From vulnerable subjects to research partners: a critical policy analysis of biomedical research ethics guidelines and regulations

Abstract

Over the last three quarters of a century, international guidelines and regulations have undergone significant changes in how children are problematised as participants in biomedical research. While early guidelines enacted children as vulnerable subjects with diminished autonomy and in need of special protection, beginning in the early 2000s, international regulatory frameworks defined the paediatric population as vulnerable due to unaddressed public health needs. More recently, ethical recommendations have promoted the active engagement of minors as research partners. In this paper, I adopt a post-structuralist approach to policy analysis to examine deep-seated assumptions and presuppositions underlying the changes in the problematisation of children as biomedical research participants over time. While biomedical research ethics focuses on the autonomy and vulnerability of minors, ethical guidelines are situated in specific sociocultural contexts, shaped, among other things, by contingent public health needs and changing conceptions of the value of research and science for society. In the process, I demonstrate the challenge of moving away from an approach that in taking adults as the model overshadows the complexity of children’s lived experiences as well as their personal, cultural, and social lives. The lack of acknowledgement of this complexity makes children vulnerable to epistemic injustice, which is particularly crucial to address in public involvement initiatives.

Keywords

Biomedical research ethics childhood vulnerability autonomy epistemic injustice public involvement

Introduction

Over the years, the conception of children in biomedical research ethics has undergone profound changes ranging from considering them as vulnerable ‘subjects’ in the mid-20th century to today’s view of paediatric participants as active research partners (Das et al., 2020). In the aftermath of World War II, a series of international guidelines, regulations, and deontological statements were developed to define ethical standards in biomedical research (e.g. the Nuremberg Code, the Declaration of Helsinki, the Belmont Report). The standards concerning paediatric research sparked considerable debate and were revised several times (Delfosse et al., 2009; Johnson and Unguru, 2015). Initially, children¹ were defined as vulnerable subjects in need of special protection. Beginning in the 1990s, however, this approach was called into question as it became apparent that the methodological, legal and ethical requirements for paediatric studies were limiting the production of evidence needed to adapt treatment to different age groups (Lanzerath and Rietschel, 2018; Wendler, 2020). Criticism of these limitations occurred in the context of a general growing consensus about the need to develop clinical trials to improve care (Lantos, 2018; Shirkey, 1968). At the same time, the role of children as political and social persons has profoundly changed in Western countries. The 1989 United Nations Convention on the Rights of the Child established that children have the human right to be consulted and have their views taken into account, to have access to information, freedom of speech and opinion, and to challenge decisions made on their behalf (Convention on the Rights of the Child, 1989). In clinical practice and research, the acknowledgement of children’s rights promoted, among other initiatives, public involvement in paediatric research (Das et al., 2020; Gaillard et al., 2018).

While the biomedical research ethics literature typically examines the ethical issues of children’s participation in research with topics such as assent, best interest standards, age of maturity, and parental authority (cf. Johnson and Unguru, 2015; Lanzerath and Rietschel, 2018), little attention has been afforded to how children are conceived as research participants. And this, despite the fact that other fields and disciplines have extensively discussed and debated the conceptualisation of children in research (Christensen and James, 2017; Uprichard, 2010). Biomedical research ethics guidelines mainly adopt the stance that there is some degree of tension between vulnerability and autonomy for the involvement of children (Thèry, 1994). However, this tension has taken different forms in specific documents over time. What is the rationale for these changes? What is their ethical relevance? The purpose of this paper is to examine deep-seated underlying assumptions and presuppositions concerning how biomedical research ethics guidelines and regulations have enacted minors as participants. To do so, I have adopted a post-structuralist approach to policy analysis called ‘What’s the Problem Represented to be?’ (hereafter WPR; Bacchi, 2009, 2016; Bacchi and Goodwin, 2016).

Methods & materials

WPR is an approach to policy analysis that may be applied to documents that are not policies in the strict sense of the term, but that represent a ‘problem’ and provide a solution (Marshall, 2012; Murano, 2020):

The key distinguishing characteristic of the material that can be adopted for a WPR analysis is that it is prescriptive—that it can be understood, possibly in a loose sense, as a form of proposal and a guide to conduct (Bacchi and Goodwin, 2016: 18).

This approach does not analyse how specific problems are solved within documents, focusing rather on identifying how they are produced, constituting them as particular sorts of problems (Bacchi, 2016: 8). In addition, it allows for consideration of the contingent and situated component of the research ethics agenda.

