. Approved For Release 2000/08/08 : CIA-RDP96-00788R001700250001-7 | Page 4 PART 46--PROTECTION OF HUMAN SUBJECTS ‘Subpart A—Basic HHS Policy for Protection of Human Research Subjects See. 46.101 48.102 46.103 46 104 46.105 46.106 46.107 46.408 To what do these regulations apply? Definitions. Assurances. Section reserved. Section reserved. Section reserved, IRB membership. IRB functions and operauons. 46.109 IRB review of reseasch. 46.110 Expedited review procedures for certain kinds of research iavolving no more than minimal risk, and for minor changes in approved research. 46.101 Criteria for IRB approval of research. 46.543 Review by institution. 40.113 Suspension or termination of IRB approvai of research. 46,114 Cooperative research. 40.545 IRB records. 46.146 General requirements fo: informed consent. 46.117 Documentation of informed consent. 46.118 Applications and proposals lacking definite plans for invelvement of human subjects. 46.169 Research undertaken without the intention of involving human subjects. 120) LEvaluanon and disposition of applications and proposais. 46.121 Investigaional new drug or device JOQ-day delay requirement. 46.122 Use of federal funds. 40.123 Early termination of research funding: evaivation of subsequent applications and proposals. 46 124 Conditions. 46. Subpart B—-Additional Protections Pertaining to Research, Development, and Related Activities [Involving Fetuses, Pregnant Wemen, and Human in Vitro Fertilization Sec. 46.205 46.202 46.203 Applicability. Purpose Definitions. 46.204 Ethical Advisory Boards. 46.205 Additional duties of the Lostitutional Review Boards in connection with activities involving fetuses, pregnant women, or human in vitro fertilization. 46.206 Gerezal limitations. 46.107 Activities directed toward pregnant women as subjects. 45.208 Activities directed toward fetuses in utero at subjecis. 46.209 Activities directed toward fetuses ex utero, including nonviable fetuses, as subjects. 46.210 Activites involving the dead fetus, feral material, or the placenta. 46.211 Modification or waiver of specific requirements. Subpart C--Additional Protections Pertaining to Biomedical and Behaviorsi Research lavelving Prisoners as Subjects Sec. 46.301 46.302 Applicability. Purpose. 46.303 Definisions. 46.304 Composiiion of Institutional Review Boards where prisoners are involved. 46.305 Additional duties of the Institutronal Review Boards where prisoners are involved. 46.306 Permitted activities involving prisoners. Subpart D-- Additional Protections for Children Involved ag Subjecta in Research Sec. 46.401 46.40} To what do these regulations apply? Definitions. 46.403 IRB duties. 46.404 Research not involving yreater than minimal civk, 46.4053 Research involving greater than minimal risk bul presenting the prospect of direct benefit to the individual subjects, 46.405 Research involving greater than minimal risk and no prospect of direct benefit tu individual subjects, but likely to yield generalizable knowledge about the subject’s disorder or condition. 46.407 Research not otherwise approvable which presents an opportunity to understand, prevent, or alleviate s serious problem affecting the health or welfare of children. 46.408 Requirements for permission by parents of guardians and for assent by children. 46.409 Wands. Authoriiy: § U.S.C. 30h. sec 474(a), 88 Stat. 352 (42 U.5.C, 289/-3ta). 48 CFR 46 Subpart A~-Basic HHS Policy for Protection of Human Research Subjects Source: 46 FR @386, January 26, 1981, 48 FR G 9269, March 4, 1983. § 46.101 To what do these regulations apply? (a) Except as provided in paragraph (b) of this section, this subpart applies to all research involving human subjects conducted by the Department of Health and Human Services or funded in whole or in part by a Department grant, contract, cooperative agreement or fellowship. (1) This includes research conducted by Department employees, except each Principal Operating Component head may adopt such nonsubstantive, procedural modifications as may be appropriate from an administrative standpoint. (2) It also includes research conducted or funded by the Department of Health and Human Services outside the United States, but in appropriate circumstances, the Secretary may, under paragraph (e) of this section waive the applicability of some or all of the requirements of these regulations for research of this type. (b) Research activities in which the only involvement of human subjects will be in one or more of the following ategories are exempt from these” regulations unless the research is covered by other subparts of this part: (1) Research conducted ia established or commonly accepted educational settings, involving normal educational practices, such as (i) research on regular and special education instructional strategies, or _ (ii) 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), if @ Approved For Release 2000/08/08 : CIA-RDP96-00788R001700250001-7
