Requirements Affecting the Rights and Welfare of Individuals as
Research Subjects, Patients, or Recipients of Services

NIH appropriated funds may not be used to support human embryo research under any extramural award instrument. NIH funds may not be used for the creation of a human embryo(s) for research purposes or for research in which a human embryo(s) is destroyed, discarded, or knowingly subjected to risk of injury or death greater than that allowed for research on fetuses in utero under 45 CFR 46.208(a)(2) and subsection 498 (a) and (b) of the PHS Act. The term "human embryo(s)" includes any organism not protected as a human subject under 45 CFR 46, as of the date of enactment of the governing appropriations act, that is derived by fertilization, parthenogenesis, cloning, or any other means from one or more human gametes or human diploid cells.

In addition to the statutory restrictions on human fetal research under subsections 498 (a) and (b) of the PHS Act, by Presidential memorandum of March 4, 1997, NIH is prohibited from using Federal funds for cloning of human beings.

Research on Human Fetal Tissue

Human fetal tissue is defined as tissue or cells obtained from a dead human embryo or fetus after a spontaneous or induced abortion or stillbirth. This definitions does not include established human fetal cell lines.

NIH Guidance for Research on Human Fetal Tissue

NIH has issued guidance for grantees conducting research on human fetal tissue. The guidance and other information on the governing federal statute, Sections 498A and 498B of the Public Health Service Act, 42 USC 289g-1 and 298g-2, are available on the NIH web site at http://grants.nih.gov/grants/guide/notice-files/not93-235.html

The scientific and ethical challenges associated with research utilizing human fetal tissues make it imperative that researchers and their institutions be clearly aware of and in compliance with the federal requirements particularly section 498B. Violation of this statute carries criminal penalties that are applicable to both the suppliers and the acquirers of human fetal tissue for valuable consideration.

When an application involving human fetal tissue research is submitted to the NIH, the authorized institutional official certifies (by signing the face page) that researchers using these tissues are in compliance with Sec 498B of the Public Health Service Act, 42 U.S.C. 289g-2. This statute specifically prohibits any person from knowingly acquiring, receiving, or transferring any human fetal tissue for valuable consideration. "Valuable consideration" is a concept similar to profit, and does not include reasonable payment for costs associated with the collection, processing, preservation, storage, quality control or transportation of these tissues.

There are additional legal requirements for research on the transplantation of human fetal tissue for therapeutic purposes that is conducted or supported by the NIH. (See Sec 498A and Sec 498B(b) of the Public Health Service Act.) Under section 498A the institutional official who signs the application must certify that the research on transplantation of human fetal tissue will adhere to the following provisions:

• The woman who donates the fetal tissue must sign a statement declaring that the tissue is being donated for therapeutic transplantation research, that the donation is being made without any restriction regarding the identity of individuals who may receive the transplantation, and that the donation is being made without the donor knowing the identity of the recipient.

• The attending physician must sign a statement that the tissue has been obtained in accordance with the donor’s signed statement and that full disclosure has been provided to the donor with regard to the physician’s intent, if any, in the research to be conducted with the tissue, and any known medical risks to the donor or risks to her privacy associated with the donation that are in addition to risks of the type that are associated with the woman’s medical care. In the case of tissue obtained pursuant to an induced abortion, the physician’s statement must also state that the woman’s consent for the abortion was obtained prior to requesting or obtaining consent for the tissue to be used; no alterations of the timing, method, or procedures used to terminate the pregnancy was made solely for the purposes of obtaining the tissue for research; and the abortion was performed in accordance with applicable State and local law.

• The principal investigator must sign a statement certifying that he or she is aware that the tissue is human fetal tissue obtained pursuant to a spontaneous or induced abortion, or pursuant to a stillbirth, that is being donated for research purposes. The principal investigator must also certify that: this information has been shared with others who have responsibilities regarding the research; and prior to eliciting informed consent from the transplantation recipient, the researcher will obtain written acknowledgement that the patient is aware of the aforementioned information. Moreover, the principal investigator will certify in writing that he or she has had no part in any decisions as to the timing, method, or procedures used to terminate the pregnancy that were made solely for the purposes of the research.

• Research involving the transplantation of human fetal tissue must be conducted in accord with applicable State and local law.

The institutional official must certify that the physician’s statement, statement of the researcher, and the acknowledgement of the transplantation recipient will be available for audit by the Secretary, DHHS, or designee.

