A pr or Release 2000/08108: CIA-RDP96-0078BROO1700250001-7 0 ovt, CODE OF FEDERAL REGULATIONS TITLE 45 PUBLIC WELFARE DEPARTMENT OF HEALTH AND HUMAN SERVICES NATIONAL INSTITUTES OF HEALTH OFFICE FOR PROTECTION FROM RESEARCH RISKS PART 46-PROTECTION OF HUMAN SUBJECTS REVISED AS Of MARCH 8,1983 Approved For Release 2000108108: CIA-RDP96-00788ROO1700250001-7 Approved For Release 2000/08/08 : CIA-RDP96-00788ROO1700250001-7 Pa .ge 4 45 CFR PART 46-PROTECTION OF HUMAN SUBJECTS -Subpart A-Basic HHS Policy for PrelMlon of Human Research Subjects Sec. 46 101 To what do thiese regulations apply? 46.1().l Definitions. 46.103 Assurances. 46 104 Section reserved. 46.105 Section reserved. 46.106 Section reserved. 46.107 IRS membership. 46.109 IRS functions and operations. 46.104) IRR review of research. 46.110 Expedited review proccdurci (Or certain kinds of research involving no more then minimal risk, and for minor changes in approved rescarch~ 46. 1 If Criteria for IRS approval of research. 4ty 11.1, Review by institution. 4N, 113 iuspension or termination of IRS approval of rescan~h. 4h. 114 Coopcrmive reicarch. 4ti ! 15 1 R 11 records. 4b I 16 General requirements, foi informed cotiseN. 41) 117 Documentaiionofinfoinicd consent. 46 118 Application-, and proposals lacking definite plans for involvement of human lubjects. 46~ 119 Research undertaken without the intention of involving human subjects. 46. 120 Evaluxiion and disposition of applicaitons and proposals. 46,121 Investiginional new drug or 4evice 10-day delay requircmeril. 46 122 Use of federal funds. 40. 123 Early termination of research fundlng~ CV31UU91011 Of SUbSrqUC111 applications and pvoposals~ 46 124 Conditions. Subpart B-Additional Protections Pertaining to Research, Development, and Related Activities Involving Fetuses, Pregnant Women, and Hurnan In Vitro Fertilization Sec. 46.7,01Alipficability. 46 FurNsc 202 46.20)Nfinitions. 46.204Ethical Advisory Boards. 46.205Ad4ilsonal duties of the Institutional Review Boards in connection with activitizz involving fetuses, pregnant women. or human in vitro fcrliliratlofl~ 46,206 Gerire*) limitations. 46.207 Activities directed toward pregnant women as subjects. 46.208 Activitici directed toward (ctu%c3 in uterto as iubjects. 46.209 Activities directed toward fetuse, & ex atero, including nonviable fetuses. as subjects. 46,210 Activates involving the dead fetus, fetal material. at the placenta. 46,211 Modification or waiver of specific rctititierrients, Subpart C.-Additional Protections Pertaining to Biomedical and Behavioral Research Involving Prisoners as Subjects Sec. 46.301 Applicability, 46.302 Purpose. 46.303 Definizionit. 46.304 Composition of Institutional Review Boards where prisoners are involved. 46.305 Additional duties of the Institutional Review Boards where prisonerv are involved. 46.306 Permitted activities involving prisoners. Subpart D-Additional Protections for Children Involved as Subjects in Research SM 46.401 To whot do these regulations; apply? 46,402 Dtfini6arm 46.403 IRRdkilirx. 46.404 Rcw.&j,:h not involving greater than minimal risk. 46A05 Rese-Arch involving greater than mimmal risk but prewnting the prospect oftlitect benefit to the individual subjmts, 46 436 Research involving gteater than minimal risk and no prospect of direct benefit to individual subjects, but likely to yield gwicrLdi7rable knowledge about the subject's disorcirr or condition. 46.407 Rruarch not otherwise approvable which prruots an opportunity to understand, prevent, or alleviate a serious problem affecting the health or welfare Of children. 46.408 Requirt-mersks for permission by PareaLs Of Riaudians and for assent by children. 46-409 Warci%. Authority; 5 U.S.C. 301; sec 4741a), 88 Stat. 352 (42 I.T.S.C. 2891-31(a)). Subpart A-Basic HHS Polky for Protection of Human Research Subjects Source: 46 FR 6396, January 2k 1981, 49 FR 9269, Match 4, 1983. 46.101 To what do thesie regulations apply? (a) Except as provided in paragraph (b) of this section. this subpan 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, tinder 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 lategorics are exempt from . t6ise regulations unless the research is covered by other subparts of this part; 1) Research conducted in established or commonly accepted educational settings. involving norinal educational practices, such as (I) research on regular and special education instructional strategies. OT 00 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), it Axt Approved For Release 2000/08/08 : CIA-RDP96-00788ROO1700250001-7 45* CAplgoved For Release 2000/08/08 : CIA-RDP96-00788ROO1700250001-7 information taken from these sources is recorded in such a manner that subjects cannot be identified, directly or through identifiers linked to (he subjects. M Research involving survey or interview procedures, except where all of tile following conditions exist: fi) responses are recorded in such a manner '"hat the human subjects can be identified. directly or through identifiers linked to the subjec(s. (ii) Ole subject's responses, if they ho, ame kiown outside the research, Could reasonably place the subject at risk of criminal or civil liability or be dai , ilaging to the subject's financial st.-inding or employability, and (iii) the research deals with sensitive aspecl,!, of the subject*s own behavior, such as illegal conduct, drug use, SCAUal behavior, or use of alcohol. All rese3rch involving survey or interview procedures is exempt, without cxception~ when tile respondents are elected or appointed public officials or candidates for Vuhlic office. (4) Rcsearch involvini! tile obscr%ation (including g obsel-Vation by panicipants) of public bohavior. cxcept where all of the folliwong t:ondilions exist: 0) obwrvarions are recorded in such a manner that the hurnan Subjects can be identified, dircctly or throuell identifiers linked to the subjects, 00 the obscrNmions recolded abou( tile individual, if the), becanie known outside the research, Cou;Ad reasonably place the subject at risk ol'criminal or civil liability or be daimi.ging it) tile subject's financial standing or employability, and (iii) the rcscar'ch deals With sensiti%e aSJ)eLtS 01 tile %'UhJCCCS Own behavior Such a~ illegal conduct, drug UW, w~u.Al behavior. or use of alcohol, (5) Research involving the collection or study of existing data, docurnents. records, pathological ,pociniens, or diagnostic specimens, it these sources are publicly avaiiable or if tile information is recorded by ific invesilgator in such a nianner (flat subjects cannot be identified. directly or through Identifiers linked it) the subjects, (6) Unless sju-cificilly requiied by wtute (arid except to the extent specified in piragraph (i)), research and demonstration projects which are conducted by or suhjft~t to the approval of the Department of flealth and Human Services, and which are designed to study, evaluate, or otherwise examine: (i) programs under tile Social Security Act, or other public beriefit or service prog.Tanis; (ii) procedures for obtaining bcnefits or services under those prograras; (iii) possible changes in or alternatives to those prograr"s or procedures, or (iv) possible changes in mei-hods or leve)s of payment for benefits or servicas under those programs. (c) The Secretarv has final authority to dvierinine whether a particular ac?ivity is covered by these regulations. (d) Tile sc-cretary illay require thal specific research activities or classes (-A research aciivitic% conducted or funded by the Department, but not otherwise covered by these regulations, comply Aith sorne or all of these regulations. (e) The Secretary inay also wai,~c applicability o' these regulations to Npecific reseatch activities or classes of research activities, otherwise covered by these regulations. Notices of these actions will be published in The Federal Registej- as they occur. (f) No indivdual maw receive Department funding for' research covered b, theme regulations unless the indi-vidual is affiliated with (-.),r rponsored by ~-m institution which assullics rc-sponsibifity for the research tinder an assuranc-t %.ansfying the requirements of this part, or the individual inak~-s other arranpcments Witt) tile Dep4rlment, (g) Con-1pharce %vith these regndatioii~ v"ill in no way render inapplicabic pcrtment t'Cdcral, stac, or local law% or ceg"lations. PaRt 5 (h) Each subpan of these regulations contains a separate section describing to what the subpart applies. Research which is covered by more than one subpart shall cornpiy with all applicable subparts. (i) If, following review of proposed research activities 'hat are exerript from these regulations under paragraph (b)(6), the Secretary determines that a research or demonstration project presents a dam er to the physical, menta.1, or emotional well-bLing of a participant or subject of the research or demoa,~Lration project, then federal bc funds may not , expended for such a project without the written, informed consent of each participant or subj fti. 46.102 Definitions. (a) -Secretary" means the Socreviry of Health and Hunian Services and any other officer or employee of the Department of' Health and Human Services to whom authority has been delegated. N "Departnient- or -HHS- means ,he Deparinwri( of Health and Hurrian Services. (c) -105titutiop, * Ineans, afty dic or private entir -61"b46 q Onclu ng federal, state, and oftr 4gcn~ieg) (d) -U-gally