‘ 1 information taken from these sources ‘is recorded in such a manner that subjects cannot be identified, directly or through identifiers linked to the subjects. (3) Research involving survey or interview procedures, except where all of the following conditions exist: (i) responses are recorded in such a manner that the human subjects can be identified, directly or through identifiers linked to the subjects, (ii) the subject's responses, if they became known outside the research, could reasonably place the subject at risk of criminal or civil liability or be - damaging to the subject's financial standing or employability, and (iii) the research deals with sensitive aspects of the subject's own behavior, such as legal conduct, drug use, sexual behavior, or use of alcohol. All research involving survey or interview procedures is exempt, without exception, when the respondents are elected or appointed public officials or candidates for public office. i4) Research involving the observation (including observation by participants) of public behavior, except where all of the following conditions exist: G) observations are recorded in such a manner that the human subjects can be identified, direclly or through identifiers linked to the subjects, (ii) the observations recurded about the individual, if they became known outside the research, eouid reasonably place the subject at risk of criminal or civil ability or be damaging to the subject's financial standing of employability, and (iii) the research deals with sensitive aspects uf the subject's own behavior such as illegal conduct, drug use, sexual behavior, or use of alcohol. (5} Research iavolving the collection or study of existing data, documents, records, pathological specimens, of diagnostic specimens, W these sources are publicly available or if the information is recorded by the investigator in such a manner chat ‘ ‘as cAPRFOVed For Release 2000/08/08 : CIA-RDP96-00788R001700250001-7 Pn se AH AR Am ce HEN De Re Am DRE RM — LV eemn EAPR  l subjects cannot be identified. directly or through identifiers linked to the subjects, (6) Unless specifically required by statute (and except to the extent specified in peragraph (i)), research and demonstration projects which are conducied by or subject to the approval of the Department of Health and Human Services, and which are designed to study, evaluate, or otherwise examine: (1) programs under the Soctal Security Act, or other public benefit or service programs; (ti) procedures for obtaining benefits or services under those progratas; (iii) possible changes in or alternatives to those programs or procedures; or (iv) possible changes in methods or levels of payment for benefits or services under those programs. (c) The Secretary has final authority to determine whether a particular activity is covered by these regulators. (d) The Secretary may require that specific research activities or classes of research activities conducted or funded by the Department, but not otherwise covered by these tegulatons, comply with some or all of these regulations. (e)} The Secretary may also waive applicability of these regulations to specific research activities or classes of research activities, otherwise covered by Uiese regulations. Notices of these actions will be published in the Federal Register as they occur. (f) No individual may receive Department funding for research covered by these repulations anless the individual is affiliated with or sponsored by un institution which assumes responsibility for the research under an assurance satisfying the requirements of this part, or the individual mukes other arrangements with the Deparcunent, (g} Compliance with these regulations will in ae way render inapplicable pertinent federal, state, or local liws or regulations. Page 5 (h) Esch subpart of these regulations contains a separate section describing to what the subpart applies, Research which is covered by more than one subpari shall compiy with ail applicable subparts. (i) If, following review of proposed research activities that are exempt from these regulations under paragraph (6)(6), the Secretary determines that a research or demonstration project presents a danger to the physical, mental, or emouonal well-being of a participant or subject of the research or demoastration project, then federal funds may not be expended for such & project without the written, informed consent of each participant ar subject. § 46.102 Definitions. (a) “Seeretary'’ means the secretary of Health and Human Services and any other officer or employee of the Depariment of Health and Human Services to whom authority has been delegated, (ob) “Department or "HHS" means the Department of Health and Human Services. (c) “astitution’’ means any public or private entity? agency (including federal, state, and other agencies). (d) “‘Legally authorized representative'’ means an individual of judicial or other body authorized under applicable law to consent on behalf of a prospective subject to the subject's participation in the procedure(s) involved in the research. (e) Research" means a systematic investigation designed to develop or contribute to generalizable knowledge. Activities which meet this definition constitute ‘research "* for purposes of these regulations, whether or not they are supported or funded under a program which is considered research for other purposes. For example, some ‘demonstration and *‘service programs may include research activines. ‘ Approved For Release 2000/08/08 : CIA-RDP96-00788R001700250001-7