Confidentiality

NIH expects grantees and others involved in NIH-supported research to take appropriate actions to protect the privacy and confidentiality of individuals participating in those projects. Investigators, Data Safety Monitoring Boards, IRBs and other appropriate entities should ensure that policies and procedures are in place that protect identifying information and that they oversee compliance with those policies and procedures.

Protection of Research Subjects' Identity

Section 301(d) of the PHS Act provides that the Secretary may authorize persons engaged in biomedical, behavioral, clinical, or other research activities to protect the privacy of research subjects by withholding the names and other identifying characteristics of those subjects from individuals not engaged in the research. Authorized persons may not be compelled to disclose subjects' identities in any Federal, State, or local civil, criminal, administrative, legislative or other proceeding. An applicant may request a certificate of confidentiality to protect research subjects' identities under a specific research project. The request should be submitted to the IC GMO, and, subject to IC review and approval, a certificate may be issued pursuant to 42 CFR 2a.

Confidentiality of Patient Records

Section 543 of the PHS Act requires that records of substance abuse patients be kept confidential except under specified circumstances and purposes. The covered records are those that include the identity, diagnosis, prognosis, or treatment of any patient maintained in connection with any program or activity relating to substance abuse education, prevention, training, treatment, rehabilitation, or research that is conducted, regulated, or directly or indirectly assisted by any department or agency of the United States. This requirement is implemented at 42 CFR Parts 2 and 2a.

Controlled Substances

If controlled substances are proposed to be administered as part of a research protocol or if research is to be conducted on the drugs themselves, applicants/grantees must ensure that the requirements of the Drug Enforcement Administration (DEA), including registration, inspection, and certification, as applicable, are met. Regional DEA offices can supply forms and information concerning the type of registration required for a particular substance for research use. The main registration office in Washington, DC may be reached at (202) 254-8255. Information also is available from the National Institute on Drug Abuse at (301) 443-6300.

Human Subjects

HHS regulations for the protection of human subjects, at 45 CFR Part 46, implement section 491(a) of the PHS Act and provide a systematic means, based on established, internationally recognized ethical principles, to safeguard the rights and welfare of individuals who participate as subjects in research activities supported or conducted by NIH or other HHS components. Under the governing regulations, a grantee may not conduct research involving human subjects or expend Federal funds for research involving human subjects at any site, domestic or foreign, unless it has an Office for Human Research Protections (OHRP)-approved assurance of compliance with the requirements of 45 CFR Part 46 and the research has been approved by an Institutional Review Board (IRB) in accordance with the requirements of 45 CFR Part 46. They stipulate that the applicant/grantee, whether domestic or foreign, is responsible for safeguarding the rights and welfare of human subjects involved in NIH grant-supported research activities. Subpart A of the HHS regulations constitutes the Federal policy (common rule) for the protection of human subjects.

For purposes of this public policy requirement, the definitions at 45 CFR 46.102 apply. A "human subject" is defined as a living individual about whom an investigator (whether professional or student) conducting research obtains (1) data through intervention or interaction with the individual or (2) identifiable private information. The regulations extend to the use of human organs, tissues, and body fluids from individually identifiable human subjects as well as to graphic, written, or recorded information derived from individually identifiable human subjects. The use of autopsy materials is governed by applicable State and local law and is not directly regulated by 45 CFR 46.

"Research" is defined as "systematic investigation designed to develop or contribute to generalizable knowledge." Unless an activity is "exempt" (see 45 CFR 46.101), any activity meeting the regulatory definition of "research" constitutes research for purposes of applying the regulations, even if supported by a grant that might have as its overall purpose an activity that is not primarily research. (For example, some training programs may include research activities.) OHRP should be consulted if there is any question concerning the classification of research as exempt or nonexempt.

Assurance Requirements and Institutional Review Boards

Applicant organizations proposing to involve human subjects in nonexempt research must file (or have previously filed) a written Assurance of Compliance with the Office for Human Research Protections (OHRP) setting forth the commitment of the organization to establish appropriate policies and procedures for the protection of human subjects. Affiliated organizations or organizations that will serve as additional performance sites for the grant-supported research also must file an Assurance. OHRP is responsible for negotiating and approving the Assurance. Previously OHRP (and its predecessor organization—the Office for Protection from Research Risks) negotiated several types of assurances, e.g., a Multiple Project Assurance (MPA) or a Single Project Assurance (SPA) as well as an Inter-Institutional Amendment if employees of an organization with an MPA routinely conducted their grant-supported research at an affiliated institution, thereby avoiding the need for an SPA for each separate project performed at such sites.

