Health-related research involving children is essential for advancing child health and wellbeing.1 Children must be included in the research unless a good scientific reason justifies their exclusion. As children have distinctive physiologies and health needs, they merit special consideration by researchers and research ethics committees. However, their distinctive physiologies and emotional development may also place children at increased risk of harm when conducting research. Moreover, without appropriate support, they may not be able to protect their own interests because of their evolving capacity. Specific protections to safeguard children’s rights and welfare in research are therefore necessary.2
Current ethical principles for conducting research involving children have evolved from the Nuremberg Code,3 which emerged after the Second World War, and notably included a bar on research involving children. Research has been seen as a potential harm from which vulnerable people should be protected. Later, in 1964, the Declaration of Helsinki4 advised that research involving minors could be carried out where the research is necessary to promote the health of the population represented and cannot otherwise be performed on legally competent persons. The US Department of Health, Education, and Welfare issued guidelines that were codified into the Federal Regulations 45 CFR 46 in 1974.5
The US National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research laid down ethical principles and guidelines for the protection of human subjects of research. In their report, ‘Respect for Persons’ is mentioned as the first of three basic ethical principles. Informed consent is described as containing three elements: information, comprehension, and voluntariness. It is noted that information generally includes the following items: the research procedure, its purpose, risks, anticipated benefits, and a statement offering the subject the opportunity to ask questions and withdraw at any time from the research.6 This report had a major impact on subsequent research ethics.
In 1995, the American Academy of Pediatrics (AAP) stated in its application to paediatric practice:
Only patients who have appropriate decisional capacity and legal empowerment can give their informed consent to medical care. In all other situations, parents or other surrogates provide informed permission for diagnosis and treatment of children with the assent of the child whenever appropriate… in most cases, physicians have an ethical (and legal) obligation to obtain parental permission to undertake recommended medical interventions. In many circumstances, physicians should also solicit a patient assent when developmentally appropriate.7
This description includes consideration of children’s developing capacities for participating in decision-making and indicates that a child’s consent consists of parental permission and the child’s own assent.
The World Medical Association (WMA) 52nd General Assembly 2000 amended the Declaration of Helsinki, stating:
When a subject deemed legally incompetent, such as a minor child, is able to give assent to decisions about participation in research, the investigator must obtain that assent in addition to the consent of the legally authorised representative. The potential subject’s dissent should be respected (WMA, 2000).4
From this declaration, the term ‘assent’ might be recognised internationally by health-related research investigators.
Presently, one of the most acceptable definitions is ‘Assent means a child’s affirmative agreement to participate in research. Mere failure to object should not, absent affirmative agreement, be construed as assent’.5 Another similar accepted definition was provided by the WHO:
A variation on consent where a person who does not possess full competence to give informed consent gives affirmative agreement to participate in research. However, it is important to note that assent does not eliminate the need to obtain permission from a parent or other legally authorised decision-maker.8
Concerning the quality of information for children, the Ethics Working Group of the Confederation of European Specialists in Paediatrics mentions that all information, including language and drawings, should conform to the child’s capacity to understand.8 The group states that the content of information that needs to be provided to the children and their guardians should include the following:
- What is going to be done?
- Why is it going to be done?
- What is the intended outcome?
- What are the benefits and risks of the treatment proposed?
- What are the alternatives, including benefits and risks?
- What will happen if nothing is done?
In relation to the capacity of children, the Medical Research Council (MRC) described in their Ethics Guide:
…competence of a child is considered not to depend primarily on age, but rather on the ability to understand and weigh up options. It can be influenced by the way information is presented—many children will be competent if information is presented in an appropriate way and they are supported through the decision-making process.1
In the case of children deemed incompetent to consent to participate in research, if the child is able to give assent, the investigator must obtain that assent in addition to the consent of the legally authorised representative, and if the child does not assent, this should be respected.
The current conception of a child’s assent is included in international ethical guidelines for health-related research involving humans.2 The items to be noted are summarised as follows:
- Children who are legally minors cannot give legally valid informed consent, but they may be able to give assent.
- To give assent means that the child is meaningfully engaged in the research discussion in accordance with his or her capacities.
- Assent must be considered as a process and not merely the absence of dissent.
- The researcher must involve the child in the actual decision-making process and use age-appropriate information.
- It is of major importance to inform the child and obtain assent as described above, preferably in writing for children who are literate.
- The process of obtaining assent must take into account not only the age of children but also their individual circumstances, life experiences, emotional and psychological maturity, intellectual capabilities, and family situation.
- In general, a deliberate objection by a child to participate in research must be respected, even if the parents have given permission, save in exceptional circumstances.
- In this case, the parents’ decision must be overridden if the researcher believes it is not in the child’s best clinical interest to enrol or continue study participation.
