163.
To Conclude...
The generally increased inclusion of women in clinical trials is a step in the right direction, but, evidently, it is not enough: the frequency of adverse drug reactions in women is still too high. The need for specific sex analysis in clinical trials is obvious as a way to lower adverse reactions in women and produce more specific dosing of drugs. Whether this becomes legally mandated, or a result of tightened journal policies is the question. While this change would increase the cost of a clinical trial, the overall cost to healthcare would likely decrease, with less women hospitalised and less drugs being prescribed (if evidence based dose reductions also occur).
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All in all, this site has demonstrated the importance of sex in clinical trials, with reference to the major advancements in the history of clinical trials, and the specific discussion of Valium (Diazepam). As per the quote below, the importance of sex in clinical research is only a contributing variable and this work does not suggest that the way forward is separate medications for men and women, but just that this factor is taken into consideration during drug design, clinical trials and the drug prescription processes.
‘Sex is a contributing variable, and its contribution is not binary but has a modulating influence… we don’t want to play into a situation where pharma makes a pink and a blue pill’.
Margaret McCarthy. (May, 2016, p1372).