Medicinal product safety and efficacy need diversity

What can be done to ensure that medicinal products are truly suitable for everyone who needs them? The effects medicines have can vary, depending on the patient's sex, age or background. Swissmedic examines these factors during authorisation and continues to monitor how medicinal products perform in practice once they are on the market.

How representative is the study?

One of Swissmedic's roles is to guarantee that the Swiss public has access to safe and effective medicinal products. Christine Haenggeli, Head of the Clinical Assessment Division, explains: "The authorisation process for new treatments is based on the clinical trials data submitted by the pharmaceutical companies, which we use to assess the benefit-risk ratio".

To obtain authorisation, the clinical trials have to be representative of the population for which the medicinal product is intended, as defined in its indication. That means that sex-related factors have to be included in the assessment in the same way as ethnicity- or age-related considerations. This is because illnesses may sometimes manifest differently in men and women, as may the effects of medicinal products. "If a medicinal product has only been studied in a particular sub-population of patients, and the authorisation application covers the entire patient population, that has to be stated in the Information for healthcare professionals". Doctors can then draw on this information and their clinical experience to guide patients and establish whether a specific medicinal product is appropriate or not.

There are no fixed gender quotas

Clinical trials are not subject to fixed quotas when it comes to the percentage of women or men to enrol. The proportions of men and women have to be representative for the indication in question. Depending on the trial medication, women of childbearing age have to take precautions to avoid becoming pregnant during the trial because of the potential risks to the unborn child. All clinical trials have to be carried out in accordance with international guideline E6 "Good Clinical Practice" issued by the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH).

After authorisation: Market monitoring provides a reality check

Factoring in specific sex-related considerations does not end with authorisation. A new medicinal product's benefit-risk ratio continues to be assessed once it is on the market. "There are important differences between the populations studied before a medicinal product is launched and those that receive it once it's on the market", Frédérique Rodieux, Vigilance Assessor in the Safety of Medicines Division, tells us. Clinical trials involve a restricted number of patients chosen specifically for the trial and last for a limited period. However, once medicinal products are on the market, they are prescribed to a much larger, heterogeneous population that includes people of all ages with different pathologies and who are sometimes undergoing other treatments.

This diversity can impact the real-life efficacy and safety of medicinal products and is why post-marketing surveillance, also called pharmacovigilance, is carried out. "This follow-up is crucial for detecting rare or unexpected adverse reactions and for assessing the efficacy and safety of treatments in the real world", says Frédérique Rodieux. "One of the parameters we assess as part of post-marketing surveillance is whether men and women respond differently to the treatments".

More adverse reactions in women

"Plenty of data and studies show that taking all medicines together, women report 1.5 to two times as many adverse reactions as men", Frédérique Rodieux explains. This finding stems from a combination of biological, medical and social factors. Biologically, differences such as women's lower body weight, greater body fat levels or smaller blood volume affect the way their bodies absorb, distribute, metabolise and eliminate medicinal products. As a result, some medicinal products may remain in women for longer and at higher concentrations than in men.

"These sex-related differences are compounded by other gender-linked social and behavioural factors", the specialist from the Safety of Medicines Division adds. "Women are often given more prescriptions than men, which can also increase the risk of interactions between medicines. Studies show that women also pay more heed to their symptoms and are more likely to report them".

Raising awareness among the population as a whole

When post-marketing surveillance reveals significant differences between men and women in terms of a medicinal product's safety or efficacy, regulatory authorities such as Swissmedic can demand that the Information for healthcare professionals and package leaflet be updated. The modifications may include particular precautions or specific recommendations based on sex.

Elena Gobet, Scientific Assistant in the Clinical Assessment Division, reminds us that although sex is an important factor in people's response to medicines, it cannot be considered in isolation. It has to be viewed in context with the other factors that can affect response to medicines, such as age, weight, other diseases, concomitant treatments or just each individual's genetic features.

Post-marketing surveillance of medicinal products is based particularly on real-world observational studies, but spontaneous, anonymous reporting of adverse reactions by healthcare professionals and patients also plays an important role. "Adverse reactions are significantly under-reported. What's more, information on the patient's sex is not provided in more than 10 percent of cases", says Frédérique Rodieux. "That's a pity because this information would enable us to analyse adverse reactions that could potentially be specific to each sex more accurately. It's essential that we raise awareness of the importance of this information". Christine Haenggeli agrees, adding: "Awareness-raising needs to target the population as a whole".