The DHHS regulations for the protection of human subjects 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 the DHHS. The regulations Stipulate that an applicant organization, whether domestic or foreign, bears responsibility for safeguarding the rights and welfare of human subjects in DHHS-supported research activities. The regulations require that applicant organizations proposing to involve human subjects in nonexempt research, file a written Assurance of Compliance with the Office for Protection from Research Risks (OPRR), establishing appropriate policies and procedures for the protection of human subjects. These regulations, 45 CFR 46, Protection of Human Subjects, are available from the OPRR, National Institutes of Health, Bethesda, MD 20892, Telephone: (301) 496-7041.
The regulations define "human subject" 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 activities in which the only involvement of human subjects will be in one or more of the following six categories are exempt from coverage by the regulations:
(1) Research conducted in established or commonly accepted educational settings, involving normal educational practices, such as (a) research on regular and special education instructional strategies, or (b) research on the effectiveness of or the comparison among instructional techniques, curricula, or classroom management methods.
(2) Research involving the use of educational tests (cognitive, diagnostic, aptitude, achievement), survey procedures, interview procedures or observation of public behavior, unless: (a) information obtained is recorded in such a manner that human subjects can be identified, directly or through identifiers linked to the subjects; and (b) any disclosure of the human subjects' responses outside the research could reasonably place the subjects at risk of criminal or civil Iiability or be damaging to the subjects' financial standing, employability, or reputation.
(3) Research involving the use of educational tests (cognitive, diagnostic, aptitude, achievement), survey procedures, interview procedures, or observation of public behavior that is not exempt under paragraph(2)(b) of this section, if: (a) the human subjects are elected or appointed public officials or candidates for public office; or (b) federal statute(s) require(s) without exception that the confidentiality of the personally identifiable information will be maintained throughout the research and thereafter.
(4) Research, involving the collection or study of existing data, documents, records, pathological specimens, or diagnostic specimens, if these sources are publicly available or if the information is recorded by the investigator in such a manner that subjects cannot be identified, directly or through identifiers linked to the subjects.
(5) Research and demonstration projects which are conducted by or subject to the approval of department or agency heads, and which are designed to study, evaluate, or otherwise examine: (a) public benefit or service programs; (b) procedures for obtaining benefits or services under those programs; (c) possible changes in or alternatives to those programs or procedures; or (d) possible changes in methods or levels of payment for benefits or services under those programs.
(6) Taste and food quality evaluation and consumer acceptance studies, (a) if wholesome foods without additives are consumed or (b) if a food is consumed that contains a food ingredient at or below the level and for a use found to be safe, or agricultural chemical or environmental contaminant at or below the level found to be safe, by the Food and Drug Administration or approved by the Environmental Protection Agency or the Food Safety and Inspection Service of the U.S. Department of Agriculture.
Investigators who conduct research involving fetuses, pregnant women, children, human in vitro fertilization, or prisoners must follow the provisions of the regulations in Subparts B, C, and D of 45 CFR 46, which describe the additional protections required for these subjects.
No DHHS award for nonexempt research involving human subjects will be made to an applicant organization unless that organization is operating in accord with an approved Assurance of Compliance and provides certification that an appropriate Institutional Review Board (IRB) has reviewed and approved the proposed activity in accordance with the DHHS regulations. No award to an individual will be made unless that individual is affiliated with an assured organization that accepts responsibility for compliance with the DHHS regulations. Foreign applicant organizations must also comply with the provisions of the regulations.
The Center of Biologics Evaluation and Research (CBER), FDA, regulates the use of biological products in humans, at the investigational and marketing phases, including somatic cell therapies and gene therapies. If your work involves these areas or preclinical research which will support later work in these areas: please see the NIH Guide to Grants and Contracts.
a. Research on Transplantation of Fetal Tissue
In signing the application face page, the duly authorized representative of the applicant organization certifies that if research on the transplantation of human fetal tissue is conducted, the applicant organization will make available for audit by the Secretary, DHHS, the physician statements and informed consents required by section 498A (b)(2) and (c) of the Public Health Service Act, 42 U.S.C. 289g (b)(2) and (c), or ensure HHS access to those records, if maintained by an entity other than the applicant organization.
b. Gender and Minority Inclusion Policy:
Research involving human subjects must comply with the "NIH Guidelines on the Inclusion of Women and Minorities as Subjects in Clinical Research." The following excerpts provide the key policy statements. Investigators should obtain full copies of the Guidelines from NIH staff, the NIH Guide for Grants and Contracts (March 18, 1994, Volume 23, Number 11 ) or the Federal Register (59 FR 11146-11151 ).
Research Involving Human Subjects: The policy of NIH is that women and members of minority groups and their subpopulations must be included in all NIH-supported biomedical and behavioral research projects involving human subjects, unless a clear and compelling rationale and justification establishes inclusion is inappropriate with respect to the health of the subjects or the purpose of the research. Exclusion under other circumstances may be made based on a compelling rationale and justification. Cost is not an acceptable reason for exclusion except when the study would duplicate data from other sources. Women of childbearing potential should not be routinely excluded from participation in clinical research. All NIH-supported biomedical and behavioral research involving human subjects is defined as clinical research. This policy applies to research subjects of all ages.