- If children reach the legal age of maturity during the research, their consent to continue participation should be obtained.
- Before undertaking research, the researcher and the research ethics committee must ensure that the child’s assent has been obtained in keeping with the child’s capacity, after having been provided with adequate information tailored to the child’s level of maturity.
As mentioned in point 10 above, the adjudication concerning capacity is the responsibility of the researcher and the research ethics committee; thus, they must address the real issues and questions regarding the age at which to seek assent and how to measure the child’s capacity. Previous studies indicate that assent from children as young as seven years for medical interventions may help them become more involved in their medical care and foster moral growth and the development of autonomy in young patients.7,10 However, as mentioned in point six above, researchers must take into account the child’s individual circumstances, intellectual capabilities, and so on.
Cheah and Parker11 note that the concept of assent in the current guidelines is confusing, and there is an urgent need for the development of clearer guidelines that can be adapted for all types of paediatric research. They argue that there is a pressing need for further empirical work and ethical analysis in this important area. Weisleder12 also indicates that, based on a systematic review, the challenge is that empirical data supporting researchers’ use is limited. Oulton et al. argue the following:
The debate about assent needs to move away from terminology, definition and legal issues. It should focus instead on practical ways of supporting researchers to work in partnership with children, thus ensuring a more informed, voluntary, and more robust and longer-lasting commitment to research.13
Some empirical studies related to assent have been conducted. In 2011, O'Lonergan and Forster-Harwood14 reported the results of a study in which they combined visual and audio media to improve the comprehension of the process of assent. The authors suggest that multimedia approaches may improve the overall understanding of research participation for children and parents, and the approach is particularly well-suited for the assent process. Annett et al.15 consider that minors cannot dissent under social pressure, and seeking assent from minors separate from their parents would be a more meaningful exercise. When families were randomly assigned to remain together or separated during a consent/assent process, results showed that the separate procedure improved knowledge of study risks and benefits for older adolescents and their parents. Massetti et al.16 developed a comic book created to facilitate children’s understanding of what constitutes informed assent with clear and simple language. Twenty children between 7 and 12 years of age were enrolled in the study, and most of the participants answered that they perceived the content of the text to be excellent or very good. Researchers concluded that the construction of a simple and clear model of informed assent is possible, and this model should be used in experiments with children.
In Japan, the Ministry of Health, Labour, and Welfare (MHLW) and the Ministry of Education, Culture, Sports, Science and Technology (MEXT)17 have declared the Ethical Guidelines for Medical and Health Research Involving Human Subjects, which indicate the assent-capable age of children, as a reference, as above seven years. However, previous studies that clarified the appropriate age are not available in Japan. Therefore, we aimed to first research and then develop a measure to assess children’s capacity for assent. If our study shows that assent is possible in children under the age of seven, it becomes clear that assent is possible above the age of seven years. In this study, we sought to conduct a study with no invasion or intervention, which is the first of many kinds of studies we intend to carry out in our research on children’s assent.
To develop a measure for assessing children’s capacity for assent, we referenced the MacArthur competence assessment tool for clinical research (MacCAT-CR) 18, a semi-structured interview instrument for assessing decision-making capacity to consent to participation in human subject research. It is composed of four sections: understanding, appreciation, reasoning, and ‘expressing a choice’. Based on a review of instruments, Dunn et al.19 stated that the MacCAT-CR was the best competence assessment tool for adults among the available tools. In a previous study, Hein et al.2 used the MacCAT-CR to assess 6- to 18-year-old children’s competence to consent, and clarified years of age as the factor that explains most of the variance in children’s competence to consent, followed by intelligence. We intended to assess four- to six-year-old children’s capacity to assent using a modified MacCAT-CR to make it applicable to late childhood.
We selected children aged four to six years as the study subjects with reference to the composition of Wechsler Preschool and Primary Scale of Intelligence-Third Edition21 (WPPSI-III), a personalised clinical test that measures the intellectual abilities of infants. The test consists of two parts, two years six months to three years 11 months, and four years zero months to seven years three months, considering the volatility of cognitive development in young children. According to the Japanese version of the WPPSI-III: Technical and Interpretative Manual, dividing the age range by four years is based on empirical evidence and practical needs. Subtest batteries over the age of four include the formation of language concepts, abstract reasoning, and fluidity reasoning. From this, it was speculated that children over the age of four might be able to answer questions for measuring assent capacity. In addition, since children over the age of seven have reached school age, it is estimated that they might have assent capacity under various ethical guidelines. This study focused on developing an instrument to measure the capacities of preschool age children.
The aims of this study were to develop an instrument to assess children’s capacity for assent and to compare the capacity for assent among four- to six-year-olds. We sought assent from the children for a study with no invasion or intervention.