authorize d representative" nicans 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" incans 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 considcrcd research !"Or other purp~oses. For example, some -dcrnonstra(ion- and "service" programs may include researrh activities. Approved For Release 2000/08/08 : CIA-RDP96-00788ROO1700250001-7 P"!A rov d For Re -RDP96-00788RO01 700250001-7 45 CYR 46 _[~;~§e 2000/08/08 : CIA "1111110001/r (f) "Human subject..' means a living individual about. whorn an investigator (whether professional or student) conducting research obtains (1) data through intervention or interaction with the individual, or (2) iden(ifiable private inforriliflion . "Intervention' includes both physical procedures by which data are gathered (for example, veniptincture) and manipulations of the subject or the subject's environment that are pci-formed for research purposes. "lnicractior~- includes communication or interpersonal J 46.103 Auurances. (a) Fach immution engaged in research cover,.d by (hese regulations shall provide written assurance satisfactory tv the Secretaiy that it will comply with the requirements set forth in diese regulations. (b) The Department will conduct or fund research covered by these regulation% only if the institution has an assurance approved as provided in this section. anti only if the institution has ceitified to the Secretaty that the reseat-ch has been reviewed and approved by an IRB provided for in the assuranle, and will be subject to continuina review by the IRB. This 'assurance shall at a minimum include: '~I) A statement of principles governing the institution in the discharge o. its responsibilities for g protecting the rights and wellare of human sub -iects of research vonducted at or sponsored by the institutiOn, regardless of source of funding. This nav includo an appropriate existing Qode. deciaration, or stateirient of' ethical principles, or a statcuient (ortnuiatcd by the institutitin itself. This requirement does [lot preetript provisions of these regulatiOn" applicable to Departmeni-fundod research and is not applicable to ally rescarch in an exempt catelgory listed in § 46.101 (2) Designation of uric or more lRBs established in accordance with the requirements of' this subparl, and for which provisions are made for niceting space and sufficient staff to suppon like IRB's review and tccordkeep~rig duties. (3) A list of ~hc [RD members idcntifi~--J by name,. earned degrees, represcf1tative capacity; indications of expcricnc~~ such as board certifications, liccn%es. etc., sufficient lo ditscribe each tnember's chief aimcipatrd contributions to IRB dcllberati~wi,~, and any employment or other nAationship hetwe .en each member and the institutions for example: full-time cmploy(-V, part- lime ernployee. member of governing papul or board, stockholder,' paid or Unp3id consultant. Changes in IRB membership shall be reported to the Socretary. I (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 projects require review more often than annually and which projects need verification from sources other than the investigamrs that no material changes have occurred since previous IRB review; (iii) for insuring prompt reporting to the IRB of proposed changes in a research activity, and for insi;ring that changes in approved research. during the period for which IRB approval has already been given, mjy not be initiated without IRB review and approval except where necessary to climinate apparent inunediate hazards to the subject: and (iv) for insuring prompt reporting to the IRB and to the Secretary I of unanticipated problems involving risl.s to subjects or others. (c) The assuiance shall be executed hy an individual authorized to act for the institution and to assume on bchalf of the institution the obligations imposed by these regulations', and shall be filed in such form and manner as the Secretary may pirescribe. (d) The Secretary will evaluate all assurances submitted in accordance with these regulations through such officers and employees of the Depatiment and such experts or consultants engaged for this purpose as the Secretary determines to be appropriate. 'T~e Secretary's eva!uatiou.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 ~ 1, VIEW, contact between investigator and subject. -,Privaic information" includes inforniation 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 b,v an individual and whict. the individual can reasonably cxpect will not be made public ifor example, a inedical record). Private informall'Oll must be individually identifiable (i.e.. (tic identity of tile subject is or FIrlay readily be ascertained by the itivesligator or associatcd with the information) in order for obtaining the infurniation to constitute research involving human subjects. (g) "Minimal risk',*4means that'the risks of harm'an6cipated in the ~` praposed research are riot great6r, considering probability and magnimdo, than those ordinarily encountered in daily life or during the perfortilance of routine physical or psychological examinations or tests. (h) -Certification' nicans the official notification by the institution to the Department in accoruance with thc requirements of this pari that a research project or activity involving human subjects has been reviewed and approved by theJogipitional Rciiricw PORN (14B) in accordance with. the approved assurance on file at HKS: Wenification is requirc.-d when tile research is funded by the Department and not otherwise exempt in accordance with § 46.101(b)). Reporis should be filcd with the Officc for Protection from Research Risks, National Institute% of Hcaith, Depannient of Health and Human Services. Bcthe%da, Maryland 202105 Approved For Release 2000/08/08 : CIA-RDP96-00788ROO1700250001-7 4~ OW06ved For Release 2000/08/08 : CIA-RDP96-00788ROO1700250001-7 Page 7 involved, the appropriateness of the proposed initial and continiiing review procedures in light of the probable risks, and the size and complexity of the institution. W 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, linift the period during which any particular approved assurance or class of approved assurances shall remain effective or otherwise condition or restrict approval. M Within 60 days after the (late of submission to HIIS of an application or proposal. an institution with an approved assurance COVCTing the proposed research %hall certify that the application or proposal has been reviewed and approved by the IRB. Other institutions shall certify that the application or proposal has been approved by the IRB within 30 djys utter receipt of a request for such a ,-ertificailon from the Departnient. If ,he certification is not submitted within these linle linlit!" tile application or proposal may be returned to the institution. J 46.104 (Restrved] 4,16-105 [Rmrvedi 46-106 [Reserved] 1 46.107 IRB membership. (a) Each IRB shall have at least five members, with varying backgrounds to promote complete and ide-quate review of research activities commonly conducted by the institution. The IRB shall be sufficiently qualified through the. expenence and expertise of its memboers, and the diversity of the niernberS' backgrounds including consideradon of the MCi0l Rnd cultural backgrounds of members and sensitivity to such issues as cominunity attitudes, to promote respect for its advice and counsel in safeguarding the rights and welfare of human subjects. In 3ddition to possessing tale professional competence necessary to review specific rescarch activities, the IRB shall be ahle to ascertain the acceptability of proposed research in terms of inktautional 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 regtilarly reviews research that involves a vulnerable category of subjects, includi,ig but not limited to subjects covered by t)[her subparts of this part, the IRR shall include one or more individuals who are primarily concerned with the welfare of these subjects. (b) No IP%8 may consist entirely of men Or Cnliraly Of WQMCn, or entirely of members Iof one proifessiov. (c) Each IRB shall include at least one member whose primary concerns are in nonKientific areas; for examp!t-: law) cis, cthici~,ts, member% of the clergy. (d) Lach IRB shall include at least one mernbcr 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 rcview of any project in which the member has a conflicting interest, except to provide information Ecquested by the IRB. (f) An IRB inay. in its discretion, invite individuals with competence in special areas to assist in the review of complex is%ues which require expertise beyond or in addition to that availablc on the IRB. Thcse individuals inay not vote with the IRD. 46AM HUPo functions and operations. In ordcr to fulfill the requifements of these regulations each IRB shall: (a) Follow written procedures as provided in § 46.103(b)(4). (b) Except when an expedited review procedure is used (see 46.110), review proposed research at convened meetings at which a majority of the members of the IRB 3rc present, including at least one member whose primary concerns 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 I any serious or continuing noncompliance by investigators with the requirements and determinations of (lie IRB. J 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. 