OHRP is now negotiating Federal-wide Aassurances (FWA) covering all of an organization's federally supported research activities involving human subjects. Therefore, for organizations proposing research involving human subjects and not currently holding an approved assurance(s), OHRP will negotiate an FWA. Under the new system, each legally separate entity must file its own FWA even if the organization does not operate its own IRB and designates another IRB (registered with OHRP and agreeing to the designation) for that purpose. Organizations currently operating under SPAs, MPAs and/or other Aassurances will continue to operate under the terms of their current assurances, including time of submission of certification of IRB review, until converted to an FWA Federal-wide assurance^[8]. Detailed information concerning FWAs, including the OHRP Assurance Training Module, are available on the OHRP web site.

NIH will not award any grant for nonexempt research involving human subjects unless the organization is operating under an approved Assurance andprovides certification, as part of its application, that an appropriate Institutional Review Board (IRB) has, within 12 months of the budget period start date, reviewed and approved the proposed activity in accordance with the regulatory requirements. NIH will not award a grant in which human subjects are involved for non-exempt research unless the grantee has an OHRP-approved assurance and the grantee provides a certification to NIH that the research has been approved by an appropriate IRB, consistent with 45 CFR Part 46, within 12 months prior to the budget period start date. Under "just-in-time" procedures, the certification of IRB approval is deferred until just prior to funding. IRB approval is not required prior to NIH peer review of an application. Therefore, following peer review and notification of priority score/percentile, applicant organizations should proceed with IRB review for those applications that have not yet received IRB approval and that appear to be in a fundable range. Regardless of when the IRB review occurs, the IRB should ensure that the research described in the application is consistent with any corresponding protocols reviewed and approved by the IRB. Any discrepancies should be resolved prior to the involvement of human subjects.

It is the grantee organization's responsibility to ensure that all sites engaged in research involving human subjects have an appropriate OHRP-approved assurance and IRB approval of the research consistent with 45 CFR Part 46, and to comply with NIH prior approval requirements related to the addition of sites not included in the approved application (see "Administrative Requirements—Changes in Project and Budget—Prior Approval Requirements"). The list of organizations with approved assurances is available at the OHRP web site (http://www.hhs.gov/ohrp). Grantees may not draw funds from the payment system or make obligations against Federal funds for research involving human subjects at any site engaged in non-exempt research for any period not covered by both an OHRP-approved assurance and an IRB approval consistent with 45 CFR Part 46. In addition, no human subjects may be involved in research at an affiliated institution prior to approval by OHRP of an applicable Assurance for that organization. If an organization submits an application with the knowledge that human subjects may be involved within the project period, but definite plans are not set forth in the application, the research activity must be reviewed and approved by an IRB and a certification submitted to NIH before human subjects may be involved in covered research activities supported by the award.

As specified in 45 CFR 46.111, the IRB review must include a determination that, for research covered by the regulations:

• The procedures to be used will minimize risks to subjects;
• Risks to subjects are reasonable in relation to expected benefits, if any, to subjects and the importance of the knowledge that may reasonably be expected to result;
• Selection of subjects is equitable;
• Informed consent is sought from each prospective subject or the subject's legally authorized representative and is appropriately documented in accordance with, and to the extent required by, the regulation;
• Where appropriate, the research plan makes adequate provision for monitoring the data collected to ensure the safety of subjects, the protection of privacy, and the confidentiality of data; and
• Where some or all of the subjects are likely to be vulnerable to coercion or undue influence, such as persons with acute or severe physical or mental illness or persons who are economically or educationally disadvantaged, appropriate additional safeguards are included in the study to protect the rights and welfare of these subjects.

If an IRB considers the impact of potential financial (or other) conflicts of interest on the research and the protection of human subjects, it should refer to the organization's policies and procedures for identifying and monitoring conflicts of interest .(see "Public Policy Requirements and Objectives—Ethical and Safe Conduct in Science and Organizational Operations—Standards of Conduct—Financial Conflict of Interest").

The regulations specify additional protections for research involving fetuses, pregnant women, and human in vitro fertilization (Subpart B); prisoners (Subpart C); and children (Subpart D).

No individual may receive NIH grant funds for covered research involving human subjects unless the individual is affiliated with or sponsored by an organization that assumes responsibility for the research under an applicable written Assurance or the individual makes other arrangements with OHRP.

Information concerning the preparation and negotiation of Assurances, as well as copies of the regulation, may be obtained from OHRP at the address shown in Part III or from its home page at http://www.hhs.gov/ohrp. OHRP also has produced a publication available through the Government Printing Office^[9] and an instructional videotape.

