Psge“pproved For Release 2000/08/08 : CIA- RDP96- 00788R001700250001 au bree narrcminac na sntncnanel a statement of the reasons for its - - g@ecision and give the investigator an opportunity to respond in person or in writing. oo {e) Ao IRB shall conduct continuing review of research covered by these regulations at intervals appropriate to the degree of risk, but not less then once per year, and shall have authority to observe or have a third party observe the conseni process and the research. $46.110 Expedited review procedures for certain kinds of research inveiving no more than minimal risk, and for minor changes in approved research. (a) The Secretary has established, and published in the Federa! Register, a list of categories of esearch that may be reviewed by the IRB through an expedited review procedure. The list will be amended, as appropriate, through periodic republication in the Federal Register. ib) An IRB may review some or all of the research appearing on the list through an expedited review procedure, if the research involves nv more than minimal risk, The [RB 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 may be carried out by the IRB chairperson or by one or more experienced reviewers designated by the chairperson from among members of the IRB. In reviewing the research, the reviewers may exercise all of the authorities of the IRB except thai the reviewers may not disapprove the research, A research activity may be 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 Se CTA ee ROMP RNR FARE RRA CR EA OER NM I Nf Es Oe ewe proposals which have been approved under the procedure. (d) The Secretary may restrict, suspend, or terminate an institution's or IRB's use of the expedited review procedure when necessary to protect the rights or welfare of subjects. §46.811 Criteria for IRB approval of research. (a) In order to approve research covered by these regulations the IRS shall determine that all of the following requirements are satisfied: (1) Risks tc subjects are minimized: (i) By using procedures which are consistent with sound research design and which do not unnecessarily expose subjects to risk, and (ii) 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 sublects, and the importance of the knowledge that may reasonably be expected to result. In evaluating risks and benefits, the IRB should consider only those risks and benefits that may result from the research (as distinguished from risks and benefits of therapies subjects would receive even if not participating in the research). The IRB should not consider 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) Selection of subjects is equitable. In making this assessment the IRB should take into account the purposes of the research and the setting in which the research will be conducted. (4) Informed consent will be sought from each prospective subject or the sublect’s legally authorized representative, in accordance with, and to the extent required by § 46.116. vos 1h ala AR RNa ac hd a ARS A LCE ag 45 CFR % (5) Informed consent ¥ will be appropriately documented, in accordance with, and to the extent required by § 46.117. yi (6) Where appropriate, the research plan makes adequate provision for monitoring the data collected to insure the safety of subjects. (7) Where appropriate, there are adequate provisions to protect the privacy of subjects ‘and to maintain the confidentiality of data. (b} Where some or all of the subjects are likely to be vulnerable to coercion or undue influence, such as persons with acute or severe physical or mental illness, or persons who are economically or educationally disadvantaged, appropriate additional. safeguards have been included in the study to protect the rights and welfare of these subjects. $ 46.112 Review by institution. 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 research if it has not been approved by an IRB. 346.113 Suspension or termination of IRB approval of reseurch, renee research that is not being « conducted in accordance with the IRB’s requirements or that has been associated with uneapected serious harm to subjects, Any suspension or termination of approval shall include a Statement of the reasons for the “HARB 's action and shall be reported promptly to the investigator, appropriate institutional officials, and the Secretary. ! ' Reports should te filed with the Office for Protection from Research Riska, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland 20205. @ Approved For Release 2000/08/08 : CIA-RDP96-00788R001700250001-7
aera AND aa Ae SS AA AP MAE RSPR TN at ENED ies ERP WETS LN AF . 45 CER 46 ere monn $ 46.114 Cooperative research. Cooperative research projects are ' those projects, normally supported through grants, contracts, or similar arrangements, which involve insiitutions in addition to the grantee or prime contractor (such as a coniractor 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 with these regulations as though it received funds for its participation in the project directly from the Department, except that in complying with these regulations institusions muy use joint review, reliance upen the review of another qualified IRB, or similar arrangements aimed at avaidance of duplication of effort. $ 46.115 IRB records.” (a) An institution, or where appropriate an IRB, shall prepare and maintain adequate documentation of IXB activities, including the following: (1) Copies of all research proposals reviewed, scientific evaluations, if any, that accompany the proposals, approved sample consent documents, progress reports submitted by investigators, and reports of injuries to subjects. (2) Minutes of IRB meetings which shall be in sufficient detail to show attendance at the meetings; actions taken by the IRB; the vote on these acuions including the number of members voting for, against, and abstaining, the basis for requiring changes in or disapproving research; and a written summary of the discussion of controverted issues and their resolution. (3) Records of continuing review ACHIVEHES, Approved For. Release. 