Representation of women in Clinical Trials a fashionable topic or an ethical issue? Dr Marie-Charlotte Bouësseau Ethics and health (ETH)

Overview History Reasons for exclusion of women Current situation Future perspectives UNAIDS/WHO guidance document Rol of RECs

Several decades of history  1977 Guidelines issued by FDA excluding women from phases I and II  1980s  evidence about gender differences in pharmacodynamics  NIH and FDA surveys  1990s rol of AIDS groups to include more women in early phases of CT and change an "overprotective policy" in the US  2000 – 2003 EMEA, Swedish medical research council, Japan etc.

Reasons for exclusion of women from CT 1.Lack of knowledge of physiology pre clinical experiments with female animals 2.Paternalism applied to research women considered as a vulnerable population and "over protected" ("Thalidomide effect")

Consequence of exclusion Lack of gender specific information about dosing of drugs etc. and underrepresentation bias

Current situation The situation has improved in CT, however it depends on the area of research e.g. 32% for antiviral to 83% for urologic products (see surveys conducted in the US also EMEA and Japan - source Peter Kleist 2005). Women are still underrepresented in safety trials (phase I and II: 20% to 25%) and academicals studies (non industry sponsored) Need to compare women enrolled in CT with overall disease prevalence in female population e.g. cardiovascular diseases 40% population and 38% women included in CT

Breaking the vicious circle –Need for a different understanding of vulnerability layers of vulnerability should be addressed depending on the situation instead of the population ways to limit vulnerability should be identified as well as responsibilities involved –Ethical duty to improve feasibility of research in vulnerable situations, avoiding the discriminatory effect of paternalism

Ethical considerations in biomedical HIV prevention trials Researchers and trial sponsors should include women in clinical trials in order to verify safety and efficacy from their standpoint, including immunogenicity in the case of vaccine trials, since women throughout the life span, including those who are sexually active and may become pregnant, be pregnant or be breastfeeding, should be recipients of future safe and effective biomedical HIV prevention interventions. During such research, women’s autonomy should be respected and they should receive adequate information to make informed choices about risks to themselves, as well as to their fetus or breastfed infant, where applicable. Guidance Point 9 Women

Implications for RECs Representation of women, in particular in early phases of CT should be evaluated as an issue of non discrimination and risk- benefit balance Vulnerability should be evaluated with all relevant factors in each situation

"I want my leadership to be judged by the impact of our work on the health of two populations: women and the people of Africa." Dr Margaret Chan

Articulating ethical and evidence-based policy options