The inclusion of women and members of minority groups and their subpopulations must be addressed in developing a research design appropriate to the scientific objectives of the study. Describe the composition of the proposed study population in terms of gender and racial/ethnic group, and provide a rationale for selection of such subjects. Include a description of the proposed outreach programs for recruiting women and minorities as participants.
Clinical Trials: A Phase III clinical trial is a broadly based prospective investigation, usually involving several hundred or more human subjects. The objective is to evaluate an experimental intervention in comparison with a standard or control intervention or to compare two or more existing treatments. Often, such investigations strive to provide scientific evidence for considering a change in health policy or standard of care. The definition includes pharmacologic, non-pharmacologic, and behavioral interventions given for disease prevention, prophylaxis, diagnosis, or therapy. Community trials and other population-based intervention trials are also included. When a Phase III clinical trial is proposed, evidence must be reviewed to show whether clinically important gender, race or ethnicity differences in the intervention effect are to be expected. This evidence may include, but is not limited to, data derived from: prior animal studies, clinical observations, metabolic and genetic, research, recreation studies, pharmacology, natural history, epidemiology and other relevant studies.
Consider the following when planning a Phase III clinical trial for NIH support:
· Prior data strongly indicate that the intervention will show significant clinical or public health differences among gender, racial, and/or ethnic subgroups. In this case, the primary question(s) to be addressed and the design of that proposed Phase III trial must specifically accommodate these differences. For example, if men and women are thought to respond differently to an intervention, then the Phase III trial must be designed to answer two separate primary questions, one for men and the other for women, with adequate sample size for each.
· Prior data strongly support no significant clinical or public health differences among subgroups from the intervention. In this case, gender, race, and/or ethnicity will not be required as subject selection criteria. However, the inclusion of gender, racial and/or ethnic subgroups is still strongly encouraged.
· Prior data neither strongly support nor negate the existence of significant clinical or public health differences among subgroups. In such cases, the Phase III trial must include sufficient and appropriate gender, racial and/or ethnic subgroups, so that valid analysis of the intervention effect on subgroups can be performed. However, the trial will not be required to provide statistics for each subgroup.
Cost is not an acceptable reason for exclusion of women and minorities from clinical trials.
Funding. Awards will not be made if the research project does not comply with this policy. In addition, awardees must report annually on enrollment of women and men, and on the race and ethnicity of research participants in the Annual Report Format shown below.
Additional Information. In conducting peer review for scientific and technical merit, IRGs must evaluate proposed plans for inclusion of minorities and both genders, the design of clinical trials, and recruitment/outreach as part of the scientific assessment and assigned score.
Under DHHS regulations to protect human subjects from research risks, certain research areas are exempt from these regulations (Exemptions 1-6). Nonetheless, NIH-supported biomedical and behavioral research projects involving human subjects that are exempt from the human subjects regulations should still address in the study design the inclusion of women and minorities. Therefore, all biomedical and behavioral research projects involving human subjects will be evaluated for compliance with this policy. For example, research involving the collection or study of existing data, documents, records, pathological specimens, diagnostic specimens, or tissues that are individually identifiable should also be included within the term "research involving human subjects."
Annual Report Format:
The following definitions apply for the racial and ethnic categories.
(1) Minority Groups
A minority group is a readily identifiable subset of the U.S. population which is distinguished by either racial, ethnic, and/or cultural heritage. The Office of Management and Bud get (OMB) Directive No. 15 defines racial and ethnic categories. NIH has chosen to use these definitions because they allow comparisons to many National data bases, especially National health data bases.
American Indian or Alaskan Native: A person having origins in any of the original peoples of North America, and who maintains cultural identification through tribal affiliation or community recognition.
Asian or Pacific Islander: A person having origins in any of the original peoples of the Far East, Southeast Asia, the Indian subcontinent, or the Pacific Islands. This area includes, for example, China, India, Japan, Korea, the Philippine Islands, and Samoa.
Black, not of Hispanic Origin: A person having origins in any of the black racial groups of Africa.
Hispanic: A person of Mexican, Puerto Rican, Cuban, Central or South American or other Spanish culture or origin, regardless of race.
(2) Majority Group
White, not of Hispanic Origin: A person having origins in any of the original peoples of Europe, North Africa, or the Middle East.
NIH recognizes the diversity of the U.S. population and that changing demographics are reflected in the changing racial and ethnic composition of the population. The terms "minority groups" and "minority subpopulations" are meant to be inclusive, rather than exclusive, of differing racial and ethnic categories.
(3) Subpopulations
Each minority group contains subpopulations, which are delimited by geographic origins, national origins and/or cultural differences. It is recognized that there are different ways of defining and reporting racial and ethnic subpopulation data. The subpopulation to which an individual is assigned depends on self-reporting of specific racial and ethnic origin. Attention to subpopulations also applies to individuals of mixed racial and/or ethnic parentage. Researchers should be cognizant of the possibility that these racial/ethnic combinations may have biomedical and/or cultural implications related to the scientific question under study.