ITALIAN BIOETHICS COMMITTEE PHARMACOLOGICAL TRIALS ON WOMEN 28 November 2008

‘gender medicine’ women have a “longer life expectancy” (in comparison to men), but their life seems to have “less health” medicine does not take into adequate account sexual differences in prevention, diagnosis and cure medicine tends to reflect predominantly a male perspective, assimilating women to men

‘gender pharmacology’ there is an increase in the consumption of medicines by women in comparison to men the effects of drugs on women are less studied or not adequately studied with regard to female specificity women are more exposed to: less efficacy/ more serious side-effects in the use of the drugs

NBC Opinion (2008) - analysis of the data on clinical experimentation on women - analyses of the main reasons for this shortcoming, the ethical problems arising from it, the international and national rules on the issue - final recommendations

starting point women appear to be “weak subjects” - from a quantitative point of view (number of enlisted women in comparison to the number of men) -from a qualitative point of view (analysis of the data)

female pathologies increase of studies carried out on women as regards female pathologies - fertilization, pregnancy, breast cancer, the menopause (etc.) -greater attention to phases II and III; scarce attention to phase I and IV

male-female pathologies the areas of disadvantage for women are highlighted on pathologies that affect both sexes 1)non-differentiation in enlistment: the percentage of women recruited in the experimentation is low 2)non-differentiation in data analysis: drug dosage is generally measured on men and women are considered a “variation” of the male model

male-female pathologies but there are a lot of physical differences between men and women which determine a considerable variation in the pharmacokinetics and in the pharmacodynamics

male-female pathologies - women are generally included (if they are) in phase III of the enlistment in the trails, but not in phases I and II (important to establish drug dosage, side-effects and safety) - the lack of differentiated analysis and specific studies on women, does not make it possible to measure the real efficacy of the drugs on women, but it could also have limited the identification of a specifically female drug

male-female pathologies - some of the illnesses considered traditionally “male”, today tend to be more frequent in women due to the recent change in the conditions of women’s health/illness within the context of the general change in the female condition (above all in western societies)

negative side effects women consume more drugs (take better care of themselves, have better awareness of their pathological condition) drugs have not been adequately tested on them the result is inevitably a higher frequency and seriousness of adverse reactions

reasons for women’s non participation in clinical trials a)social reasons: lack of time, low income, lack of attention to the practical and psychological needs of women b) external environmental reasons: lifestyle (exposure to substances that can interact with the experimental drugs: diet/use of natural remedies)

reasons for women’s non participation in clinical trials c) economic reasons: rise in costs for pharmaceutical industry d) biological reasons: the physiological variations during childbearing and non- childbearing age and the possible use of contraceptives

reasons for women’s non participation in clinical trials e) possible pregnancy during childbearing age: -the possibility that the trial of a new drug could damage the foetus in case of pregnancy -possible negative effects even after the end of the trial, months later the pharmaceutical industry generally imposes the use of specific hormonal contraceptives as condition for the participation in research that can be considered “without risk” for the foetus

pharmacological experimentation on women of childbearing age 1) some feel that the inclusion of women of childbearing age in the trails is ethically important -the a priori exclusion is unjust, as women do not have the same opportunities as men -the possible damage to the foetus is considered not a sufficient reason against experimentation -the obligation to use oral contraceptives is criticised as restrictive to women’s self- determination

pharmacological experimentation on women of childbearing age 2) others maintain that exclusion of women of childbearing age in the trails is ethically important -because of possible danger to the foetus recognised as a subject having dignity - the imposition of oral contraceptives is not considered morally acceptable as detrimental to freedom and responsibility - woman’s explicit commitment to avoid pregnancy is sufficient (including abstaining from sexual intercourse)

pharmacological experimentation on women of childbearing age 3) intermediate position: - a personal informed consensus is necessary (with an explicit commitment of the woman to avoid pregnancy and to undertake laboratory tests which can ascertain the absence of pregnancy) - the imposition of contraceptive use is not ethically illicit, as does not modify personal values and behaviours

NBC recommendations 1. promotion of women’s health against “neutralistic” ideology of medicine; promotion of fairness in pharmacological trial (through identification and removal of the causes of this unfairness) 2. improvement of analysis of the condition of women’s health in the light of recent changes in their psychological-social and cultural condition

NBC recommendations 3. an increase of clinical trials on women, as an important step towards an equality of care in comparison to men 4. drug labels should indicate whether the drug has been specifically tested on women or not and should clarify any element that could generate a different response in men and women

NBC recommendations 5. improve the participation of women of childbearing age in pharmacological trials, provided that an adequate protection of the future child can be guaranteed - necessity of clear statement of a conscious and responsible commitment to avoid intercourse that could lead to pregnancy - request for the commitment to take contraceptives as a safety measure can be included in the criteria to participate in the study - women’s husbands or partners must be involved in the counselling

NBC recommendations 6. raise awareness in the local health authorities and motivate the pharmaceutical industry to support sex differentiated trials, even if not very lucrative 7. promote the participation of women in clinical trials, giving adequate information (even through the media) on the negative consequences of the lack of differentiated trials 8. ensure a greater presence of women as experimenters and as members of ethical committees in order to achieve an active participation in women to the elaboration of the procedures for the protocols

NBC recommendations 9. promote greater attention from ethical committees to sexual difference in research protocols 10. boost health training which focuses on the female dimension within pharmacological trials, as well as within research and cure 11. increase international cooperation, as well as national and local, with the focus on the female condition within clinical trials, involving health authorities and the pharmaceutical industry