When incentives are offered to parents and their children to partake in research, there are concerns that parents may be unduly influenced by the incentives, and the children may be exploited. We present a case from a low- and middle-income country and consider the ethical issues that arise when the children are asked to participate in a multinational, double-blind, randomized, placebo-controlled trial of the effects of a nutritional supplement on growth. The first commenter, from Malaysia, notes that their residents might not share Americans’ expectations regarding children’s role in the consent process from a cultural perspective, which may alter the analysis of the concerns. The authors of the second commentary emphasize the use of incentives that benefit the child participant rather than their parent or are provided directly to the child participant to address the concerns. The third commentator discusses the importance of minimizing the study’s risks and balancing the benefits and the risks, which attenuates the concerns.

Effectively recruiting research participants can be challenging in all clinical research. However, longitudinal studies, especially those involving children, compound these challenges because there is a need to follow participants over time while involving both parents and children. When incentives are offered to parents who provide permission for their children to partake in research, a number of questions can be raised. Can parents be unduly influenced by the incentives? Can the incentives result in the exploitation of the children? What is excessive? What forms of incentives are preferable? In this Ethics Round, we present a case from a developing country, and commentators consider how cultural and economic aspects may bear on the ethical issues surrounding incentives in pediatric research conducted in developing countries.

You are the primary investigator of an industry-funded, multinational, double-blind, randomized, placebo-controlled trial of the effects of a dietary supplement on prepubertal children. The participants are healthy boys and girls between 7 and 12 years old from 9 public schools in an urban poor population of Malaysia, Thailand, and Indonesia. They are provided supplements in sachets to make a drink. All sachets are produced by the study sponsors in identical packaging. The placebo sachets do not contain any supplements but are equal in appearance and taste to the treatment sachets. Participants consume the products twice a day for 1 year, and outcomes are measured at baseline, 6 months, and 12 months. Outcome measures require venipuncture on each visit. Parents or legal guardians provide written informed consent, and the participants provide assent.

Because the validity and reliability of the study depend on a high adherence rate to the intervention, parents or legal guardians are also asked to record the participant’s consumption in a diary. Nonmonetary incentives, such as school fees, textbooks, school supplies, and sports equipment, are given throughout the year to participants who achieve a high adherence rate. As the study proceeds, more and more parents volunteer for their children to participate in the study. In discussing the study with them, it becomes apparent to you that many parents are motivated mainly by the incentives. You wonder whether the children might be exploited and what you should do.

The involvement of children in research in developing countries is important and necessary for several reasons. Children make up a significant proportion of the population in the developing world, but they are often underrepresented in areas of research. It is not only scientifically problematic to conduct research with adults and extrapolate the findings to children because of their physiologic differences, but it is also morally problematic to permit children to be harmed by treatments inadequately studied in them. A more equitable inclusion of children in research will also strengthen the generalizability of studies and obtain sufficient information to be able to prescribe therapies safely. The vignette presented raises 2 related ethical considerations: firstly, is the relationship between limited assent in pediatric research and parental exploitation, and secondly, determining when an incentive becomes an undue influence on the parents.

The question of exploitation and assent needs to be considered within the social context of the community. The dynamics of Malaysian society rely on a rich, but conservative, culture with an underlying rigid social hierarchy. Similar to many low- and middle-income countries, the age-old saying “children should be seen and not heard” applies.1  Children’s rights and interests are viewed as inseparable from their parents’. Customarily, parents play an important role in constructing their children’s decisions by subtly reframing issues. In the research setting, seeking a child’s affirmative assent as an independent activity may be culturally inappropriate and even insulting, especially if parents have already given their permission.2  A child’s dissent may result in guilt, resentment, and interfamilial conflict.

