Currently over 50% of drugs prescribed to children have not been properly evaluated for safety and efficacy in their age group. One key reason why children have been excluded from clinical trials is that they are not considered capable of understanding research information. This means that they are not considered able to exercise meaningful autonomy over the decision on trial participation. By Dutch law, competence to consent in children is presumed to be present at the age of 12 and above. In pediatric clinical practice, though, children’s competence is not that clearly presented. Children may express an increasing degree of competence over time as their abilities are developing, so there is a gradual transition from assent to the more active consent.
If we knew which children were competent to consent and which were not, it would be possible to involve them in the decision-making process about clinical trial participation in a conforming way. Non-competent children would no longer have to be burdened by the full informed-consent procedure, while competent children would be more actively engaged in that procedure, with extra weight given to their opinions. This would facilitate the implementation of clinical trials in children and adolescents and still protect the vulnerable subjects.
Previous studies show that children’s competence has never been systematically examined in a standardized manner . The aim of this study is to develop a standardized competence assessment tool for children and to investigate the correlation between competence and age, IQ and patient characteristics. Once an objective tool for competence assessment becomes available, it can be implemented in inclusion stages of clinical trials in children.
This prospective observational study seeks to examine whether children’s competence to consent to research can be assessed in a reliable and valid way by means of a clinical tool.
Nature of competence
Individuals are competent if they are able to make decisions based on understanding and on rational reasons . Competent decisions represent informed, free, self-determined choices and should be respected. This applies to informed consent as well as to informed refusal. Competence is task- and context-specific, which means that assessment of competence should be regarded as a specific judgment at a specific moment of the ability of the patient to fulfill the concrete task that he is facing . Legal competence in health care requires being able to communicate a choice, understanding information one is given, appreciation of one’s circumstances and mental capacities to reason and deliberate [3, 4].
In current pediatric practice, parents and children undergo an informed consent procedure. According to the Dutch Medical Treatment Contracts Act (WGBO), which applies to treatment situations, parents decide for their children younger than 12 years of age, who are considered by definition incompetent to act for themselves. For these children, no actual assessment of competence is necessary. For children aged 12 to 15, informed consent is required both from children and parents, provided the children are judged competent to decide. From 16 years of age, children are deemed adult in medical decision making. In the Dutch Medical Research Involving Human Subjects Act (Wet Medisch-wetenschappelijk Onderzoek met Mensen, WMO), the same arrangements apply but age limits are set at 12 and 18 years of age. Children are deemed competent if they appear to understand information designed for their level of comprehension to an extent appropriate to the nature and scope of the decision. Internationally, the statutory age limits differ for clinical research: the lower age limit varies form 7 to 15, the upper age limit is set at 17 or 18 years .
In the Netherlands, the Doek Committee was installed to advise the State Secretary of Health, Well-being and Sports and the Minister of Justice  on the desirability of adapting the current regulations for medical scientific research with minors that does not benefit them directly. They concluded that the protection criteria in the Medical Research Involving Human Subjects Act give children little room to make decisions based on their own ideas and values. Children under 12 who wish to refuse participation in clinical research can formally only make that known through resistance. Children older than 12 may withhold permission, but if they do decide to participate, that can formally be nullified by their parents’ refusal. This conflicts with the prevailing view that children have the right to make decisions consistent with their value systems and life view. Children may be seen as moral agents, possessing autonomy . The Doek Committee  therefore recommends that the will (the assent or refusal) of a younger child be taken into account to the degree that the child can understand the issues. The Task-force in Europe for Drug Development for the Young  issued recommendations to be implemented Europe-wide, stating, amongst other things, that minors should be involved in the informed-consent process in proportion to age and degree of maturity . By assessing competence to consent in children and adolescents more objectively than is now the case, greater justice could be done to the ideal of respect for the developing autonomy of children in decision making, in accordance with national and international recommendations.
Competence assessment in current pediatric practice
At present, clinical investigators are able to make only intuitive assessments of children’s competence, because no standardized method is available to test it more objectively. Conceivably, the age standards prescribed by law may have too much influence on that intuitive decision by the assessor. Research evidence indicates that children under 12 may also be capable of making well-considered decisions [9, 10] and that children as young as 9 can understand the issues involved in clinical trials . This suggests a mismatch between children’s developmental level of decision-making maturity and the age limits set by legislation. The assessment of competence is subject to two pitfalls: complex research decisions may be imposed on children who are unable to make them, while capable children who want to take part may be inadvertently excluded . It is recognized that age is, at best, a proxy for developmental capacity, and that experience, maturity and psychological state are key determining factors. This means that children’s competency to make important decisions ought to be assessed more individually than is presently the case.
