3 Approved For Release 2000/08/08 CIA-RDP96-00788ROO1500140003-9 NIH Eu- n c'm 0: HIUKAPIATINII SBU&JEC 1 111*4 FT10 CODE OF "'E. EIAL. REGULATIONS (.'P'FR 46 Revised aS of March 3, 1983 PHS HHS Approved For Release 2000/08/08 CIA-RDP96-00788ROO1500140003-9 C, Approved For Release 2000/08/08 CIA-RDP96-00788ROO1500140003-9 NATIONAL RESEARCH ACT PUBLIC LAW 93-348 JULY 12,1974 INSTITUTIONAL REVIFW SUARDS, MUCS GUIDANCE PkOGRAM SEC. 212. (a) Part I of title IV of the Public Health Service Act, as amended by section 103 of this Act, is amended by adding at. the end the following new section: -INSTITUTIONAL REVIEW BOARDS; ETHICS GUIDANCI PROGRAM "Six, 474. (a) The Secretary shall by regulation require that each entity whichi ai)plles (or a grant or cuntra-ct under this Act for any project or program which involves Clic conduct of bi6medical or behavioral research involving human subjects submit in or with its application for such giant or contract assurances satisfactory to the Secretary that it has established (in accordance with regulations which the Secretary shall prescribe) a board (to be known as an 'Institutional Review Board') to review biomedical and behavioral i-esearch involving human subjects conducted at or sponsored by such entity in order to protect the rights of the human subjects of such research. .,(b) The Secretary shall establish a prograrn within the Department under which requests for efarification and guidance with respect to ethical issues raised in connection with biomedical or bellavioral research involving human subjects are responded to promptly and appropriately . - (b) The Secretary of ff.Calth, Education, and Welfare shall within 240 days of the date of the enactment of this Act promulgate such regulations as may tw required to carry i-,)ut secti()n 474(a) ofthe Public Health Service Act. Such regulations shall apply with respect to applications for grants and conmicts under such Act submilled after promulgation of such regulations, THE (7ODE OF FEDERAL REGULATIONS, 45 CFR 46, IMPLEMENTS THESE AMENDMENTS TO THE PUBLIC' HEALTH SERVICE ACT. sidus ubi Inuld consdiarh 47) Approved For Release 2000/08/08 : CIA-RDP96-00788ROO1500140003-9 Approved For Release 2000108108: CIA-RDP96-00788ROO1500140003.9 CODIE OF FEDERAL REGULATIONS 17 PART 46-PROTECTION OF HUMAN SUaJECTS REVISED AS OF MARCH 8, 1983 Approved For Release 2000108108: CIA-RDP96-00788ROO1500140003-9 Approved For Release 2000/08/08 : CIA-RDP96-00788ROO1500140003-9 1page 4 45 CFR 46 PART 46-PROTECTION OF HUMAN SUSJECTS Subpart A-Basic IIHS Policy for Protection of Human Restarch Subjects 46 101 To what do these rcgulations apply'! 46.102 Definitions. 4 6 103 Assurances. 4 6 i 04 Section reserved. 4 6. 105 Section Yestrved. 46 106 Section reserved. 4wlw IRB membership. 46.108 IRE) function% and oprrmions. 416 109 IRB review of research. 1,6 110 Expedited review procedures for certain kinds of rcse-arch involving no more than mininial risk, and for minor changes in appruved tcNearch. 46 111 Criteria for IRD approval of research~ 4(; ]1.' Review by institution. ,16~ 113 Suspension or ierminai:ion of IRR approval of re%carch~ 4(P.114 Cooperm i ve resc Arch. 46. 1 15 1 K IJ recort.1% 44 116 Gtncrai tcquiremcniN lor infornied Consent. V, 117 Documentation of infurmed consent. 4.5~ 118 AppliC361111S and proposals lacking definite pl4as for involvemcrt of hurnan subjects. -16. 119 Research undertaken without the intention or involving human subjects. -to cv,) I-ivaluation And disposirion of appitlations and proposals, 46 E21 lnve~ligauoniil new dtt,,g or device 30-dav delay requirement. 46.122 Use of federal funds. 4oi. 123 FArly acrmin311011 of re-icatch fundin.,; evaluation Of SUbit-ClUC111 3PP111:3 (tons and proposdW At, 124 Conditions. Subpart B-AdditionAl Protections Pertaining to Research, Development, and Related Activities involving Fetuses. Pregnant Women, and Human lin Vitro Fertilization sec. 46 Applicability 201 44 Purpose. .1,02 46.203Definilions. 46.2(9Ethical Advisory Board-i. 46 Additional duties 205 of the Institutional Rev iew Boards in connection with &c1i%1tk:s Involving fetuses, pregrialit worrien, or human in vitro fcrtilization. 46.2M, General limitations. 46,201' Activities directed toward pregnant worne" as WbJects. 46,20S iictiviiiq~i directed toward fetuses in utero as, subjects. 46,209. Aciivitirs directed toward fetuses ex ulcro, including nonviable fetuses. &~ subjects. 46.210 ~~ctivities involving ific dead fetus, fetal ma(crial, or the placenta. 46.211 Modific:ition or waiver or specific requirenicills. Subpart C-Additional Protections Pertaining to Biomedical and Behavioral Research Involving P65oners; as Subjects Sec. 46.301 Applicability. 46.302 Purpose. 46.303 Definitions. 46.304 Composition of lni(iiutiogial Review Boafds ,where prisoners are involved. 46.303 Additional dkilics of the Institutional Rewic* Bodids where prisoners Are involved, 46.306 Peinsitird aciivitic% involving priscincr&. Subpart ID-Additional Protections for Children Involved as Subjects in Rellft!Ch Sol. 46-401 Tc, what do thm regulations apply? 46.402 131crinitions. 46-403 IRD dutim, 46.4064 Rciewch not involving Sgreater thin mininial risk. -16.405 Re%esrch involving greater than niinigiaaJ risk but presenting the prospect ofditcct benefit to the individual subjects, 46-436 Rewarch involving greater than minimal nsk and no prospmi of direct bcrit-fit to individual subjects, but likely to yirld 9cni:raJi7,Wc know lcdgc about tile subj,-ct's disordirr or condition. 46.407 11mearch not otherwise approvable Which presents 'in opportunity it) understand. prevent, or alleviate asciinis P10bleal &ffircting tile health or welfare of childle". 46.408 Rot~uircmeziqs for pcrrniiii~ion by parcir3ti cr guArdisuis and fog, asset,( by childifeu. 46,409 qWaj ils. Atithorilly: S U.S~C. 301; sec. 474(a), 88 Stal. 352.(42 U.S,C. 2891-3(gij). Subpart A-3-asic 1111S Policy for Protection of Human Research Subjrcts Source: 46 FR 633(s, January 26, 19 81, 48 FR 9269, March 4, 198.1. 46-101 To what do these reguiations 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 pan by a Department grant, contract, cooperative agreement or fellowship, 1) This includes research conducted by Department crriploycei, .1 except cacti Principal Operating Component licad may adopt such nonsubstantive, procedural modifications as may be appropriate from an adrnini~,trative standpoint. (2) It also includes research conducted or funded by the Department of Health and Husnan Services outside the United State:,;, but in appropriate circumstances. the Secretary may, under paragraph (C) Of this section waive the applicability of Some or all of the requirements of these regulations for research of this type. W Research activities in which the only involvement of human subjciAs will be in ione of more of the followinglate " 'gorles 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 sctfings, involving noinial educational practices, such as 0) research on rc,gular and special education instructional strategies, or 00 research on the effectiveness olf or the curnpari!~on airiong instructional techniques, (.=rigula. or classroom Management mC11hCKJS. (2) Reseatch involving the use or educational testi (cognitive. diagnostic, aptitude. achievement). if 91 Approved For Release 2000/08/08 : CIA-RDP96-00788ROO1500140003-9 . , A naroved For Release 2000/08/08 : CIA-RDP96-00788ROO1500140003-9 A 45 CM Page 5 f", information taken from these sourccs i~i io()rded in such a nianneir that subjects cannot be identified, directly or through identifiers linked to (he sUbjects. (3) Research involving survey or ~wcrview procedures. except where allf of' the following conditions exist: 6) responses are recorded in such a nianner that the human subjects can be identified, directly or through identifiers linked to the subjects. (ii) the subject's responses, if they ho,ame known outside the research, could reasonably place the subject at risk of criminal or civil liability or be damaging to the subject's financial standing or employability, and (iii) thc research deals with sensilive js.,iects of the subject's own behavior, such as illegal conduct, drug use, SCA Lial behavior, or use or aicohoi, .401 research involving survey or olcili'vie'A' PfOCedures is exempt. widiout exception, when the respondents are elected or appolvied pUblik' officials or candidates for putilt': office. (4) Rcscarch involvine tile .f,,~scrN.'aion (including observation by pamcipants) of' public behavior, oxcept where all of' the follok~bli! ("Ollditions exist: (i) observations .11'C I,CCOI'ded in such a manner that the hunian subjects can be identified. diiucily or through identifiers linked to I)e subjects, (ii) the observations 1(-C0YdOd about tile individual, if they hocame known outside the research, ct.m.d reasonably place the subject a( risk of' criminal or civil liability or he to tile siibjc(,t*s financial SUIL11111.! or employability, and (iii) reicarch (leafs with Ncnsiti~e iv,pccts of* the subject's own hch;ivior ,I.icii ii~ illegal conduct, drug use. ,,vYtj,-d behavior, or use of alcohol. (5) Research involving the coUcction or study of existing data, diii:urncnis, records, pathological or diagnostic specimens, it aiesi- sources are publicly avallable M It' the inforl"nation is recordod by thc investigator in such a nianner ihat subjects cannot be identified, dirccfly or [hrough identifiers linked to fire subjects. (6) Unless specifically required by statute (wid excel-it to tile extent specified in paragraph (i)), research, and deirnoriqration projects wbich are conducted by or subject to tile approval of the Department of