1b) An IRB shall require that information, given to subjects as part of informed consent is in accordance with § 46.116, The IRB may rcquire that information, in addition to that SPCC;fiC31ty mentioned in § 46.116, be given to the subjects when in the 111,13's judgment the information would meaningfully add to the protection of the rights and welfare of subjects. (c) An iRB shall require documentation of inforrried 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.du- proposed research activity, or of mmlifications 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 Reporti shuuld bc 61ed with the Officz for Prutcciion from kcscarch RiAs. National Institutes 4 flealth, Dcparimcnt oi Health atO Human Sc-rviccs, sethesda, 16firyland 20201 Approved For Release 2000/08/08 : CIA-RDP96-00788ROO1700250001-7 pxePWproved For Release 2000/08/08 : CIA-RDP96-00788 ROO 1700250001 -7 a statement of the reasons for its clt.cisiorn and give the investigator an opportunity to respond in person or in writing. (c) An IRB shall conduct continuing review arest4rch covered by these regulations at intervals appropriate to the degree of risk, but nix less than once per year, and shall have authority to observe or have a third party observe the conscrit process and the research. §46.110 Expedited review procedures for certain kinds of research involving no more than minimW risk, and for minor changes in approved research. (a) The Secretary has established, and published in the Federal Register, a list of categories of msurch that may be reviewed by the IRB through an expedited review procedure. The list will be aniended, as appropriate, through periodic republication in the Federal Register. N An IRB may review some or all of the research appearing on the list t1trough an expedited review procedure, if the research involves no more than minimal risk. The JRB may also use the expedited review procedure to review minor changes in previously approved research during the period for which approval is authorized. Under an expedited review procedure, the review itiay be cavried out by the IRB chairperson or by one or more experienced reviewers designated by the chairperson from among members of the IRR. In reviewing the research. the reviewers may exercise all of the authofilies of (he IRB except that the reviewers may not disapprove the research, A research activity may he disapproved only after review in accordance with the non-expedited procedure set forth in § 46.108(b). (c) Each IRB which uses an expedited review procedure shall adopt a method for keeping all members advised of research proposals whlich have been 3pproved under the procedure. (d) The Secretary may restrict, suspend, or terminate an Institution's or IRB's use of the expedited review proccclurc when necessary to protect the rights or welfare of subjects. §46.111 Criteria for IRR approval of reseurch. (a) In ordcr to approvc r-.-search covered by these regulations the IRB shall determine that all of the following requirements are ratisfied: (1) Risks to subjects are mirtimized: (i) By using procedures %vhich are consistent with sound research design and which do not unnecessarily expQsc subjects to risk, and 00 whenever appropriate. by using procedures already being performed on the subjects for diagnostic or treatment purposes. . (2) Risks to subjects are reasonable in relation to anticipated benefits. if' any, to subjects. and the importance of the knowledge that may reasonab!y be expected to result. In evaluating risks and bcnefits, the IRB should consider only those risks and benefits that may result from the research (as distinguished from risks and ben efils of therapies subjects would receive even if riot participating in the research). Thr IRB should riot consider pos3iblc long-range effects of applying knowledge gained in the rescarch (for c:tample. the possible effects of the research on public policy) as aniong those research risks that fall within the purview of Its r"ponsibility. (3) Selection o'f subjects is equitable. In making this assessment the IRB should take into account the parposes of the research and the setting in which the research will be conducted. (4) Infonned consent will be sought frorn each prospective subject or the subject's legally authorized representative, in accordance with, and to the exient required by § 46.116. 45 CFR 46 (5) Informed conseq will be apPropri&iiIy_d-m-'u'iii~'n9 ed. in accordance with, and to the extent required by § 46~ 117. (6) Where appropriate, the research plan ruakes adequate: provision for Monitoring the data collectcd to insure the safety of subjects. (7) Where appropriate, there 21f, adequate provisions to protect the privacy of subjects *and to maintain the confidentiality of data. (b) Where sonic or all of the subjects are likely to be vulnerable to cmrcion or unduc influence, such as persons with acute or severe physical or mental illness, or persons who are economically or educationally disadvantaged, appm . _priatc, additional, safeguard% have bwn istcludeiin the study to protect the rights and welfare of thew subjects. 146.112 Review by inslitution. Research covered by these regulations that has been approved by an IRB may be subject to further appropriate review and approval or disapproval by officials of the institution. However, those officials may not approve the rewarch if it has not been approved by an IRB. 46-143 Suspension or termination of IRB approval of research, An IRB shall have 4thariti. to suspend or te"ninate approval of' research that is nw being conducted in accordance with the IRB's requirements or that has been associated with unexpected serious harm to subjects. Any suspension or termination of approval shall include a statement of the reasons for the - - I R B 'S "tiop 40 SbAll. be repor" promptly to the investigator, appropriate institutional officials, and the SecTetary. Reports should be filed with the Office for Protection from Reimarch Risks, National lastitutel of Health. Department of Health and Hurnen services. Bethesda. Maryland 20205. Approved For Release 2000/08/08 : CIA-RDP96-00788ROO1700250001-7 45 CER 46 0 1 ,-,Ap pinuaf.1-fiar 700250001-7 PORC 9 46,114 Cooperative research. Cooperative research projecv; are those projects, normally supported through grants, contracts, or similar arrangements, which involve institutions in addition to the grantee or prime contractor (such as a contractor with the grantee, or a subcontractor with the prime contractor). In such instances, the grantee or prime contractor remains responsible to the Department for safeguarding the rights and welfare of human subjects. Also, when cooperating institutions conduct some or all of the research involving some or all of these subjects, each cooperating institution shall comply widi these regulations as though it received funds for its participation in the project directly from the Department, except that in complying with these regulations institugions ma.~ use joint review, reliance tipon the review of' another qualifit-d IRB, or similar arrangements aimcd at avoidance of dupilication of effort. 46.115 IRS rec'oias. (a) An institution, or where apprropriate an IRB, shall prepare and JJJJ intain adequate documentation of IRB activities, including the following: ( 1) Copies of ill research proposals revirwed, scientific evaluations, if any, that accompany the proposals. approved simple consent documents, progress reports submitted by jnv,;~stigafors, and reports of injuries to subjects. (2) Minutes of IRB meetings which shall be in sufficient detail to show 4ittendance at the meetings; actions taken by the IRB; the vote on these actions including the number of nternbers voting for. against,.and abstaining. the basis for requinng changes in or disapproving research-, and a written summary of the discussion of controverted issues and their resolution. (3) Records of continuing review activities. (4) Copies of all correspondence between the IRB and the investigators, (5) A list of IRB rnembers as required by § 46,103(b)(3). (6) Written procedures for the IRB as required by 4 46.103(h)(4). (7) Statements of significant new findings provided to subjects, as required by I 46.116(b)(5). (b) TJrJC records required by this regulation shall be retained- for at least 3 years afwr completion of the research, and the records dhall bc accessible for inspection and copying by authorized representatives of the Department at reasonable times and in a reasonable nianner. 46.116 General requirements for inforined consent. Except as provided elsewhere in this or other subparis, no investigator may involve a human being as a subject in research covered by ihc%e regulation-% unless the investigator has obtained the legally effective informed consent of Ow subject or the subject's legally authorized iripreseatativt~. An investigator shall seek such consent only under circuinstiklices that provide the prospective subject or the representative sufficient opportunity to consider whether or not to participate and that minimize the possibility of coercion or uadue influence. The information that is given to ~hc subject or the representative 5hall be in Ian uage k_ . 