Before funds are awarded for competing applications involving human subjects, investigators must provide a description of education completed in the protection of human subjects for each individual identified as "key personnel" in the proposed research. Key personnel include all individuals responsible for the design or conduct of the study. The description of education should be part of a cover letter that accompanies the description of "other support," IRB approval, and other information submitted prior to funding in accordance with "just-in-time" procedures. For non-competing continuations, the description of education should be part of the documentation submitted as a prerequisite to award (whether under the Streamlined Noncompeting Award Process or submitting a full non-competing continuation application).

Data and Safety Monitoring

NIH requires oversight and monitoring of all human intervention studies to ensure the safety of participants and the validity and integrity of the data. This policy is in addition to any monitoring requirements imposed by 45 CFR Part 46 (see "Human Subjects" in this subsection), FDA, or the NIH Guidelines for Research Involving Recombinant DNA Activities. The level of monitoring should be commensurate with the risks and the size and complexity of the clinical trial. Oversight and monitoring under Phase III clinical trials should be in the form of Data Safety Monitoring Boards (DSMBs). A DSMB also may be appropriate for Phase I and II clinical trials if the studies have multiple clinical sites, are blinded (masked), or employ particularly high-risk or vulnerable populations. The DSMB monitoring function is above and beyond that traditionally provided by IRBs; however, the IRB must be cognizant of the procedures used by DSMBs, and the DSMBs must provide periodic reports to investigators for transmittal to the local IRB.

For competing research applications involving Phase I or II clinical trials, the applicant must include a general description of the data safety monitoring for review by the Scientific Review Group. A detailed monitoring plan must be included as part of the research protocol, be submitted to the local IRB, and be reviewed and approved by the funding IC prior to initiation of the trial. At a minimum, monitoring plans must include a description of the reporting mechanisms for advising the IRB, FDA, and NIH of adverse events. In specific cases where the funding IC is the sponsor of the test agent, i.e., the holder of the Investigational New Drug Application, investigators must submit individual adverse event reports to the IC in accordance with FDA regulations. If a safety monitoring committee has been established for Phase I or II trial, summary reports of the committee's discussions must be submitted to the IC and to the IRB. The funding IC may specify the reporting requirements for adverse events, which are in addition to annual report to the IRB.

For multi-site Phase I and II trials, investigators should organize a central reporting entity that will be responsible for preparing timely summary reports of adverse events for distribution among sites and the IRBs of participating sites. The frequency of summary reports will depend on the nature of the trial. Organizations with a large number of clinical trials may develop standard monitoring plans for Phase I and II clinical trials. However, such plans should always be evaluated for appropriateness for the particular investigation.

All multi-site trials with DSMBs are expected to forward summary reports of adverse events to individual IRBs in order for them to address reports related to the site for which they have responsibility. Grantees should address questions on this subject to the NIH Program Official.

Further information concerning these requirements is contained in several NIH Guide for Grants and Contracts notices (http://grants.nih.gov/grants/guide/notice-files/not98-084.html) and (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-038.html).

All clinical research involving investigational new drugs (IND), drugs approved for a different indication, or experimental combinations of drugs, must meet the Food and Drug Administration's (FDA) IND regulations, FDA's human subjects protection requirements, and the HHS human subjects' requirements to be eligible for funding. As provided in the FDA regulations, an IND or Investigational Device Exception (IDE) also may apply to biologics or devices. The FDA regulations are published at 21 CFR Parts 50 and 312.

The official sponsor of the IND/IDE, whether NIH, a grantee, or a third party, is legally responsible for meeting the FDA IND requirements. If a third party, such as a pharmaceutical company or research organization under contract to a grantee or to a pharmaceutical company, is the IND/IDE sponsor, the legal responsibility for monitoring the clinical trial and reporting to FDA rests with the INDsponsor rather than the grantee. This generally will be the case for larger, multi-site clinical trials. If the grantee is the IND/IDE holder, commonly referred to as an "investigator-initiated IND/IDE," the grantee or the investigator serves as the INDsponsor and assumes the legal responsibility. In any case, the grantee is ultimately responsible to NIH for ensuring compliance with the requirements for protection of human subjects, including compliance with FDA's IND requirements.

Following the filing of an IND, FDA has a 30-day period in which to review it. FDA may allow the IND to proceed or may defer approval of the IND until changes it deems acceptable are made. FDA also may order a clinical trial to be suspended or terminated, at any time, based on information it receives about that clinical trial. The FDA regulations are published at 21 CFR Parts 50 and 312.

