chapter, as elsewhere in the report, when the text mentions requirements for the approval of research, it is referring to research covered by federal regulations because it is federally supported, conducted, or regulated or because an individual institution has extended the regulations to all of its research.
Although the interpretation and application of risk criteria to research protocols are sometimes straightforward, disagreements between investigators and reviewers of proposed research and disagreements among reviewers are not uncommon. The analysis and recommendations presented in this chapter are intended to encourage greater consistency in regulatory interpretation and promote explicit attention to all the criteria for approving research protocols that include children.
It is important to note at the outset that much research—whether having a prospect of benefit or not—cannot be known to be entirely free of risk. If applied to studies without prospect of benefit, a “no risk” standard for approving research would make impossible much research that can advance the health and well-being of children. The risk categories analyzed in this chapter—involving minimal risk or a minor increase over minimal risk—are intended to allow important research to go forward by permitting children who do not have the potential to benefit directly from research to be exposed to only a small risk of harm. Still, a clear tension can exist between the goal of advancing clinical research that may benefit future children and the goal of limiting the risks to individual children who participate in clinical studies. That tension underscores the importance—as discussed further in chapter 5—of a sound process for explaining to parents and, as appropriate, children the purposes of a study, its potential harms and benefits, and the rights of prospective research participants to refuse participation.
Risk is a complex concept that has different meanings in different contexts. Broadly, risk refers to a potential harm or the potential of an action or event to cause harm. Specific risks can be characterized along several dimensions, including the probability of a given harm as well as its likely severity and duration.
A harm is a hurtful or adverse outcome of an action or event. It makes one’s situation worse, temporarily or permanently. Research harms can occur or be evident close in time to the research intervention, but they also may occur or become apparent long after the research has been completed.
Harms resulting from research participation may be physical (e.g., pain, disability, discomfort, or death), psychological (e.g., fear, anxiety, depression, or embarrassment), or social (e.g., peer disapproval, economic loss, or