+ BetABprove (f) ‘‘Human subject’’ means 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, “Intervention Y includes both physical procedures by which data are gathered (for example. venipuncture) and manipulations of the subject or the subject's environment that are performed for research purposes. “Interaction: * includes communication or interpersonal conlact between investigator and subject. “Private information" includes information about behavior that occurs in a context in which an individual can reasonably expect that no observation or recording is taking place, and information which has been provided for specific purpuses by an individual and which the individual can reasonably expect will not be made public (for example, a medical record). Private information must be individually identifiable (i.e., the idenuty of the subject is or may readily be ascertained by the investigator or associated with the information) ia order for obtaining the fafurmation to constitute research involving human subjects. (g) “Minimal risk’, means thaf the ftake of harm inilicipated in the ” praposed research are not greatér, considering probability and magnitude, than those ordinarily encountered in daily life or during the performance. of routing physical or psychological examinations or tests. (h) “Certification! means the official notification by the mstitution ta the Department in accordance with the requirements of this pari that a research project or activity involving human subjects has been reviewed and approved by thejnstitutional Review Board (HEB) in accordance with che approved assurance on file at HHS. (Certification is required when the research is funded by the Department and not otherwise exempt in accordance with § 46. 101(b)). ed For Release 2000/08/08 : CIA-RDP § 46.103 Assurances. (a) Each institution engaged in research covered by these regulauions shall provide written assurance satisfactory ta the Secretary that it will comply with the requirements set forth in these regulations. (b) The Department will conduct or fund research covered by these regulations only if the institution has an assurance approved as provided in this section, and only if the institution has certified to the Secretary that the research has been reviewed and approved by an IRB provided for in the assurance, and will be subject to continuing review by the IRB. This “assurance shall ata minimum include: (1) A statement of principles governing the institution in the discharge of its responsibilities for protecting: the rights and welfare of human subjects of research conducted ator sponsored by the institution, regardless of source of funding. This thay include an appropriate existing wode, declaration, or statement of ethical principles, or a statement formulated by the institution itself, This requirement does not preempt provisions of these regulations applicable: to Department-funded research and is not applicable to any research in an exempt category listed in § 46.10) (2) Designation of one or more IRBs established in accordance with the requirements of this subpart, and for which provisions are made for meeting space and sufficient staff to support (he IRB's review aad recordkeeping duties. (3) A lise of the IRB members identified by name. earned degrees: representative capacity; indications of expericonce such us board certifications, licenses, etc., sufficient to describe each member's chief anticipated contributions to IRB deliberations; and any employment or other relationship between each member and the institution: for example: full-time employee, part- lime employee, member of governing pane! or board, stockholder, paid or -00788R001700250001-7 reared een een Lian anna a 45 CFR 46 NC en Tate a ee unpaid consultant. Changes in IRB membership shall be reported to the Secretary. ! (4) Written procedures which the IRB will follow (i) for conducting its initial and continuing review of research and for reporting its findings and actions to the investigator and the institution; (ii) for determining which Projecis require review more often than annually and which projects need verification from sources other than the investigators that no material changes have occurred since previous IRB review; (ili) for insuring prompt reporting to the IRB of proposed changes in a research activity, and for imsuring that changes in approved research, during the period for which IRB approval has already been given, may not be initiated without [RB review and approval except where necessary to eliminate apparent inuntediate hazards to the subject: and (iv) for insuring prompt reporting to the IRB and to the Secretary! of unanticipated problems involving risks to subjects or others, (c) The assurance shall be executed by an individual authorized to act for the institution and to assume on behalf of the institution the obligations imposed by these regulations, and shall be filed in such form and manner as the Secretary may prescribe. . (d) The Secretary will evaluate all assurances submitted in accordance with these regulations through such officers and employees of the Depariment and such experts or consultants engaged for this purpose as the Secretary determines to be appropriate. The Secretary's evaluation, will take into consideration the adequacy of the proposed IRB in light of the anticipated scope of the institution's research activities and the types of subject populations likely to be  Reporis should be filed with the Office for Protection from Research Risks, National Institutes of Health, Deparment of Health and Human Services, Bethesda, Maryland 20205 Approved For Release 2000/08/08 : CIA-RDP96-00788R001700250001-7