For this study, I selected eight international ethical guidelines, regulations and deontological statements on biomedical research published between 1947 and 2015, dividing them into three groups based on how they problematise minors’ participation in biomedical research. These groups were classified as follows:

(1) Four early ethical guidelines on biomedical research: the Nuremberg Code ([1947] 1996), the Declaration of Helsinki (WMA, 2013), the Belmont Report (National Commission for the Protection of Human Subjects of Biomedical and Behavioural Research, 1979) and its preliminary commission Recommendation on Research Involving Children (National Commission for the Protection of Human Subjects of Biomedical and Behavioural Research, 1977).

(2) Three documents that constitute regulatory and technical frameworks for medications in the paediatric population: the EU Paediatric Regulation (EU Regulation, 1901/2006), and two documents by the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use: ICH Topic E11 Clinical Investigation of Medicinal Products in the Paediatric Population (International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH E11), 2000) and its addendum, Guideline on Clinical Investigation of Medicinal Products in the Paediatric Population (International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH E11R1), 2016).

(3) The 2015 Nuffield Council on Bioethics Report entitled Children and clinical research: ethical issues.

Context of the selected documents and rationale for selection

This paper aims to analyse how children are enacted as participants in biomedical research in different ethical guidelines and regulations over time. Each set of documents mentioned above presents different problematisations with some consistency in the main assumptions and presuppositions about the ethical relevance of biomedical research for society. While early guidelines assume that research is potentially harmful to research participants, the international regulatory framework presents research as ‘a public health need’, and the Nuffield Council on Bioethics Report defines research as a ‘joint enterprise’.

The first set of guidelines selected here were profoundly shaped by questionable research conducted during the 20th century (Beecher, 1966). The Nuremberg Code was written in 1947 by members of the court and two doctors who advised the American military tribunal sentencing Nazi doctors who conducted criminal experiments on concentration camp prisoners during World War II. In their ruling, the judges established a list of 10 principles to determine the criteria under which research with human subjects should be considered legally acceptable. This list was later extracted to become a core document in biomedical research ethics in Western countries. In turn, the Declaration of Helsinki was developed by the World Medical Association (2013) to provide ethical guidelines to physicians and professionals involved in medical research. It was issued for the first time in 1964 and revised nine times up to the most recent version dated 2013. Finally, the Belmont Report was issued in 1979 by the U.S. National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research. The Commission was created as a result of the National Research Act of 1974 and involved nearly 4 years of deliberations before releasing the final ethical principles and guidelines. Prior to the final Report, a specific recommendation on Research Involving Children was issued in 1977. The Belmont Report refers to previous questionable research such as the Tuskegee experiment (1932‒1972), which studied the natural course of syphilis in a Black population without providing treatment even after it was made available.

These early documents were primarily motivated by the need to prevent and regulate ‘unethical’ research and focused on defining the duties and responsibilities of researchers to participants and society, establishing a burden of proof for the need for research involving children. While the value of research for society is acknowledged, the underlying assumption is that research is potentially harmful:

When vulnerable populations are involved in research, the appropriateness of involving them should itself be demonstrated. A number of variables go into such judgments, including the nature and degree of risk, the condition of the particular population involved, and the nature and level of the anticipated benefits (National Commission for the Protection of Human Subjects of Biomedical and Behavioural Research, 1979: iv).

The National Commission for the Protection of Human Subjects of Biomedical and Behavioural Research (1977) recommends that clinical research should first be conducted on animals and adults before testing children, and in the case of paediatric research, older children should be tested prior to infants (National Commission for the Protection of Human Subjects of Biomedical and Behavioural Research, 1977: 2).

As mentioned in the introduction, the approach suggested by the first set of guidelines was later criticised by the medical community as overly protective. According to this view, early guidelines reiterated attitudes of suspicion and distrust towards researchers and science, and overshadowed more positive accounts of research, for instance, as an opportunity to contribute to common knowledge, or as reinforcing people’s right to participate in a study as volunteers (Amiel, 2011; Lantos, 2018). The medical community also criticised the lack of evidence-based research in paediatric care that followed. Children were termed ‘therapeutic orphans’ (Shirkey, 1968) to describe the inadequacy of knowledge in pharmacotherapy for treating different paediatric conditions.

