February 2006

Careful attention must be paid to research that includes children as participants. The Belmont Report includes special provisions regarding respect for persons and providing the opportunity for children to choose to the extent that they are able to participate or not in research. This provision known as assent is an affirmative agreement of the child to participate and follows permission from the parent or legal guardian.

The Belmont Report also describes the issue related to justice and the use of children as research participants. According to the principal of justice, an order of preference in the selection of classes of subjects is advocated in that children should not bear the burdens of research unless absolutely necessary. In essence, the inclusion of children in research should be one where their participation is necessary to answer the scientific question being investigated. Additionally, justice addresses how participants are selected and that selection avoid the injustice that arises from exclusion based on social, racial, sexual, and cultural biases.

In research with children, the Belmont Report addresses the risks associated with participation. The risks must be reasonable in relation to anticipated benefits, if any to participants as well as the importance of the knowledge that may reasonably be expected to result. The explanation given in the FDA E11 guidance document states that research with children should consider the age and development of the participants and the possibility of risk to physical and cognitive growth and development along with possible effects on skeletal, behavioral, cognitive, sexual, and immune maturation and development.

Additional safeguards are required to protect the rights and welfare of children involved in research. These special protections can be found in Subpart D of 45 CFR 46 and 21 CFR 50 and apply to all participants who have not attained the legal age under the applicable law of the jurisdiction in which the research will be conducted. For example, the regulations encourage the protection of children by allowing the conduct of research only if it falls into one of the following three conditions:

• Research presenting "no greater than minimal risk to children".
• Research involving an intervention or procedure presenting more than minimal risk to children that offers the "prospect of direct benefit" or may "contribute to the…well-being" of the child.
• Research involving an intervention or procedure that presents only a "minor increase over minimal risk," yet does not offer any "prospect of direct benefit" or "contributes to the well-being" of the child.

If the Institutional Review Board (IRB) cannot approve the research using one or more of these three categories, it must either not approve the research or refer it to the Secretary of the DHHS and /or the FDA Commissioner.

Although research that includes children as participants requires extra care and precautions, when done correctly it can provide important information to further the understanding, prevention, or alleviation of conditions affecting the health and welfare of children.

*Nelson, R. M.. (2005). Research Involving Children. In E. A. Bankert and R. J. Amdur (Eds.), Institutional Review Board Management and Function (pp. 366-372). Sudbury, MA: Jones and Bartlett.