On the other hand, there is legitimate reluctance to expose children to the risks of clinical research unless there is a reasonable chance that the patients will benefit in a significant way. In fact, the federal regulations governing research on children forbid research that entails more than minimal risk unless the individual patient might benefit. This is in contrast to rules for adults, who may be asked to participate in research of potential scientific importance that will not personally benefit them.

The National Institutes of Health has implemented a formal policy to include children in clinical research where appropriate. Under the new policy, researchers who want to do clinical research on disorders that may affect both adults and children will be asked to describe their plans for including or justifications for excluding children in the research.

An announcement in the January 31, 1997 NIH Guide to Grants and Contracts said, "There is valid concern that treatment modalities developed based on research conducted on adults, without adequate data from children, are being used to treat children for many diseases/disorders..."

"The NIH concluded that when there is a sound scientific rationale for including children in research, investigators should be expected to do so unless there is a strong overriding reason that justifies their exclusion from the studies. Although this is the same scientific rationale that is the basis for the policy requiring the inclusion of women and minorities in clinical research, this policy does not mandate the inclusion of children in all clinical research. Because the issues and sensitivities surrounding children's participation in research are significantly different from those regarding women and minorities, such a mandate would be inappropriate. Nonetheless, even though the inclusion of children is not an absolute requirement, applicants for NIH funding will be expected to address this issue in their proposals."

On March 6, 1998, the National Institutes of Health issued the following policy on inclusion of children in NIH-sponsored research. The goal of this policy is to increase the participation of children in research so that adequate data will be developed to support the treatment modalities for disorders and conditions that affect adults and may also affect children.

Policy

It is the policy of NIH that children (i.e., individuals under the age of 21) must be included in all human subjects research, conducted or supported by the NIH, unless there are scientific and ethical reasons not to include them. This policy applies to all NIH conducted or supported research involving human subjects, including research that is otherwise "exempt" in accord with Sections 101(b) and 401(b) of 45 CFR 46 - Federal Policy for the Protection of Human Subjects. The inclusion of children as subjects in research must be in compliance with all applicable subparts of 45 CFR 46 as well as with other pertinent federal laws and regulations. Therefore, proposals for research involving human subjects must include a description of plans for including children. If children will be excluded from the research, the application or proposal must present an acceptable justification for the exclusion.

In the research plan, the investigator should create a section titled "Participation of Children". This section should provide either a description of the plans to include children and a rationale for selecting or excluding a specific age range of child, or an explanation of the reason(s) for excluding children as participants in the research. When children are included, the plan must also include a description of the expertise of the investigative team for dealing with children at the ages included, of the appropriateness of the available facilities to accommodate the children, and the inclusion of a sufficient number of children to contribute to a meaningful analysis relative to the purpose of the study. Scientific review groups at the NIH will assess each application as being "acceptable" or "unacceptable" in regard to the age appropriate inclusion or exclusion of children in the research project, in addition to evaluating the plans for conducting the research in accord with these provisions.

Justifications for Exclusions

It is expected that children will be included in all research involving human subjects unless one or more of the following exclusionary circumstances can be fully justified:

1. The research topic to be studied is irrelevant to children.
2. There are laws or regulations barring the inclusion of children in the research. For example, the regulations for protection of human subjects allow consenting adults to accept a higher level of risk than are permitted for children.
3. The knowledge being sought in the research is already available for children or will be obtained from another ongoing study, and an additional study will be redundant. Documentation of other studies justifying the exclusions should be provided. NIH program staff can be contacted for guidance on this issue if the information is not readily available.
4. A separate, age-specific study in children is warranted and preferable. Examples include:
a. The relative rarity of the condition in children, as compared to adults (in that extraordinary effort would be needed to include children, although in rare diseases or disorders where the applicant has made a particular effort to assemble an adult population, the same effort would be expected to assemble a similar child population with the rare condition);

b. The number of children is limited because the majority are already accessed by a nationwide pediatric disease research network, so that requiring inclusion of children in the proposed adult study would be both difficult and unnecessary (in that the topic was already being addressed in children by the network) as well as potentially counterproductive (in that fewer children could be available for the network study if other studies were required to recruit and include them);

c. Issues of study design preclude direct applicability of hypotheses and/or interventions to both adults and children (including different cognitive, developmental, or disease stages or different age-related metabolic processes). While this situation may represent a justification for excluding children in some instances, consideration should be given to taking these differences into account in the study design and expanding the hypotheses tested or the interventions to allow children to be included rather than excluding them.
5. Insufficient data are available in adults to judge potential risk in children (in which case one of the research objectives could be to obtain sufficient adult data to make this judgment). While children usually should not be the initial group to be involved in research studies, in some instances, the nature and seriousness of the illness may warrant their participation earlier based on careful risk and benefit analysis.
6. Study designs aimed at collecting additional data on pre-enrolled adult study participants (e.g., longitudinal follow-up studies that did not include data on children).
7. Other special cases justified by the investigator and found acceptable to the review group and the Institute Director.

Implementation

This policy applies to all initial applications (Type 1) proposals and intramural projects submitted for receipt dates after October 1, 1998.

See Also:
NIH Policy on Inclusion of Children in Research