When NIH funds all, or part of, a clinical study involving an IND or an IDE, NIH must be knowledgeable about any significant communications with FDA concerning the study. The grantee organization must report certain types of FDA communications to the NIH IC within 72 hours of receiving a copy of or upon being informed of the FDA communication (through the PI or another person acting on behalf of the grantee), whichever occurs first. This notification requirement applies to any of the following communications from FDA with the sponsor of the IND or IDE:

• Warning letters (whether sent to the grantee and/or to the commercial sponsor(s)).
• Notice of Initiation of Disqualification Proceedings and Opportunity to Explain (NIDPOE letters).
• Notice of Opportunity for Hearing (NOOH).
• Notice of Disqualification.
• Consent Agreements.
• Clinical hold letters that pertain to breaches of either good manufacturing practices, good clinical practices, or other major issue requiring significant changes in the protocol

The notification should be made in writing, but may be done by telephone if a written notice would delay the notification. It should include a statement of the action taken or contemplated and the assistance needed to resolve the situation. These requirements apply to the grantee even if the grantee or the NIH-funded PI is the sponsor. Failure to comply with this requirement may result in NIH imposing a corrective and/or enforcement action (see "Administrative Requirements—Enforcement Actions"). FDA communications are considered grant-related records for purposes of retention and access (see "Administrative Requirements—Monitoring—Record Retention and Access").

Pro-Children Act of 1994

Public Law 103-227, Title X, Part C—Environmental Tobacco Smoke, also known as the Pro-Children Act of 1994 (Act), imposes restrictions on smoking in facilities where federally funded children's services are provided. NIH grants are subject to these requirements only if they meet the Act's specified coverage. The Act specifies that smoking is prohibited in any indoor facility owned, leased, or contracted for and used for the routine or regular provision of kindergarten, elementary, or secondary education or library services to children under the age of 18. In addition, smoking is prohibited in any indoor facility or portion of a facility owned, leased, or contracted for and used for the routine or regular provision of federally funded health care, day care, or early childhood development (Head Start) services to children under the age of 18. The statutory prohibition also applies if such facilities are constructed, operated, or maintained with Federal funds. The statute does not apply to children's services provided in private residences, facilities funded solely by Medicare or Medicaid funds, portions of facilities used for inpatient drug or alcohol treatment, or facilities where Women, Infants and Children (WIC) coupons are redeemed. Failure to comply with the provisions of the law may result in the imposition of a civil monetary penalty of up to $1,000 per violation and/or the imposition of an administrative compliance order on the responsible entity.

Because of the nature of NIH programs and funding, individual transactions, rather than entire programs, may be subject to these requirements. The signature of the applicant's authorized official will indicate the intent to comply. Any questions concerning the applicability of these provisions to an NIH grant should be directed to the IC GMO.

Research on Transplantation of Fetal Tissue

In submitting an application to NIH, the authorized organizational official that signs the application is certifying that, if research on the transplantation of human fetal tissue is conducted under the grant-supported project, the organization will make available for audit by the Secretary, HHS, or designee, the physician statements and informed consents required by subsections 498A(b)(2) and (c) of the PHS Act or will ensure HHS access to those records, if maintained by an entity other than the grantee. This requirement is in addition to the human subjects in research requirements.

Animal Welfare

The PHS Policy on Humane Care and Use of Laboratory Animals (the Policy) requires that applicant organizations proposing to use vertebrate animals in NIH-supported activities file a written Animal Welfare Assurance with the Office of Laboratory Animal Welfare, NIH. The Policy, which defines "animal" as "any live, vertebrate animal used or intended for use in research, research training, experimentation, or biological testing or for related purposes," stipulates that the applicant/grantee bears responsibility for the humane care and use of animals in NIH-supported research activities. The Policy implements and supplements the U.S. Government Principles for the Utilization and Care of Vertebrate Animals Used in Testing, Research, and Training. It requires the applicant to establish appropriate policies and procedures for humane care and use of animals, based on the Guide for the Care and Use of Laboratory Animals, and to comply with the Animal Welfare Act and its implementing regulations. This includes appointment of an Institutional Animal Care and Use Committee (IACUC) with specified responsibilities.

No NIH award for research involving live vertebrate animals will be made unless the applicant organization and all performance sites are operating in accordance with an approved Animal Welfare Assurance and provide verification that the IACUC has reviewed and approved those sections of the application that involve use of vertebrate animals, in accordance with the requirements of the Policy. Applications from organizations with approved Assurances will be considered incomplete if they do not include verification of IACUC review or do not contain the information concerning the use of vertebrate animals required as part of the application's research plan (see instructions for completion of the PHS-398 for the five specific points that need to be addressed). In the case of apparent or potential violations of the Policy, NIH may refer applications back to the applicant for further IACUC review.

