In the aftermath of the Second World War, investigations into the experiments conducted “on” humans in the Nazi-controlled territories highlighted how these crimes against humanity exposed the humans involved to absolute vulnerability to the extent of being used in experiments without the appropriate safeguards. Precisely because of these brutal facts, the Nuremberg Code establishes a point of no return by recognizing the free and informed consent of the potential participant in research as a prerequisite for any research.
Here begins a long journey of inclusion and recognition of the other as a participant, still in progress, and of making researchers aware of their own role that may increase the risk of vulnerability of individuals involved in the research, if not acted upon responsibly. In order to understand the cultural and scientific paradigm shift at stake, this document will focus on a specific group of vulnerable populations: minors.
Biobanking, especially with children may prove to be the ideal training ground for both Responsible Research Innovation (RRI) and scientific citizenship, fostering the cultural change towards collaborative and participatory science, towards scientific citizenship, and reciprocal engagement. The challenge also offers a great opportunity to face complex processes regarding ethical, legal, and societal issues (ELSI) and innovative research practices, allowing us to learn together in a very sensitive field without the possibility of direct physical harm for the participant. While not all biobanking research includes genetic profiling, a minor may be exposed to the so-called informational risk related to it. The informational risk can undermine the right to an open future, for instance in the case of adult-onset. A minor in research may only be exposed to a proportionate informational risk that does not affect her choices and quality of life in adulthood.
Minor’s temporary vulnerability
Children are by definition a vulnerable population, thus, according to Art. 25(2) of the Universal Declaration of Human Rights, they are “entitled to special care and assistance”.
They are subjects in evolution, in need of protection, who often cannot participate or take control of the decisions affecting them.
Even if, as the Belmont Report statutes
“Respect for the immature […] may require protecting them as they mature […] The extent of protection afforded should depend upon the risk of harm and the likelihood of benefit. The judgment that any individual lacks autonomy should be periodically reevaluated and will vary in different situations.”
Here, the Report introduces a key concept in terms of RRI and participatory biobanking with both children and the vulnerable, highlighting as respecting persons is often a matter of balancing, of weighting together with all the actors at stake, beginning from the potential participants:
“Respect for persons requires that subjects, to the degree that they are capable, be given the opportunity to choose what shall or shall not happen to them. […] For these persons [immature], however, respect requires giving them the opportunity to choose to the extent they are able, whether or not to participate in research.”
And it is really interesting the recognition of third parties as fundamental:
“Respect for persons also requires seeking the permission of other parties in order to protect the subjects from harm. Such persons are thus respected both by acknowledging their own wishes and by the use of third parties to protect them from harm.”
Research Ethics Committees as well as biobanks can be considered as the third party for excellence within the research biobanking horizon: as shared before, their role in recognizing and including minors as participants as well as guaranteeing their rights, promoting their capabilities is central.
In the ongoing debates about paediatric biobanking and research, it is essential to define what safeguards and oversight processes are set up to protect minors. There may be a tension between protection measures, scientific research progress, and parents’ expectations in terms of both tailored diagnosis and treatments, as well as between obligation to protect and motivation for scientific discovery. The conflicts of interest cause tension and can augment the minor’s vulnerability, if not assumed with responsibility by adults and within an ELSI paradigm shift that moves from a paternalistic model to a participatory one.
Moreover, although children are a vulnerable research population, in the sense that at the beginning they lack the capacity for consenting to their participation, they are different from other vulnerable populations, such as people with cognitive problems.
They are different because their vulnerability is temporary and does not arise from a disorder; most children will become healthy adult members of society. Therefore, it is imperative that paediatric biobanking and research framework are based on empowerment processes ensuring that the minor’s participation increases as maturity develops.
In a nutshell, minors are:
- “entitled to special care and assistance” (minors in needs of protection, but also subjects in evolution),
- with a risk of subordination (due to the differential power relationships between adult researcher and child participant),
- with a risk of manipulation in interaction with adults, and,
- therapeutic misconception as a factor increasing vulnerability.
An ELSI paradigm shift: RRI maturation with the minors
It is both an ethical, legal, societal duty/responsibility and an enriching cultural investment to promote equipping participants with necessary capabilities. The target category not only includes minors but also indirectly adults, i.e., their parents as well as the researchers (e.g., to understand and to act with awareness in the new scientific horizon, based on data and sample access and use). Biobanking has the potential to expand empowerment and engagement. Considering that participants’ exposure to possible clinical risks is often minimal, biobanking provides an understanding of the biomolecular turn of research and medicine, the impact of genetic knowledge on the life of each individual and on society in general, and the collaborative horizon at stake.
Moreover, as paediatric biobank-based research grows and an ethically healthy balance between the protection of vulnerable populations and the development of FAIR/fair research in the age of genomic medicine is needed, it is critical to support researchers in rethinking the consent process with minors. This includes a wide range of elements from minor’s wish, opinion, assent to ethical consent and free choice, stressing those older children and adolescents, the mature minors, are often developmentally capable of meaningful deliberation about the risks and benefits of participation in research.
We should reconsider the legal framework at stake, thinking of the ethical consent of the minor in extended terms.
As early as 2000, the Charter of Fundamental Rights recognized the great challenge, highlighting the following:
“Balancing the right to protection and care of children with the duty to take them seriously and to co-opt them according to their age and degree of maturity.”
And, in particular, according to article 24:
“Children shall have the right to such protection and care as it is necessary for their well-being. They may express their views freely. Such views shall be taken into consideration on matters which concern them in accordance with their age and maturity.”
We are not surprised by the outcome of this long-running process. The Regulation on clinical trials states that the minor participates while the legally designated representatives authorize his/her participation. The Regulation explicitly requires that children and young people should “take part” in the consent process.
In sum, the minor is the participant, neither the parent nor the guardians. This is the core of the new scientific paradigm in paediatric biobanking, where the cultural, practical, ethical change is played out:
- Minors are transformed from being “entitled to special care and assistance” to having the right to be listened to, taken seriously, and involved.
- Parents’/guardians’ consent is transformed from being the sine qua non for biobank-based research to being part of a positive minor’s agreement, a practical/ethical consent.
The updated Recommendation on research on biological materials of human origin, states directly in article 21, the opinion of the minor, in particular, his/her disagreement, as a dynamic determining factor as well as introducing the re-consent:
“4. […] If the person not able to consent is a minor, his or her opinion should be taken into consideration as an increasingly determining factor in proportion to age and degree of maturity. Any objection by the person not able to consent should be respected. Any wishes previously expressed by such a person should be taken into account.
5. Where a person not able to consent, whose biological materials have been stored for future research, attains or regains the capacity to consent, reasonable efforts should be made to seek the consent of that person for continued storage and research use of his or her biological materials.”