Participant autonomy

A first dimension in the ethical reflection on the return of individual results in genetic research on stored tissue samples is related to the autonomy principle and the right of participants to decide whether they want to receive certain information about their health or not. Authors that stress this autonomy would opt for the second line of thought in our above summary: individual results should be returned if participants do so wish. We believe that the situation in the case of paediatric biobanks enrolling incompetent minors is slightly different, as the persons making this choice are not the participants themselves.

First, we believe the right not to know does not apply to parents with regard to information for early-onset treatable or preventable diseases. In the case of paediatric biobanks, if the biobank has a policy to return such information, with the option of opting out, this option should not be made available if the consent form is filled out by the parents of under-age participants. We agree that competent adults have the right not to know their genetic status, even if this can save their own lives. In this respect we follow the paper by Andorno25 that this right not to know is based on autonomy and on people’s interest in not being psychologically harmed by the results of genetic tests or genetic research. Our situation of parents deciding for their children is somewhat different, in the sense that the decision is made for a third person. The autonomy in question is thus that of the parent and not of the child, and is always limited by considerations about the best interest of the child. It is not unthinkable that some parents might opt out of receiving such information as a result of magical thinking (‘ignorance is bliss’). Although there are many areas in which parental decisions should not be questioned, this is one area in which others can take the decision to return information, even against the parents’ wishes. Take the example of familial adenomatous polyposis (FAP). Early detection of mutations in the APC gene can lead to screening for colonic and extracolonic tumours and can be potentially lifesaving.26 A parent does not have the right of opting out of receiving such information about his or her child.

Second, based on the principle of respect for participant’s autonomy and the right to know, some biobanks may have the option to provide access to participants to all their individual genetic information if they do so want. However, this should not apply when parents have enrolled their children in the biobank. In the clinical context, literature on genetic screening and testing of minors has amply discussed the negative side-effects of allowing parents access to non-crucial genetic information. On a practical level, knowing that a child carries a certain gene associated with a condition later in life may cause anxiety in a family. Parents may start treating their children as if they already have the condition.27 28 Carrier status may be interpreted as having an effect on their child’s health. On a more theoretical level, children should have a right to an open future,29 to decide on the information they want to know about themselves when they are ready to do so, and be shielded from too much curiosity from their parents’ side. We believe, based on these data, that allowing parents full access to all genetic data of their children, possibly out of respect for parental autonomy, is not in the best interest of the children in question and should be prohibited.

In a research context, the same considerations apply. One guideline on research on human tissue of the UK Medical Research Council30 even explicitly specifies that ‘Tests of known predictive value for adult-onset diseases should not be done for research purposes on individually identifiable samples from children’. Even if anonymous epidemiological research on such diseases may, for practical purposes, in some cases be allowed on paediatric samples such as DNA from blood spot cards, we agree that the same restrictions should apply with regard to return of individual research findings. If postponing the access to such information does not deprive children of possible preventable treatment, it should be delayed until later and left to the choice of the participant when he or she becomes an adult.31 Some may argue that there can be some benefit in knowing early-onset unpreventable or untreatable disorders.31 However, these benefits are not completely transparent, and as we are speaking here of non-sought-for information in a research context, we believe such information should not be communicated.

In the case of research on stored tissue samples and data, a complicating issue is the fact that such tissue samples are often stored for longer periods of time, and that the research can continue after the child has reached the age of competence. At this point, the participant should be allowed to make the same decisions as other ‘adult’ participants. If the biobank gives web access to participants to their genetic data, this should be given to participants when they turn 18 years of age.

Duty of researchers

Up till now, our suggestions focused on the right (not) to know and on participant’s autonomy. However, a difficult question is still untouched: is a ‘no individual results shall be returned’ policy for adults, like that of the UK Biobank still defensible when children are concerned? As we have seen before, the advocates of such a position (our first ‘line of arguments’) refer to the fact that genetic results are inconclusive and can cause anxiety, the therapeutic misconception, the duty to solidarity to participate (and not expect anything back) and the fact that the administrative burden of a policy of returning results would stall important research.

The first argument refers to the fact that genetic results are inconclusive and cause anxiety. However, for well-known early-onset treatable or preventable conditions this argument does not hold. Of course communication of such information may never be only communication of the plain facts, and may thus be outside of the researcher’s competence. We observe that the genetic research children participate in is often of the type of a longitudinal cohort study, which allows for frequent contact with researchers and research nurses. Or children who already have a medical condition are enrolled through their physician or clinical geneticist. Therefore, the infrastructure for good follow-up is already there. Moreover, there is a fundamental difference between adult and paediatric research participants. The latter have limited autonomy and are as such vulnerable. They have not enrolled themselves in the research, and as such it is acknowledged that they are in need of extra protection. In the literature on clinical trials, there is often the requirement that research on children should be for the benefit of children.32 Although we admit that research on paediatric tissue samples is different from clinical trials due to the minimal physical risk involved, we think that the communication of findings of early-onset treatable and preventable diseases can be interpreted as a benefit in this context. In this respect, the ‘therapeutic misconception’ argument is also flawed. We agree that parents and children should be aware that research is not done for their own benefit; we do not believe that this potential misconception is enough reason not to return important health information about vulnerable participants.