An international regulatory framework was therefore established to encourage paediatric research. While the International Conference of Harmonization of Technical Requirements for Pharmaceuticals for Human Use had brought together regulatory authorities and the pharmaceutical industry to develop guidelines for harmonised practices in the pharmaceutical sector worldwide in the 1990s, ICH E11 2000 and its addendum ICH E11(R1) 2016 specifically sought to facilitate the development of paediatric medications. The EU Paediatric Regulation took this one step further, establishing ‘a system of both obligations and rewards and incentives’ (EU Regulation, 1901/2006: 6). At the same time, these documents stress the need to avoid unnecessary clinical trials, and to limit the number of participants and procedures.

Research is presented by the International Conference of Harmonization as necessary when addressing an ‘important paediatric public health need’ (ICH E11R1, 2016: 4), representing both an opportunity for society and a right of the paediatric population. The strategy put forward to fill gaps in existing paediatric knowledge by the International Conference of Harmonization consists of including cohorts of children in studies conducted with adults:

Drug development programs should usually include the paediatric patient population when a product is being developed for a disease or condition in adults and it is anticipated the product will be used in the paediatric population (ICH E11, 2000: 3).

This second set of documents also highlights the ethical responsibility held by stakeholders other than researchers, such as the pharmaceutical industry, regulatory authorities, and society as a whole (ICH E11, 2000: 3). This expansion reflects the changes within the research enterprise such as the increasing role of the industry, the growing number of multiregional paediatric studies, and the need to set international standards to make knowledge shareable, reliable, and comparable (ICH E11R1, 2016: 6).

To conclude this section, the Nuffield Council on Bioethics is a UK-based independent body established in 1991 that produces reports and makes policy recommendations on ethical issues arising from developments in bioscience and health. The stated purpose of the 2015 report is to assess the ‘current systems for regulating [paediatric] clinical research’ (p. xi). It acknowledges the positive impact of EU regulation in increasing the number of paediatric clinical trials and in producing a ‘fundamental change of culture’ in pharmaceutical companies, as these now consider the collection of evidence for children as part of the development of medications (p. 74). Nonetheless, it suggests that the EU waiver system be reconsidered, given its lack in effectiveness in promoting all beneficial research on paediatric conditions. For example, while waivers exempt industry from conducting paediatric studies on medications for conditions that affect only adults, the same medication could be relevant for a different paediatric condition. At the same time, it highlights the need for further research on off-patent medications and rare conditions.

All in all, the Nuffield Council on Bioethics (2015) takes a strong stand on the ethical value of research, stating:

Scientifically valid and ethically robust research, that addresses questions of importance to the health of children and young people, should be seen as intrinsically good, and as a natural and necessary part of a healthcare system. . . . Such an approach is certainly not a blanket prescription of ‘research at all costs’ – but rather a challenge to the complacent notion that it is safe or ethical to continue promoting care to children without seeking to improve the evidence on which that care is based (Nuffield Council on Bioethics, 2015: xvi).

In addition, this advisory body suggests that the quality of research should no longer be assessed solely in terms of scientific and clinical expertise and must also include public involvement. It is important to involve stakeholders to identify the most urgent research questions. Produced with the participation of children, parents, experienced clinicians, and other entities, this report presents research as a ‘joint enterprise’ undertaken by different stakeholders (Nuffield Council on Bioethics, 2015: 172).

Analysis

In this section, the analysis of the documents shows that: (1) in early ethical guidelines, children were considered ‘vulnerable subjects’ due to their diminished autonomy, thereby requiring special protection from research. (2) More recent regulations by the EU and ICH proposed that children represent a vulnerable population due to the lack of evidence-based research in paediatrics. According to this perspective, research should be encouraged in different age groups, as they are unique from a biological and pharmacological point of view. (3) Finally, in the Nuffield Report, children are represented as research partners, along with their parents, with a focus on shared family decision-making.

It should be noted that there is a meaningful shift of language across these sets of documents. In early guidelines, research participants are referred to as ‘research subjects’ or ‘experimental subjects’. This choice of words underscores the fact they were not considered ‘on an equal footing’ with researchers (Dresser, 2017: 4). The other two sets of documents speak rather in terms of ‘research participants’ and ‘research partners’, respectively. These changes in terminology highlight the transition in discourse on research governance and its recent participatory turn.

Early ethics guidelines

In early ethics guidelines, children are constituted as vulnerable research subjects who have developmental or ‘diminished’ autonomy and therefore are particularly vulnerable to be harmed by research.