Ethical standards for research do permit some forms of cultural accommodation. Regulations in the United States, for example, permit the requirement for written documentation of informed consent to be waived in cultural groups in which this would be inappropriate. Although there is a consensus that assent should be sought in international contexts,3  the process of seeking assent should, however, be modified to different cultural contexts. For example, whether children’s assent or parent’s permission is sought first may depend on cultural norms. In Malaysia, the family may take priority over an individual’s autonomy; hence, family-facilitated and collective decision-making is a consequence of this social structure. Decision-making is conceived to be a collective process rather than an individualistic one. In this cultural context, an assent process that prioritizes the parental role should not be considered exploitative of children because such a decision is considered to be appropriate for parents to make.

The second concern is that incentives that might otherwise appear appropriate might be an undue influence on those of lower socioeconomic status. For example, inordinate incentives might promote misrepresenting their degree of adherence in their diaries in this case. These might have unintended consequences on the research. Ideally, we want research participants to be motivated by altruism, by which they would share and be motivated by the goals of the researchers. In reality, parents volunteer their children in research for many other concurrent reasons. These include perceived health benefits, inducements, such as free medical care or free medications, and compensation payments. This is morally permissible. As Ross4  analogized, if some parents are willing to expose their children to take some risks to instill values by volunteering in community services, why should they not be allowed to enroll their children in a research study for their child to both serve science and earn incentives? We also agree that the nonfinancial incentives used in this case were more appropriate. The incentives were not just essential to motivate the child–parent unit to encourage adherence, which was itself vital to the whole scientific study, but such incentives contribute to a positive impact on child health, especially in the underprivileged. The ultimate benefits of books and school supplies, for instance, are to help motivate, inspire, and support learners.

In addition, regardless of the amount of an incentive, the determination of whether the incentive is an undue influence also depends on the risks of participation. The key question is whether this research study involving children is appropriately designed. Are the risks minimal, or at least minimized? An incentive should not be considered an undue influence on a parent if the risks are minimal. Ethical review committees or community advisory boards can assess the risks of the study.5  Emanuel6  suggests that inappropriate incentives exist when all of the following 4 criteria are met: an offered good, excessive offer, poor judgment, and risk of serious harm. Even if the first 3 criteria are met, incentives only become unduly influential if it encourages the parent to take a substantial risk that they would not do otherwise. If the study is otherwise minimal risk, inducements do not lead people to assume unreasonable risks.

Involvement of underprivileged children as research subjects in a conservative society remains a challenge needing cultural humility and proper assent practices. Assent is not just a form; it is a dialogue between the researcher and the potential participant. Additional time to address cultural and economic differences can augment research’s professional self-awareness and promote children’s participation in the decision whether to enroll in a trial. This partnership is a process and not an end in itself. The key to these dialogues lies in the practice of actively listening to the feedback of the child–parent unit while embracing the feelings and thoughts of their decision-making process.

In summary, incentives provided should be sensitive to the cultural variations and norms of the people, be it of ethnic minority communities or societies from less socioeconomically privileged countries. There ought to be necessary safeguards against any form of possible influences on parents or exploitation of children when it comes to incentives in research, no matter where we are.

In this case, there is a concern that the parents’ adherence to giving their 7- to 12-year-old children dietary supplements for 1 year is influenced by the incentives and that the children are being exploited by their parents. Exploitation is a fundamental concern in research and, as defined by Wertheimer, occurs when 1 party takes unfair advantage of a second party.7  The concern of exploitation in research becomes more exaggerated when the second party receives little benefit or may even be worse off. This is a central concern regarding research in the developing world, especially when that research is sponsored by entities in more developed countries. In this study, involving a placebo randomized trial of a dietary supplement, the chance that the children will be worse off because of participation seems remote. This attenuates the concern for exploitation. However, if the benefit to the parents was so substantial, the transaction could still be exploitative, especially if the children were asked to do a lot. In this case, the benefits to the parents are related to the children, including school fees, textbooks, school supplies, and sports equipment. Thus, the children may also be benefiting from the incentives. This too attenuates the concern about exploitation (that parents are taking unfair advantage of their children). We could speculate that the study team was intentional in proposing incentives that were focused on the children, rather than an incentive that would be more appealing to an adult participant or the parent, such as cash.