9 understandablc to ;hi;_subject or the representative. N'o informed consent, 'z ~ ii - i whether oral Or written. may include any exculpatory language through which the subject or the representative is made to waive or appear to waive any of the subject's legal rights, or releases or appears to release the itivestigator, the sponsor, the institution or its agents from liability for negligence. (a) Basic elernents of informed consent. E`xcept as provided in paragraph (c) or (d) of this section, in seeking itiformed conseptific following information shall-be Provided to each subject~- (1) A statement that the study involves research, an explanation of the purposes of the research and the expected duration of the subject's participation, a description of the procedures to be followed, and identification of any procedures which are experimental-. i!1 (2) A description of any reasonably 'foreseeable risks or discomforts to the 4subject; (3) A description of any benefits to the subject or to others which may ,I!reasonably be expected from the 41research; _M'A disclosure of appropriate alternative procedures or courses of treatment, if any, that might be advantageous to the subject.. - (3) A statement describing the extent, if any, to which confidentiality of records identifying the subject will be maintained; (61 For research involving more than minimal risk, art explanation as to whether any compensation and an explanation as to whether any medical treatments are available if injury occurs and, if so. what they consist of, or where further iff;jrpation niay be obtained,, 'An explanation of whom to contact for answers to pertinent questions about the research and Jesearch subjects' rights, and whom to contact in the event of a research- related injury to the subject; and 4f) A statement that participation is voluntary, refusal to participate will involve no penalty or loss of benefits to which the subject is otherwise eIntitlcd, and the subject may discontinue panicapation at any time without penalty or loss of benefits to ,which the subject is otherwise "entitled. I N Additional elements of informed consentr When appropriate. one or more of the following elements of information shall also be provided to cach subject: Approved For Release 2000/08/08 : CIA-RDP96-00788ROO1700250001-7 ~.'~gefiproved For Release 2000/08/08 : CIA-RDP96-00788ROO1700250001-7 Als CFR 46 (1) A statement that the particular treatment or procedure may involve 4~isks to the subject (or to the embryo tror fetus, if the subject is or may 21becomc pregnant) which are currently =unforeseeable; t. (2) Anticipated circumstances i under which the subject's participation may be terminated by ,.the investigator wi0out regard to the I subject's consent. (3) Any additional costs to the ,subject that may result from JParticipation in the rescarch~ 1 (4) The consequences of a '~subject's decision to withdraw from It V.the research and procedures for *orderly termination of participation 1by the subject; (5) A statement that significant riew findings developed during the i,,course of the research which may 4relate to the subject's willingness to continue participation wiN be provided to the subject, and i 16) The approximate number of -:,%iubjecis involved in the study. (c) An IRB axonalpt, dwaa4c,liciiide, or W,111chil=&;Aomc or, *lLo1.thS,,. Wormed consent set forth ab~oVe. or waive the requirement to obtain infornied consent provided the IRB finds and documents that: (1) T'he research or dcrrionstration project is to be conducted by or subject to the approval of state or hwal govemillent officials and Is designed to study, evaluate, or otherwise examine: (i) programs under the Social Security Act, or other public benefit or service 317 programs; (ii) procedures fi. obtaining benefits or services tinder those Progirmis; (iii) possible changes in or alternatives to those programs or procedurcs; or (iv) possible chariges in methods or levels of payment for benefits or services under tho!w programs; and (2) The research could not practicably be carried out without the waiver or alteration. '- " * " ' (d) An IRB rany'approve a consent procedure which does not include, or hich alt=6,some or all of the Y. clergents of Wormed consent set forth, abovej or waive the requirements to obtain informed consent provided the IRB finds and documents that: (1) Tile research involves no more than minimal risk to the subjects, (2) The waiver or alteration will not adversely affect the rights and welfare of the subjects-. (3) The rcsearch could not practicably be carried out without the waiver or alteration; and (4) Whenever appropfiate, tile subjects will be provided with additional pertinent information after panicipation. (e) The informed consent ms are requirements in these regulatic not intended to preempt any applicable federal, state, or local laws which require additional information to be discloscd in order for informed consent to be legally effective. (f) Nothing in these regulations is intended to limit ~hc authority of a physician to provide emergency medical carc, to tile extent tile physician is permiticd to do so tinder applicable federal, state, or local law. 0 46.117 Documentation of Informed coment. (a) Except as provided in paragraph (c) of this section, informed consent shall be documented by the use of a written consent form approved by the IRB and signed by the subject or the subject's lee, ally authorized representative. A copy shall be given to the person iigning the form. N Except as provided in paragraph G) of this section, the consent form may be either ofthe following: (1) A written consent document that ertibo~dics the elements of informed consent required by 0 46-116~ This form may he read to tile subject or the subject's legally authori7.cd representative, but, in any event, the investigator shall give either iliesubject or the representative adequate opportunity to read it before it is signed-, or qJmm' I iiikie~ (2) A 1,'09t consent document stating that the elements of informed consent required by J 46.116 have been presented orally to the subject or the subject's legally authorized representative. When this method is used, there shall be a witness to the oral presentation. Also, die IRB shall approve a written summary of what is to be said to the subject or the representative. Only the short form itself is to be signed by the subject or the representative. However, the witness shall sign both the short form and a copy of the elimmary, and the person actually ontsining consent shall sign a copy of tile summary. A copy of the summary shall be given to the subject or the representative, in addition to a copy of the -short form, (c) An IRD tmlywaivi requirement for the' investigatorloi obtain a signed'consent (am for s6me or all subjects if it finds either: (1) That the only record linking the subject and the research would be the c.onsent document and the principal nsk would be potential ham resulting from a breach of confidentiality. Each subject will be. asked whether the subject wants documentation linking the subject with the research, and the subject's wishes will govern; or (2) Thg the, leir more than m _,;irch presents.1o lhibij riA of ha~9_ to subjects anClavelycs no Proccaut s for which writt -_ ' i ' qp J'". _ 4.14 _rTi4lly re4uired ouOidt V91rresearch cOntext. In cases where the documentation requirement is waived, the IRB may require the invcstig3tor to provide subjects with a written statement regarding the research. 146.118 Applications and proposals lacking definite plans for involvement of human subjects. Certain types ol'applications for grants, cooperative agreements. or contracts are submitted to the Department with the knowledge that subjects may be involved within the Approved For Release 2000/08/08 : CIA-RDP96-00788ROO1700250001-7 45 (*RMved For Release 2000108/08: CIA-RDP96-00788ROO1700250001-7 peTicid of funding, but definite plans would not normally be set forth in the application or proposal. These include activities such as institutional type grants (including bloc grants) where selection of specific projects is the institution's responsibility-. rescarch training grants where the ;ictivities involving subjects remain to he selected; and projects in which hunian subjects' involvement will depend upon completion of instruments. prior animal studies, or purification of compounds. These applications need not lie reviewed by an IRB before air award may he made. However, except for research descr,ibed in § 46. 10 1 (b), no human subjects may be involved in tiny project supported by these awards until tile project has been reviewed and approved by the IRB. as provided in these regulations. and certsficition .NiArnitted to tire Department. 46.119 Research undertaken without the intention of involving huinan suhjects. In the event research iconducted or funded by the Department) is undertaken without the intention of rivolving human subjects, but it is later proposed to use human subjects in the research, the research shall first be reviewed and approved by an IRB, ,ks pruvided in these regulations, a certification submitted to the Departincal, and final approval given to tile proposcd change by the Department. the subjccis and othcrs., and the importance of the knowledge to he gained. (b) On the basis of this evaluation, the Secretary may approve or di-iappro-ve the application cfr proposal, or enter into negotiations to develop ,in approvable one. 46.121 Investigational new drug or device .14,day dehi mqWrement. When an institution is required to prepare or it) submit a certification with an ~ippfication or proposal Unjiff these regulations, and the application or proposal involves an investigational now drug (within the meaning of 21 U.S-C. 3550) or 357(d)) or a significant risk device (as defined in 21 CFR 812.3(m)), the institution shall identify the drug or device in the Qertification. The institution shall also state whethcr tile 30-day interval required for investi gationao' new drugs by 'I CFR 312. 