Children have developmental or ‘diminished’ autonomy

Despite the involvement of children in the experiments conducted by Nazi doctors during World War II, the Nuremberg Code refers only to adult research participants. This omission has been read by some as suggesting that paediatric research is considered inacceptable per se (Delfosse et al., 2009). Whether or not this is the case, the Nuremberg Code was crucial to establishing the basis for the understanding of autonomy in biomedical research ethics debates. Following the Western philosophical tradition, it interprets autonomy as the self-determination of a rational and independent person. Therefore, in research ethics, autonomy primarily refers to informed and voluntary consent, defined as ‘absolutely essential’. Participants should have the ‘legal capacity to give consent’, ‘sufficient knowledge and comprehension’ to inform their decision and should be able to decide independently of any element that could constrain their choice. Research participants therefore have a rather limited possibility of exercising autonomy: they can either accept or refuse to participate (Amiel, 2011).

This conception of autonomy is reiterated in the Declaration of Helsinki, where children are included in the category of vulnerable groups and individuals (Hurst, 2008). Because children are unable to provide informed consent, such consent must be obtained from their ‘legally authorised representative’ (WMA, 2013: 28). Nonetheless, their assent should be obtained whenever they become capable of granting it, and their dissent should be respected. This approach, which is again proposed in the Belmont report, by the National Commission for the Protection of Human Subjects of Biomedical and Behavioural Research (1977, 1979), is inspired by theories in developmental psychology. The Belmont Report refers to children as having ‘diminished autonomy’; autonomy being understood on a continuum rather than as an either/or situation. An autonomous person is defined as ‘an individual capable of deliberation about personal goals and of acting under the direction of such deliberation’ (National Commission for the Protection of Human Subjects of Biomedical and Behavioural Research, 1979: B1). This capacity is progressive and ‘matures during an individual’s life’ (National Commission for the Protection of Human Subjects of Biomedical and Behavioural Research, 1979: B1). Therefore, the information provided should be adapted to the ‘subject’s capacities’ (National Commission for the Protection of Human Subjects of Biomedical and Behavioural Research, 1979: C1). Researchers are responsible for ensuring that participants understand the information provided and, if necessary, should provide some ‘oral or written tests of comprehension’ (National Commission for the Protection of Human Subjects of Biomedical and Behavioural Research, 1979: C1). Even if infants and young children are defined as ‘incompetent subjects’ (in the same way as ‘mentally disabled patients, the terminally ill and the comatose’; National Commission for the Protection of Human Subjects of Biomedical and Behavioural Research, 1977: xvii), they should be granted the opportunity to choose ‘to the extent they are able, whether or not to participate in research’ (National Commission for the Protection of Human Subjects of Biomedical and Behavioural Research, 1979: C1). Assent should be requested, whenever possible, from children 7 years of age or older (National Commission for the Protection of Human Subjects of Biomedical and Behavioural Research, 1977). The older the child is, the greater the weight of their wishes should be considered. However, this self-determination is limited by the best interest of the child. While a child’s objection to participation should be honoured, in the case of research that provides a therapy otherwise unavailable, parental authority is what counts (National Commission for the Protection of Human Subjects of Biomedical and Behavioural Research, 1979: C1). In exceptional circumstances, parental authority may not be requested. For example, when the condition studied is among those for which mature minors are able to consent to treatment for certain conditions (e.g. pregnancy, drug addiction, venereal diseases) without parental permission, or when children are neglected or abused.

Children are vulnerable and need special protection

In this first set of guidelines, children are enacted as intrinsically vulnerable. The Declaration of Helsinki states:

Some groups and individuals are particularly vulnerable and may have an increased likelihood of being wronged or of incurring additional harm. All vulnerable groups and individuals should receive specifically considered protection (WMA, 2013: 9).

Physicians and healthcare professionals bear the responsibility for protection. Research involving vulnerable groups is only justified if it addresses the health needs of the group, risks are minimal, and it cannot be conducted on other non-vulnerable groups. Those involved should stand to benefit from ‘the knowledge, practices or interventions that result from the research’ (WMA, 2013: 10).

The National Commission for the Protection of Human Subjects of Biomedical and Behavioural Research (1977) states that children’s vulnerability ‘arises out of their dependence and immaturity’ (National Commission for the Protection of Human Subjects of Biomedical and Behavioural Research, 1977: 2). Their reduced autonomy and ‘incompetence’ to give informed consent are considered the cause of this vulnerability. Including vulnerable participants in research could be a source of injustice, if conducted ‘solely for administrative convenience, or because they are easy to manipulate as a result of their illness or socioeconomic condition’ (National Commission for the Protection of Human Subjects of Biomedical and Behavioural Research, 1979). Therefore, such individuals need to be protected:

Some persons are in need of extensive protection, even to the point of excluding them from activities which may harm them; other persons require little protection beyond making sure they undertake activities freely and with awareness of possible adverse consequences. 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 (National Commission for the Protection of Human Subjects of Biomedical and Behavioural Research, 1979: B1).