The observation that the incentive was effective in promoting adherence is not prima facia evidence of exploitation of the children by the parents. In addition, the incentive seems reasonably generous. We would be more concerned about exploitation if the incentive was less and it was still effective in increasing adherence. In other words, the best way to address the concern about unfair advantage is to ensure that participants are receiving fair benefits.

Often intuitive concerns about problematic research are framed in familiar terms, such as exploitation, as in this case. Although we do not think the design of this study creates conditions of exploitation, we are sympathetic to the concern that “something is not right”. Perhaps the concern is about the incentives to the parents. Will the incentives cause parents to make poor decisions that harm their children? Are we treating the children with adequate respect?

When considering research incentives for children, Wendler et al suggest 11 safeguards to minimize the likelihood that the payment will distort the parents’ or the child’s decision-making.8  Relevant to this case are the notions that payment should be directed to the person who bears the burden and that, to minimize parents’ access to the child’s payment, “gift certificates redeemable at children’s stores or the choice of an age-appropriate gift, such as a book, video, or movie pass, could be offered in lieu of money.”9  With this study, the child bears most of the burden of participation (ie, consuming the supplements twice daily), whereas the parent(s) also assumes some burden (ie, recording consumption in a diary). Therefore, it is sensible for the incentive to provide value to both the child and parent(s), with the child taking precedence as the primary partner in the research. In addition, as Wendler et al suggest, the incentive should be something that minimizes the parents’ access or, in this case, something that minimally influences the likelihood that the parents would disregard the child’s decision.

Providing some of the incentives to the children directly allows the researchers to more actively engage with the children and treat them as equal partners in the research. It can also have instrumental value for the children to feel more connected and more positive about research, which can be a valuable civic lesson to prepare them for adult responsibilities. The notion of treating children respectfully, as children, is inspired by the writing of Bill Bartholome, who advocated for the concept of assent in the 1980s and 1990s as a way to treat children with respect.9,10  Bartholome’s view of assent was motivated by a concern that adults often disregarded children’s wishes and interests and often took advantage of their explicit power over children to make them do what others want. Bartholome was committed to treating children respectfully, with caring, kindness, and concern for their preferences and interests.

So, although the approach to incentive, in this case, does not meet the definition of exploitation laid out by Wertheimer, we think that providing some incentives that are aligned with the children’s values (as well as the parents because they are responsible for ensuring adherence) is more respectful of them as both children and partners in the research.

In research with adults, payment or incentives are offered to the person who will undergo the risks of research: the participant. In pediatric studies, by contrast, incentives are sometimes offered to the parent or guardian, someone who will not undergo the risks of research, rather than the child. This raises the possibility that parents might be motivated by incentives to accept risks that their children, not themselves, must undergo.

Is this ethically problematic? Imagine that the parents in our case are motivated solely by the incentives. In addition, let us also imagine that the incentive is ethically acceptable for international research in low- or middle-income countries and that the parents do not have their judgment clouded by the incentives offered, a common concern.11,12  Rather, let us imagine that the parents make a clear-headed calculation that the incentive by itself makes enrolling their child worth it, without considering the risks of the study for their child. I venture that many people would consider this a moral failing. A good parent would take much more than incentives into account, if they take them into account at all, when deciding whether their child should enroll.

There are 2 levels at which we can assess the ethics of this case. The first asks whether it would be acceptable for a research ethics board to approve the offer of incentives, knowing that some parents may be motivated by them. I share the sense that parents motivated solely by incentives exhibit a moral failing but worry about affording it weight in the context of ethics review. Human motivation is complex, often opaque, and difficult to predict. From the perspective of ethics review bodies, the acceptability of research participation for children, and of offering payment to parents, should not depend on the ability to predict the motives of parents or anyone else.