Health and Human Services, arid which are designed to study, evaluate, or otherwise examine: (i) programs under the Social Security Act, or other public benefit or service pro,.:ravis, (ii) procedures for obtaining bc-iiefits or services under those programs; (iii) possible changes in or alternatives to those programs or procedures; or (iv) possible changes in methods Or levels (A payment for benefits or services under those programs. (c) Tire Sccretiry has final authorirv to deterinine whelher a artiCULir activity is covered by these P regulation". (d) The Secretary rnay require that Specific ru-scarch activities or classes of' research acfivikies conducicd or funded by the Department, but not otherwise covered by these rceulations. comply %ith sorne or all of these regulations. (e) The Sek-rclary inay also waive applicabil t~ oA; these ret I gulations to specific rescaich activities or classes of research htivitics, otherwise covered by these regulations. Notices of these acItions will be published in the Federal Register as they txwcur. (f) No individual may rcceive Departinent funding for research coverod t~y Lhe-sc regulations unless the individual is affiliated with or sponsored by Jn institution which assumes responsibility for the research under an assurance . Nalisfying the requiti:ntents of' this part. or the ;ndividual makes other at rail gement s %vith the I)eparimenf. . (g) Comphanct~ with these it~,gkllatiow, \,kill in Oo way render inapplicable pi.-rfinent federal, sw(e, or local laws or regulations. (h) Each subpart of these regulations contairis a separate section describing to what the subpart applies. Research which is covered by more than one, subp;~rt shall comply with all applicable subparts. (i) 11'. following review of proposed research activities that are exempt from these regelations under paragraph (b)(6), the Secretary determines that a research or demonoration project presents a danger to the ph, sical, mental, or emotion-ld vveii-bt.-ing or a participant or subject or the research or demonstration project, then Federal funds may not be expended for, such a project withowit the written, informed consent of each participant or subject. Derinitilons. (a) -Secretacy - ineans the Secreiary of I-lealih and Human Services arid any other officer or employee of the U~partrnent of' Health jird Ilumart Services to whom authorit, has been delegated. y (b) "Departincrit" or "HHS" ineans the Devav.r.,)cnt of Health and Hurnan :iervices. M "Institution" 'means any public or private entity w agency OncludinL.,, federal. state, and other agencies). (d) -Ugally 2111horized reprcscricative" mcatis an individual or judicial or other body authorized under applicable )wN to consent on behalf of' a prospective subject it) tile subject's partii:ipation in the procedurc(s) ijivolv~!d in the research (e) "Research" Picans a systematic investigation designed to develop or contribute to generalizable knowledt!e. Activities which meet this definition constitute -resc3rch- for purposes of these regulations, whether or not aicy are supported or funded under a program which is considered rese,irch for other purposes, For example. some "demonsiration" and -servicc- prograins may include research activities. Approved For Release 2000/08/08 : CIA-RDP96-00788ROO1500140003-9 Paftpfoved For Release 2000/08/08 : CIA-RDP96-00788RO01500140003_9 45 CFR 46 (0 "Humain subject.',' meam a li.ving individual about whom an M*'stigator (whether prcfessional or itudent) conducting research obtains ( 0 data through intervention or interaction with the individual. or (2) identifiable private information, "Intervention',' includes both physical procedures by which data are gathered (for example, veniptincture) and manipulations of the subject or the stibject's environniene, ftit are performed fL)r rcsearch purposes. "Interaction," includes communication or interpersonal contact between investigator and stlbjdct *'Privaw information- includes information about behavior thm occurs in a context in which an individual can reasonably expect that rio observation or recording is taking place, and information Which 113S heen provided for specific purposes 11'~ .111 Individual and WhiLh the individual can reasonably cxpect will not he made public (for example. a 11%,dical rek~ord). Private information tnust be individually identifiable O,e.. (he identity of the subje ct is or may readily be ascertained hi, the investigalor 01 associated with the intormation) in order for obtaining the infomiation to constitute research involving human subjects. tg) "Minimal risk',`ilmeans that the criks of harm anticipmed in the proposed research are not greater, considering probability and Magnitude, than those ordinarily encountered in daily life or during the performance of routine physical or psychological examinations or tests. (h) -CcrtificationIV nicans the ,ifficial notification by the institution zo the Oepartnicnt in accordance with the requirements of this part that a re.scarch project or activity involving hunian subjects has been reviewed and approved by the Institutional Review Board ORR) in accordance with the approved assurance, oil file at 1M.S. (Certification is required when the research is funded 6y the Department and not otherwist. exempt in accordance with § 46,101(b)). 46. 10 Assurances. (a)i Fach inAitution engaged in researth ~:over~-tl by (hese regulations shall provide written as,,tirance satisfai:tory to the Secretary that it will compiv with the requircinenv% set forth in these regulations. (b) Tht: Department will conduct or fund rese3rch covered by these regulations only if the institution has an assiValice approved as provided in this seciion. and only if the institution has certified tA) the Secr,.-tafY that the reseatch has been revievied and approved by an IRB provided for in the assurance, and will be subject to continuing review by the IRB, This ~assurancc shall at a mininium include: ~~ 1) A statement of' principles govetning the institution in the discharge of its responsibilities for protecting the rights and weltire of hurnan Nubjects of research conducted at or sponsored by the institution, regardless of wurcc of funding. This may include an appropriate existing code. declaration, or statenjent of ethical prill'Aples, or a slaccillent formulated by thu instatition itself. This rciluilclilcill does not preenint prOVUSIOnS 0 f these regulatiMIS applicabic it) Departnient-fund0d research and is not applic,ibli: to ally rescarch in an exempt catcgory listed in § 40. 101. (2) Designation of one or more IRBs established in accordance with the requirements (it this subpart, and for which pi,ovV;ions are roade for rneeting, space and sufficient staff to suppoo (lic IRB's review and rccordkcep~.ng duties, (3) A list of' the IRB nicinbers identified by named earned degrees; representative capacity; indications of experience sucli as board certifications, licen%es, etc., sufficienit to di.-scribt each member's chief' anticipated contributions to IRB dcllberaimnN~ and any ernployniew or other ridationship between each membcr ;inl thie institution; for example: full-time caiployec, part- tinie emplovee, mcniber of governing panel or board, stockholder, paid or Unpold consultant. Changes in IRB membership shall be reported to the S-1-Tretary, (4) Written procedures which the IRB will follow (i) for conducting its initial and continuing review of rcscarch aid for reporting its f'indings and actions to the investigator and tile instiiutioni~ (ii) for determining which projects require review more often than annually and which projects need verification front sources other than the investigators that no material changes have occurred since previous IRB review-, (iii) for insuring prompt ircliorting to the. IRB of' proposed changes in a rc!;earch activity, and for instiring that changes in approved research, durin?, the period for which !RB approval has; already been yiven, inay not be initiated without IRB ieview and approval except where necessary to eliminate apparent innnediate hazards to the subject. and Ov) for insuring prompt reporting to, the IRB and to the Secretary I of' uninticip.,ited p~lloblcms involving ri%L, to subjects or- others. (c) The assur,,ince shall be executed by .in individual authorized to act for 1 the nstitution and to assume on Mialf of thi: institution the obligwion% imposed by these regulations, and shall be filed in such form and manner as the Secretary may in-escribe. (d) The Secreiary will cvaluate all assurances submitted in accordance with these regulations through such officers and ernployees of the Depatiment ant] such experts or consultants engaged for this purpose. as the Secretary determines to be appropriate. 'r~c Secretary's evaluation,will take into consideration the adequacy of the proposed IRB in light of the anticipated scope of the institution's rescarch activities and the types of subject Populations likely to be Relkiris 5hould Z~c filed with the Office for Proteclion from Research Risks, Natiunal Institutc.s of Hcalo, Department of licalth and Hurnan Services. Bethc,,da, Marylatul 20205 Approved For Release 2000/08/08 : CIA-RDP96-00788ROO1500140003-9 4F, ApWved For Release 2000108108 : CIA-RDP96-00788ROO1500140003-9 Page 7 involved, the appropriatcncs5 of the 1)rop?scd initial and continuing re%~tew procedures in light of the probable risks, and the size and complexity of the institution. (e) On the basis of this evaluation. the Secretary may approve or s.lisapprove the assurance. or enter Inio negotiations to develop an approvable one. The Secretary may, limit the period during which any particular approved assurance or class (if approved assurances shall remain effective or otherwise condition or restrict approval. W) Within 60 days after the date of submission to 1-111S of an application or proposal. an institution with an af)proved assurance covering the ?ioposed research shall ecruify that 4iv application or proposal has been rt'!,viewed and approved by the IRB. Oiiher institutions shall ccriiiy that the application or proposal his been -,p, proved by the IRB withi,ii 30 day,, Litter receipt of a request for such it L-crtificaiion front the Department. If ,he certification is not submitted 'AH11111 these little litnits, [tic application or proposal may be returned it) the instllution~ 46. 