In addition, the National Commission for the Protection of Human Subjects of Biomedical and Behavioural Research (1977) highlights some categories of children that need special protection, such as children who are wards of the state, residents in institutions for ‘the mentally infirm’ or those confined in correctional facilities.

International regulatory framework

The international regulatory framework, defining research as a public health need, marks a change in perspective from the individual to the population level. Children are enacted as research participants belonging to a population group with specific biological and pharmacological developmental features. They are not only vulnerable as individuals, but also as a group.

Biological and pharmacological development of the paediatric population

The set of regulations examined within the regulatory frameworks of the 2000s suggest an idea of autonomy similar to that presented in the previous section but with a focus on children’s biology and pharmacology. As with earlier guidelines, the understanding of children’s autonomy is based on a developmental approach, and its forms of expression are related to assent, consent, and withdrawal from participation. Children should always receive information adapted to their understanding. Even after the legal guardian’s consent, it may be necessary to reassess children’s assent and/or consent over the course of a clinical study (ICH E11, 2000; ICH E11R1, 2016). Local laws define when minors are ‘emancipated’ or ‘mature’ and therefore capable of providing informed consent. Nonetheless, all children should be informed of their right to decline or withdraw participation from the study (ICH E11, 2000: 12). Parental authority is maintained in the event of a child’s refusal to participate or withdrawal from the study in life-threatening situations as continued parental consent is sufficient to allow participation (ICH E11, 2000).

The different documents analysed here propose an age classification of paediatric patients based on ‘developmental biology and pharmacology’ (ICH E11, 2000: 9). While acknowledging that this is just ‘one possible categorisation’ the International Council for Harmonization, for instance, points to the existence of ‘considerable overlap in developmental (e.g. physical, cognitive, and psychosocial) issues across the age categories’ (ICH E11, 2000: 9). The main idea is that ‘paediatric populations’ should have their needs addressed by appropriate specialists, and medications should be adapted to different subsets (EU Regulation, 1901/2006: 8). The EU Paediatric Regulation triggered the constitution of the Paediatric Committee within the European Medicines Agency (EMA), with specific expertise and competence covering the scientific areas relevant to paediatric medications, minimally including: pharmaceutical development, paediatric medicine, general practitioners, paediatric pharmacy, paediatric pharmacology, paediatric research, pharmacovigilance, ethics, and public health. Paediatric research requires specific expertise, methodology, and facilities, and should be conducted by appropriately trained researchers.

The paediatric population is vulnerable

The concept of vulnerability across this set of documents is proposed at both the individual and collective level. Nonetheless, the vulnerability of the paediatric population is the very reason for which research should be implemented. The lack of evidence-informed knowledge makes the paediatric population vulnerable to harm. While children should be granted the right to be treated, without research the safety and efficacy of treatments remain unknown. Vulnerability is again presented as intrinsic to children, but also determined by how the research is conducted. Researchers with experience in paediatrics can minimise discomfort and distress, implementing practical considerations to ensure that participants’ experiences in clinical trials are as positive as possible. For instance, they can adjust aspects of the environment, making it more familiar, or of the procedures, such as limiting the number of venipunctures (ICH E11, 2000).

This framework also suggests measures to balance participation and protection, maintaining a hierarchy of protection. When a medication can be used for the same indications as studied in adults, extrapolation from adult efficacy data may be appropriate. The same process applies in the case of extrapolations from older to younger paediatric patients (ICH E11, 2000). The importance of conducting studies in different age groups is justified by the fact that dosing recommendations are usually based on mg/kg body weight, or occasionally on mg/square metre body surface. Studies in disabled or institutionalised paediatric populations should be limited to diseases or conditions found principally or exclusively in these populations, and efforts should be made to include ‘individuals representing the demographics of the region and the disease being studied’ (ICH E11, 2000: 12).