It is far more important that the research meets reasonable and accessible ethical standards, including the opportunity for children to provide assent, risk minimization, and a requirement that the study provide a prospect of direct benefit for the children or that the risks to them be minimal or close to minimal.13  If a study meets these and other reasonable criteria, the study can be acceptable to perform apart from considerations of incentives, in which case offering reasonable incentives does not seem inherently troubling.14 

This is not to say that parental motives are irrelevant. The second level of ethical analysis asks how an investigator should approach the enrollment of children when there is reason to believe that parents are motivated by incentives. Informed consent, the chance for individuals to decide whether the research coheres with their own interests, is critical. It is primarily the role of the investigator to ensure a robust informed consent process and to be attentive to situational factors that make participation unadvisable for certain people. For example, if the investigator in our case knows that a particular child has small or hard-to-find veins and that, as a result, the child is traumatized at the prospect of blood draws, the investigator may conclude that this child is not a good candidate for inclusion in the study (because it requires venipuncture), even if eligible and their parents want them to participate.

In pediatric research, when investigators have reason to believe that parental motives are dubious or self-serving, many of us may feel that researchers should pay closer attention to the child’s perspective and willingness to assent and less attention to their parents. This, however, embodies a substantive ethical viewpoint that may not be shared across cultures, namely, that individual autonomy and decision-making should be honored, to the extent possible, in children. Cultures and value systems that place less emphasis on individual autonomy or child decision-making might privilege the interests of the parents, the wider family, or the community over the interests of the child, or find it hard to distinguish sharply between them.

This case thus encourages us to consider our commitment to pediatric assent as a condition of ethical research, in contexts in which it may not be shared. Although working through this is important, we should also resist too quickly assuming an intractable conflict of cultural ideals, which may blind us to possible resolutions. In particular, it is imperative to remember that children themselves are influenced by their cultures and the value systems in which they are embedded. Does the child perceive their parents’ motives as troubling? Do they feel pressured and conflicted? Or are they comfortable deferring to their parents’ wishes for them? If the child has a strong desire to please their parents or sees their own welfare as inextricably tied up with the welfare of their parents, the child may not have the same reaction to their parents’ motives that perhaps we do.

Notably, the ideals of autonomy that undergird the importance afforded to pediatric assent in Western medicine and ethics cut both ways. If the child is deferential to the parents without seeming conflicted, we should generally be willing to accept that as a good indicator that the child perceives participation to be in their own best interests, especially if they are given an opportunity to voice concerns to the contrary.

The role of the investigator sketched here demands high levels of attention and sensitivity to the child’s own perspective and interests. It demands a willingness to engage the child in conversation and make them feel welcome to express any apprehension. This is unlikely to be easy, especially in cultures with less regard for pediatric decision-making. Still, relying on investigators is preferable to restricting incentives, which is too blunt an instrument. Prohibiting the use of appropriate incentives unfairly penalizes parents who act from nonobjectionable motives (which one hopes would be the majority of cases) and elides the fact that most children would not be harmed, and indeed may benefit, from study participation. It would also remove a reliable mechanism for encouraging study enrollment, retention, and adherence, potentially resulting in socially valuable and important research being hindered in contexts in which it is needed most.

The primary investigator reviewed the literature on incentives and exploitation and discussed the investigator’s concerns with the chair of the institutional review board. The investigator was reassured that the study was well-designed, the risks to the child participants were minimal, and the incentives benefited the children. The investigator nonetheless took additional care during the informed consent process to solicit the potential participants’ preferences and support their ability to give or withhold assent.

Special thanks to the late Evelyn Khoo Xiling; she inspired the writing of the case.

Dr Khoo conceptualized and designed the study, drafted the manuscript, and reviewed the manuscript; Mr Duenas and Drs Wilfond, Gelinas, and Matheny Antommaria designed, drafted, and reviewed the manuscript; and all authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.

FUNDING: This publication was supported by the National Center for Advancing Translational Sciences of the National Institutes of Health under Award Number UL1 TR002319. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Funded by the National Institutes of Health (NIH).

CONFLICT OF INTEREST DISCLOSURES: The authors have indicated they have no potential conflicts of interest relevant to this article to disclose.

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