Foreign organizations proposing activities involving vertebrate animals are required to comply with the Policy or provide evidence that acceptable standards for the humane care and use of animals will be met. NIH will not make an award for research involving live vertebrate animals to an individual unless that individual is affiliated with an organization that accepts responsibility for compliance with the Policy and has filed the necessary assurance with OLAW.

The Policy does not affect applicable State or local laws or regulations that impose more stringent standards for the care and use of laboratory animals. In addition, all organizations are required to comply, as applicable, with the Animal Welfare Act, as amended, 7 U.S.C. 2131 et seq., and other Federal statutes and regulations relating to animals.

Information concerning the preparation and submission of Animal Welfare Assurances as well as copies of the Policy and other relevant materials are available from OLAW (see Part III for contact information). Information concerning ways in which to reduce the administrative burden associated with these requirements also is available at OLAW web site http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-007.html.

Requirements for Inclusiveness in Research Design

NIH requires grant-supported research projects to be as inclusive in design as possible in order to extend the validity of research findings and allow for enhancement of the health status of all population groups.

Inclusion of Women and Minorities as Subjects in Clinical Research

Research involving human subjects of any age must comply with the NIH Guidelines on the Inclusion of Women and Minorities as Subjects in Clinical Research (NIH Guide for Grants and Contracts, Vol. 23, No. 11, March 18, 1994, and Federal Register, 59 FR 14508-14513, March 28, 1994), implementing section 492B of the PHS Act. These guidelines require that women and members of minority groups and their subpopulations be included in any NIH-supported research project involving human subjects, unless a clear and compelling rationale and justification establishes, to the satisfaction of the IC Director, that inclusion is inappropriate with respect to the health of the subjects, the purpose of the research, or other circumstances. Cost is not an acceptable reason for exclusion, except when the research would duplicate data already available from other sources. Women of childbearing potential should not be routinely excluded from participation in clinical research, i.e., any biomedical or behavioral research involving human subjects. The guidelines should be reviewed for policy concerning inclusion of these groups in Phase III clinical trials.

Peer reviewers will evaluate proposed plans for inclusion of members of minority groups and both genders, the design of clinical trials, and recruitment and outreach as part of the scientific assessment. Failure to comply with this policy may result in NIH not making an award. Grantees are required to report annually on the enrollment of individuals by gender and racial or ethnic minority group as part of the noncompeting continuation request or other annual progress reporting (see "Administrative Requirements—Monitoring—Reporting").

Inclusion of Children as Subjects in Clinical Research

NIH has a separate policy on inclusion of children as subjects in clinical research that is similar to the policy regarding inclusion of women and minorities. All new applications involving human subjects research must include children (i.e., individuals under the age of 21) in the research design unless there are scientific or ethical reasons not to include them^[10]. If children will be excluded from the research, the application must present an acceptable justification for the exclusion. This policy applies to both exempt and nonexempt research activities (see "Human Subjects" in this section). The inclusion of children as subjects in research must comply with all applicable provisions of 45 CFR Part 46 and other pertinent Federal laws and regulations. This policy is not mandatory for awards made prior to October 1, 1998 and for new applications submitted for earlier receipt dates.

Civil Rights

Before an NIH IC may make an award to any domestic applicant organization, the organization must certify (by means of the authorized organizational official's signature on the application) that it has an Assurance of Compliance with the statutes described in this subsection on file with the Office for Civil Rights (OCR), Office of the Secretary, HHS. The Assurance, Form HHS-690, is filed on an organizational basis and is not required for each application; however, the certification is required with each application. If the application has been recommended for funding and the applicant organization does not have an Assurance on file, it will receive, from the responsible IC, the required form and instructions for completion and submission. The Form HHS-690 also is available from GrantsInfo@nih.gov or by telephone at (301) 435-0714.

Domestic organizations that receive funding from grantees rather than directly from NIH, including contractors under grants, are required to file this Assurance, and the applicant/grantee is responsible for determining whether those organizations have the required Assurance on file and, if not, ensuring that it is filed with OCR.

Age Discrimination Act of 1975

The Age Discrimination Act of 1975 prohibits discrimination on the basis of age in any program or activity receiving Federal financial assistance. The HHS implementing regulations are codified at 45 CFR Part 91.

Civil Rights Act of 1964

Title VI of the Civil Rights Act of 1964 provides that no person in the U.S. shall, on the grounds of race, color, or national origin, be excluded from participation in, be denied the benefits of, or be subjected to discrimination under any program or activity receiving Federal financial assistance. The HHS implementing regulations are codified at 45 CFR Part 80.