The Nuffield Council on Bioethics report

This section examines the Report by the Nuffield Council on Bioethics titled Children and clinical research: ethical issues (Nuffield Council on Bioethics, 2015). This report constitutes research as a joint enterprise with children as research partners, together with their family. Accordingly, the role of parents and the relevance of the context for ethical considerations in biomedical research is highlighted. On the one hand, the Report provides guidelines on parental responsibility and educational role in decision-making (without side-lining the obligations of healthcare professionals). On the other hand, it puts forward that the context is what increases or decreases the degree of vulnerability of individual children.

Family decision-making

As with earlier documents, the Nuffield Council on Bioethics adopts a developmental understanding of childhood, in this case, primarily in reference to children’s ability to choose for themselves. The report describes three cases of childhood development: (1) that of complete dependence on others, (2) children with the ability to form opinions and express wishes without being able to make independent decisions, and (3) children or young people with the capacity to make decisions, without legal power. Children in Cases 1 and 2 should be involved in decision-making appropriate to their understanding and development, while consent should be sought for those in Case 3 (regardless of any requirements of national legislation). Children, it proposes, should be understood as people who:

in the context of their own family and social environments, have the potential from an early age to play an active role in determining their own lives and in engaging with others. . . . Such an approach, which is commonplace in thinking about the role of children in many other areas of life, stands in stark contrast to many of the implicit assumptions of research governance, which tend to emphasise vulnerability and lack of competence (Nuffield Council on Bioethics, 2015: xvi).

Although the Nuffield Council on Bioethics concludes that children and young people should be considered ‘genuine partners’ and ‘active participants’ in research (Nuffield Council on Bioethics, 2015: 172), a distinction between the role of adults and children remains clear:

We are making the claim that there is a morally significant difference between ‘competent children’ and ‘adults’, which may potentially justify differential treatment. Children, however intellectually capable, do not have full adult powers – and the corollary of that is that they also do not have full adult responsibilities. Parents are there, both ethically and legally, to share that responsibility until the agreed threshold of adulthood is reached (Nuffield Council on Bioethics, 2015: 118).

Parents should accompany children during their stages of development and assume an educational role, considering their child’s immediate and longer-term welfare, which includes shaping their character and values. Considerations of welfare should therefore include those of ‘social solidarity’ and ‘care for others’:

The language of ‘best interests’ is often used to capture this general concern for children’s welfare, but is misleading in the context of clinical research, given that research-related procedures are not, primarily, carried out for the personal benefit of participants. We therefore suggest that parental consent to research should be based on their confidence that participation in the proposed research is compatible with their child’s immediate and longer term interests (Nuffield Council on Bioethics, 2015: xx).

Professionals should seek a shared family decision, in which both parents and children are involved. Although parental preferences should be respected, researchers also have an important duty for professional discretion and judgement (Nuffield Council on Bioethics, 2015: xxii). In the event disagreement about research participation arises within families, they should negotiate an acceptable solution that respects all parties. The explicit and consistent dissent of children should be respected despite parental willingness to proceed. If, conversely, children want to participate and their parents disagree, researchers may try to ‘inform and encourage’ parents. However, if they are unable to convince them, participation in the research should not proceed. The primary concern of professionals should be to develop trusting relationships with children and communicate information appropriately throughout the research project.

Children’s vulnerability is context dependent

The Nuffield Council on Bioethics proposes an understanding of vulnerability not intrinsic to children, arising ‘in the context of the developmental nature of childhood’ (Nuffield Council on Bioethics, 2015: xxii). For example, a child may need practical and or emotional support in understanding what is at stake or could experience anxiety about the impact of participation. Because these forms of contextual vulnerability can be reduced by modifying some aspects of the research, researchers should reflect on the role they can play in this regard. Previous approaches to vulnerability risked adopting overly protective responses, excluding children and young people from ‘opportunities to participate in research activities’ (Nuffield Council on Bioethics, 2015: xxii). The Nuffield Council on Bioethics, in contrast, advocates for their active involvement, arguing that being overprotective may be just as harmful as being insufficiently protective. Of course, due consideration of risks and benefits should be given, and an acceptable balance determined with ‘the active encouragement of research that has the potential to improve children’s healthcare, while ensuring risks are kept to a minimum acceptable level’ (Nuffield Council on Bioethics, 2015: 140).

Active engagement itself can be a tool to minimise children’s vulnerability:

Such an approach implies a fundamental shift from seeking to protect children ‘from’ research, to protecting them through their own active engagement with how research with children and young people is designed and carried out (Nuffield Council on Bioethics, 2015: xxiii).

