REVIEW AND AWARD CODES FOR THE NIH INCLUSION OF CHILDREN POLICY

I.	Introduction to Children Codes	2

II	Children Representation Codes	4

II	Instructions for Use of New Codes for Children	5

IV	Codes on Summary Statement Headers	7

V.	Summary Card of Inclusion Codes for

Scientific Review Group Reviewers	8

NOTE:	These codes and procedures are applicable to all initial (type 1) applications received after October 1, 1998.

Division of Research Programs, Training and Review Policy

Office of Extramural Programs

Office of Extramural Research

Office of the Director, NIH

March 26, 1999

I. INTRODUCTION TO CHILDREN CODES

In the March 6, 1998, issue of the NIH Guide for Grants and Contracts, guidelines were published on the NIH policy on inclusion of children in research involving human subjects. ()

The guidelines and policy provide that applicants:

▪	Include children in research unless there are scientific and ethical reasons not to include them.

▪	Address the age-appropriate inclusion or exclusion of children in their applications under a special heading "Participation of Children"

▪	Justify not including children; 7 possible exemptions are allowed with justification(see below).

Codes for Children Representation: A three-character coding scheme has been developed to enable the NIH to track applications and proposals in relation to the new policy. Codes pertaining to Children will start with "C". A detailed description of these codes and guidelines for their use follows.

Applicability: The codes are intended to apply to applications for research grants, individual fellowships and individual career awards, cooperative agreement awards, and for contract proposals and awards, as well as intramurally supported research. They are in addition to the codes used for inclusion of women and minorities.

▪	Codes need not be applied to applications for Institutional research training grants or Institutional career awards, since most appointees will be involved in research projects that have already been approved.

▪	When the research under review is essentially a service (e.g., statistical center or analysis laboratory) in support of another activity already found to be in compliance with this policy, a second review is not necessary.

▪	Training grants (T32, T34, T35) are exempt from coding requirements but a term or condition of award will specify that all projects to which trainees are assigned must already be in compliance with the NIH policy on inclusion of children in research involving human subjects.

Human Subjects Research to be Coded: The policy extends to all research involving the use of human organs, tissues, and body fluids from living individuals as well as to graphic, written, or recorded information derived from living individuals. The policy uses the definition in Federal regulations for human subjects: "...living individual(s) about whom an investigator conducting research obtains: (1) data through intervention or interaction with the individual; or (2) identifiable private information." [45 CFR 46.102(f)] However, research exempted from human subjects protection regulations as defined by 45 CFR 46.101(b) is not exempted from the NIH policy on inclusion of children and must be evaluated and coded. Autopsy material is not covered by the policy.

Justifications Allowed for Exclusions of Children in Research (from the NIH GUIDE)

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.

II. CHILDREN REPRESENTATION CODES

DEFINITION: Children are defined as individuals under the age of 21.

CODE FORMAT: Single alphanumeric field, 3 characters, e.g., C2A

1st character:	C (indicates that code is for representation of children)

2nd character:	1/2/3/4 (representation proposed in project or in award)

3rd character:	A/U (acceptable/unacceptable)

Representation Proposed in Project

1 =	Both children and adults

2 =	Only children

3 =	No children included

4 =	Representation of children is unknown

Acceptability/Unacceptability of Representation of Children

A =	Representation of children is scientifically acceptable and recruitment/retention has been realistically addressed, OR an acceptable justification for exclusion has been provided.

U =	Representation of children is unacceptable. Application fails to conform to NIH policy guidelines in relation to the scientific purpose of the study; OR fails to provide sufficient information; OR does not adequately justify that children are not included; OR does not realistically address recruitment/retention. (This code constitutes a bar to funding unless or until resolved by NIH staff.)

Examples:

C1A - Both children and adults are included; inclusion is scientifically acceptable.

C1U -	Both children and adults are included; no rationale is provided for selecting

or excluding a specific age range of children. Scientifically unacceptable.

C2A -	Only children are represented in the study; inclusion is scientifically acceptable.

C2U -	Only children are represented in the study, but age range is too restricted to be

scientifically acceptable, e.g., including only children of ages 18-21.

C3A -	No children included. Acceptable justification for exclusion is provided.

C3U - No children included. Acceptable justification for exclusion is not provided.

C4A - Representation of children is not known. The information on age of individuals providing specimens or in existing datasets cannot be accurately determined (e.g., pooled blood samples, stored specimens), and this does not compromise the scientific objectives of the research. Scientifically acceptable.

C4U -	Representation of children is not known. The application does not provide sufficient information about the age distribution of the study population. The application does not comply with requirements and is unacceptable.

III. INSTRUCTIONS FOR USE OF NEW CODES FOR CHILDREN

1.	All applications for research grants, individual fellowships, individual career awards, cooperative agreement awards, and all proposals for research and development contract awards, that involve human subjects are covered by this policy. Each project or protocol must be individually evaluated for compliance with the policy.

2.	It is only necessary to assign codes to applications that are scored by the Scientific Review Group (SRG).

3.	Reviewer's written comments explaining the basis for the codes assigned should be included in a critique section entitled "PARTICIPATION OF CHILDREN".

4.	For foreign applications, proposals and awards, as well as foreign components of domestic awards, the policy on inclusion of children is the same as for research conducted in the U.S.