_ Seen: rn tr involved, the appropriateness of the proposed initial and continuing review procedures in light of the probable risks, and the size and complexity of the institution. (¢) On the basis of this evaluation, the Secretary may approve or disapprove the assurance, or enter into negotiations to develop an approvable one. The Secretary may. limit the period during which any particular approved assurance or class of approved assurances shall remain effective or otherwise condition or restrict approval, (f} Within 60 days after the date of submission to HHS of an application ar proposal, an institution with an approved assurance covering the proposed research shall certify that the application or proposal has been reviewed and approved by the IRB. Oiher institutions shall certify that the application or proposal has been approved by the IRB within 30 days after receipt of a request for such a certification trom the Department. If the certification is not submitted within these time limits, the application or proposal may be retumed to the institution. § 46.104 [Reserved] $ 46.105 [Reserved] $.46.106 [Reserved] $ 46.107 IRB membership. (a) Each IRB shall have at least five members, with varying hackgrounds to promete complete and adequate review of research activities commonly conducted by the institution. The IRB shall be sufficiently qualified through the experience and expertise of its members, and the diversity of the members’ backgrounds including consideration of the racial and cultural backgrounds of members and sensitivity to such issues as community attitudes, to promate respeet for its advice and counsel in safeguarding the rights and welfare of human subjects. In addition to IRE ALT e  eCAI : NRRPN ABH BAS anche rede Rinne Metts unex fab nan a | 45 @ijipréved For Release 2000/08/08 : CIA-RDP96-00788R001700250001-7 | ent enero mRNA CER possessing the professional competence necessary to review specific research activities, the IRB shall be able to ascertain the acceptability of propased research in terms of institutional commitments and regulations, applicable law, and standards of professional conduct and practice. The IRB shall therefore include persons knowledgeable in these areas. If an IRB regularly reviews research that involves a vulnerable category of subjects, including but not limited to subjects covered by other subparts of this part, the [RE shail include one or more individuals who are primarily concerned with ihe welfare of these subjects. (b) No IRB may consist entirely of men or entirely of women, or entirely of members of one profession. (c) Each IRB shall include at least one member whose primary concerns are in nonscientific areas: for example: lawyers, ethicists, members of the clergy. (d) Each IR & shall include at least one member whe is aot otherwise affiliated with the institution and whe is not part of the immediate famiiy of a person who ts affiliated with the institution, (e) No IRB may have a member participating in the IRB's initial or continuing review of any project in which the member has a conflicting interest, except to provide information requested by the IRB. (D An IRB may, in its discretion, invite iadividuals with competence in special areas to assist in the review of complex issues which require expertise beyond or in addition to that avanable on the IRB. These individuals may not vote with the IRB. § 46.108 IRE functions and operations. In order to fulfill the requirements of these reguiations each IRB shail: (a) Follow written procedures as provided in § 46. 1063(b)(4). i ae ko AT ARC Sd a a ERT oe AE 6 i Ro Page 7 A Rt a aa (b) Except when an expedited review procedure is used (see § 46.110), review proposed research al convened meetings at which a majority of the members of the IRB are present, including at least one member whose primary concems are in nonscientific areas. In order for the research to be approved, it shall receive the approval of a majority of those members present at the meeting. _ (c) Be responsible for reporting to the appropriate institutional officials and the Secretary ' any serious or continuing noncompliance by investigators with the requirements and determinations of the IRB. § 46.199 IRB review of research. {a) An IRB shall review and have authority fo approve, require modifications in (to secure approval), or disapprove. all research activities covered by these regulations. (b} An IRU shall require that information given to subjects as part’ of informed consent is in accordance with § 46.116. The IRB may require that information, in addition to that specifically mentioned in § 46.116, be given to the subjects when in the IRB's judgment the information would meaningfully add to the Proicction of the rights and welfare of subjects. (c) An IRB shail require documentation of informed consent or may waive documentation in accordance with § 46.117. (d) An IRB shall notify . investigators and the institution in writing of its decision to approve or disapprove.the proposed research activity, or of modifications required fo secure IRB approval of the research activity. If the IRB decides to disapprove a research activity, if shall include in its written notification ' Reports should be filed with the Offics for Protection from Research Risks. National Instututes of Health, Department of Health and Human Services, Hethesda, Maryland 20205 Approved For Release 2000/08/08 : CIA-RDP96-00788R001700250001-7