104 (Reserved) 46,105 [Reserved] 46.106 lReserved) 46.107 IRB mernhershil). o) Each IRD shall have at least five memtw-rs. with varying ba~:ki-,rounds to promele cornpliete and 'deil" uate ieview of research activities corunionly conducted by the i,m,titution. The IRB shall be j,ufflcienfly qualified throughi the c,xperience and expertise of its rncrribers, and the diversity of the 11c,"n6ers' backgrounds including coniideradon of the mcial and j.ultural backgrounds of mcrril-'.~ers and ,~,-nsmvity to such issues as ~-oairnunity attitudes, to promote resl)ect for its advice and COLInsel in ~atcguarding the rights and welfare of hurnan subjects. In addition it) possessing the professional cornlv(cnec ncc-cssary it) review sPecdic research activities, the IRB shall be ible it) ascertain the acceptability of proposed research in terms of inslautional commitments. and tegulattions, applicable law, and standards of professional conduct anti practice. The IRB shall therefore include pcnsons knowledgeable in these areas. Ifan IRR regularly reviews research that involves a vulnerable category of subjects, including but not limited to subjects covered by other subparts of this pan. the IKB shall illnclude one or more individuals who are primarily concerned with the welfare ofthesc subjects. N No IRB -,P,-ciy consist entirely of men or entirely of women, or entirely of mernt4rs of oric profession. (c) EaA IRB shall include at least one meeriber whose primary concerns are in nonscientific areas; for example: lawyers. ethicists, incirthcrs of the clergy. (d) E"~Ich IRB shall include at least one rnernbcr who is not o0erwise affiliated with the institution and who is not part of the immediale family of' a person who is affiliated with the institution. (e) No IRB may have a member participating- in tile IRB's initial or continning, review of any project in which the niciviber has a conflicting interest, cxcept to provide informaiion ieqiwsled by the IRB. (f) An IRB may, in its discretion, invite individuals with competence in %pecial ircas to assist in the review of COMPIeK ISSUCS which require expertise heyond or in addition to that available on the IRB. These individuals :nay not vote widi the [RD. 46.10S IRB functions anti operations. In ordrr 10 fulfill (tie reqUi1-CnlCRt& of these r,.-gjjlalions each ITZIJ shall: (,a) Follow written procedures as ptovided in 46~ 103(b)(4). N Except when an expedited review procedure is used (see § 46. 110), review proposed research at ccinverred meetings at which a majority of the members of the IREI are presents including at least one member whose primary concents arc in nonscientific areas. In order for the research to be approved, it shall receive the approval of a majority of those inembeis present at the meeting. (c) Tic 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 tile IRB. 1463-39 IRB review of research. (a) An I1`ZB shall review and have authority to approve, require modifications in (to secure approval), or disapprove all research activities covered by these regulations. (b) Ali IP.B shall require that intot-mation given to subjecis as pim ofinformed con--iont is in accordance with § 46.116, The IRB may require that inforniztion, in addition to that specifically mentioned in § 46.116, be given to [lie subjects when in the IRB*s judgment the information would meaningfully add to the protection of the rights and welfare of -.0jects. M An IRB shall require documentation of informed consent or may waive documentation in accordance with § 46.117, (d) An IRB shall notify investigators and ft institution in writing of its decision to approve or disapptove du- proposed !research kctivity, or of'rrimlifications required to Secure IRB approval of the te-%earch activity. Iftlic IRB decitics to disapprove a research activity, it shall include in its written notification kepuris 0ould tic tiled wiih the Officc fM Ptotection from Research Risks, Naiional lntwuici of 11calth, r.)epjrrmcnt of 14cidth and fluman Scrvices, Sethesdas, Maryland 2102", Approved For Release 2000/08/08 CIA-RDP96-00788ROO1500140003-9 A- Pnewproved For Release 2000/08/08 C IA-RDP96-00788 ROO 1500140003-9 45CFR,16 a statement of the reasowt f~v its decipipn lind give the investigator an opportunity to respond in person or in writing. (e) An IRB shall canduct C01364nuing review at research covered by these regulations at inici-vals ippropriate to the degree of risk, but ncK less than once per year, and shall have authority to observe or have a third party observe the consent process and the research. Ji46.110 Expedited revitiv procedures for certain kinds of research Involving no more than ittinimal risk, and for minor changes in approved research. (a) The Secretary has established, and published in the Federal Rr ister. a list of categories of 9 r6search that may be reviewed by the H-114 through an expedited review procedure. The list will he arliclided, ai. appropriate, through periodic repitblication in the Federal ReKister. ib) Ali IRB may review some or all of (he research appearing co the list through an expedited rcvic~w piocedure, if the ;escarch involves no rnore than minimal risk. Ile IRB may ako use the expedited review piocedurc to review minor clianges in previously approved research during the period for which approlval is aUthorized. Under an expedited review procedure, the review may be c:gKried out by the IRB chairperson or bY 011C or more experienced reviewers designated by the chairperson from aniong members of the MR. In reviewing the research, the reviewers may exercise all of the authorities of (.tic IRB except that the reviewers may not disapprove the research. A research activity may be disapproved only after review in accordance with the non-expcclited procedure set forth in § 46~ 108(b). (c) Each IRB which uses an expedited review procedure shall adopt a method for keeping all inembers advised of researcii propo~sals which have been approved under tl-,ic procedure. (d) The Secretary may restrict, suspend, or terminate art institution's or IRBi use of the expedited review procedure when necessary to protect the rights or welfare of subjects. §46.111 Criteria for IRR approval of research. (a) In order to approve T,~scarch covered by these regulations the IRB shall determine that all of the following mquirements are sa(isfied: (1) Riski to subjects are rninimized: (i) By using procedures which are consistent with sound research design, and which do not unnece.ssanly expose subjects to risk, and 60 wheiievcr appropriate, by using procedures already being I perfori-ned cm thc subjects for diagnosiic or trea tinent putposes. (2) Risks to subjects are reasonable in rela(ion to anticipated benefits. it' any, to sub.!ects, and the importance ') f the knowledgc that may reasonably Z he CK[ICACd to result. fit evaluating risks and benefits, the IRIA should considcr oftly those risks and bene its Rhat Ina, result from t1 -arch (as Y lc rCS4 distinguished from risks and benefits of therapies subjects would, receive even if not participating in the research). The IRB should riot considcr possible long-range effects of applying knowledge gained in the rescarch (for example. the possible effects of the research on public policy) as among those research risks that fall within the purview of its responsibility. (3) Sclecti ,Oil of subjects Is equitable, Ill making this assessment the IRF1 should take into account the purposcs of' the research and the setting in which the research will bc conducted, (4) Infonned consent will be sought from each prospective sub~Ject or the subjcct's legally authofizcd representative, in accordarize with, and to the extent required by § 46AW (5) Informed crinseak will be appropriawly documenWi, in accordance witil, and to the extent required by § 46,117. (6) Where appropriate, the research plan makes adequate provision for monitoring the dwa collected to insure the safrity of subjects, (7) Where appropriate, there aitp adequate provisions to protect the privacy of tubjects'and to maintain the confidentiality of data. (b) Where some or 311 of the subjects are likely to be Yul.notable to- coercion or tindur. influence, such as persons with acute or severe physical or mcntal illness, or persons who are economically or educationally disadvantaged, appropriate oq4idona.l, safeguard% have been included in the study to protect the rights and welfare, of them.- subject!;. 