Nonetheless, such engagement is understood at the family level, maintaining and emphasising the role of parents. The Nuffield Council on Bioethics (2015) suggests working ‘in partnership with children, young people and parents throughout the whole endeavour of research’ (p. xxii) to ensure that the procedures they have put in place have been developed with ‘the input of others in a similar situation to themselves’ (p. xxiii).

Discussion. Paediatric research and epistemic injustice

This analysis has shown that the problematisation of children as participants in biomedical research has shifted dramatically over time from vulnerable subjects to research partners. While biomedical research ethics focuses primarily on the autonomy and vulnerability of minors, such changes underscore the fact that ethical guidelines are situated in specific sociocultural contexts, shaped, amongst other things, by contingent public health needs and changing conceptions of the value of research and science for society. Seeking to contest initial negative views, research is presented, respectively, as potentially harmful, as a public health need, and as ethically good. Assumptions about research as either harmful or beneficial has impacts for the definition of children as research participants, their modes of participation, and the possibility of conducting paediatric research itself. Today, opposing viewpoints concerning children’s participation coexist. On the one hand, protection is deeply rooted in biomedical research ethics standards. The early guidelines analysed above, that focus on minors’ protection, are still central in biomedical research ethics assessments and evaluations carried out by institutional review boards and research ethics committees (Dresser, 2017). On the other hand, respect for children’s rights of participation in biomedical research has been increasingly defended (Das et al., 2020; Gaillard et al., 2018; Lanzerath and Rietschel, 2018). Previous literature has demonstrated the difficulties posed by this incongruity and raised concerns about children’s protection in participatory approaches (Bradbury-Jones and Taylor, 2015; Spriggs and Gillam, 2019).

The three sets of documents examined here also present a degree of continuity in the assumptions underlying the understanding of children’s autonomy and vulnerability. In the first set of documents, the category of ‘vulnerable subjects’ is quite broad, comprised of children and populations such as racial minorities, the economically disadvantaged, the very sick, and the institutionalised, among others. Including children in this group highlights the relevance of power dynamics in research. However, power in this context is understood in the narrow sense of the researcher/participant relationship. In other words, research participants are vulnerable because researchers can harm them. Potential harm is especially problematic in the case of persons with diminished autonomy, such as children, who may be harmed because they do not fully understand the risks and benefits of research. In all the documents assessed here, autonomy is strictly related to legal requirements and in line with a mainstream Western philosophical tradition of freedom and self-determination. Influenced by the philosophies of Emmanuel Kant, John Stuart Mill and John Rawls, this perspective assumes that people are rational and independent, free from any form of coercion. Autonomy in a clinical research setting is expressed primarily in terms of consent/assent and the ability to withdraw or refuse participation (Amiel, 2011; Mackenzie and Stoljar, 2000). In this sense, it could be asked whether this understanding of autonomy is useful to the medical realm at all, where lived experiences of illness and disease are overshadowed by numerous aspects that escape logical thinking, such as empathy, dialogue, and interpretation (Svenaeus, 2018). In the case of children, this account of autonomy is particularly ill-suited due to the developmental and individual variations in cognitive abilities and the relational construction of individual wishes.

An alternative to individualistic, ideal, and rationalistic theories of autonomy is offered by understandings of autonomy as relational. While different accounts of relational autonomy exist, they generally consider that choices are made by individuals who are in relationship with others, situated in specific contexts, and involve non-rational aspects in decision-making, such as emotions, feelings and beliefs (Mackenzie and Stoljar, 2000). While the Nuffield Council on Bioethics’ recommendation to focus on family decisions implies that relationships are important, rationality and legal responsibility continue at the core of the discussion. Moreover, the Nuffield Council on Bioethics Report does not problematise power dynamics within and outside the family. It recommends that parents accompany children according to their level of maturity while researchers develop relationships of trust with children. This approach neglects the inevitable power imbalance between adults and children, experts and laypeople, healthy individuals and patients, as well as the epistemic injustice suffered by children in medicine (Carel and Györffy, 2014). As a form of epistemic injustice, Fricker (2007) defines hermeneutical injustice as ‘a gap in collective interpretative resources [that] puts someone at an unfair disadvantage when it comes to making sense of their social experiences’ (p. 1). One clearly identifiable gap in the collective interpretative resources of these documents consists of not being able to consider the complex realities of childhood. Childhood is regarded as a general and transitory period of life below the threshold of adulthood and articulated in stages of development. However, children in fact have multifaceted life experiences, subtle strategies of communication, intricate emotions and mechanisms of meaning making, while situated in specific socioeconomic contexts (cf. Bluebond-Langner, 1980; Laforgue et al., 2022). Such complexity is well recognised in fields of study outside the biomedical sciences (e.g. Lee, 1999; Prout, 2000; Qvortrup et al., 2009; Uprichard, 2008) and so there is much that the biomedical sciences could learn from these longstanding debates and developments in understanding.