1(a) and for significant risk- devices by 21 CFlZ 812.30 hash elapsed, or whether the Food and Drug Administration has waived that requirement. if the 30-day intot-val has expired, the iu%stitutio'n shall statc wKether the F00d and Drur Administration has requested that ?hv %ponsor continue to withhold or restrict the use of the drug or device in hunian subjects. If the 30-day interval has not expired, and a %4aiver has not been received. tile institution shall send a staternem to the Department upon expiration of tile interval, The Department will not Consider a ccrzificulion acceptable until the institution has submittod a statement that the .30-day interval has elapsed, arid the Food and Drug Administration has not requested it to limit the use ofthe drug or device, or that the Food in(] Drug Administration his walved the 30-day interval. regulations, including all subparts of these regulations, have been satisfied. 146.123 Early termination of research funding; evaluation of subsequent applications and proposals. (a) The Secretary may require that Department funding for any project be terminwed or suspended in the manner prescribed in applicable program requirements, when the Secretary finds an institution has materially failed to comply with the terms (if these regulations. (b) In making decisions about funding applications or proposals covered by these regulations the Secretary may take into account, in addition to all other eligibility requirements and program criteria, factors such as whether the applicant has been subject to a termination or suspensiun under paragraph (a) of this section and whether the applicant of the person who would direct the scicntific and technical aspects of an activity has in the judgment of the Secretary materially failed to discharge responsibility for the pmtection of the rights and wclfar,~ of hurnan subjects (whether or not Depattrilent fuads were involved), 146-124 Conditions. With respect to any research project or any class of research projects the Secretary may impose additional conditions prior to or at the time of funding when in the Secrelury'5 judgment additional conditions arc necessary for the protection of human subjects. Subpart R-Additional Protections Pertaining to Research Development, and Related -Activitles fil ivitir Fetuses.-, Pregivant Women, and Human lit Vitro Fertilization' .1"ot.,Rt E. 40 FR. 11S28, Aug. 8, 1975, 43 FR - 1718, January I I , 1979. 4.1 FR )I ~5P, Novem1wr 3. 197M J 46.120 Fvaluation and disposition of applications and proposals. (m The Secretary will evaluate .all aj,,?p1hcations and proposals involving hunian subjects submitted to the Department through such officers and cinployees of tile Department and I such expens and consultants as the S,~,crciarv determines to he appropriate. 'This evaluation will take into consideration the risks to the wbicct%, (he adeqL13CY of protection agamst these risks, the potential benefits of the proposed rescarch to § 46,122 Use of Fedvral funds. Federal funds adrainiitered hy th:- Dep.itirnent may not he expeild~~tl (fir research involvtng hitmais suhiects unless tile requinerilent of these S 46.201 Applicahility. (a) 'i fie ri.-,g-ilations in this subpart are appLcabl-e to ail Department of lic:.d0h, F(lucation, and Wclfarc Approved For Release 2000/08/08 : CIA-RDP96-00788ROO1700250001-7 nb~ -W( VAMP", Approved For Release 2000/08/08 : CIA-RDP96-00788ROO1700250001-7 Page 12 45 CFR grants and contract supporting research, development, anti related activities involving: (1) Th,~- fetus, (1) pregnant women. and (3) human in vitro fertilization. (b) Nothing in this subpart Oall be construed as indicating that compliance with the procedures set forth herein will in any way render inapplicable per(inent State or local law-, hearing upon activities covered by this subpart. (c) The requirements of this subpart are in addition to 1'riose imposed under the other subparts of this part. 46.202 Purpose. It is the purpose of this subpart to provide additional safeguards in reviewing activities to which this subpart is applicable to assure that they conform to appropriate ethical swridards and relate to important societal needs. 46.203 Definitions. ,As used in this subpart.- (a) -Secretary" means 1h e Secretary of Hcalih, Education, arid Welfare and any other officer or employee of the Department of Health, Education,,and Welfare to whom authority has been delegated. (h) -Pregriancy- encompasses the. period of time from confirmation of implantation (through any of the presumptive signs of pregnancy, such as missed mcnses, or by a medically acceptable pregnancy test). until expulsion or extraction of the fetus, (c) "Fetus" ineans the product of conception from the time of implantation (as evidenced by any of the presumptive signs of pregnancy, such as missed menses. or A medically acceptable pregnancy test). until a determination is made, following cxplusion or extraction of the fetus, that it is viable. (d) -Viable" as it pertains to the fetus means being able. after either spontancous or induced delivery, to survive (given the benefit of available medical therapy) to the point of independently maintaining heart beat and respiration. The Secretary may froin (imc to time. taking into account medical advances, publish in the FEDE-RALRF61STER guidelines it) assist in determining whether a fetus is viable for purposes of this subpart. If a fetus is viable after delivery. it is a premature infant, (e) "Nonviable fetus" nicans a fetus ex utero which, although living, is not viable, M -Dcaul fetus" means a fetus ex utero which exhibits neither heartbeat, spontaneous respiratory activity, spontaneous movement of voluntary muscles, nor pulsation of the umbilical cord (if still attached). (g) "In vitro fertilization" means. any fertilization of human ova which occurs outside the body ofa female, either through admixture ofdonor human sperm and ova or by any other means. § 46.1.04 'EtWeal Advisory Boards. P (a) One ot more Ethical Advisory Boards shall be established by the Secretary. Members of these board(s) shall be so selected that the board(s) will be competent to deal with medical, legal. social, ethical. and related issucs and may include, for example, research scientists, physicians, psychologists, sociologists, educators. lawyers, arid ethicists, as well as representatives of the general public. No board inember may be a rcgular, full-time employee of the Department of Heal(h, Education, and Welfare. (b) At the request of the Secretary. the Ethical Advisory Board shall render Litivice consistent with the policies and requirements of this Part as to ethical issues, involving activities covered by this subpart, raised by individual applications or proposals. In addition, upon request by the Secretary, the Board shall render advice as to classes of applications or proposals and general policies, guidelines, and procedures. (c) A Board may establish, with the approval of the Secretary, classes of applications or proposals which: (1) Must be submitted to the Board, or (2) need not be submitted to the Board. Where the Board so establishes a class of applications or proposals which must be submitted, no application or proposal within die class may be funded by the Department or any component thereof until the application or proposal has been reviewed by the Board and the Board has tendered advice &i to its acceptability from an ethical standpoint, (d) No application or prGposal involving human in vitro fertilization may be funded by the Department or any component thereof until the application or proposal has been reviewed by the Ethical Advisory Board and the Board has tendered advice as to its acceptability from an ethical standpoint. 46.205 AdditkmW duties ottfie InsflIvtWiAA1iAi-w -Boards In connection with activities involving fetuses, pregnant women, or human in vitro fertilization. (a) In addition to the responsibilities prescribed for Institutional Review Boards under Subpart A of this part, the applicant's or offeror's Board shall. with respect to activities covered by this subpart, carry out the following additional duties: (1) Determine that all aspects of the activity meet the requirements of this subparts (2) Determine that adequate consideration has been given to the manner in which potential subjects will be selected, and adequate provision has been made by the applicant ar offeror for monitoring the actual informed consent process (e.g., through such mechanisms. when appropriate, as participation by the Institutional 'Review Board or subject advocates in: 0) Overseeing the Actual process by which individual consents required by this subpart are secured either by approving induction of each individual into the activity or Approved For Release 2000/08/08 : CIA-RDP96-00788ROO1700250001-7 45'C!AR*oved.For Release 2000/08/08 : CIA-RDP96-00788ROO1700250001-7 Page 13 verifying. perhaps through sampling, that approved procedures for induction of individuals into the activity are being followed, and 00 monitoring the progress of the activity and intervening as necessary through such stcps as visits to the activity site and continuing evaluation to dolermine if any unanticipated