Abstract
One of the more frequently debated questions about the ethics of research with children is that of informed consent. This raises a twofold problem: the legally valid consent given by the person or persons exercising parental authority, and the consent of the minor when he or she has adequate decision-making capacity. Another ethically important issue is the weighing of risks and benefits. Any assessment of the benefits will embrace the controversial problem of balancing the direct benefits to the individual and the social benefits to other children in similar medical circumstances deriving from increased knowledge. The highly significant questions of risk and of the advancement of knowledge are often – perhaps too emphatically – taken together with that of consent, as though the existence of legally valid consent and, where possible, the assent of the minor were sufficient to justify exposing a child to serious or probable risks.
Introduction
There is a substantial body of specialist literature covering many of the numerous ethical issues posed by paediatric research. 1 The debate on paediatric trials focuses largely on the issue of informed consent, with the risk of obscuring another crucial problem: the ratio between risk and benefit. The ethical issues involved in the treatment of persons unable to give valid consent can be traced to two key questions: “Who decides?” and “What to decide?” The first is a question of procedure, the second of substance.
The procedural element
Much of the literature on the subject of ethics in child health care (both ordinary clinical treatment and research trials) concurs that, where minors are concerned, consent to participation in research must comprise both the permission of the person or persons acting in loco parentis and the assent of the minor if he or she is able adequately to grasp the situation and to express his or her wishes with sufficient awareness. The relative weights of permission and assent will vary according to the circumstances. For example, several authors hold that, in the event of disagreement in cases of research using biological samples, the opinion of the minor should prevail over the permission of the parents or their representatives. 2 In other circumstances, such as emergency interventions or therapy to protect or restore a child's health, the situation is different and it may be not only legitimate but obligatory to override the child's wishes. 3 The consent of minors thus poses complex problems, as can be seen by the considerable disagreement in the literature over the definition of “assent of a minor”. 4 There are also procedural difficulties, such as the fact that in order to decide whether or not a minor's wishes should be taken into consideration his or her ability to comprehend the situation and to express a conscious opinion should first be ascertained. Validated tests and scales are indeed available to assess such factors, but the significant subjective elements involved seriously complicate any attempts at quantification.
When evaluating research protocols for children, ethical committees often attribute crucial importance to informed consent (comprising, where possible, both permission and assent). Without diminishing the importance of informed consent, one could ask whether, where adequate safeguards are in place, it should take precedence over other irrevocable requisites. In other words: while the procedural aspect may be crucial in the case of some categories of so-called “vulnerable” populations unable to express consent, in the case of minors the question of substance is probably of greater significance.
The element of substance
The element of substance can be divided into two key factors: the avoidance of harm (which also includes an appropriate risk/benefit ratio) and the priority of the direct benefit to the individual over the benefit for future subjects deriving from the advancement of knowledge.
In the field of research involving minors the notion of “avoidance of harm” offers a more solid basis than the concept of “best interests”. The “best interests” approach generally “promotes an effort to be more objective, weighing the potential benefits and burdens for a particular child”. 5 In the case of clinical research, however, it is too generic, as it lends itself to ambiguous interpretations. The concept of “avoidance of harm” in turn recalls that of “minimal risk”, which has also been variously defined. In the Code of Federal Regulations, minimal risk “means that the probability and magnitude of harm or discomfort anticipated in the research are not greater in and of themselves than those ordinarily encountered in daily life or during the performance of routine physical or psychological examinations or tests”. 6 But this definition also lends itself to ambiguous interpretations. The risks we face in our daily lives in fact vary widely in their probability and seriousness. The risk of being involved in a road accident, for example, varies according to a person's age (being highest for adolescents) and both its entity and its probability may be unacceptable in a situation of clinical research. The concept of “avoidance of harm” also embraces the notion of “risk optimisation” typically used in the context of radiation protection, which means keeping risk “as low as (is) reasonably achievable” while not neglecting the risk/benefit ratio.
The question of the relationship between individual benefit and the advancement of knowledge for the benefit of future populations is a constant subject of lively debate. According to the “Belmont Report”, “the term ‘research’ designates an activity designed to test an hypothesis, permit conclusions to be drawn, and thereby to develop or contribute to generalizable knowledge”. 7 While all the key documents on the subject recognise this characteristic of research, they agree with the Declaration of Helsinki in specifying that “in medical research involving human subjects, the wellbeing of the individual research subject must take precedence over all other interests”. 8 In this difficult task of balancing individual benefit and collective interests the latter are often accorded greater weight. According to UNESCO:
“Research activities involving children are carried out to learn more about the nature of paediatric development, disease and potential treatments. Though one might hope that it will in some cases be beneficial to the research participant, the activity cannot be said to be specifically designed for this purpose because of the nature of the research question”. 9
It must certainly be acknowledged that for a child to participate in a research project can have a profound social significance and demonstrate considerable altruism. But it must also be acknowledged that each individual, even one with limited social relations, is a part of the human community. Consequently, consent to research is often not just a matter of the permission given by one person to another person, but is rather a matter of assent to do something with other persons. Nonetheless, Kant's 10 categorical imperative “Act in such a way that you treat humanity … as an end and never merely as a means to an end” absolutely cannot be disregarded. And Kant also offers the correct interpretation when he emphasizes not only people's rights and our duty to respect those rights, but also people's duties to one another. The duty to consider each person as an end comprises a responsibility to cooperate with other people, within reasonable limits. In the case in point, the acceptable risk is the measure of those limits.