Clinical trials are key to ensuring scientific progress in the medical field and gaining breakthrough knowledge on safety and effectiveness of drugs and therapies, but they entail risks for enrolled participants, as one deals with non-validated interventions.
Alongside an adequate assessment of the scientific foundation of inquiry hypotheses, it is necessary to stress the importance of obtaining an informed consent from human participants, in order to protect their dignity and autonomy. A decision to take part in clinical trials is, thus, a very sensitive one and must be free and well-informed. For this reason, informed consent to participate in clinical research is a topic, which deserves primary ethical consideration.
Moreover, the increasing development of translational/clinical research with human subjects – which aims at transferring scientific knowledge from the lab and preclinical research to clinical research on human subjects, as well as translating biomedical research into positive impacts for human health (as a “two way road”, including the reverse path of transition from clinical practice to research)- poses new challenges to the fulfilment of ethical standards for the protection of the human subjects involved, particularly in terms of:
- Risk: in clinical trials with human subjects, the emphasis placed on scientific research may prevail over the necessary protection and best interest of research participants;
- Uncertainty: drugs tested in first-in-man trials present a high degree of uncertainty, since preclinical research has a margin of error: it can predict benefits that are not confirmed in research with humans, as well as risks that do not exist in humans;
- Safety: benefits and risks should be carefully balanced, as the focus of research must always be on the patient’s interest;
- Minimal risk: defining the threshold of “minimal risk” is of primary concern especially when vulnerable populations are involved.
The information conveyed to enrolled subjects should have specific characteristics (completeness and accuracy; clarity and understandability; tailored to the person who is meant to receive it), to carry out an appropriate risk-benefit assessment, as well as to foster an adequate understanding of the nature, goal, limits of the experimentation, and participants’ rights.
Hence, informed consent should be designed as a communication process and not only as a detailed and complicated document, difficult to read, and drafted without considering the patient’s perspective: nevertheless, this still seems to be the most common interpretation of informed consent, while the current debate surrounding this topic thrives on the need for innovative proposals aimed at improving the informed consent process, adapting it to specificities of individual patients and relying on ICT tools, which are available thanks the development of new technologies.
Age and gender-related issues may become a huge challenge in terms of appropriateness, completeness and clarity of information and consent.
“Informed consent should be designed as a communication process.”
Ethics and regulations concerning informed consent are based on the idea that competent decisions should be respected: this means that competence is a major factor to take into account when assessing if informed consent is valid. In this context, minors’ condition becomes an ethical issue because of their low competence, on one hand, and continuous development, on the other.
In the ethical debate, appreciation for minors’ involvement in clinical trials and for children’s autonomy is evident, but it has to be combined with parental and social moral duty to protect them. At the European level, there are discrepancies in hard law and soft law regarding the risk/benefit balance and the importance of child’s objection. Minors’ assent seems to be mandatory to carry out clinical trials, but there is no agreement about the age to provide a valid assent. The assent’s importance grows in relation to minor’s age and risk associated with clinical trials, but there are differences concerning age limits, age ranges and circumstances to consider (e.g. direct benefit for involved subjects).
It also seems that ethical documents seldom provide in depth examination of consent or assent procedures in paediatric clinical trials, nor recommendations about the way to assess the comprehension of information.
Ethical documents rarely focus on gender considerations in informed consent to clinical trials; there are no gender-tailored methods and procedures, in terms of effective communication strategies meant to improve the informed consent process.
However, particular attention is devoted to the changing physiologal condition of women: namely, raising awareness on safety methods and devising special sections within consent forms with inclusion/exclusion criteria relating to fertile/pregnant/breastfeeding women. There is often consideration for cultural or social aspects, which may lead to specific gender vulnerabilities, but these observations are not translated into specific tailored procedures to be implemented in the informed consent process.
There are a number of social and cultural aspects, which may challenge the notion of autonomy and generate vulnerabilities in the informed consent process, some of which are also directly linked to gender issues: in the context of research participation, women living in a social context of patriarchal authority, having a low literacy level, may adopt a passive behaviour with regard to enrolment procedures or not seek interaction with researchers in case of insufficient understanding of the study development. These women are particularly vulnerable, beyond their hesitancy or inability to ask questions, also because they may suffer negligence or harm due to their submission to authority, and have a cultural tendency to deny or tolerate pain and suffering.
More specifically, there are cultural contexts where the community dimension may coerce women into participating or not participating in clinical trials, affecting their freedom to decide; particularly, there are a number of circumstances in which they could be vulnerable in research, such as studies with female sex workers, trafficked women, refugees and asylum seekers. Therefore, it is essential to put in place effective communication strategies to adequately assess the degree of voluntariness involved in the woman’s decision.
“It is essential to put in place effective communication strategies to adequately assess the degree of voluntariness involved in the woman’s decision.”
An appropriate awareness of these social and cultural factors is of paramount importance for informed consent. Hence, the investigator should exercise special care in handling the consent process to ensure adequate time and a proper environment – also relying on cultural intermediation – in which a decision to participate can be made.