2000/08/08. RT PR ORAS RAE AURA SOIR SMES 3 RB (4) Copies of all correspondence between the IRB and the investigators. (3) A list of IRB members as required by § 46, 103(b)(3). (6) Written procedures for the IRB a3 tequired by § 46. 103(b)(4), (7) Statements of significant new findings provided to subjects, as required by 4 46.116(b)(5). (b) The records required by this regulation shall be retained: for at least 3 years after completion of the research, and the records shall be accessible for inspection and copying by authorized representatives of the Department at reasonable times and in a reasonable manner. §$ 46.116 General requirements for informed consent. Except as provided elsewhere in this or other subparts, no investigator may involve a human being as a subject in research covered by these regulations unless the investigator has obtained the iegally effective informed consent of the subject or the subject’s legally authorized representative, An investigator shall seek such consent only under circumstances that provide ihe prospective subject or the representative sufficient opportunity to consider whether or not to paricipate and that minimize the possibility of coercion or undue influence. The information that is given to the subject or the representative shall be in language understandable to the. subject or the representative, No, informed consent, 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 telease the investigator, the sponsor, the institution or its agents trom liability for negligence. (a) Baste elements of informed consent. Except 45 provided in paragraph (c) or (d) of this section, in ..CIA-RDP96-00788R001700250001-7 FA MESSE en ah SE OR tate Page 9 et meme Pr selene enn BR ad seeking informed consent the 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 4 identification of any procedures « which are experimental; Hl (2) A description of any reasonably , foreseeable risks or discomforts to the Jeubject: » (3) A description of any benefits to “ ‘the subject or to others which may “reasonably be expected from the dresearch; * (4) A disclosure of appropriate ‘ ulternative 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; (6) For research involving more than minimal risk, an explanation as _ {0 whether any compensation and an tv fh . ¢xplanation as to whether any medical treatments are available if injury occurs and, if so, what they * consist of, or where further information may be obtained: (7) An explanation of whom to - contact for answers to pertinent . questions about the research and Tesearch subjects’ rights, and whom to contact in the event of a research- related injury to the subject; and 48) A statement that participation is "voluntary, refusal to participate 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 ot loss of benefits to which the subject is otherwise “entitled. “(b) Additional elements of informed consent; When appropriate, one of more of the following elements of information shall also be provided to each subject: Bee" teen Approved For Release 2000/08/08 : CIA-RDP96-00788R001700250001-7
ate ABproved For Release 2000/08/08 : CIA-RDP96-00788R001700250001-7 2 “C)A statement that the particular Ftreatment or procedure may involve Lyisks to the subject (or to the embryo -¥or fetus, if the subject is or may shecome pregnant) which are currently “unforeseeable: # (2) Anticipated circumstances g under which the subject's ¢ participation may be terminated by tghe investigator without regard to the “subject's consent, % (3) Any additional costs to the subject that may result from participation in the research: (4) The consequences of a asubject's decision to withdraw from gthe research and procedures for gorderly termination of participation by the subject; 5, (5) A statement that significant jnew findings developed during the y course of the research which may relate to the subject's willingness to ‘continue participation will be Provided to the subject; and ¥ (6) The approximate number of “gubjects involved in the study. ic) An IRB May approve &. conse t . procedure * daee.agk daclude; or which “alvexg,;20me | or albaf the clemeusa a i informed consent set forth above, or waive the requirement to obiain informed consent provided the IRB finds and documents that: {1) The research or demonstration project is to be conducted by or subject to the approval of state or lacal government officials and is designed to study, evaluate, or otherwise examine: (i) programs under the Social Security Act, ar other public benefit or service programs; (ii) procedures for obtaining benefits or services under those programs; (Hi) possible changes in or altermatives