46.112 Review by Institution. Research covered by these regulations that has been approved by an IRB May bC Subject to further appropriate review and approval or &approval by officials of the institution. Howcver, those officials may not approve the research if it has rot been approved by an IRD. 46.143 Suspension or termination of MIR approval of research. An IRB shall have i~tharity.Jo suspend or terTri 'vrate approval of research thag is no~ being conducted ill accordance with the IRB's requireinents or that has been associated with unexpected serious harm to subJec -ts. Any suspension or terininalion of approval sball include a statement of the reasons for the 11113's lictioll &nd ;Wl-be repmted, promptly to I the.investigator, appropriate institutional officials, and the Secretary. Repits thould bt filcd with the Office for Protection frorn Research Risks. Natioiial Institmci; of Hcslth~ Ulepartnient of Health and Human serviccs, Bethesda, Maryland 202105. Approved For Release 2000/08/08 : CIA-RDP96-00788ROO1500140003-9 CAbl*oved For Release 2000/08/08 : CIA-RDP96-00788RO01 500140003-9 Page 9 46.114 Cooperative research. c9operative research projects are ~Jiose projects. noniially supported ihrou'gh grants, contracts, or similar arrangements, which involve institutions in addition to the grantee Or prime contractor (such Lis a con.ractor with the grantee, or a subcontractor with the prinic contractor). In such instances, the grantec or prime contractor remains iesponsible to the Departm,crit for safeguarding the rights and welfare of human subjects. Also. when cooperating institutions conduct some or all of the research involving sonic or all of these subjects. each Cooperating institution shall comply wit4i these regulations as though it reecived funds for its participation in tilt.- project directly from the I)epartment, except that in complying with these regulations institugions may use joint review, reliance upon tht- review of another qualified IRB, 01, Similar arrangements aimed at AVOidance of duplication of effort. ~J 46. 115 JRB rec`or~s. (a) An institution, o-r where appropriate an IRB. shall pnopare and in:ilntain adequate documentation of IR11 activities, including the followin g: ( 1) Copies of ail research proposals ireviewed, scientific evaluations, if any, that accompany the proposal s approved sample consent documents, progress reports submitted by iiiv.!stigators, and reports of injuries to SUbjects. 2) Minutes of IRB m"tings which shad be in sufficient detail to show ~iaendancc at the meetings; actions tak-en by the, IRB; the vote on these actions including the number of nwinber% voting for, against, .a.nd 111)~,taining; the basis for requiring cliangcs in or disapproving research, atji,l a written summary of the dv~cussion of controverted issues and thea. resolution. (3) Records of continuing review activities. (4) Copies of all correspondence between the IRB and the invest ig a tors. (5) A list of lIZB members as requirL:d hY § 46.103(h)(3), (6) Writi.en procedures for the IRB as requircd by § 46.103(h)(4). (7) Statements of significant new findings provided to subjects. as required by § 46.116(b)(5). (b) The record% required by this regulation shall be retained for at least 3 years after completion of the rmarch. and the records shall he accessible for inspection anti copying by authorized representatives of the Department at reasonable times and in a reiasonoble manner. 0 46.116 General requirements for Informed consent. Except as provided elsewhere in this or other subparts, no investigaror may involve. a hunian being as a subject in research covered by these regulations unless the investigator has obtained the legally effective informed consent of the sub "iect or the subject's legally authorized represenlative. An investigator shall s4I-ek such consent only under circumstances that provide the PrOSPCCRiVC~ SUbjCCI Or the represcutative sufficient opportunity to consider whe-ther or not to participaic and that minimize the possibility of coercion or undue influcric,~ The information that is given to the subJect or the rcpreSentative shall be in language understandable to It.c.subjcct or the representative, P?,informed consent, whether oral or-wnitien, may include any exculpatory language through which the subject or the representative is made to waive or appear tco %va ive any of the subject's legal rights, or releases or appears to, release the investigator, the sponsor, the institution or its agents I'[0n) liability for negligence. (a) Basic eltments of informed consent. H.Acept as provided in paragraph (0 or (d) of this section, in seeking informed consent the following information shall be provided to each subject: .~*. (1) A statement that the study involves research, an explanaficith of the purposes of the research and the expected duration of the subject's participation, a description of the procedures to be followed. and It identification of any procedures which are experimental; 11 (2) A description of any reasonahly ' foreseeable risks or discomforts to the 4subject, ', (3) A description of any beneffts to J the subject or to others which ma 1;reasonably be expected from the ~rescarch, J (4) A disclosure of appropriate alternative procedures or courses of treatment. J any, that might be advantageous to ~hc subject. (5) A statement describing the extent, if any, to which confidentiality of records identifying the subject will be maintained; (6) For research involving more than minimal risk, an explanation as to whether any cc~mpcnsation and an D explunation as to whether any medical ireatryiews arc available if injury occurs and, if so, what they consist of, or where further information ntay be obtained, (7) An explanation of whom to contact for answers to pertinent questions aboui the research and research subjects' rights. and whom to contact in the event of a research- ;related injury to the subject; and (8) A statement that participation is voluntary, refusal to participale will involve no penalty or loss of benefits to which the subject is otherwise entitled, and the subject may discontinue participation at any time without penalty or loss of benefits to which the subject is otherwise 'entitled. (b) Additional elements of infoirned consent, When appropriate, one or more of the following clerrients of information shall also be provided to cach subject: Approved For Release 2000/08/08 : CIA-RDP96-00788ROO1500140003-9 -.Ntgefiffi D roved For Release 2000LOQLO 45 OR 46 (1) A statement that the pirticular whicti Altai6,&omeor ali of the adequate opportunity to read it before S.Ltre4tment or procedure may involve i ji%k~ to the subject (or to the embryo T tOr fetus, if the subject is or may ;,"become pregnant) which arc currentIv Zuriforesecable; (2) Anticipated circumstances 4 under which the subject's i. r-irricipanon may be terminated by ~.thc investigator without regard to the 1subject's consent; 11 (3) Any additional costs to the ,'subject that may result from 1, !Punicipation in the research-, 1 (4) The consequences of' a ,,subject's decision to withdraw from 10 ,~the research and procedures for jorderly termination of participation 4hv the subject, (5) A statement that significant 4 newfindings developed during the 'course of the research which may !relate to the subject's willingness to ~zontinuc participation will be piovided to the subject. and I The approximate number of* 6) -.1lubjec(s involved in the study. W An IRB m4t,~pRpvc &.cwwwst or aftut"the _&~ informed con'sint so fori:h above, or waive the riquireivient i,,o obtain informed consent provided tfic IRB finds and documents that: (1) The research or demonstcation project is to be conducted by or stjbj~ s --ct to the approval of state or hwal government officials and Is designed to study, eValLiatc, or otlaerwisc examine: (i) programs under the Social Security Act, or ottier public benefit or service programs; (ii) procedures 15or obtaining benefits or services tinder t1irose programs; (iii) possible changes in or alternatives to those programs or procedures, or (iv) possible changes in methods or levels of payment for b-LnCfitS or scrieices under I hose pCOgraMS; and (2) The research could not practicably be caffied out without the waiver or alteration. (d) An IRB may-approve a consent procedure which does not include, or '~Icmciats of Wormed consent set forth abovtj or waive the requirements to obtain informed consent provided the IRB find,. and documents that: (1) 'The research involves no more than mininial 6sk to the stibrieCtS' (2) 'The waiver or alteration will not adversely affect the rights and welfare of the subjects, (3) The rescarch could not practicably be carried out without the waivet or alteration; and (4) Whenever appropriate, the subjects will be provided with additional pertinent information after participation. W 1-he informed consent requirements in these regulations are not intended to preempt any applicable federal, state, or local laws which require additional information to be disclosed in order for informed Consent to be legally effective, (f) Nothing in these regulations is intended to limit the authority of a physician it) provide emergency medical care. to the extent the physician is permitted to do so tinder applicable federal, state, or local law. 146.117 Documentation of Infornbed consent. (a) 17,~'xcept as provided in paragraph (c) of this section, informed consent shall he docunientcd by the use of a written consent foim approved by the IRB and signed by the subject or the subject's legally authorized representative. A copy shall be given to the person signing the form. N E"Acept as provided in paragraph M vil* this section, tile conscrit form inaty be either of' the following: (1) A written consent document that en.R-Wics the elements of informed consent required by 146.116. This form may be read to (tie stAbjeci or the subject's legally authorized rcTrcientative, but in any event, the investigator shall give either the :iuhject or the representative it is signed; or (2) A "short form- written consent document stating that the elements of informed consent required by ; 46. 