Ethical concerns when recruiting children with cancer for research: Swedish healthcare professionals’ perceptions and experiences | BMC Medical Ethics

The results describe the HCPs’ perspectives and experiences of recruiting children with cancer for research, including ethical values, challenges and ethical competence. It is important to note that recruitment was not always associated with ethical challenges for the interviewed HCPs, but was sometimes perceived as a straightforward and unproblematic process. Most HCPs in the study had long experience of working with recruiting children for research and felt confident and competent to manage ethical challenges. Nevertheless, and in line with the aim of the present study, the results will emphasize situations that the HCPs did perceive as ethically challenging. The analysis resulted in five categories: Establishing relationships and trust, Meeting informational needs, Acknowledging vulnerability, Balancing roles and interests, and Ensuring ethical competence. Several subcategories were derived (see Table 2). In the following, all categories are described and illustrated by quotes. The categories are not mutually exclusive, but sometimes overlap.

Establishing relationships and trust

Many HCPs highlighted the importance of mutual trust and relationships with families, in relation to recruitment. At the same time, trust also had problematic implications for informed consent. This category comprised two subcategories: Building relationships, and The dilemma of trust.

Building relationships

HCPs echoed the significance of establishing a relationship with the family before inviting the child to participate in research. Relationship building, for example by chatting with the child about everyday topics, served to establish mutual trust with children and parents, and facilitated conversations about research:

One thing that’s very important…is to establish some sort of relationship with the family, otherwise it’s not possible [to have these conversations], it’s a lot about them daring to trust you and building trust. (Nurse 1)

The informants described that the established relationship enabled them to assess the suitability of proposing research to the family, and to identify ethical challenges:

Having a relationship with the families and knowing that it will actually be doable, that it’s ok to ask them [about research participation]. (Nurse 8)

However, the HCPs sometimes faced barriers to relationship building with families who had less trust, or were angry or distressed following the child’s diagnosis. Further, COVID-19 pandemic restrictions minimized the number of care contacts to reduce the risks of infection, which made relationship building more difficult, primarily for clinical research nurses without care responsibilities.

The dilemma of trust

HCPs described that parents, with few exceptions, had high trust in them and in healthcare in general, as well as in research. Most parents were positive to research and consented to participate in the studies they were asked about. The informants associated research positivity to the widespread societal awareness in Sweden about the importance of childhood cancer research. Some parents, more frequently foreign-born, were perceived by HCPs as having lower trust and willingness to enrol. HCPs attributed this to distrust in authorities, fears of registration and confidentiality issues, and fear of exploitation/experimentation.

HCPs were grateful for parents’ trust and committed to maintaining it. At the same time, they regarded parents’ trust as a dilemma and as a possible threat to informed consent:

It’s also a dilemma, actually, that many families do as we say…they have very high trust in the healthcare system…the parents almost always do as we say…if you go in and just ask for a consent, you will probably get it (Physician 7)

Hence, the interviewed HCPs were concerned about parents’ consent not always being sufficiently informed. They described that they frequently had to insist on providing information to parents who wanted to consent instantly, based on trust and despite being poorly informed. One HCP described conflicts between respecting the family’s will to abstain from information, and fulfilling the requirement for informed consent:

I get a lot of parents telling me they can’t take any more and just want to sign…they prefer to trust us to do what’s best, but we have to get a consent and we want them to be informed. But at the same time you also have to respect them when they say, I can’t take any more, I don’t want to hear more now, but I want to consent. You cannot torment them with loads of information against their will. (Physician 4)

Meeting informational needs

HCPs in our study also highlighted the importance of providing tailored information, to provide a good basis for decision-making and ensuring understanding. They sometimes experienced information-related challenges, such as the family being overwhelmed by information or language barriers. This category consists of three subcategories: Tailoring information and communication, Information burden at diagnosis and Difficulties due to language barriers.

Tailoring information and communication

The results showed how HCPs stressed the importance of being flexible and responsive to understand and meet the informational needs of families. Addressing children with age-appropriate information was seen as a key aspect:

We see to the whole family and we think it’s very important that the children get information as well. That we don’t exclude them… It’s really important that they are involved, because they are the ones who are sick and will go through the treatment. (Nurse 3)

Aspects important in communication mentioned were being culturally sensitive and respectful in conversations about difficult topics. Also, the importance of body language, such as not placing oneself higher than the child, was brought up. The HCPs described how they strived for a dialogue-based and dynamic communicative approach, with an emphasis on listening and ensuring understanding, alongside providing written and verbal study information.