A recent study has shown that doctors and researchers tend to judge a child as competent if the child’s decision conforms to their own ideas of the child’s best interest [11, 12]. That means that competence is gauged by the content of the decision rather than by the process of reasoning in deciding about participation. It is therefore vital for clinical researchers to get access to a standardized, objective method to aid them in the informed-consent procedure, and thus improve the rigor of their judgment of children’s competence to consent.
Assessment of competence by MacCAT-CR
Until recently, literature on children’s competence assessment was limited. Two reviews [1, 10] summarize the empirical literature on children’s competence to consent in research and treatment settings. A variety of different definitions and measures emerge from studies on children’s competence. Two quantitative instruments, namely the Competency Questionnaire – Child Psychiatric (CQ-ChP)  and the Hopkins Competency test (HCAT) , were examined, and some other authors (e.g. ) used semi-structured interviews. Only Weithorn’s interview  examined all four sub-domains of competence (see below).
Empirical studies on adults have resulted in a variety of operational translations of the concept of competence into assessment instruments. Dunn  assessed 23 existing instruments in terms of format, content, features of administration and psychometric properties and concluded that the MacArthur Competence Assessment Tools for Clinical Research (MacCAT-CR) and for Treatment (MacCAT-T) receive the most empirical support. These instruments have been tested in particular in samples of people with dementia, mental disabilities, schizophrenia and other psychiatric disorders. There are initial indications of validity  and a high degree of reliability .
The MacCAT-CR is a semi-structured interview format that helps clinical investigators to assess research candidates’ competence to give informed consent to participation in trials. It measures the four aspects of decision-making capability that reflect the standards for competence to consent in most jurisdictions: (1) understanding the disclosed information about the nature of the research and its procedures; (2) reasoning in the process of deciding about participation, with a focus on abilities to compare alternatives in the light of their consequences; (3) appreciation of the effects of research participation (or failure to participate) on their own situation; and (4) expressing a choice about participation . Whilst an assessment of these abilities is essential, supplemental information may be needed about a candidate’s diagnoses, mental status and medical and social circumstances .
The MacCAT-CR provides a format for disclosing selected information on the research project at hand. A standard set of questions then assesses candidates’ abilities to understand the information, reason about it, appreciate its consequences and express a choice. The interview samples their abilities using representative content, rather than testing them on the full content of a typical informed-consent disclosure. The MacCAT-CR is based on the structure of the MacArthur Competence Assessment Tool for Treatment . In the MacCAT-CR, the number and focus of questions in each section have been altered to suit a research context. Unlike the MacCAT-T, the MacCAT-CR questionnaire does not have to be individualized for each candidate. This facilitates both the research and the routine use of the interview.
The MacCAT-CR involves two steps: the interview itself (approximately 15, maximal 20 minutes) and the rating. The rating criteria provide a way for the assessing clinician to note opinions on the adequacy or inadequacy of each item response. The MacCAT-CR provides a summary rating for each of the four capacities assessed: 0 to 6 for understanding, 0 to 4 for appreciation, 0 to 8 for reasoning and 0 to 2 for expressing a choice . A serious deficit in any of these abilities may translate to a clinical opinion of incompetence. The scale does not provide ‘cut-off scores’ that represent competence or incompetence, nor is there an overall MacCAT-CR total score . The ratings provide the assessing clinician with a structured overview of the capacities needed for competent decision making.
In 2008, a Dutch translation of the MacCAT-T was made available by van Eyk . Comments on the use of the MacCAT-T in the Dutch clinical setting were positive: it was judged as practicable and a valuable addition to current competence assessment practice . Before administration, information on the content of the treatment needs to be thoroughly considered by the treating physician, which was viewed as a major advantage. The MacCAT-T aided the physician to structure the information required for the decision making of the individual patient .
In children, research on the MacCAT scales has been limited to two small studies. Koelch  used an adapted MacCAT-CR to study the decision-making process in 19 children aged 7 to 15 with psychiatric diagnoses; Tan  used the MacCAT-T to study thinking processes in 10 adolescents aged 13 to 21 with anorexia nervosa. Both studies confirmed the feasibility of using the MacCAT scales for children, but neither tested their validity and reliability More rigorous research is needed on the applicability of the MacCAT instruments for children.