116 have beer presented orally to the subject or the subject's legally authorized representative. Men this mcthcKi is used. there shall be a witness to -the oral presentation. Also, the IRB 5hall approve a wtitten summary of what is to he said to the subject or the representative. Only the short fosm itself is to be signed by the subject or the representative, However. the witness shall sign both the short forni and a copy of' din astritimary, and die person actua lly omaining consent, shall sign a copy of the summary. A copy of the summary shall be given to the subject or th,, representative, in addition to a copy of the -shon form. (c) An IRB may waive the requirement for tile investigator to obtain a signed consent form for some or all snbjects if it finds either: 1) That the only record linking the subject and the research would be the consent docurnent and the principal risk would be potential harm resulting, from a breach of confidentiality. Each subject will be asked whether the subject wants documentation linking the subject with the 17M.3rCh. and the subject's wishes will govero; or (2) That the research presents no more than minim,al risk of harm to subjects and involves no procedures for which written consent is normally required outside of the research context. In cases where the documentation re4uircment is waived, the IRB may require the invesipgator io provide subjects with a written statement regarding the rc~icarch. 46.118 Applications and proposals lacking denniite plans ~ar Involvementr of human subjects. Certain types of applications for grants, cooperafive agreements. or contracts are: submitted to the Department with the knowledg,c that subject!; may be involved within the Approved For Release 2000/08/08 : CIA-RDP96-00788ROO1500140003-9 -------------- 45APPMved For Release 2000/08/08 CIA-RDP96-00788ROO1500140003-9 period of funding, but definite plans lvvoiAd not normally be set forth in the application or proposal. These include activities such as institutional type grants (including bloc, grants) whert: selection of specific projects is ilic- institution's responsibility; rt-~,e3rch training grants where the activities involving subjects remain to bi.- selected: and projects in which hunian subjects' involvement will depend upon completion of ifis,~ruments, prior anirnal studies, or r~Urification of compounds. These applicatiosis need not be reviewed by an IRB before an award may be made. However, except for research described in § 46. 101 (b). no human subjects may be involved in 4111Y project supported by these awards until the project has been reviewed and approved by the IRB, as provided in ibese regulations, and certAication submitted to ific Department. 46A19 Research undertaken without the initention of involving hurrian stilliects. In the event research (conducted or lunded by the Department) is undertaken without the intention of involving hunrian subjects, but it is later proposed to use human suhjects in it)e research, the research shall first be reviewed and approved by in IR.D. x, provided in these regulations, a certification submitted to the De,pnionent. and final approval givell to the proposed chang ,e by tho DC11:11-tilicilt. 1i Jts.120 Evaluation and 6sposition of application% and prtpllOsals. (~o 'The Secretary will evaluate all appitc.ations and proposals involving !Iuw-n subjects submitted to the De.p~irlment through such officers and einployees or tile Department and sw-h experts and corisultatits as the Sccrctarv determines to he al'J,110priato.. 'This evaluation wiii take ;Firo consideration the risks to the subl,:cts, the adC(JUaCy of [)17011!Cti~)n ar'Llitst these risks, tile potential bt:nc,til,, of the proposed research to tile suhiect-i arid others, and the importance of the knowledge to be, gained. (b) On (lie basis of this evaluation. the Secretary irtay approve or disapprove the application or proposal, or enter into negotiations to develop an approvuhle one. 146.121 Inveitigational new drug or device 30-day deWy reqWrement. When an institution is required to prepare or to submit a certification with an upplication or proposAl undew these rCgL1lati011S, and the application or proposal involves an investigational new drug (within the nicaning of 21 U.S,C. 3550) or 357(d)) or a significant risk device (as defined in 21 CFR 8123(m)), tile institution shall identify the drug or device in the certification. The institution shall Aso state whether the 30-day intrval required for investigational new drugs by 21 Cf-R 312, Va,~ and for significant risk devices by 21 CFR 812.30 has elapsed. ov whether the Foo,d and Drug Adinirtistrwion has waived that requirenirrit. If the 30-day inici-val has expircci, ffie institution shall estate: whether itic l"ood and Drug Administration has requested that the sponsor continue to withhold or res(rict the use of the drug or tlevice in hunian subjccts. If the 30-day interval has not ckpired, and a waiver has not b0c,"I received, tile inNflintion shall send it statement to the Department upon expiration of the intervai, The Dep,.-.trtment will not consider .1 cernfication acceptable until (he illSlitUtiOll IMS SUbMitted a staictrient that tile 30-day interval has elapsed, and the Fo%,Ki and Drug Administrafion liw. not requested it to linlit the us(., of' the drug or device, or that, the FoM and Drug Administration has %aived the 30-day interv at . § 46. 1 ~2 2Use of Federal funds. Foderal (Ityids administercd 11~ ifi~, Deparinient ma). rict he expended for research involving litintaft subic-cts unless the requirement of these regulations, inciuciing ail subparts of these regulations. have been satisfied, J 46A23 Early termination (W research funding.; evaluation of subw4luent applications and proposalv. (a) The Stcretary may requim that Departirriew funding for any project be terrainaied or suspended in the manner prescribed in applicable ptograrn requirements, when the Secretary finds an institution has materially failed to comply with the terrins of these ir~gulations. (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 requirement 's and program criteria, factors such as whether tile applicant has been subject to a termination or suspension under paragraph (a) of this section and whether [he applicant or the person who would direct the scientific and technical aspects of an activity has in the judgment of the Secretary materially failed to discharge re%ponsibility for the pirotection of tile rights and welfare of hurnan subjects (whether or not Depaitnient funds were involved 46.124 Conditions. With respect to any rcsearch pruject or any class of research projects the Secretary may impose additional conditions prior to or at the tinic of funding when in the Secretary's judgment additional conditions are necessary for the protection of human subjects. Suboart B-Additional Protections Joertaining to Research DCVef0Pk11e11t, and Related '-Activities finiolving Feluses. Pregnant Women, and Human In Vitro Fertilization' SoUN(i: 40 FR 13528, Aug X. 1971. .43 IT 1758, Januar:. It, 1978, 43 f-R It ~59, Noyenwl)cr 3, 1979 § 46,201 Applicability. (a) Fhe rc-pulatiom in this suhptrt arc applicable to ail Deparinien, of Health, Eldtication, and Welflire Approved For Release 2000108108 : CIA-RDP96-00788 ROO 1500140003-9 a" Approved For Release 2000/08/08 : CIA-RDP96-00788ROO1500140003-9 A P~ge 12 45 CF14 46 erims and contract supporting research. development, and related activities involving: ( 1) The- fetus, (2) pregnant women, and (3) hutnan in vitro fertilization, (b) Nothing in this subpart shall he construed as indicating that compliance with the procedures %C( forth herein will in any way render inv,pplicahle pertinent State or local laws hearing upon activities covered by this subpart. (c) The requirements of this subpart are in addition to those imposed under the other subparts of this part, 46.202 Purpose. It is the purpose of this, subpart to provide additional safeguard% in reviewing activities to which this subpart is applicable to aSSUre that they conform to appropriate ethical ~t;mdards and relate to important societal needs. 46.203 Definitions. As used in this subpart: (a) "Secretary" means the Secretary of Health, Education, arid Welfare and arty other officer or c,mployec of the Department of I lealth, Education, and Welfare to whorn authority has been delegated. (b) "Pregnancy" encompasses the period of time from confirmation of ignplAntation (through any of the presumptive signs of pregnancy, such as missed mcnses, or by a medically acceptable pregnancy test), until c%palsion or extraction of the fetus. (c) "Fetus" nicans the product of concep(ion fiom the time of iraplantation (as evidenced by arty of' t1w presumptive signs of pregnancy. such as missed menses. or a raedicaily acceptable pregnancy test), unid a determination is made. explusion or extraction of the fetus, that it is viable. (d) "Viable" as it pertains to the I'VILIS mcans being able, after either .p.witancous. or induced delivery, to survive (given the benefit ofavailable ruedical therapy) to the point of independently maintaining hcart beat and mNpiration, The Secreiary may from, tirric to time. taking into iccount medioal ad,~ances, publish in the FEDE'RAi. R EGMER guidelines to assist in determining whether a fetus is vmble for purposes of this subpart. If a fetus is liable after delivery, it is a premature infant, (c) "Nativiable fetus" means a fetus e-v u,fero which, although living, is not viable. M "Dead fetus" means a fetus ex utero which exhibits neither heartbe.1a, spontaneous respiratory activity. spontaneous movement of voluntary muscles, nor pulsation of the umbilical cord (if still attached). Q) -In virro fertilization" means any fertilization of hunian ova which occurs outside the body of a female, either through admixture of donor human sperni and ova or by any other means. § 46.