Education Amendments of 1972

Title IX of the Education Amendments of 1972 provides that no person in the U.S. shall, on the basis of sex, be excluded from participation in, be denied the benefits of, or be subjected to discrimination under any educational program or activity receiving Federal financial assistance. The HHS implementing regulations are codified at 45 CFR Part 86.

Rehabilitation Act of 1973

Section 504 of the Rehabilitation Act of 1973, as amended, provides that no otherwise qualified handicapped individual in the United States shall, solely by reason of the handicap, be excluded from participation in, be denied the benefits of, or be subjected to discrimination under any program or activity receiving Federal financial assistance. These requirements pertain to the provision of benefits or services as well as to employment. The HHS implementing regulations are codified at 45 CFR Parts 84 and 85.

Environmental Impact and Other Requirements Related to Acquisition, Alteration and Renovation, and Construction of Facilities

Public policy requirements that apply to construction activities are described in "Construction Grants—Public Policy Requirements and Objectives." However, they also may apply to alteration and renovation (A&R) activities. A grantee undertaking an A&R project under a non-construction award should consult the GMO concerning potential applicability of these requirements.

Availability of Information

With the exception of certain types of information that may be considered proprietary or private information that cannot be released, after the grant is funded, most grant-related information submitted to NIH by the applicant or grantee in the application or in the postaward phase is considered public information and is subject to possible release to individuals or organizations outside NIH. The statutes and policies that require this information to be made public are intended to foster an open system of Government and accountability for governmental programs and expenditures, and, in the case of research, to provide information about federally funded activities.

NIH routinely makes information about awarded grants, including project title, the name of the PI, and the amount of the award, available to the public through the NIH Computer Retrieval of Information on Scientific Projects (CRISP) system, available from the Office of Extramural Research Home Page. The project description provided by an applicant for a funded research grant application is sent to the National Technical Information Service (NTIS), U.S. Department of Commerce, where the information is used for dissemination of scientific information and scientific classification and program analysis purposes. The public may request these descriptions from NTIS. Other information may be released on a case-by-case basis as described in this subsection.

Several policies require acknowledgment of support and a disclaimer for publications, inventions, and other research products, as provided in "Administrative Requirements—Availability of Research Results: Publications, Intellectual Property Rights, and Sharing Biomedical Research Resources" and elsewhere in this policy statement. The following disclosure requirement ("Acknowledgment of Federal Funding") is included in HHS appropriations statutes.

Acknowledgment of Federal Funding

All HHS grantees must acknowledge Federal funding when issuing statements, press releases, requests for proposals, bid invitations, and other documents describing projects or programs funded in whole or in part with Federal money. Grantees are required to state (1) the percentage and dollar amounts of the total program or project costs financed with Federal money, and (2) the percentage and dollar amount of the total costs financed by nongovernmental sources.

The Freedom of Information Act

The Freedom of Information Act (FOIA), 5 U.S.C. 552, and implementing HHS regulations (45 CFR Part 5) require NIH to release certain grant documents and records requested by members of the public, regardless of the intended use of the information. These policies and regulations apply to information in the possession of NIH and generally do not require grantees or contractors under grants to permit public access to their records. An exception related to certain research data is described in this subsection.

NIH will generally release the following types of records pursuant to an FOIA request:

• Funded applications;
• Pending and funded noncompeting continuations;
• Grant progress reports; and
• Final reports of any audit, survey, review, or evaluation of grantee performance that have been transmitted to the grantee.

This includes information of this type maintained in electronic format.

NIH will generally withhold the following types of records or information in response to an FOIA request:

• Pending competing grant applications;
• Unfunded new and competing continuations and competing supplemental applications;
• Financial information regarding a person, such as salary information pertaining to project personnel;
• Information pertaining to an individual, the disclosure of which would constitute a clearly unwarranted invasion of personal privacy;
• Predecisional opinions in interagency or intra-agency memoranda or letters expressed by Government officers, employees, or consultants;
• Evaluative portions of site visit reports and peer review summary statements, including priority scores;
• Trade secrets and commercial, financial, and otherwise intrinsically valuable items of information that are obtained from a person or organization and are privileged or confidential;
• Information which, if released, would adversely affect the competitive position of the person or organization; and
• Patent or other valuable commercial rights of the person or organization.

