ae ‘ ‘Approved For Release 2003/09/10 : CIA-RDP96-00789R003000020002-5 Page 4! or HUMAN SUBJECTS Subpart A—Besic HHS Policy for Protection of Human Research Subjects | See. 46 101 46.102 46.103 46 104 46.105 46.106 46.107 46.108 To what do these regulations apply? Definitions. Assurances. Section reserved Sectian reserved, Section reserved. IRB membership. . IRB functions and operstions. 46.109 IRB review of research. 46.1)0 Expedited review procedures for cettain kinds of research involving no more than minimal risk, and for minor changes in approved research. 46.191 Criteria for IRB approval of research, 46.112 Review by institution. 46.113 Suspension or termination of IRB approval of research. 46.114 Cooperative research. 46.515 IRB records. 46 146 General requirements for informed consent, 46.517 Documentation of informed consent. 46.118 Applications and proposals tacking definite plans for involvement of human subjects. 46.119 Research undertaken without the "intention of involving human subjects. 46.120 Evaluation and disposition of applications and proposals. 46.121  lovestigacional new drug or device 30-day delay requirement. 46.122 Use of federal funds. 46.123 Early termination of research funding: evaluation of subsequent applications and proposats. 46 124 Conditions. io Subpart B—Additional Protections Pertaining to Research, Development, and Related Activities Involving Fetuses, Pregnant Women, and Human In Vitro Fertilization Sec. 46.201 46.202 46.203 Applicability. Purpose., Definitions. 46.204 Ethical Advisory Boards. 46.205 Additional duties of the Institutional Review Boards in connection with Approved For Release 2003/09/10 : CIA-RDP96-00789R003000020002-5 esi stim ks th ve cre rene od af woten, of human ain vita icriiiscation, 46.206 General limitations S0.cU0) 0 Activites dtrected toward pregnant women as sutyects. 40.cu8 Activines directed toward teluses in utero at subjects. 46.209 Activities directed toward fetuses ex uiero, including nonviable fetuses. 35 subjects. 46.210 Activities involving the dead fetus, fetal material, or the placenta. 46.211 Modification or waiver of specific fequirements. Subpart C-—Additional Protections Pertaining to Biomedical and Behaviors! Research Involving Prisoners as Subjects Le ace. 46.301 46.302 Applicability. Purpose. 46.303 Definitions. 46.304 Composition of Institutional Review Boards where prisoners are involved. 46.305 Additional duties of the Institutional Review Boards where prisuners are involved. a 46.306 Permitted activities involving prisoners. Subpart D—Additional Protections for Children Involved as Subjects in Research Sec. 46.401 46.402 To what do these regulations apply? Definitions. 46.403 IRB duties. 46.404 Research not involving greater than minimal risk. 46.405 Research involving greater than minimal risk bui presenting the prospect of direct benefit to the individual subjects. 46.406 Research involving greater than minimal risk and no prospect of direct benefit to 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 a serious problem affecting the health or welfare of children. 46.408 Requiremenis for permission by parents or guardians and for assent by children. 46.409 Wards. Authority: $US C. 301, sec. 474(a), BB Stat 382 (42 U S.C. 289/-3tan). 45 CFR 46 renee ee eres een Seopart Aa Liasic HHS Fulicy for Proiection of Human Research Subiects Source: 46 FR 6386, January 26, 1981, 48 FR 9 2265, March 4, 198). § 46.101 To what do these repuiatons 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 employces, except. cach 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 tategories are exempt from these regulations unless the research is covered by other subparts of this part: (1) Research conducted in established or commonly accepted educational settings, involving normal educational practices, such as (1) 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, diasnostic, aptitude, achievement), if
a eo Nu ae . ‘Approved For Release 2003/09/10 : CIA-RDP96-00789R003000020002-5 “45 CFR 46 Sopmiatien takes from thos source. is tovorded in such a manner that subjects cannot be identified, directly or through identifiers linked to thy subjects. (3) Kesearch involving survey or interview procedures, except where alf of the following conditions exist: (1) Tesponses ure recorded in such a manner that the human subjects can be identified, directly or through identifiers linked to the subjects, (ii) ihe 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 emplayability, and (iii) the research deals with sensitive aspects of the subject's own behavior, such as illegal conduct, drug use. sexual behavior, or use of alcohol. All research involving survey or interview procedures 15 exempt, without exception, when the respondents are elected or appointed public officials or candidates for public office. (4) Research involving the observation (including observation by participants) of public behavior, except where all of the following conditions exist. (i) observations are recorded in such a manner that the human subjects can be identified, directly or through identifiers