~'INl 'Mical Advisory' Boards. 0 (a) 0ne or inore Ethical Advisory Boards shidl be established by the Secretary. kictribers of these board(s) shall be so selecutd that the hoard(s) will be. competent to deal with medical, lcgal, social, ethical, and related issues and may inc!udc, for example. msearch scientists, physicians, psyt:hologists, sociologists, educators, lawyers, and ethicists, as well as reprebenlatives of the general public. No board inember may be a regular, full-time employee of the Departnivrit of Health, Educacion, and Welfare. (b) Al thc request of the Secretary, the Ethical Advisory Board sh.M render ~idvice consistent with [tic policies and requirements of this Part as to ethical issues, involving activitics covered by this subpart, raised by individual applications or proposals. In addition, upon requesi by the Necretary, Ilic Board shall render advicc as to classes of applications or proposals and general p~,Olicies, guidelines, . and procedures. (0 A Board rnay establish, with aic approval of the Secretar, , classes Y o1' applicatioas or proposals which: (1) Must be suhmitted to the Board, or (2) need not be submitted to the Board. Where the Board so establishes a cuss of applications or proposals which must be submitted. no application or proposal within the class may be fundc4 by the Depiatment or any component thereof until the application or proposal has been reviewed by the Board and the Board has rendered advice as to its acceptability from an ethical standpoint. (d) No application or proposal involving human in vitro fefiflization may be funded by the Department or any component thereof until the application or proposal has been reviewed by the Ethicil Advisory Board and the Board has rendered advice as to its acceptability from an ethical standpoint. 46.205 Addidenatf duties ot tfw Institutiii6ii-IRaii~'t'W'B~ards in connection with activities involving fetuses, pregnant women, or human In vitro fertili*zation. (a) In addition to the Ic3ponsibil i ties prescribed for Institutional Review Boards under Subpart A of this part, the applicant's or offeror's Board shall. with resi:)w to activities covered by this subpart, carry out the following additional duties:- ( 1) Determine that all aspects of the activity mect the requirements of this subpart: (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 tile applicant or offeror for monitoring the actual informed consent procczils (e.g., through such mechanisms. when appropriate, as participation by the Institutional R.cview Board or subject adv(watcs in: (i) Oversecing the actual process by which individual consenis required by this subpart arc seew-ed either by approving induc,ion of each individual into thc activity or Approved For Release 2000/08/08 : CIA-RDP96-00788ROO1500140003-9 7, , "-AV Tw '.. I ----r7TWk'FC' 7'41'r~ 4-~'c.ApProved For Release 2000108108 : C IA-RDP96-00788 ROO 1500140003-9 Page 13 verifying, perhaps through sampling, ul,~,at ~.pproved procedures for induction of individuals into 1he activity are being followed, and (ii) monitoring the progress of the activity and intervening as ;necessary through such steps as visits to the activicy site and continuing .-valuation to determine if any unanticipated risks have arisen), (3) Carry out such other responsibilities as may be assigned by the Secretary. (b) No award may be issued until the applicant or offeror has certified to the Secretary that the Institutional Review Board has made she determinations required under paragraph (a~ of this section and the Secretary has approved these dewi-minations, as provided in § 46. 120 of Subpart A of this part. ic) Applicants or offerors seeking support for activities covered by tills Subpart Must provide for the designation of an institutional Review I341.fTd, subject to approval by the ~ecrctary, where no such Board has beer. established under Subpart A of this parts 46.206 General limitation%. (a) No activity to which this SUbpart Is applicable may be undertaken unless: ~ 1) Appropriate studies on ;iniruals .~~nd nonpregnant individuals have hec;.i completed, Q) Except where the puqiose of (lie activity is to meet the health -ds of the mother or the pafticular ttn~is, the risk to the fetus is minimal ands in all cases. is the least possible risk for achieving the objectives of flic activity. Individuals engaged in the JCtIVITV Will have no part in: (i) Any t3ccisions as to the timing, method. aiw~ procedures used to terminate the pregnancy, and (it) determining the viat)i1ky of the fetus at the ' termination of the pregnancy. and (4) No procedural changes which may cause greater than minimil risk to dhe fetus or the pregnant woman d I lie introduced into the procedug-c for terrainating the pregnancy solely in the interest of the activity. M No in4lucements. monetary or otherwise, may be offered to terminite pregnancy for purposes of the activity. (40 FR 3.1528. Aug. R. JY75. as amtroled at 40 FR 51638. Nov. 6. 19751 46.207 .11ctivitles directed lowaird pregnant women as subjects. (a) No pregnatit woman may be involved as a subject in an activity covered by this subpart unless: ( 1) The purpose of the activity is to meet the health needs of the mother and the fetus will be placed a( risk only to the minimum extent necessary to meet such needs, or (2) the risk to the fetus is minimal. N An activio permitted under pmagraph (a) ofthis section may be conducted k.,,nl if the mother and y father are legally competent and have given thtnt informed consent after having been full), 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 inect the health needs of the mother; (2) his identity ~or whereabouts canflot reasonably be jsi-Trtained; (3) he is not reasonably avaiiable: or (4) the pregnancy resulted from rape. 46.208 Activities directed loward f,~Iuws in utero its subjects. (it) No fetus in ntero may he involved as a subject in any activity covered, by this subpart unless: (1) The purpose of the activity is it) meet the health needs of the particular fetus and the fews will he placed at risk only it) the inininium extent nece ss ary to niect such need:*, or (2) the risk to the fetus inposed by the research is minimal and the purpose of the acOvily is the development of important biumedical knowle(lge which cat-inot be obtained by o(her rlleans~ (b) An activity permitted under paragraph (a) of this section may he conducted only if the inother and father arc legally competent and have given their infortned consent, except that the father's consent need not lit secured if: ( 1) His identity or whereabouts canncR reorsonably be ascertained, (2) he is not reasonably available, or (3) the pregnancy resulted front rape. 46.209 Activides directed towaird fetuses ex utero, including nonviable fetuses, as subjects. (a) Until it has been ascertained whether or not a fetus cx utcro is viable, a fetus ex utero may not be! involved as a subject in an activity covered by this subpan unless: (1) There will be 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 obtaincd bv other means, or I (2) The purpose of the activity is to enhance the possibility of survival of the particular fctils to the point of viabilitv. N No nonviable fetus may be involved: as a subject in an activity covered by fts subpart unless: ( 1) Vital functions of the fetus will not be artificially maintained, (2) Experimeritaf activities which of themselves woulld terminate the licaitheat or respiration of the fetus will not be erriployed, and (3) The purpose of the activity is the development ofimportant biomedical knowledge which cannot be obtained by other means. (0 In the event the fetus ex utera is found to be viable. it may be included as a SUbjCrCt in the activity only to the extent permitted 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 he conducted only if the mother and father are legally competent and have given their informed consent, except that the father's intoffned consent need not be secured if: (1) his identi!y or whereabouts cannot rei!,%onably be ascertained, (2) lie is Approved For Release 2000/08/08 : CIA-RDP96-00788ROO1500140003-9 ~",tk !~~J*r(jv lease 2000/08/08 : C IA-RD P96 -00788 ROO 1500140003 -9 4scli.R4K ed For 1~elease,' not reasonably available, or (3) the prepiincy resulted from rapc. 46.210 Activities involving the dead fetus, fetal materhil, or the placenta. Activities involving the dead fetus, mascerated fetal material. or cells, tissue, or organs excised from a dead fetus shall be conducted only in -able State accordance with any applic or local laws regarding such 3CtiViliCS. f 46.211 Modification cir waiver (of specific requirements. Upon the request of an ipplicant or offeror (with the approval of its Institutional Review Board), the Secretary may modify or waive specific requirements of thiis subpart, with the approval of tile Ethical ory Board after such opportunity for public comment as the Ethical Advisory Board considers appropriate in the particulir instance. in making such decisions, the Set~reiairy will consider whether tile risks to the subject are so outweighed by tile sum of the berlefit to the uh ,~cct and the importance of the ~flovdedee to be gained as to "arrant suJi nWifWation or waiver und diat stich henefits cannot he gained "cept through a modification or Waiver, ,uch modifications or %vaivers v~df he published a,-~ notices In we Fi~m KAt RFwsri-p, Subpart C-Additional Protectiows Pertaining to Biomedical and Behavioral Research Involving Prisoneers as Subjec-ft- 'i"W(ce: 43 FR 53655, Nov 16. 