This relation between vulnerability and benefit requires some further elaboration. A concept that can be of help here is the ‘duty of care’ of researchers. In this respect, the term ‘ancillary care’ has been framed. Such care is care that is not required to make a study scientifically valid. For example, the following up on a diagnosis found by protocol tests or treating ailments that are unrelated to the study’s aim would be ancillary care.33 34 The return of findings about early-onset treatable or preventable diseases in genetic studies fits this description. This model is based on the fact that the relationship between participant and researcher involves a partial entrustment of the former’s health to the latter. Indeed, participants entrust medical information and samples to researchers, and the informed consent process transfers rights to use these to researchers. In this respect participants are vulnerable to researchers. Richardson and Belsky34 acknowledge a general duty to act compassionately towards the needy, vulnerable and dependent. However, given the research context, this duty is limited to specific aspects of the participant’s health. A researcher is not responsible for all aspects of the health of participants, only those that arise within the study. The strength of the ancillary care duty is moreover influenced by different factors, such as the participants’ vulnerability, the risks and burdens of the study, the depth of the relationship between the researchers and participants and the modes of alternative access. Do participants have other means to obtain the same information?

We think that this ancillary care model is specifically applicable to children in genetic research. First, genetic information is not typically acquired in ordinary health care. Second, many of such research, when done on children, involves a close contact between researchers and under-age participants. Third, children are recognised as a vulnerable population, which would make them especially entitled to ancillary care from researchers. Richardson and Belsky34 link the vulnerability of research participants to the fact that they transfer certain aspects of their health to researchers. With children, this is further complicated by the fact that they often do not make the decision to participate themselves. Indeed, vulnerability in children is linked to their lack of autonomy. As we do not know (with small children) what their choice would be, or as their current choice (as an older child) may not be their ‘definite’ one, children may seem vulnerable in their choices. Indeed, we should prevent them from making choices that are too definite and that would close down other options later on.29 Therefore, the fact that the participants are children would make the ancillary care duty higher in the case of paediatric biobanks.

We think returning results about early-onset treatable and preventable diseases could also satisfy the requirement that research should be somehow beneficial to children. True, such research is potentially beneficial to children in general. However, the fact that these participants are even more vulnerable, because they have a limited autonomy, may suggest that there should also be some limited personal benefit. Such benefit may be interpreted in many ways, but we think the opportunity to be informed of potentially severe conditions suits this purpose better than, for example, a monetary compensation. Indeed, as is argued by Brock,35 children may even have a higher claim to health care than do adults. This is again linked to their vulnerability, which also consists of the fact that they do not understand their own need, and cannot provide for their own health care, unlike consenting adult participants. Therefore, he argues, access to health care is not enough, we must make sure children actually receive it.35 Although it is true that paediatric biobanks are not diagnostic tools, we believe these reflections do enhance the ancillary care duty of researchers to provide information about early-onset treatable and preventable diseases, if they accidentally stumble upon it.

The third argument, that of solidarity is also problematical. The principle of solidarity has been used by some authors to suggest that participants should participate in biobank research without expecting anything back.36 37 However, the principle of solidarity cannot be applied without restrictions to children.37 Children are exempt from certain duties such as paying taxes and having a job, although other civilised behaviour is expected from them. At least researchers have the right to appeal to children to participate in biobank research. This does not automatically entail that children need to participate without expecting any benefit back, especially if this in the form of found information about preventable or treatable disorders. Moreover, solidarity has an additional meaning, referring to the idea that the weakest and most vulnerable in society should be protected and some of their burdens should be carried by others. Although it is true that biobank research is not so invasive or burdensome that children should be exempted from being solidary in this respect altogether, they may be compensated by at least providing them with information.

The fourth argument may make the most sense. In some context, such as (anonymous) epidemiology on blood spot cards it may be unfeasible to provide individual results because the infrastructure is not there. We agree with Affleck,14 that in the context of pure economics, a policy of not returning results may be allowed. We might extend this argument even for paediatric biobanks, especially if the burden for the children is very low and the contact between researchers and children is minimal, as is sometimes the case for research on older, archived collections. Related to this, the duty to return individual results is higher if a GP or a clinician who is in frequent contact with the patient is involved in the recruitment of the samples than if the recruitment is done by a researcher or a research nurse and there is no further contact with donors afterwards. However, deciding not to return individual results may never be just an easy way out: if the subjects are incompetent minors, the issue of returning individual results may require even more consideration for incompetent minors than when adults are concerned, because the former are vulnerable research subjects with limited autonomy. This is especially the case in contexts in which there is a frequent contact between minors and the research institute.