Further, it was highlighted that communication about research should not impede basic understanding of the child’s disease and care. The informants underscored that the difference between research and care should be clarified. However, one HCP believed that the ‘therapeutic misconception’ (i.e., failing to differentiate research from care) was not only held by parents, but also by HCPs:

I think it often falls back on us that we do not always acknowledge the difference [between research and care] and then it’s not clear to the family, either. And I believe there are families who go through cancer treatment without having really reflected upon this. (Nurse 7)

Moreover, the HCPs saw communicating the voluntary nature of research participation as especially important:

For me, the most important thing has been that they understand that it’s voluntary. They participate in many different studies and it’s probably hard for them to say no. In my experience, this patient group is very grateful that so much is being done for them. (Nurse 6)

Information burden at diagnosis

Recruitment for research near diagnosis was perceived as a major challenge. HCPs were concerned for the family’s wellbeing when introducing complex decision-making in a situation when they were already overwhelmed:

They are drowned in information, and at the same time they are often emotionally blocked after getting the diagnosis. All of this is pouring over them. It’s like an avalanche of information. (Physician 7)

The informants expressed conflicts between the value and necessity of paediatric research, and its potential burden on families:

If treatments in paediatric oncology could advance without studies, it would of course be better, we would not have to burden them…If they could be spared these kinds of decisions, that would be great. But then again, we have our responsibility as physicians to make treatments better and safer and with improved survival. So, we must have studies. (Physician 2)

The participants also described how they avoided or postponed recruitment if they perceived families as overburdened and unable to meaningfully engage in decision-making. However, sometimes enrolment could not wait and decisions had to be made, and at these times recruitment was particularly ethically challenging:

What we see is that, really, they need more time…so that they are not so distressed due to their diagnosis and everything that’s happening around them. That is actually the greatest difficulty we face right now…that inclusion and sometimes also randomizations are required very early on. (Physician 7)

It was also mentioned that legislative requirements contributed to the information burden by prescribing juridical and lengthy study information sheets, posing barriers to informed decision-making. Further, decision-making burden often increased with the number of studies the child was invited to, as well as with study complexity, uncertainty concerning the implications of participation and the start of treatment being contingent upon study enrolment. Randomized controlled studies, phase I drug trials and genetic studies were described as particularly challenging, due to study complexity and uncertainty concerning implications of participation.

Suggestions to mitigate the recruitment-at-diagnosis dilemma were mentioned by the participants. Among these were adopting a step-wise recruitment approach, repeating information throughout the research experience, implementing broader consents encompassing several similar studies and coordination of research at the organizational level, to reduce research burden on families.

Difficulties due to language barriers

Interviewed HCPs regarded it as their main responsibility to provide accessible and tailored high-quality information to children and parents, thereby ensuring correct understanding. Therefore, the HCPs were concerned about the quality of communication in consent processes conducted via interpreters, with non-native speaking parents and children. Moreover, they expressed frustration over the lack of translated study information sheets in many commonly spoken languages:

If a family is of foreign origin… then, sadly, you have nothing to provide, which I think is a huge shortcoming, actually… They usually sign up, but I don’t think they always understand what they are signing up for. (Nurse 3)

I don’t understand why consent forms are not produced in different languages, when we are living in a multicultural country… We can’t include only people who speak Swedish or English. (Nurse 2)

Informants were concerned about the risks of social alienation and unfair exclusion from research among non-Swedish-speaking families. They described how they did their best to inform and facilitate decision-making for these families, despite information and language barriers.

Acknowledging vulnerability

The analysis revealed several challenging recruitment situations related to children’s and parents’ vulnerability. This category consists of three subcategories: Parent-dependency, Power asymmetries and conflicts of interests, and Children with a poor prognosis.

Parent-dependency

HCPs described how children’s vulnerability and need for support following a cancer diagnosis could reinforce their dependency on their parents. This dependency on parental support had implications for the informed consent process, as it could make it difficult for children to question their parents’ views and express their own:

To feel as safe as possible, they want to be on the same side as their parents… At times, you wonder what they would think if mom and dad weren’t there. (Nurse 1)

The informants asserted the importance of talking to primarily older children and adolescents without the parents present, to allow them to share their views without parental influence.

However, parents’ capacity to act as decision-makers was sometimes compromised by distress in the form of anger, desperation and grief following diagnosis, according to the interviewees. One HCP believed that distressed parents might be less likely to object to research proposals, or even feel a pressure to enrol:

They are so traumatized and shocked. And then it’s easy to end up in a subordinate position because you lack the strength to resist or question things. So, they might just enrol… trying to be at ease, because they think that’s the best for their child (Physician 3)

According to HCPs, personal psychological difficulties, intellectual disabilities, social problems and low educational background could further increase vulnerability in decision-making.