If NIH has substantial reason to believe that information in its records could reasonably be considered exempt, before the information is released in response to an FOIA request, the applicant or grantee will be notified of the request by the appropriate NIH FOIA office, through the PI, and will be given an opportunity to identify potentially patentable or commercially valuable information that should not be disclosed. After NIH consideration of the grantee's response, if any, the grantee will be informed of the agency's decision as to what documents will be released and to whom. If a document contains both disclosable and nondisclosable information, a designated NIH or HHS FOIA Officer will delete the nondisclosable information, and the balance of the document will be disclosed.

Access to Research Data

By regulation (45 CFR 74.36), grantees that are institutions of higher education, hospitals, or non-profit organizations are required to release research data first produced in a project supported in whole or in part with Federal funds that are cited publicly and officially by a Federal agency in support of an action that has the force and effect of law (e.g., regulations and administrative orders)^[11]. "Research data" is defined as the recorded factual material commonly accepted in the scientific community as necessary to validate research findings. It does not include preliminary analyses; drafts of scientific papers; plans for future research; peer reviews; communications with colleagues; physical objects (e.g., laboratory samples, audio or video tapes); trade secrets; commercial information; materials necessary to be held confidential by a researcher until publication in a peer-reviewed journal; information that is protected under the law (e.g., intellectual property); personnel and medical files and similar files, the disclosure of which would constitute an unwarranted invasion of personal privacy; or information that could be used to identify a particular person in a research study.

These requirements do not apply to commercial organizations or to research data produced by State or local governments. However, if a State or local governmental grantee contracts with an educational institution, hospital, or non-profit organization, and the contract results in covered research data, those data are subject to these disclosure requirements.

Requests for the release of research data subject to this policy are required to be made to NIH, which will handle them as FOIA requests. If the data are publicly available, the requestor will be directed to the public source. Otherwise, the IC FOIA coordinator, in consultation with the affected grantee and the PI, will handle the request. This policy also provides for assessment of a reasonable fee to cover grantee costs as well as (separately) the NIH costs of responding.

The Privacy Act

The Privacy Act of 1974, 5 U.S.C. 552a, and its implementing regulations (45 CFR Part 5b) provide certain safeguards for information about individuals maintained in a system of records, as identified by the Act (i.e., information may be retrieved by the individual's name or other identifying information). These safeguards include the rights of individuals to determine what information about them is maintained in Federal agencies' files (hard copy or electronic) and how it is used, to have access to such records, and to correct, amend, or request deletion of information in their records that is inaccurate, irrelevant, or outdated.

Records maintained by NIH with respect to grant applications, grant awards, and the administration of grants are subject to the provisions of the Privacy Act. NIH has two Privacy Act systems of records that cover NIH grant records:

• 09-25-0036, Extramural Awards and Chartered Advisory Committees: IMPAC (Grant/Contract/Cooperative Agreement Information/Chartered Advisory Committee Information), HHS/NIH/OER and HHS/NIH/CMO.
• 09-25-0112, Grants and Cooperative Agreements: Research, Research Training, Fellowship and Construction Applications and Related Awards, HHS/NIH/OD.

These two systems provide guidance on requirements for the management of grant records in the possession of NIH and include appropriate routine uses of such information. They also include requirements for safeguarding the records and for record retention and disposal.

In considering a request for information concerning an individual made by a party other than that individual, NIH must take into account both the requester's right to know under FOIA and the individual's right to privacy under the Privacy Act.

Records maintained by grantees ordinarily are not subject to the requirements of 45 CFR Part 5b.

Other Public Policy Requirements and Objectives

Consistent with Executive Order 12770 (July 25, 1991), Metric Usage in Federal Government Programs, measurement values in applications and grantee-prepared reports, publications, and other grant-related documents should be in metric. See "Construction Grants" for requirements for metric usage in construction activities.

Military Recruiting and Reserve Officer Training Corps Program Access to
Institutions of Higher Education

NIH is subject to section 588 of the National Defense Authorization Act of 1995, as implemented in 32 CFR Parts 23 and 216, that precludes grant awards to schools that the Department of Defense (DoD) determines have an anti-ROTC (Reserve Officer Training Corps) policy or practice (regardless of when implemented) that either prohibits or, in effect, prevents, the Secretary of Defense from gaining entry to campuses or access to students or information for military recruiting purposes. DoD publishes each determination of ineligibility in the Federal Register as well as publishing, once every 6 months, a list of all currently ineligible schools. If DoD makes its determination of ineligibility during an ongoing project period, NIH may either continue the award or take an action to end the award as provided in "Administrative Requirements—Enforcement Actions—Suspension, Termination, and Withholding of Support." Funding eligibility may be restored on the basis of new information provided to DoD.