Child-specific factors in competence judgment
1.Developmental aspects of competence
In children, decision-making abilities develop over time, as their cognitive, social and emotional abilities advance. Elementary school children develop the capacity for logical, systematic thinking using multiple pieces of information and the ability to perceive underlying reality despite superficial appearance. Cognitive advances, social relationships and emotional development work together to promote moral development in middle childhood and children become increasingly able to consider other people’s feelings . But still, they face cognitive limitations: they lack the broad base of knowledge that adults possess. They still sometimes have trouble combining their cognitive skills into a larger problem-solving system. They cannot reason maturely about abstract and hypothetical problems . In adolescence, the brain undergoes substantial change with an increase in efficiency of brain functioning. New cognitive skills such as hypothetico-deductive reasoning – the ability to think of hypothetical solutions and to formulate a systematic plan for deducing which of these solutions is correct – are acquired . Social cognitive changes lead to increased maturity in reasoning about moral issues , giving space to altruism. Even with these advances, compared to adults certain cognitive limitations remain, mostly involving inconsistent application of recently acquired cognitive abilities .
The ability to balance risks and benefits depends on life experience as well as cognitive abilities. Children’s personal experiences of illness and their responses to it can provide them with greater insight and understanding than children of comparable age who lack this experience . Over time, therapeutic relationships with children evolve and children grow and develop, and their response to the experience of illness alters. Competence assessment should respond to those changing circumstances.
2.Provision of information
Competence can be enhanced by improvement of information provision. Children and adolescents do not have the same comprehension level as adults. Their abilities to read and write and their working memory have not reached optimal growth yet. This implies that the information supply to children should be tailored to their developmental stage. Techniques for communication include both verbal and non-verbal forms of information supply, and breaking up the information into smaller pieces . Information for children needs to be clearly worded, using simple language, and must connect to the perception of the child. Innovative techniques can contribute to conveying information . Children sometimes need more time .
It has been found in current practice that communication with parents and children is often flawed [27–29] and even that children are incompletely informed . As knowledge is a basic requirement for valid consent , assessment of competence needs to attend to the information process. Competence assessment taking the real-life situation as a starting point, containing the necessary information appropriate to the child’s level of development, provides the best basis.
Growing-up children are, to a greater extent than adults, dependent on other people that surround them, especially their carers or parents. An exploration of the systemic influences is indispensable. Children may be particularly susceptible to the influence of parents and health-care professionals due to their need for approval or fear of negative consequences from authority figures [1, 31]. Tates [32, 33] states that the communication pattern in medical meetings is dominated by adults, and that physicians’ communication is parent-related. This illustrates the dependence of children on their parents and physicians for the information supply and level of involvement. Peer relations play an important role in development in middle childhood and adolescence. In interaction with friends, school-age children adhere very closely to peer group norms. In early adolescence, peer influence increases, and then declines . Assessment of competence needs to pay attention to the influences of important others on the child’s decision-making process.
Modifications in MacCAT-CR for Children and Adolescents
The original MacCAT-CR by Appelbaum and Grisso  was translated into Dutch by a certified professional translator. In the next step the language was adapted to a simple level to be understood by children of elementary school age. We followed the guidelines of BureauTaal  to adjust the text to groups with low language skills. An expert on Dutch language and communication, who is also a teacher at the University of Primary Teachers, reviewed the text. Three child psychiatrists and three pediatricians carried out a final review of the text. In our study, the delivery of the interview has been customized to reflect the details of the particular trial in which candidates are asked to participate.
Ditters  says in his research that in Dutch clinical practice some wordings of the MacCAT-T interview and scoring manual are not familiar. Some of his interviewers showed difficulties understanding the conceptual framework, and they were uncertain as to when to probe for the right answer. We tackled this problem by applying simple language for the interviewers’ instructions and scoring manual as well. We added directions on when and how to probe, providing sample sentences. We aim to make the instrument available to different disciplines. Similarly, the patient information form and the informed-consent form for subjects in this study have been adapted to simple understandable language.
Additional to the worded information, Apppelbaum  recommends that subjects be given a card containing the disclosed information for each section and asked to read along as the disclosure is read to them. In children, reading performance, if present, might not have reached adult level. Equally, children might have problems dividing their attention between a written text and a spoken text. We thought it appropriate not to use text cards, and to provide cards with pictures disclosing information about medical procedures unfamiliar to the patient (e.g. an electroencephalogram) instead of written information.
The Dutch version of the modified MacCAT-CR for Children and Adolescents was translated back into English by another certified professional translator. One of the original authors of the MacCAT-CR, Appelbaum, provided comments on this version, which were processed. A special remark needs to be made on a modification to questioning the child’s understanding of the consequences of participating in the trial or not. We added the questions: “What do you think your parents will think about it if you take part or don’t take part? And what do you think your friends will think?” Scoring the answers, we note whether the child can mention consequences for daily life or social relations. With this approach we give more attention to the influence of social relationships than in the adult version of MacCAT-CR.