linked to the subjects, (ii) the observations recorded about the individual, if they became known outside the research, couid reasonably place the subject at risk of criminal or civil lability or be damaging to the subject's financial standing of employability, and (iii) the research deals with sensitive aspeets of the subject's own behavior such as illegal conduct, drug use, sexual behavior, or use of alcohol, (5) 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 informution is recorded by the investigator in such a manner that or through identifiers linked to the suayects. (6) Uniess specifically required by Statute (ond caccpi io the extent specified in paragraph (i)), research and demonstration projects which ta the eat be eo titin are conducted by ar subject approval of the Department of Health and Human Services, and which are designed to study. evaluate, or otherwise examine: (i) programs under the Social Security Act, or other public benefit or service programs; (ii) procedures for obtaining benefits or services under those programs; (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 regulations. (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 regulations, comply with some or all of these regulations. (e) The Secretary may also waive applicability of these regulations to specific Tesearch activities or classes of research activities, otherwise covered by these 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 regulations unless the individual is affiliated with or Sponsored by an institution which assumes responsibility for the research under an assurance éatisfying the requirements of this part, or the individual makes other arrangements with the Department, (g) Compliance with these regulations will in no way render inapplicable pertinent federal, state, or focal laws or regulations, ; ad Pape § Pete Sub atL OF Mhese Fees STONS Contains @ separate sectean des ribine to whet the subpari applies. Research which is covered by more than one subpert shall comply with aif applicable subparts. (i) If, following review of pranoced reccarch activities Uatare exempt from these regulations under paragraph (b)(6), the Secretary determines that a research or demonstration project presents a danger to the physical, mental, or emotional well-being of a participant or subject of the research or demonstration project, then federal funds may not be expended for such a project without the written, informed consent of each participant or subject. § 46.102 Definitions. (a) ‘‘Secretary'’ means the Seeretary of Health and Human Services and any other officer or employee of the Department of Health and Human Services to whom authority has been delegated. (b) ‘‘Department'’ or “‘HHS"* means the Department of Health and Human Services. “Legally authorized representative’’ means an individual or 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 activities, Approved For Release 2003/09/10 : CIA-RDP96-00789R003000020002-5
* . Pare 6 Approved For Release 2003/09/10 - CIA-RDP98-00789R003000020002-5 — () ‘Humas subject'’ means a ley individual about whar an mv student) conducting research obtains (1) data through intervention or interaction with the individual. identifishle private information, “Intervention Y includes both physical procedures by which data are athac 7 hee gathered (fur examine. y EaiOh Uwe bed peeressbonat ak or (2) and manipulations of the subject or the subject's environment that are performed for research purposes. ‘Interaction: ' includes communication or interpersonal contact 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 purposes by an individual and which the individual can reasonably expect will not he made public (for example, a medical record). Private information must be individually identifiable {i.e., the identity of the subject is or may readily be ascertained by the investigator or associated with the information) in order for obtaining the information to constitute research involving human subjects. esifogance: of: Croat ayereae; aesychpingical examinations or tests. (h) ‘'Certification}’ means the official notification by the institution to the Department in accordance with the requirements of this part that a research project or activity involving human subjects has been reviewed and @ approved by hegdapiep?! es’ (Certification i is y required when the research is funded by the Department and not otherwise exempt in accordance with § 46.101(b)). Approved For Release 2003/09/10 : CIA-RDP96-00789R003000020002-5 § 44.302 Assurances. (a) bach tn : Voss an Mee DS tig Hunen en yar edn te re geluarss shall provide written assurance salstactory to the Secretary that at wilh comply with the requirements set forib in these regulations. (b) The Department will conduct or fund research covered by these kote anus if tie insiititiud das 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 at or sponsored by the institution, regardless of source of funding. This may include an appropriate existing code, declaration, or statement of ethical principles, or a statement tormulated 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 § 46.101. (2) Designation of one or more IRBs established in accordance with the requirements of this subpart, and fur which provisions are made for meeting space end sufficient staff to support the IRB's review and recordkeeping duties. (3) A list of the IRB members identified by name; earned degrees; representative capacity; indications of experience such as 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 panel or board, stockholder, paid or 45 CFR 46 unpcid consultant: Cheapec in TRB todibershrp shall be remored ro the clay (4) Written procedures which tne 6 TRB wall follow co fer comfuctine its initial snd continuing revieve of research and for repeiiing its fiadings and actions to the investigator and the institution: (ii) for determining which PTOjCLS TOqQuile iCvic Hie ofica than annually and which projects need verification irom svurces other than the investigators that no material changes have occurred since previous IRB review; (iti) for insuring prompt reporting to the IRB of proposed changes in a research activity. and for insuring 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 imniediate 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 Department 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 * Reports should be filed with the Office for Protection from Research Risks, National Institutes of Health, Deparment of Health | and Human Services, Bethesda, Maryland 20205 € AN 0 Ph etna Wap map: evan.
"> 45 CFR 46 Approved For Release 2003/09/10 : CIA-RDP96-00789R003000020002-5 Invelved, (he appropriates, =s ef th: review procedures in light of the probable risks, and the size and complexity of the institution. (ec) On the basis of this evaluation, the Secretary may apprave or disapprove the assurance, or enter Into Aevotiations 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 or 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. Other institutions shall certify that the application or proposa! has been approved by the IRB within 30 days. after receipt of a request for such a certification from the Department. If the certification is not submitted within these time limits, the application or proposal may be returned to the institution. § 46.104 [Reserved] $ 46.105 [Reserved] 946.106 [Reserved] § 46.107 IRB membership. (a) Each IRB shall have at least five members, with varying buck grounds 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 promote respect for its advice and counsel in safeguarding the rights and welfare of human subjects. In addition to Possessing the nrofessiona! COMPS. tetice Hee OSsary we PeView ¢ Specific research activities, the IRB shall he able te ascertain the acceptability of proposed research in terms of institutional commitments and regulations, applicable law, and standards of professional conduct and practice. The IRB shail 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 IRB shall include one or more individuals who are primarily concerned with the 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 shail include at icasi one member whose primary concerns are in nonscientific areas: for example: lawyers, ethicists, members of the clergy. (d) Each IRB shall include at least one member who is not otherwise . affiliated with the institution and who is not part of the immediate family of a person who is 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. (f) An IRB may, in its discretion, invite individuals with competence in special areas to assist in the review of complex issues which require expertise beyond or in addition to that available on the IRB. These individuals may not vote with the IRB, § 46.108 IRB functions and operations, In order to fulfill the requirements of these regulations each IRB shall: (a) Follow written procedures as provided in § 46.103(b)(4). - rr tn ern en een fh) Except whin ai expedited revjew procedure ts used (sec § 46.110), review proposed research au Convened meetings at which a majority of the members of the IRB are present, including at least one member whose primary concems are im 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. § 46.109 IRB review of research. (a) An IRB shall review and have authority to approve, require modifications in (to secure approval), or disapprove all research activities covered by these regulations. (b) An IRB 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 Protection of the rights and welfare of subjects. : (c) An IRB shall require documentation of informed consent or may waive documentation in accordance with § 46.117. (d) An IRB shail notify ; investigators and the institution in ; writing of its decision to approve or disapprove. the proposed research activity, or of modifications required to secure IRB approval of the research activity. If the IRB decides to disapprove a research activity, it shall include in its written notification ’ Reports should he filed with the Office for Protection from Research Risks, National institutes of Health, Department of Health and Human Services, Bethesda, Maryland 20205 Approved For Release 2003/09/10 : CIA-RDP96-00789R003000020002-5