197K 46,301 Applicability. (A The regulations in this subpart '11t, ifpplicable to all biornedit:ai and behavioral research conducted or ~Llp,ported by tile Department of HeAth, Education, ;md Weifare inv(dving, prisoners as sub Icc ts. J (h I Nothing in this subpart shall be CollldruCd as indicating that ComplUince WI(h tile procedures set fo.fli lwreln will authorize res~ntrQh in~(sMm! prisoners its subjects, to 7,he c.~teat such research is limited or barred by applicable State or loc-11 law . (c) The requirements of this subpart arc in addition to those imposed under the other subparts of this part. § 46.302 Purpose. Inasinuch as prisoners may he under constraints because of their incarceration which couki affect their ability to make a truly voluntary and Uncoerced decision whether or not to participate as subjects in research, it is the purpase of this subpart to provitic 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 the Secretary of' Health. Education. and Welfare, and any other officer or employee (it' the Department of Health, Education, and Welfare to whom ztulhoritv has been delegated. N "DI-11'W" nicalls tile L)eparirnent of licalth, Education, ind Welfare, (0 "Prisoner" means any ~Wdividual involuntarily confined 0t .. ~ 1. b I ~ di:taincd in a pemal institution'.-rhe IC trm i sI1,, 0 t e n d e d 't o* "c" n c a n i'p a s individuals scntenced'to such an irr'stitution, under a criminal or civil statute, individuals"jetained in ,6_i'her 17~jcilitics by, virtue of statutes or comillitialk:111,procedures, which P!oYidC.:N1t1 n;fultivei tocrimi~xal. prosrcution or incaT,ceration ill a ~nd individuals P~nal it, detained licsidilig affaign"Ient, trial, -or-sentencing, (d) "Mininial risk" is the probabilirv and magnitude ot physical or psychological harm that is normally cnCOLI(Ilcred in the daily lives, or ki the routine medical. dental, ,)I- p:svchological ex.1nimation Of healthy pe i-~ons. § 46-30-1 Comp(tsition of Institutionul Review Boards %vhere prisoners are involved. Uri addition to satiNi'ving tile requirements in § 46-107 of this part, an Institutional Review Board. carrying out responsibilitics under this part with fespect to research covered by this subpan, shall also meet the Nlowing specific requirements: (a) A majority U tha BoQ ~i I ~ 1 -1.1 - I I -~'- " " I .A (exclusive or prisonef members) Ailialf, I I - "' "' "" - , IM C no ass4xiation with the prisotl(#J! . v 1- -1 ~~ %# 1111volvod, from their membership bn tile Board! W At least one member of thiI Board shall be a prii,66er or a r8ofleTJCPrC&:S1tativc w -ith A back[Vound 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. 46.305 Addlflunal dudrs'of the Institutional Review Boards where prisoners are Involved. (a) In addilion to all other responsibilifieN piescribed for Institutional Revi,-.w Boards tinder this part, the Board shall review research covered by this subpart and approve such research only if it finds that: 1) The research under review represents one of tile categories of research permissible under § 46.306(a)(2)-, (2) Any possible advantages accruing to the prisoner through his or her particil;Pation in the research, when compaied to the general living conditions, medical care. quality of food, arricnities ind opportunity for earnings in the. prisoo, aro, not of such a Magnitude, that his or her ability to. weigh the risk:* ofilie reseatch apinst., the value of ,.uch'advantagcs in the, limited choice covironmen ,it of the prison is imptlircd, (3) The risks Involved in the research are commensurate with risks that would be accepted by noriprisoner volunle~rs, (4) Procedures for the selection'of lift subjects within the prison arc f .... ... Approved For Release 2000/08/08 : CIA-RDP96-00788ROO1500140003-9 roved For Re I ease 2000/08/08 : C IA-RDP96 -007 88 ROO 1500140003 -9 all prisoners and immune fri)m ~rhitriffyjntcrvcntion by prison au ithoriiies or prisoners. Uniess the principal investigator provides to the Board justification in writing for foilowing some other procedures, control. subjects mug be'selecW, irandomly from the group of available lytisoners who meet the characteristics needed for that particular research project. 0) The information is pirmenred in lAriguage which is understandable to the subject population, 16') Adequate assurance exists that ~* ~ . .1 , -t a iriso neir's, '. articl pition In p tile research in making decisions regarding parole, and each prisoner is clearly infornied in advance that partrcipation in the research will have no effect on his or her parole; and (7) Where the Board finds there nia'~ be a need for follow-up examinaiion ()I care of participants after the end of their participation, adequate provision has been tnade lor SLICII CKamination or care, taking into 3CCOUTIt 1hC Varying lengths 01' individual prisoners' sentence!%, and for informing participants of this fact. W The Board shall c Iarry Out Such obitr dulics as may be assigned by (c) 'The insitution shall cer,tify to dic Secretaty, in such form and rnaiin~:r as the Secretary may reclutrc, th-Ut (lie duties of the B%-.)ard under this ,wetion have bc~en fulfiliccl. 46.306 Ptcralited rtsearcli involving prisonem. t 4) Biornedical or behavioral ( conducted or supported by I-)JQ:vV may involve prisoners as %u!))CCts only if: I) I'he irstittifion responsible for the.conduct of the research his cerilfied to the Secretary that the lw,Jtutional Review Board has approved the research under § 46.305 of ti,,Is subpart; and (2) In the judgment of the Secretary the proposed research invoives solely the following: (A) Study of tile possible cjus,-.%. effects, and processes of incarcerition. and of criminal behavior, im-wided that the study presents no more than minimal risk and no more [lion inconvenience to the 5UbjC'Ct:5' ('B) Study of prison-; as institutional structures or of prisoners as incarcerated ;-wrsons, provided that the study presents no more than minimal risk and no more than inconvenience to the subjects-, W) Rcwarch tin conditions particulatly affecling prisuners as a class (for example, vaccine trials and other research on hepatitis which is Inuch mor(~ prevalent in prisons than elsewhere, and research on social and psychological problems such as alcoholism, drug adoicuori and sexual assaults) provided that the study may proceed only after the Secretary has consulted with appropriate experts including experts in penology medicine and ethics, and published notice. in the F R Lms-i r:P1 of his intent f~o approve. itich research-, or (1)) Research on practices, both Innovative and accepted, which have the intent and reasonable probability of improving the health or well- bellig of tile subjeLl. III cases in which those studies require the assignment of prisoners in a niannei cinsistent NA-iih protocols 'Approved by the IRB to crinuol groups which may not henefit Crom the resear,-h, the study may proceed ortly after die Secretary h.IS COJISLII(Cd With appropriate experv~ . kicluding experts in penology nwdicine and ethics, and Published F106CC, in the FEDF.R.,%L R ~:Gis'l F. R, of his Ingeot to approve such research. (b) E-xcept as provided in paragraph (a) of this; section, biomedical or hehavioral research conducted or supported by DIIEW shall not involve prisonets as subjects. Subpart D-A4titileniail ftotftdmg f(W CUM"s 1WVWVC4 &0 subilX-ft (a ROMUT1111. Soujr-- 48 FR 983, Idarch 9, 1983 946-401 To what do them regulad,009 apply? (a) ThLs subpart applie"I to all riesearch involving children as subjects, conducted or supported by the Department of Health and Human Services, (1) 11iis includei research conducted by Department employtTs, except that each head of an 01wraling Division (if the Department n-uiy adopt such nonsubstantive, procedural modifications m may be appropriate from an administrative standpoint. (2) It also includes research conducted or supponed by the Department of Health and Human Services outside the Unittd States, but in appropriate eircurnstarIcems, the Secretary may, under paragraph (e) of §46.101 of Subpart A, waive the aPPlicabilitY of some or all of the requirements of these. regulations for research of this type. (b) Exemptions (1), (2). (5) and (6) as listed if) Subpart A at §46,101(b) are applicable to this subpart. Exemption (4), rei~earch involving tile obseivation or public behavior, listed at §46,101(b), is applicable to this subpart where the investigator(s) does not participate in the activitin being observed. Exemption (3), research involving survey or interview procedures, listed at §46,101(b)does notapplyto research covered by this subpart. (c) Pie exceptions. additions, and provisions for waiver as they appear in paragraphs (c) through (i) of §46,,101 of Subpart A are applicable to this subpart. ".402 Deffintitioas. The definitions in §46.102 of Subpart A shall be applicable to this subpart as well, In addition, as used in this subpartt Approved For Release 2000108108: CIA-RDP96-00788ROO1500140003-9 PaApproved For Release 2000/08/08 : CIA-RDP96-00788ROO1500140003-9 45 CFFt (a) 4~ChildresiP are persons who lhav`t not attained the legal age for conknt to treatments or procedures involved in the research, tinder the applicable law of thejursdiction in which the research will bc, conducted. (b) "Assi~'V means a child's affirmative agreement to participate !it research. Mere failure to object should not, atrwilt affirmative agreement, be constnied as assent. (c) 'Permission" means fhe agreement of parent(s) or guardian to tile participation of their child or ward in research. (d) "Parent" means a child's biological or adoptive parent. *.rJu.WianF.1 W means an individ" who is authorized under applicable state or local law to consent on behalf of a child to general inedical care. §46.403 IRB duties. fit addition to other resp~)n.,;ibili tics Jssigned to IRBs under this part, i:ach IRD shall review research covercd by this SUbpJft al)J, 31)prove only research which satisfies the conditions of all applicable sections of this subpart. §46.404 greiter than minimal risk. HIIS will conduct or firad research in which the IRB finds that no greater than minimal risk- to children is presented, only if (lie IRD finds that adequate provisions Lire niade for soliciting the assent of the children and the permission oftheir parents or guardians, AS Set forth in 46.406. 