risks have arisen); (3) Carry out such other responsibilities as inay be assigned by the Secretary. M No award may be issued until the applicant or offeror has ccrtified to the Secretary that the Institutional Review Board has made the determinations required tinder paragraph (a) of this section and the Secretary has approved these determinations. as provided in 46.120 of Subpart A of this part. (c) Applicants or offerors se~lking support ,for activities covered by this subpart inust provide for the desipnation of an Institutional Review Board, subject to approval by the Secretary, where no such Board has been established under Subpart A of this part. 46.206 Gentral limitafio:ws. (a) No activity to which this subpart is applicable may be undertaken unless'. (1) Approprime studies (in animals and nonpregnant individuals have been completed-, (2) Except where the purpose of the activity is to meet the health nceds of the mother or the parlicular fetkiN, the risk to the fetus is minimal and, in all cases. is the least Possible risk for achieving the objectives of the activity. (3) Individuals engaged in the activity will have no part in: 0) Any dccisions as to the timing, method, arid procedures used to terminate the pregnancy, and (6) determining the viability of the fetus at the termination of the pregnancy; and (4) No procedural changes which may cause greater than minimal risL to Ehe fetus or the pregnant woman will he introduced into the procedure for terminating the pregnancy solely in the in(crest of the activity. M No inducements. monetary or otherwise, may be offered to terminate pregnancy for pur-poses of the activity, [40 FR 335M Aug. 8. 1975. as amerxied at 40 FR 51638. Nov. 6, 1975) 146.207 Activities directed toward pregnant wonien as subjects. (a) No pregnant woman may be involved as a subject in an activity covered by this ~iubqart unless: (1) The purpose of the activity is to meet the health needs of the mother and the fetus will be placed at risk only to the minimum extent necessary to meet such needs, or (2) the risk . to the fetus is minimal. (b) An activity permitted under paragraph (a) ofthis section may be conducted only if the mother and fattier are legally competent arid have .en their informcd. consent aiter 9'v haviniiz been fully informed regarding possible impact on the fetus, except that the father's informed consent need not be secured if: (1) The purpose of the activity is to meet the health needs of the mother-, (2) his identity or whereabouts cannot reasonably be ascertained'. (3) he is not reasonably availablc~ or (4) the pregnancy resulted from rape. 46.208 Activities directed toward feause4 In utero as subjecM. (a) No fetus in igiero may be involved as a subject in any activity covered by this subpart unless: (1) The purpose of the activity is to meet the health needs of the particular fetus and the fetus will be placed at risk only to the minimum extent necessary to meet such needs, or (2) the risk to (lie fetus imposed by the research is minimal arid the purpose of the activity is the development of important bic~medical knowledge which cannot be obtained by other means. (b) An activity permitted under paragraph (a) of this section may bc conducted only if the mother and father are legally competent and have given their informed consent, except that the father's consent nced not be secured if: (1) His identity or whereabouts cannot reasonably be ascertained, (2) he is not reasonably available, or (3) the pregnancy resulted from tape. ".209 Activities directed toward fetuses ex utero, including nanviable fetuses, as subjects. (a) Until it has b,#.cn ascertained whether or not a fetus ex utcro is viable. a fetus ex utero may not be involved as a subject in an activity covered by this subpart unless: (1) There will he no added risk to the fetus resulting from the activity, and the purpose of the activity is the development of important biomedical knowledge which cannot be obt;aincd by uther means, or (2) 'rhe purpose of the activity is to enhance the pi-mibility of survival of the particular fetus to the point of viability. N No nonviable fetus may be involved as a subject in an activity covered by this subpart unless: (1) Vital functions of the fetus will not be artificially maintained, (2) Experimental activities which of themselves would terminate the heartbeat or respiration of the fetus will no( be employed, arid (3) The purpose of the activity is the development of important biomedical knowledge which cannot be obtained by other means. 1 W In the event the fetus ex utero is found to be viable. it rnay be included as a subject in the activity only to zhe extent perrysitted by and in accordance with the requirements of other subparts of this part. (d) An activity permitted under paragraph (a) or (b) of this section may be conducted only if the mother and father are legfilly competent and have given their informed consent, except that the father's informed consent need not be secured if- (1) his identity or whereabouts cannot reasonably be ascertained, (2) he is Approved For Release 2000/08/08 : CIA-RDP96-00788ROO1700250001-7 Approved For Release 2000/08/08 : CIA-RDP96-00788ROO1700250001-7 Page 14 45 CM 46 no( reasonably available, or (3) the pregnancy resulted from rape. 46110 Activities Involving the dead fetus, fetal material, or the plactrita. Activities involving the dead fetus, mascerated fetal material. or cells, tissue, or organ% excised frorn a dead fetus shall be conducted on1v in accordance with any applicable State or local laws regarding such activities. § 46.211 Modification or waiver of specific requirements. Upon the request of in applicant or offeror (with the approval of its Institutional Review Board). . the Secretary may modify or waive specific requirements of this subpart, ,~vith the approval of the Ethical Advisory Board after such opportunity for public comment as the Ethical Advisorv Board considers appropriate in the partwular instance. In makinF such decisions, wh,,! Secretary will consider whether zhe risks to the subject are so outweighed by the stim of the benefit to the sub,~e~:t and the impoitanLe of the knov,ledee to he gained as to warrant "tich 111~,~ifwjtion or waiver and that such henefits cannot he gained except through a modification or waiver, ekny huch modi t icat tons or waivers will he published as notice-s In the F1-A)1-RALREG1.SrtFL Subpart C-Additional Protectioms Pertaining to Biomedical and Behavioral Research Involving Mxmm &q Subjft-ts Sowvc. 43 FR 51655. Nov 16, 1973 § 46.301 Applicability. (a) The regulations in this subpart are applicable to all biomedicai and behavioral research conducted or Nupported by the Department of Health, Education. arid Welfare involving prisoners as sub,ject-i, 4h) Nothing in thissubpart -.hall bc c01V%trUCd wi indicating that ~:ornpllancc with the procedures set forth hcrein will authorize research involving prisoners as subjects, to the cxtent iuch research is limited or barred by applicable State or lo~:-Al law, (c) The requirements of this subpart are in addition to those imposed under the other subparts of this part. § 46.302 Purpose. Inasmucb as prisoners may be under constraints because oftheir incarceration which could affect their ability to make a truly voluntary and uncoerced decision whether or not to participate as subjects in research, it is the purpose of this subpart to provide additional safeguards for the protection of prisoners involved in activities to which this subpart is applicable, 46.303 Definitions. As used in this subpart: (a) "Secretary" means (lie Secreturv of Health, Education, and Welfare'and any other officer or eniployec ofthe Depar(ment of Health, Education, and Welfare to whom authority has b(:en dclegaufd_ N "DIIEW" mcans ihe Department of Health, E'ducation. and Welfare. M "Prisoner- means any 1adividual involunta -rily confined of det -. ".,d- - ainc in a penal institutior'i.'The I~rm ii i~iiic'ided `to'_c`ncomipass"- ~in,dividua)s-senteriVed'to such dn institution under a criminal or civil -~~aiute, in~div~idiials etained in o t, her facilities by. yirtuc.of statutes or Comini ttncat~ procedures- which provide;aftemuVe'n to.icrfmlnaf~~ iio~ec'utfo~lo'r inc'~iccration in a 'nal'insti't'u'lion.,p4 individuals PC. detained pcndling arraignment. trial, or sentencing. (d) "Minimal risk" is the probabilit-v anti magnitude of physical or psychological harm that is normally cricountered in the daily lives, or in the routine medical. dental, or psy;:hological examination of healthy persons. 46.3W Composition of Institutional Review Boards where prisoners are involvvd In addition to satisfying the requirements in § 46.107 of this pazt, an Institutional Review Board, carrying out responsibilities under ON this part with respect to researcti covered by this subpart, shall also meet the following specific requirements: (a) A ma*ty ~f ft Board, *4,5' (excl thill? -, ~nvt oz., Onsoisti have no association with the prison(O - ~ -_-- %,p involved, jqairt from their 1,4 I membership on the Bo"., -14 N At least one member of thip B ill 6io""4` ' ' - - -' loaro sh a onsoner Ora appropirtate- background and experience to serve in that capacity, except that where a particular research project is reviewed by more than one Board only one Board need satisfy this requirement. 