The lack of recognition of the complexity of childhood within the biomedical sciences has serious consequences in formulating guidelines and regulations in biomedical research, well beyond the definition of autonomy and vulnerability. For example, although the regulatory framework insists on involvement of paediatric expertise, it shapes the research agenda based on the health needs of adults. Specifically, critics of the EU Paediatric Regulation point out that it focuses too much on the disease without considering that even if children do not present the same disease as adults, the mechanism of the medication could be of benefit for other paediatric conditions (Adamson, 2013; Rose, 2020; Vassal et al., 2013). In turn, the Nuffield Council on Bioethics Report argues that children are contextually vulnerable but does not problematise the power dynamics of that context. The underlying idea that parents decide for their children (as legal guardians) remains.

If future research continues in the direction of increasingly promoting participatory approaches (Das et al., 2020), addressing epistemic injustice is crucial. Including research participants in ethical decision-making has been advocated in different fields, such as deliberative democracy, feminist epistemology, and narrative ethics (Dresser, 2017: 9), as a way to ‘ensure social justice’ (Laforgue et al., 2022: 71). Different participatory approaches have been studied in recent years for both adults and children, underscoring the importance of carefully considering the conditions necessary to provide authentic participation (Dresser, 2017; Laforgue et al., 2022; Spriggs and Gillam, 2019).² If the complexity of childhood is not taken on its own terms, involvement initiatives run the risk of being nothing more than token efforts. In fact, previous studies have argued that active engagement could even perpetuate power dynamics regulated by the interest of a few, while actually restricting children’s agency (Raposo, 2022). At a time in which political participation among young people is decreasing (Weiss, 2020), the risk of epistemic injustice takes on even greater relevance. A careful assessment as to whether ‘increased participation from young people can be transformative, involving longer-term cultural change and greater impact on existing institutions’ (Groundwater-Smith et al., 2015: 22) is critical.

The primary limit of adopting an adult centric model is that it does not allow for a consideration of how children already participate in this system:

The current discourse of patient and child participation is based on an understanding that children need to be brought into the system. . . . If we are not willing to look at what children already disclose, it might be useless to invest in creating better opportunities for children’s participation. In fact, if we think that children can only participate when they are invited and facilitated by adults in specially designed projects, we might even be contributing to the reification of the child as passive recipient of care (Dedding et al., 2015: 2127–2128).

Children’s involvement in biomedical research has a performative power, producing a new and actively engaged generation of people. Whether this performativity conceives authentic, or token participation has consequences for the quality of research, as well as for the role of children as citizens participating in an increasingly democratic scientific endeavour. For all these reasons, epistemic injustice should be at the core of future debates on paediatric research ethics.

Conclusion

The modern recognition of the child bears the paradoxical consequence that it made us miss its specificity. If the child is a person almost like the others, how should we understand this ‘almost’? What status should be given to the difference of the equal child? (Deschavanne and Tavoillot, 2007: 326 – my translation).

In paediatric research ethics, reference to early ethical guidelines such as the Nuremberg Code, the Declaration of Helsinki, and the Belmont Report is rarely problematised in comparison to more recent guidelines. Yet changes over the years have introduced new values that present both continuities and discontinuities with the past. In this paper I have argued that despite an increasing interest in involving children in research, issues of epistemic injustice persist. Unless the complexity of children’s experiences and situations is taken into account, participatory approaches to research run the risk of being no more than token efforts.

Footnotes

Acknowledgements

I would like to thank colleagues of the Clinical Trials Unit at La Paz University Hospital and colleagues of the WPR network for discussions on previous versions of this article. I am also grateful to the anonymous reviewers who provided constructive feedback to previous versions of this manuscript.

Funding

All articles in Research Ethics are published as open access. There are no submission charges and no Article Processing Charges as these are fully funded by institutions through Knowledge Unlatched, resulting in no direct charge to authors. For more information about Knowledge Unlatched please see here: . This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement CareInTrials N° 891750.

Ethics approval

N/A

ORCID iD

Maria Cristina Murano

Notes

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