Power asymmetries and conflicts of interests

HCPs described ethical commitments to improve health for children with cancer through research. They also expressed voluntariness and not imposing undue influence as important values in the recruitment process. As such, some HCPs experienced role conflicts between safeguarding the child’s interests, while also acknowledging their own interests in recruitment success:

If you are responsible for the study, you want to include as many as possible. And you also think about your reputation among colleagues; ‘he never succeeds in including anyone, but she gets everyone to enrol’. There is a lot at stake which has to do with, well… our own ambitions for research success. This creates problems all the time. (Physician 2)

The participants problematized the fact that they knew how to communicate to increase likelihood to get consent, for example by stressing the success of research in recent decades and how it has drastically reduced childhood cancer mortality. At the same time, they were aware of the pressure and power asymmetry this created in the recruitment situation:

I mean, if you have some experience, you could persuade anyone to enrol in a study … And that puts you in a power position. Yes. I know how to express myself to get them to enrol… And unconsciously…and especially if it’s your own study, then you want to get everyone to enrol… No, you’re not that objective. You aspire to be, but no one is… (Physician 6)

The interviewed HCPs experienced that the rarity of childhood cancer cases resulted in high competition in recruiting children for research, which could also contribute to conflicts of interests.

Children with a poor prognosis

Recruitment was described as less ethically complex if the child was relatively well in the initial stages of the disease. The informants were, however, particularly concerned about the wellbeing and rights of children with a poor prognosis or in relapse, especially in recruitment for experimental, early phase I trials. They described emotional and ethical challenges related to inviting these children to participate in research:

These conversations are so difficult because with these families we first pull the rug from under their feet by saying their child has pontine glioma and will die and then we say, do you want to participate in a study… it’s always painful to see how immensely sad these parents are, and it can be really difficult to get through with your message without giving them false expectations. (Nurse 1)

The interviewed HCPs stressed the importance of being honest and clear about difficult topics, and the lack of evidence for treatments offered within early experimental phase I trials. Further, they felt that the option to choose palliative care alone should be clearly communicated to families. They also highlighted the importance of managing hopes and expectations, and respecting the child’s wishes for their remaining time. The poorer the child’s prognosis, the more influence should be given to them in decisions, according to the informants. Likewise, HCPs found it inappropriate to invite children with limited chances of survival to longitudinal follow-up research, or burdening them with further medical interventions if prospects of medical gain were small.

Balancing roles and interests

The narratives of HCPs highlighted the complexities of balancing children’s and parents’ roles and interests in decision-making. This category consists of four subcategories: Asserting children’s rights, Children’s delegation of decisions, Parent’s decision authority and burden and Disagreements.

Asserting children’s rights

HCPs’ perspectives on ethical values in recruitment were highly marked by notions of children’s rights and children’s perspectives. They placed children in the centre of the recruitment process and described engaging in practices with the goal of asserting children’s rights, for example through addressing children with adapted information and letting children know that their views were wanted and important. Even children too young to participate in decisions were present in conversations about research, with reference to their rights to be informed. HCPs expressed that research should be conducted on the child’s terms. Further, one HCP mentioned the importance of considering the child’s best interest from a holistic perspective, and regardless of study eligibility:

You have to think like this, why should this child be included in this study? For whom is it good? Not just think that the child matches this study and therefore it is good for them to be involved. You need to take care of the whole child… Not all children can be in phase I trials … and some choose not to, based on what they want with their lives. (Physician 5)

According to the informants, children’s actual role in decision-making depended on a multitude of factors, including the child’s health status, age, maturity and personality as well as developmental factors, such as reading skills, verbal intelligence, critical thinking and potential neuropsychiatric difficulties. HCPs therefore described how they relied on a case-by-case assessment of maturity:

You have to try to understand the degree of maturity of that particular child. It is usually not an exact age and more a matter of personality… And you need to understand the ability of that child, at that age. (Physician 6)

HCPs also described that involvement depended on the children’s own preferences, the type of study and risks of participation. The longer disease history the child had, the more competent to make decisions they were considered, according to the informants.

