Issue 4: We still have a problem - 30 years since women were allowed in clinical trials

It's 30 years since Jurassic Park hit cinema screens...and women were finally allowed in clinical trials

Hi, welcome to FutureFemHealth, the newsletter that brings you a weekly dose of news and inspiration about innovation in women’s health and FemTech.

I’m Anna and whether you’re a founder, an investor, someone who works in women’s health / FemTech or are simply a fan, I’m glad you’re here to join me.

In today’s issue we’re looking at what’s happened in the 30 years since women were finally included in clinical trials, including:

• why women were excluded from clinical trials before 1993

• the impact of the exclusion of women from clinical trials - and why there are still repercussions today

• the work being done to close the gender health data gap - and whether it is working or not

• what’s next for the gender health data gap and how we close it.

Let’s step back in time

The year’s 1993.

Jurassic Park is in cinemas, Beanie Babies have hit the high street and Meatloaf’s I'd Do Anything For Love (But I Won't Do That) was the best-selling single of the year.

You know what else happened that year?

The United States National Institute of Health finally mandated that women should be included in government-funded health research.

Why were women excluded from clinical trials before 1993?

Trials began to exclude women in 1977 when the FDA issued a document titled “General Considerations for the Clinical Evaluation of Drugs,” which said that only women without childbearing capabilities could participate in clinical trials.

This was largely as a result of the Thalidomide tragedy, when a drug prescribed to women for morning sickness ended up causing serious birth defects.

As well as this, there was a perception that women’s fluctuating hormones mean it’s harder to analyse results in trials consistently.

There are also the systemic issues to consider in the de-prioritisation of women in health research. This is covered excellently in Caroline Criado-Perez’s book Invisible Women - whereby men are considered to be the ‘default human’ and women are for all intents and purposes just ‘small men’ when it comes to research, without recognition of the biological differences between the sexes.

What is the impact of the exclusion of women from clinical research trials?

The impact of women not being included in clinical trials before 1993 still has repercussions today:

• healthcare professionals have incomplete knowledge and understanding of women’s health - because the information simply doesn’t exist to teach them during their trainings (menopause is still not mandatory during GP training for example).

• it takes longer to diagnose women because we know less about women’s bodies and the health issues that solely or disproportionately affect women. Even with conditions that affect both sexes diagnosis can take longer. This study for example showed how it takes women two years longer than men to be diagnosed with axial spondyloarthritis (axial SpA) a type of arthritis.

• women could be at risk of overmedication from medications where the dosage amounts have been calculated for men not women. A 2020 study by Irving Zucker and Brian J Prendergast found 86 drugs where it was clear that the body breaks the drug down differently depending on sex. For most of them, the difference was that females metabolise the drug more slowly than males - which means they then get higher levels of exposure to the drug. Essentially, they are getting too much.

• medicines that are on the market may not have been properly tested on women because they were approved by the FDA (food and drug administration) before 1993. The 2020 Zucker / Prendergast study looked at common drugs including aspirin, morphine and the antidepressant sertaline.

• all of this means women may be at risk from side effects from medications which may be incorrectly dosed because they have not been tested on women. Between 1997 and 2001, eight out of ten FDA-approved medicines pulled from the market showed higher levels of harm to women than men.

• and it makes life very difficult for women’s health innovation (FemTech) which is having to build products and services without adequate insights.

What is being done to close the gender health research gap and is it working?

The change in 1993 did not solve the issue.

In one of the most ridiculous examples, in 2015 the ‘female viagra’ Addyi was tested on 23 men and just two women to determine how it would interact with alcohol.

There also continues to be big gaps in general research. A large study in 2019 for example, found that while 49% of participants in clinical trials are now women, they are still underrepresented in many categories, particularly when looking at research into HIV/AIDS, chronic kidney diseases, and cardiovascular diseases.

In another example, the writer Hot Flash Inc. identified that while there are 1million+ studies on pregnancy on Pubmed (the US National Institute of Health’s data of clinical research), there are still less than 94,000 on menopause and less than 6,000 on perimenopause.

The issue is even more apparent when you also take into account the diversity of representation and ensuring that people of colour, different ages, disabilities are all properly represented in trials.

What is next for closing the gender data gap?

In 2015, the US National Institutes of Health (NIH) released a policy to consider ‘sex as a biological variable’ in research. This effectively said that there would need to be a strong justification to only include one sex in any NIH-funded study. However, there are few repercussions if this doesn’t happen.

Once more, this has still not solved the issue and there is still a lot to do to close the health data gap. This includes encouraging researchers to include more women in research, and also to remove the barriers for women to participate (and in particular to ensure a diverse representation of women). (This is a particularly good article on both of the above points).

Here in the UK, the Government’s new Women’s Health Strategy for England, announced in July 2022, includes an aim to work on closing the data gap when it comes to women’s health.

This will include a major investment via the NIHR (National Institute for Health & Care Research) into research on women’s health issues, including a new policy research unit on reproductive health, and it will focus on addressing data gaps, the barriers to women participating in research and improvement in the quality of data collected by the NHS

This is a good step and shows that the issue is recognised as one that needs addressing.

A recent roundtable with representatives from the Department of Health and Social Care (DHSC), the NIHR, NHS England and the Medical Research Council as well as leading academics identified four key themes arising from the research aspects of the Women’s Health Strategy, namely:

1. How can we improve the representation of women in research, including clinical trials and disaggregation of results?

2. How can we increase the representation of diverse women across NIHR awards and committees?

3. How can we ensure research prioritises women’s health, care and wellbeing, and addresses evidence gaps?

4. How can we more effectively disseminate research to women, practitioners, decision makers, community leaders and the general public.

As I covered in last week’s newsletter, FemTech is also attempting to close the gap from the grassroots level up by collectively pooling data to build a better picture of women’s health.

For example Apple’s women’s health study and Natural Cycles’ work to look at the impact of Covid 19 on periods.

We have long way to go to close the data gap

The lack of women's participation in health research before the 1990s has led to significant gaps in our understanding of women's health.

The consequences of this lack of representation are still being felt today, from incomplete knowledge among healthcare professionals to the risk of overmedication for women. While progress has been made to close the health data gap, there is still much work to be done.

FemTech is playing a significant role in this work by pooling data to build a better picture of women's health, and governments and health organisations are aiming to take steps to encourage more women to participate in research and to address evidence gaps.

It is crucial to raise awareness about this issue and continue to prioritise the inclusion of diverse women in clinical trials and research studies.