The Pharmaceutical Journal Vol 267 No 7169 p510-525
13 October 2001

BPC 2001 summary

Sexual discrimination and clinical trials

Two questions about women and clinical trials were posed by Angus Cameron, regulatory affairs manager, Inveresk Research International: why, historically, have women been excluded from clinical trials, and is there a need for female-specific drug research?

Answering the first question, Mr Cameron said women either have not been studied or only studied in much smaller numbers than men. There are many reasons for this, such as medical disasters that stopped research in women for many years, and a sense of political correctness or sensitivity in using women in clinical research.

As women are the child-bearing population, they have not been included in any pure drug research. There is also an obvious cost-saving for pharmaceutical companies. It is easier to do research in men to avoid expensive reproduction and toxicology studies; and there is a reduction in the clinical programme size. It is easier just to issue warnings against using a drug in women.

Diethylstilboestrol and thalidomide

The effects in pregnancy of two drugs had had a major effect on drug research. Diethylstilboestrol, used in the 1940s to prevent miscarriage, caused vaginal cancer in the second generation. Thalidomide, taken as an antiemetic in pregnancy during the 1950s and 60s, caused phocomelia (limb shortening) in children.

As a result of these catastrophes, young females were barred from clinical trials for many years. In 1977, the United States Food and Drug Administration issued guidelines excluding females of child-bearing age from taking part in early clinical research. The industry overreacted by assuming that the majority of females could become pregnant, and it was a convenient position for it to take. Therefore a lot of prescribing information at the time included warnings against using the drug in females, rather than including real clinical data.

Views changed during the 1980s when the women’s movement argued against this legislation, saying that it was paternalistic and overprotective, and denied young women the opportunity of taking part in clinical trials.

In 1988, there were changes to the FDA guidelines saying that trials had to be analysed by gender, age and race, but did not require the inclusion of women.

However, in 1997, the FDA Modernisation Act led to the production of guidance on the inclusion of women in clinical trials.

Expanding on his second question, Mr Cameron explained that there are several reasons why female-specific drug research is necessary:

• Physiology There are major differences in the physiology and pharmacology of males and females dictating how drugs are handled and metabolised by the body, eg, differences in body fat distribution, respiratory function and hepatic metabolism.
• Demographics There is a population bulge in the United Kingdom with the female population increasing at a greater rate than that of males mainly because of a longer life expectancy.
• Epidemiology There is a higher incidence in females of some diseases, eg, osteoporosis, multiple sclerosis and autoimmune diseases.

Ageing female population

Mr Cameron went on to say that in the past few years, there have been major improvements in disease diagnosis and treatment, which has led to greater survival rates.

Many more patients are now on long-term therapies and there is a massive population of ageing females requiring treatment. This means that there is a greater need for clinical research in females than in males.

Looking at the future, Mr Cameron said that 348 drugs are in development for diseases that disproportionately affected women.
— Contributed by Diane Langleben, editor of Hospital Pharmacist.

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