Children’s delegation of decisions

The interviewees iterated that children tend to comply with parent’s preferences in recruitment. However, for research without medical risks, such as psychosocial intervention studies or psychometric research, children were often more involved in decisions. According to the HCPs, children and adolescents faced with the physical and emotional burdens of cancer, sometimes had little energy or interest in participating in decision-making, and instead delegated the decisions to their parents:

Many teenagers don’t care, they don’t read these sheets. They have been taken out of school, have no friends and are hospitalized… They have been diagnosed with a life-threatening disease, so there are other things that matter more. They have been told they might die and that they will lose their hair and might become infertile. I mean, a study more or less, they leave that to their parents. I think so. Because they have enough to think about… Out of panic or because they trust their parents, you don’t really know. (Physician 2)

Parent’s decision authority and burden

According to the HCPs, parents typically made decisions about enrolment on behalf of their children, especially concerning medical studies. Some HCPs meant that this was often the case, independent of the child’s age:

I can say, yes, in most cases, the parents simply decide. Regardless of how old the child is. (Physician 2)

The informants further stated that parents’ behaviours and attitudes impacted the children’s opportunities to participate in the decision-making process. For example, whereas some parents involved their children, others limited their participation by dominating conversations. It could be that they wanted to protect the child from difficult topics or that they assumed decision authority:

Parents handle these situations very differently. Some are keen to include their child and ask what they think and try to explain things to the child, whereas others just decide on their own. (Physician 5)

In such cases, the HCPs saw it as their responsibility to balance the child’s and parents’ roles in decision-making, for example by addressing the child directly in the discussions.

It was further recognized by the informants that many parents experienced burdens and fears associated with the decision-making: fears of doing wrong and causing harm to their child. The HCPs felt that parents sometimes consented mostly out of a fear of negative consequences of declining, a form of decisional regret of not having done all they could to save their child.

Disagreements

Most interviewed HCPs had experienced challenges related to disagreements concerning study enrolment, either between the parents or between parent(s) and the child. Disagreements were more common in cases of children being invited to early phase I and middle phase II trials. Causes of disagreements mentioned were that the parents wanted their child to try further experimental treatments, whereas the child wished to abstain, or parent altruism, i.e., that the parents wanted to benefit future children through their child’s participation, despite potential side-effects:

At the end of life, with dying children, opinions vary more… Then the parents often think that yes, if this can help someone else, then we should do it. The altruistic view. But for their child, they cannot expect anything but side-effects. (Physician 6)

HCPs underscored the importance of agreement between children and parents. They stated that children should not have to participate in research against their will, and were of the view that the main objective should be the child’s best and thus, research should be subordinated to care. In instances of disagreement, HCPs thought that it was better not to enrol the child in research. Being responsive to a child’s unwillingness throughout the research experience, including subtle signs, was regarded as important:

I think we should be attentive, because there are situations when the parents want to, but the child doesn’t. Because the child doesn’t have the strength or has had enough [of research]. (Nurse 5)

Ensuring ethical competence

HCPs were also asked to share their perceptions of ethical competence in the context of recruitment. Unmet needs in relation to ethical support and collegial ethical dialogue were also explored. This category consists of two subcategories: Perceptions of ethical competence and Building competence in research ethics.

Perceptions of ethical competence

Ethical competence was described as consisting of clinical competence, scientific competence, formal ethical knowledge and ethical experience from the clinical context. Other competencies mentioned were a basic understanding of children’s cognitive development and psychological knowledge. Many HCPs relied on personal attributes, especially empathy, responsiveness and communicative skills:

The most important thing is to be responsive and try to assess how much and what kind of information this particular family needs in this particular situation (Physician 5)

We often talk about informing and I think that’s a strange word. I think the greatest competence is to listen…How were my suggestions received by this family? Have they understood? (Physician 2)

Calmness, honesty, sensitivity and self-reflexivity were also mentioned as important values and character traits. Further, the HCPs described collaboration as important, such as including both a nurse and a physician in the informed consent conversations, to ensure that no information is accidently left out. Time constraints were acknowledged as an obstacle to ethical conduct in recruitment, which is why having sufficient time was regarded as important.

Building competence in research ethics

Overall, HCPs felt ethically competent and confident to recruit children with cancer for studies. They did, however, highlight the importance of not becoming self-satisfied. It was acknowledged that recruitment of children with cancer for research is an ethically demanding task that requires continuous ethical reflection, dialogue and competence building.

The informants described that they had opportunities and forums to engage in collegial ethical reflection, both in formal ethical rounds and in informal discussions. The ethical climate was perceived as generally open. However, the ethical discussions mostly concerned care issues, especially acute clinical decisions, and not so often research ethics questions. As medical development is contingent on clinical research, there was a perceived need to strengthen research ethics competence, both on the personal and on the organizational level:

Research ethics issues are not really emphasized. We have to talk about them more. Our entire treatment success depends on these kinds of studies… They are so important to us, and we can make parents agree to almost anything. And that’s problematic. (Physician 2)

Further, HCPs perceived a need to develop competence in relation to ethical questions raised by specific types of studies, such as genetic studies and phase I drug trials.