4 4.6.405 Reamth involting &nater thius mialmal risk but presenflog the limspect of dbvd betwilt to the, Indiv-dusi subJtcts. UHS will conduct or fund research in which the IRB finds that more than mininial risk to chil(Iren is prt-scritcd by an intervention or procedure that holds out the prospect of direct bencitt for the ituJividual subject, or by a monitoring procedure that is likely to contribute to the subject's well-being only if the IRD finds that: (a) The risk is justified by the anticipated boiefit to the subjects; (b) The relation of the anticipated benefit to the risk is at Icast as favorable to the subjects as that presented by available alternative approaches; and (c) Adequate provisions are made for soliciting the as%ent of tile children and rcrmission of their parents or guardians, as set forth in § 46.408. § 46.406 Research involving greater titan rninintal risk wid no prospect of direct benefft to individual subjects, but likely to yleld generalizable knowledge about the subject's dfwrdey or condition. HIL5 will conduct or fund research iii which tile IRD finds that more than niinimal risk to children is presented by art intervention or procedure that does not hold out the prospect of direct benefit for tile individual subject, or by a moni(orine, prcm~cdure which is riot likely 10 C-09(rihUtC to tile WC11-bCing of the subject, only if the W13 finds that: (a)The risk represents a minor increase over minimal risk. (b) The intervention or procedure presents experiences to subjects that are reasonably commensutate with those inherent in their actual or expected medical, dental, PSYChologiCil, social, or educational Situations, (c) The, iwervention or prmTdure is likely to yield generalizable knowledge about the stibjecti' disorder or condition which is of vital importance for tile undcrstatiding or amelioration of tile subjects' disorder or condition; and (d) Adequate provisions are made for soliching assent of the children and permissicia oftheir parents or guardians, ns set forth in § 46.408. § 46AW Remarch not otherwhie approyable which presents an OPPOTtunity to usidemitand, prevent or - Alleviate a serious problem affecting tire health or w-elfam of children. HIIS will conduct or fund research that the IRS does not believe meets, the requirements of 46.404, 46.405, or 46.406 only if. (a) The IRS finds that the research presents a reitsonable 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) That the research in fact satisfies the conditions of § § 46.404, 46.405, or 46.406, as applicable, or (2) the fOllOwing: (i) Tile research presents a reasonable opportunity to further the understanding, prevention, or alleviation (if a serious problein affecting tile health or welfare of children; (ii) The research will be conducted in accordance with sound ethical principles; (iii) Adequate provisions arc made for soliciting the assent of children and the permission of their parents or guardians, as set forth in J 46-40& 1 ".443 Requirgmtnts Iror Penabdon by PAiwents at guardiatm arid for asawt by children. (a) In addition to the de(erminations required ututer other applicable Sections of this subpart, the IRD shall determine that adequate provisions are made for soliciting the assent of the childrcr4 when in the judgment of the IRB the children are* capAble of providing' anent. In determining whether children are capable of assenting, t1le. IR11 shall take into &CCCHM9 the agc!sj maturity, aml psychological scite of the childsen involvvd. This judgment V, Approved For Release 2000108108: CIA-RDP96-00788ROO1500140003-9 43 0"Aftroved For Release 2000108108: CIA-RDP96-00788ROO1500140003-9 pap 17 may be made for all children to be irivolved in research under a panicular protocol, or for cach child, 1as dic IRD deems appropriate. If the 0 IRTI determines that the capability of soinc or all of the children is, so limited that they cannot reasonably be consulted or that the intervention or procedure involved in the research holds out a prospect of' dirvct bennefit that is important to the health or well-being of the children and is available only in the context of the iresearch. the assent of the citildien is not a necessary condition for proceeding with the research. 1-1ven where the M doemiines that ffic subjocts am capable of assenting, the 11RD may SO waive the *&sent r(Nuirement under circum"wAn in which conuut may be waivoA in sm-~cord with § 46.116 of Subp&rt A. (b~) In addition to the determinations required under other applicable scctions of this subpart, the IRD shall determine, in accordance with and to the extent t hat consent is required by; 46.116 of Sobpaxl A, that adequate provisions are roade for soliciting the permission of 4mch child's parents or guardian. Wlic-re parental permission is to be ob(amcd, the IRB may find that the pci~,nission of one parent is sufficient for rttse- arch to be conducted under 4 6. 4VA or 46.405. Where research is covered by § § 46." and 46.407 and permimion is to be obtAinCd from parents, both parent.,; must give their prrniission unless one parent is decessed, unknown. incompetent, or ns-cit reasonably nvailable, or when only one parent has legal responsibility for the care and custody of the child. (c) In addition to the provisions for waiver concained in 146. t 16 a f Subpart A, if the IRD determines that a research protocol is designed for conditions or for a subject population for which parental or guardian permission is not a reassortable requireniant to protect the subjects (for example, neglected or abused children), it may waive the consent requirements in Subpart A of this part and parag 'raph (b) of this soction, provided an appropriate mechanism for protecting the children who will participate assubjects in the research is substituted, and provided further that the waiver is not inconsistent with fedeiral state or local law. The choice of an appropriate mechanism would depend uIx-ni the nature and purpose of the activities described in the protm-lol, the risk and anticipated benefit to the rewarch subjects, and their age, maturity, status, and Condition. (d) Permission by parents or guardians sliall be, docuniented in accordance with and to (lie extent requirtd by § 46. 117 ol' Subpart A. (e) When the IRB deterinines that assent is Nquired, it shall also determine, whether and flow assent must he documented. 46.409 Wards. (a) Children who arc %vards of the state or any other agency, institution, or entity can be included in research approved und". § 146.406 or 46.407 only if such msearch is- (1) Related to the status as wards; or (2) Conducted in schools, camps, hospitals, institutions, or similar SCttiDg3 in which the majority of children involved as subjects arc riot ward&. N If the research is approved under paragraph (a) of this scction~ the IRB !;hall require appointment of an advocate for each child who is a ward, in addition to any other individual acting on be-half'of the child as guardian or in kwo parenth. One individual umy serve as advocate for more rhAn one child. The advocate shall be an individual who has the background and experience to act in, and agre" to act in, the best interests of the child for the duration or the child's participation ill the research and who is riot wsscciated in any way (except in the roleas zdvocate or member of the IRB) wizh the nmearch, the invesfigator(s), or 44c guardian organization, Approved For Release 2000108108: CIA-RDP96-00788ROO1500140003-9 P is ~-CIA-RDP96-00788ROO1500140003-9 45 IMI NOTICES' HUMAN SUBJL,-CTS Elsewhere in this issue. ()f the FEDPERAL R 1-61STER, the Secretary Minimum criteria Identifying the Viable Fetus is amending 45 CFR Part 46 by , I On Niarch 13, 1975. regulations among other things, adding a new were published in the FE-:DERAI Subpart 11 to provide additional R ECISTER (40 FR protections pcrtaining to research, 11854) relating 10 'he development. anti related activities proicction of human subjects in involving fetuses. pregriant wornen, sesi-arch, development, anti reLaed and -in vitro fertilization. activities supported by Department of Section 46,203(d) of Subpart B flealth. Education, and kli'clfare provides inter alia as follows~ grants and contracts. Tlxse The. Secretary may from time to time, regulation-, are codified at 45 CFR taking into aco'~unt medical advances, Part 46. publish in the F fi)EitAL R HASTE X guidelincl 10 assi-41 in determining W betber fetus it viible fotr purposes of this subpa". This notice .2.3 published in accOrdi[ACC With § 46-20.3(d). For PurPONeii Of SUbpan B. the guideliiies indicating thilt a fetus other thein a dead fetus within the meaning of § 46,203(t) is viable include the following: an estimated gestational age of 20 wtelct; or more and a bo'0Y weight of 500 grams or more FEDERAL REGISTER. VOL 40, AUGUST 6, 1975 U.S. GOVrRNMENT PRINTING OrFICE t 1963 0 - 406-756 Approved For Release 2000108108: CIA-RDP96-00788 ROO 1500140003-9