4 46-305 AddlflarW duties of the Institutions! Review Boards where prisoners are Involved. (a) In addition to all other responsibilities prescribed for Institutional Review Boards under this vart, the Board shall review research covared by this subpart and -approve such research only if it finds thar (1) The research under review represents one of the categories of research permissible under 46.306(a)(2); (2) Any possible advantages accruing to the prisoner through his or her participation in the research, when compared to the general living conditions, medical care, quality of food. amenities and opportunity for earnings in the prisou. are. not of such a magnitude, that bi. a or her ability to~ weigh the-risks of the researcix apiast., the value of such" advantages in the limited choice environment of the prison is impaired. (3) The risks irrvolvcd in the research are commensurate with risks that would be accepted by nonprisoner volunteers, (4) Procedures for the selection,of subJects within the prison are fair to Approved For Release 2000/08/08 : CIA-RDP96-00788ROO1700250001-7 CIA-RDP96-00788 ROO 1700250001-7 PaRe IS all prisoners and immune from arbitrary intervention by prison authorities or prisoners. Unles-2- the principal investigator provides te the Board justification in writing for following some other pr(Kedures, control subkax mua be seiect.-d randomly (mm the "p of available prisoners who meet the characteristics needed for that particular research pro)ccc, (5) The information is presented in language which is understandable to the subject population; (6) Adcquale assurance exists that arolq t 0 V - - I -t va*,W , $Oka (0, 4CCOUIR a prisoner v participation in the research in making decisions regarding parole, and each prisoner is clearly informed in advance that participation in the research will have 4io effect on his or her parole; and (7) Where the Board finds there may bc a need for follow-up exammitinn or carc of participants after the end of their participalion. adequate provision has been made for such examination or care, taking into account the var ing lengths of y individual prisoners' sentences and for infutming participants of this fact. W The Board shall carry out such officr duties as may be assigned by the Secretary. ~0 The institetion shall certify to the Secretary, in such form and mannef as the Secretary may require, that the duties of the Board under this .section have been fulfilled. J 46.306 Perinitted research Involving prhsooer3.1--' - f W Biomedical or behavioral research conducted or supported by l')H[-"W may involve prisoners a.4 subjects only if: (1) The irstitution responsible for the-conduct of the research has cerlified to the Secrciary that the Insiitutional Review Board has approved the res4..-irch under § 46.305 tif this ~;uhpart: and ('21 In the judgment of the Secretary the proposed research invoives solely the following: (A) Study of the possible caus-,s. effects, and processes of incarceration, and of criminal behavior. provided that the study prcsents no more than minimal risk and no more than inconvenience to the subjects; (.B) Study of prisons as instituti~_)flal structures or of prisoners as incarcerated persons, provided that the study presents no more than minimal risk and no more than inconvcnience to the subjects: W) Research oil condifiows particularly affecting prisoners as a class (for example, vaccine trials and other research on hepatitis which is much mor,; prevalent in prisons than elsewhere-, and research on social and psychological problems such as alcoholisin, drug addiction and sexual assaults) provided that the study may proceed only after the Secretary has con5ulted with appropriate experts including experts in penology medicine and ethics, and published notice, in the Ft-.DERAL R EGISTE.P, of his intent to approve such research; (D) Research on practices, both nnovalive and .wcepted. which have the intent and reasonable probability of improving the heallh or well- bellig of the sub 'ject. In cases in which those studies require the assignment of prisoners in a manner consistent with protocols approved by the IRB to copirol groups which may not henefit from the research, the study may proceed only aher the Sccretary has consulied with appropriate expert,,, Includirig experm in penology medicine and ethics, and published notice, in the FFOE-RAL k E~Gis I F R, of his intent to approve such research. (b) Except as provided in paragraph (a) of this section, biomedical or behavioral research conducted or supported by DHEW shall not involve prisoners as subjects. Subpart D-Amauna Prowame (at CAUTM 1"Wved as Sabiaft in RftewdL SOutce: 48 PR 99 19. March 8, 1923 9 46.401 To what do thfte repladoas apply? (it) nL-. subpart applies to all reww'ch involving children as subjects, conducted or supported by the Department of Health and Human Services. (1) This includes re5earch conducted by Department employees, exccpt that each head of an Opcialing DIVINion (if tile Department may adopt such nonsubstantive, procedural modifications m may be appropriate r. Irom an administrative standpoint. (2) It also includes research conducted or supported by the Department of Health and Hurnmi Services outside the United Statrs, but in appropriate circurnstancm the Secretary may, under paragraph (e) of §46.101 of Subpart A, waivc the applicability of some or all of the requirements of these regulations for research of this type. (b) Exemptions (1), (2), (5) mid (6) as listed in Subpart A at §4&101(b) are applicable to this subpart. Exemption (4), rewarch involving the observation of public behavior, listed at § 46. 10 1 (b), is applicable to this subpart where the investigator(s) does not participate in the activities being observed. Exemption (3), research involving survey or interview procedures, listed at §46.101(b)docs not apply to research covered by this subpart. (C) I"tic exceptions, additions, and provisions for waiver as they appear in paragraplix (c) through (i) of § 46. 101 of S ubpart A are applicable to this subpart. §46.402 Ukefinitions. T'he definitions in §46.102 of Subpart A shA be applicable to this subpart as well. In addition, as used in this subpart: Approved For Release 2000/08/08: CIA-RDP96-00788ROO1700250001-7 PaRAAroved For Release 2000108/08 : CIA-RDP96-00788ROO1700250001-7 45 CFR 46 Wooe (a) '%Wdren',' are persons who have not attained the legal age for consent to treatments or prOcedures involved in the research, under the applicable law of the jurisdiction in wh.ich the research will be conducted. (b) "Ass~-WC* means a child's affirmative agreement to participate in research. Mere failure to object should not, absent affirmative agreement, be construed as assent, (c) "Permission" means the agreement of parent(s) or guardimi to the participation of their child or ward in mearch, (d) 'ParenC' means a child's biological or adoptive parent. (e) "Guardisn":mcans an individual who is authorized under applicable suite or local law to consent on bLba)f of a child to eeneral medical care. §46.403 IRD duties. In addition to other responsibilities assigned to IRUs under this part, each IRD shall review research covered by this subpart and approve only research which satisfies the conditions of all applicable sections of this subpart. §46.404 RewAmb."Outivollviag greater tb= miniml risk, HUS will conduct or fund research in which the IRB finds that ito greatcr than minimal risk- to children is presented, only if the IRB finds that adequate provisicinsare made for soliciting the assent of the cifildren and the permission of their parents or guardians. as set forth in § 46.406. § 44.405 Researth involvin% gmater Mae wfairml risk Wt presenting the prospett af dired benefit to t1w, ln&vidual auhJ*ct% HHS will conduct or fund msearch in which the IRD finds that more than minimal risk to children is presented by an intervention or procedure that holds out the prospect of direct benefit for the individual subject, or by a monitonng procedure that is likely to contribute to the subject's well-being only if the IRB finds that: (a) The risk is justified by the anticipated benefit to the subjects; (b)The relation of the anticipated benefit to the risk is at least as favorable to the subjects as that presented by available alternative approaches; and (c) AJequate provisions are made for soliciting the asient of the . children and permission of their parents or guardians, as set forth in § 46.408, 46.406 Research involving greater than minimal risk mid no "pect of direct &mcflt to Individual subjects, but likely to yield generalizable knowledge about the subject's disorder or condition. HHS will conduct or fund research in which the IRB finds that more than minimal risk to children is presented by an intervention or procedure that does not hold out the prospect of direct benefit for the individual subject. or by a monitoring pnvedure which is not likely to con(ribute to the well-being of the subject, ordy if the IRD finds that: (a) Ile risk represents a ininor increase over minimal risk; (b) The intervention or procedure prev.,.nts experiences to sub 'jectq that are reasonably commensurate with those inherent in their actual or expected medical, dental, psychological, social. or educational situation!;, (C) The intervention or procedure is likely to yield generalizable knowledge about the subject3' disorder or condition which is of vital importance for the understanding or amelioration of the subjects' disorder or condition; and (d) Adequate provisions are made for soliciting assent of the children and permission of their parents or guardians, as set forth in 146,408. 