5.	A code should be assigned to each single project application (e.g., R01 application) that is under the policy.

6.	A code should be assigned to each individual project or subproject in an application or proposal containing multiple projects or subprojects and involving distinct populations or specimen collections.

A single overall code ALSO should be assigned to the entire application as follows:

▪	Acceptability/Unacceptability - Each project/subproject must satisfy at least one of the acceptability conditions for an "Acceptable" (A) code to be assigned to the application as a whole. If any project/subproject is found "Unacceptable" (U), the overall code should be U.

▪	Representation Proposed in Project - Coding should reflect the total representation in all projects/subprojects, even if some involve no children.

7.	For any project/subproject receiving a code for representation of children that is U (unacceptable) and that is being considered for funding, designated staff in each IC will resolve the issue before attempting to process the award and have the code revised to reflect revision in design or circumstances. The code "R" will be replace the "U" for any case that is satisfactorily resolved by program staff before award.

Responsibilities:

A.	Reviewers' Responsibilities:

Complete the separate evaluation and coding for inclusion of children in each project in which human subjects are involved, and determine whether or not the scientific basis for the study population is acceptable. Evaluate each project separately for inclusion of children.

ACTION:	Assign codes for children (Cxx) for each individual project and briefly explain the basis for the acceptable/unacceptable (A/U) codes assigned.

ACTION:	Assign an overall code for the application. If there is only one project, this will be the application code; if there is more than one project or subproject covered by the policy, assign an overall code to reflect the total representation in all projects or subprojects, even if some involve no children.

B.	Review Staff (SRA/GTA) Responsibilities:

At meeting:

ACTION:	Ensure that reviewers address the inclusion of children policy when relevant for each project or subproject as well as the application overall, and assign codes for scored applications.

After meeting:

ACTION:	Prepare summary statements, reporting codes for each project or subproject and, as appropriate, the justification for those codes under a heading following the critique for each project. One section entitled "Gender/Minority/Children Inclusion" will be prepared that includes comments on inclusion of gender, minorities and children. An overall section may also be necessary for applications or proposals containing multiple projects or subprojects.

ACTION:	In IRG interface, for each scored application enter appropriate codes in response to prompts: "Enter Children Code".

NOTE: In the future, programming will permit codes for each project or subproject to be entered into the IMPAC II system. In the interim, the codes recorded in the text of the summary statements will provide for tracking of inclusion.

C. Post-Review Responsibilities of Institute/Center Staff:

For any project/subproject receiving a code for children that is U (unacceptable) and that is being considered for funding, designated staff in each IC will resolve the issue before attempting to process an award and will have code(s) revised to reflect revisions in design or circumstances.

ACTION:	After resolution of "unacceptable" codes, change the codes using IC or IAS interface to the most appropriate code (in this case the "U" will be replaced with "R", denoting "resolved").

ACTION:	Enter subproject information, if applicable, including SRG codes for subprojects, for those applications that will be funded.

ACTION:	For training grants (T32, T34, T35) that are exempt from coding requirements, include a term or condition of award , when appropriate, specifying that all projects to which trainees are assigned must already be in compliance with the NIH policy on inclusion of children in research involving human subjects.

IV. CODES ON SUMMARY STATEMENT HEADERS

One of the following Code lines will be on the Header of Summary Statements that are scored and include human subjects.

C1A - Both children and adults, scientifically acceptable

C2A -	Only children, scientifically acceptable

C3A - No children included, scientifically acceptable

C4A -	Children Representation unknown, scientifically acceptable

C1U -	Both children and adults, scientifically unacceptable

C2U -	Only children, scientifically unacceptable

C3U - No children included, scientifically unacceptable

C4U -	Children Representation unknown, scientifically unacceptable

VI.	SUMMARY CARD OF INCLUSION CODES FOR SCIENTIFIC REVIEW GROUP REVIEWERS:

Inclusion of Women, Minorities, and Children in Clinical Research

Revised Codes Effective October 1998

All biomedical or behavioral research projects involving human subjects are considered clinical research. Scored clinical applications are assigned the codes shown below. For scored applications with subprojects, such as for program projects, each subproject must receive its own gender, minority, and children codes, and an overall set of codes must also be assigned to the application.

Is this an NIH-defined clinical trial? Y or N

(For an application to be coded as a clinical trial, it must fit the NIH definition of a phase III clinical trial.)

GENDER CODE:

First character = G

Second character:

1 = Both genders

2 = Only women

3 = Only men

4 = Gender unknown

Third character:

A = Scientifically acceptable

U = Scientifically unacceptable

MINORITY CODE:

First character = M

Second character:

1 = Minority and nonminority

2 = Only minority

3 = Only nonminority

4 = Minority representation unknown

Third character:

A = Scientifically acceptable

U = Scientifically unacceptable

CHILDREN CODE:

First character = C

Second character:

1 = Children and adults

2 = Only children

3 = No children included

4 = Representation of children is unknown

Third character:

A = Scientifically acceptable

U = Scientifically unacceptable

Examples:	G1A = Both genders, scientifically acceptable

M3U= Only nonminorities, scientifically unacceptable

C2A = Only children, scientifically acceptable