146,407 Research not otherwin approvable which pments An opportunity to understand, preyent~l or, alleviate a "aus problem affecting ". health or welfare of children. HHS will conduct or fund research that the IRS does not believe meets the requirements of 1146.404. 46.405, or 46.406 only if. (a) The IRO rinds that the rescairch presents a reasonabic opportunity to further the understanding, prevention, or alleviation of a serious problem affecting the health or welfare of children; and (b) The Secretary, after consultation with a panel of experts in pertinent disciplines (for example: science, medicine, education, ethics, law) and following opportunity for public review and comment, has determined either: (1) "at the research in fact satisfies the conditions of § 146,404, 46.405, or 46.", as applicable, or (2) the following: (Wrlic research presents a reasonable opportunity to further the understanding, prevention. or alleviation of a serious problem affecting the health or welfare of children; 60 The research will be conducted in accordance with sound ethical principles; (iii) Adequate provisions are Made for soliciting the assent of children and the permission of their parents or guardians, as set forth in 146.408. § 46-408 Requimumts for Peru "2031 by Parents or guardians "d for nowmi by 01ildren. (a) In addition to the determinations required uruler other applicable sections of this subpart, the IRD shall determine that adequate provisions are made for soliciting the assent of the children, when in the jud&ffient of the IRB the chddrcn are'capible of pro~idina' msent. In determining whether children are capable, of a nting, tbe. ~ ~SC IRB shall takii into account the agm, maturity, and psychological state of the children involved. This judgment ANN W7 Approved For Release 2000108108: CIA-RDP96-00788ROO1700250001-7 a!-4=M%LE_,L, L:Zqlea~~.e~CL09108108: CIA-RDP96-00788ROO1700250001-7 P2V 17 may be made for all children to be involved in research under a articular protocol, or for each child, %owl Vs the (RD deems appropriate. If the IRB determines that the capability of some or all of the children is w) limited that they cannot reasonably be consulted or that the intervention or procedure involved in the research holds out a prospect of direct benefit that is importwit to the health or well-being of the children and is, availabic only in the context of the research, the assent of the children is not a necessary condition for proceeding with the research. Even where the IRB determines that the subjects am capable of assenting, the IRD =y &tM waive tU, assent requirement tinder circuamtsucca in wbich conw-ut may be wAived in accord with J 46-116 of Subpart A. (b) In addition to the determinations required under othvr applicable si-ctiom of this subpart, the IRB shall determine, in accordaace with and to the extent that conwnt is required by J 46. 1 It) of i%o Subpart A, tho adequate provisions are made for soliciting the pemnnimion of each chiki's parents or guardian. Where parental permission is it) be obtained. the IRD may.find that the jwz mis~iion of one parent is sufficient for research to be conducted under J § 46.404 or 46.405. Where research is covered by § J 46.406 and 4&407 and permission is to be obtained from parents, both parents must give their permission unless one parent is deceased, unknown, incompetent, or not reasonably available, or when only one parent hax leg--a responsibility for the care and custody of the child. (c) In addition to the provisions for waiver contained in 146.116 of Subpart A, if the IRD determines that a research protocol is designed for conditions or fov a subject population for which parenial or guazdian permission is not a reasonable requirement to protft-t the subjects (far example, neglected or abu,,Axi children), it mitay waive the consent requirements in Subpart A of this partand paragraph (b) of this sc%-tion, provided an appropriate mechanism for protecting the childre-n who will participate its subjects in the research is substituted, and provided further that the waiver is not inconsistent with federal siate or local law. Th~ choice of an appropriate mechanism would depend upon the nature and purpose of the activities dc,.cribed in the protocol, the risk amid anticipated benet"it to the research subjects, arid their age, maturity, status, and condition. (d) Permission by parents or guardians shall be documented in accordance with and to the exient required by J 4& 117 of Subpart A. (e) When the IRB determines that assent is required, it shall also determine whether and how assent must be documen". 46,409 Wards. (a) Children who are wards of the state of any other agency, institution. or entity can be included in research approved under 1146.406 or 46.407 only if such research is: or (1) Related to their stattm as wards; (2) Conducted in whoots, cwnp,% hospitals. institutions, or similar settings in which the majority of children involvcd an subjects are not wards. (b) If the resemch is approved under paragraph (a) of this section. the IRB shall require appointmeet of an advocate for each child who is a ward, in addition to any other individual acting on bchalfof the child as guardian or in loco parenth. One individual may serve as advocate for more than one child. The advocate shall be an individual who has the background and experience to act in, and agrees to act io, the bcst interests of the child for the duration of the child's participation in the research and who is not associated in any way (except in tile role as advocate or member of the IRB) with the rewarch, the investigator(s), or the guardian organization, k"Ir, Approved For Release 2000/08/08 : CIA-RDP96-00788 ROO 1700250001 -7 BoxJRal-e-ase 2000/08/08 : CIA-RDP96-00788 ROO 1700250001 -7 45 CFR NOTICES HUMAN SUBJECTS Elsewhere in this issue of the Minimum Criteria Identifying FEDLRA1,11MISTER, the tile Secretary Viable Fetus is amending 45 CFR Part 46 hy, Oil MArch 13, 1975. regulationsamong Other thirigN. adding a new Subpart B to provide additional were published in the FEDERAL protections pertaining to research, R MISTER (40 FR 11 $54) relatingdevelopment, and related to the activities protection of human subjects involving fetuses. in pregnant women, research. development, and rehitedand in vi(ro fertilizations activities supported by DepartmentSection 46.203(d) of of Subpart B Health, Education, and Wclfare provides inter alia as follows: grants and contracts. These The Secretary may from time to time, regulations are codificd at taking into account 43 CFR medical advances. Part 46. publish in the F r.DEaAL R EGisrkji guidelifts to assist in determining whether a fetus is viable for purposes Of this subpaFA. This notice is published in accordAnce with § 46,201(d). For Purposes Of Subpart 13, the guidelines indicating that a fetus o4her tham a dead fetus within the meaning of § 46-203(f) is viable include the following: an estimated gestational age of 20 weeks or more and a body weight of 500 grams or MOM FEDERAL REGISTER, VOL 40. AUGUST 8, 1973 U.S. GOVERNMENT PRINTING OFFICE ; 1983 0 - 406-756 Approved For Release 2000/08/08: CIA-RDP96-00788ROO1700250001-7 -0 fr_ Approved For Release 2000/08/08 : CIA-RDP96-00788RO01 7002500 PROCEDURE 13. EXPERIMENTATION ON HUMAN SUBJECTS FOR INTELLIGENCE PURPOSES A. APPLICABILITY This procedure applies to experimentation on human sub- jects if such experimentati-on is conducted by or on behalf of a DoD intelligence componenc. This procedure does not apply to experimenLation on animal subjects. B. EXPLANAVON OF UNDEFINED rERMS 1. Experimentation in this context means any research or testing activity involving himian subjects that may expose such subjects to the possibility of permanent or temporary injury (including physical or psychological dainage and damage to the reputation of such persons) beyond the risks of injury to which such subjects are ordinarily exposed in their daily lives. 2. Experimentation is conducted on 'behalf of a DoD intelligence component if it is conducted under contract to that component or to another DoD component for the benefit of the intelligence component or at the request of such a com- ponent reoardless of the existence of a contractual rela- tionship. _14DID96-00788RO01700250001-7 Approved For Release 2000/08/08 : CIA- . . . .............. Approved For Release 2000/08/08 : CIA-RDID96-00788ROM700250001-7 3. Human subjects in this context includes any person whether or not such person is a United States person. C. PROCEDURES 1. Experimentation on human subjects conducted by or on behalf of a DoD intelligence component may be undertaken only with the informed consent of the subject, and in accordance with guidelines issued by the Department of Health and Human Services, setting out conditions that safeguard the welfare of such subjects. 2. DoD intelligence components may not engage in or contract for experimentation on human subjects without appro- val of the Secretary or Deputy Secretary of Defense, or the Secretary or Under Secretary of a Military Department, as appropriate. [Requests for such approval submitted by Army intelligence components will be addressed through command channels to HQDA (DAMI-CIC), WASH DC 20310.) N%000K Approved For Release 2000108106 3-MA2RDP96-00788ROO1700250001-7