to those programs or procedures; or (iv) possible changes in methods or levels of payment for benefits or services under those programs; and (2) The research could not peacticably be carried out without the waiver or alteration, (d) An IRB may approve ‘a consent -procedure which does not include, or which altesa, some or all of the elements of informed consent set forth above, or waive the requirements to obtain informed conseat provided the IRB finds and documents that: (1) The research tavolves no more than minimal risk to the subjects; (2) The waiver or alteration will nat adversely affect the rights and welfare of the subjects: (3) The research could not practicably be carried out without the waiver or alteration, and (4) Whenever appropriate, the subjects will be provided with additional pertinent information after participation. (e) The informed consent requirements in these regulations are nol 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 fimit the authority of a physician io provide emergency medical care, to the extent the physician is permitted to do so under applicable federal, state, or focal law. §$46.117 Gocumentation of : tnformed concent, (a) Except as provided in paragraph (¢) 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 legally authorized representative. A capy shall be given to the person signing the form. (b) Except as provided in paragraph (c} of this section, the consent form may be either of the following: (1) A written consent document that embodies the clemenis of - informed consent required by § 46.116. This form may be read to the subject or the subject's legally authorized representative, but in any event, the investigator shall give either the subject or the representative 45 CFR 46 eA: NY A NARS adequate opportunity to read it before it is signed; or (2) & “shon.form"* written consent document stating that the elements of informed consent required by § 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, the 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 «immary, and the person actually oouining consent shall sign a copy of the summary. A copy of the summary shall be given to the subject or the representative, in addition to a copy of the ‘short «y (c) An IRB may waive the requirement for the investigator to obtain a signed consent form for seme or all subjects if it finds either: (1) That the only record linking the subject and the research would be the ¢ consent document 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 research, and the subjects wishes will govern; or (2) That the research perce 2 more than minimal risk of subjects and invelyss no ee ae ros for which written consent is normally required outside oF the research context. ~ In cases where the documentation requirement is waived, the IRB may require the investigator to provide subjects with a written statement regarding the research. § 46.118 Applications and proposals lacking definite plans for involvement of human subjects. Certain types of 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-RDP96-00788R001700250001-7 Bee he agape EW ag it BERN Mme open mk
= 45 C&pREpved For Release 2000/08/08 : CIA-RDP96-00788R001700250001-7 eet period 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 responsibilicy; research training grants where the ucUivities involving subjects remain to be selected; and projects in which human subjects’ involvement will depend upon completion of instruments, prior animal studies, or Purification of compounds. These applications 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 any project supported by these awards until the project has been reviewed and approved by the IRB, as provided in these regulations, and certification subrnitted to the Department. §46.119 Research undertaken without the intention of involving human subjects, in the event research tconducted or funded by the Department) is undertaken without the intention of imvolving human subjects, but it iy later proposed to use human subjects in the research, the research shall first be reviewed and approved by an IRB, us provided in these regulations, a certification submitted to the Department, and final approval given to the proposed change by the Department. $ 46.120 Evaluation and disposition of applications and proposals, (a) The Secretary will evaluate all applications and proposals involving human subjects submitted to the Department through such officers and employees of the Department and such experts and consultants as the Secretary determines to be appropriate. This evaluation will take into consideration the risks to the subjects, the adequacy of protection against these risks, the potential benefits of the proposed research to 136 2S TERRE SAE AS ER BD REE EAS ELL LA the subjects and others, and the importance of the knowledge to he gained. (b) On the basis of this evaluation, the Secretary may approve or disapprove the application or Proposal, or enter into negotiations to develop an approvable one. $46.12 Investigational new drug ov device Me-day delay requirement. When an institution is required to prepare or to submit a certification with an application or proposal under these regulations, and the application or proposal involves an investigational new drug (within the meaning of 2f U.S.C. 35$(i) or 357(d)} of a significant risk device (as defined in 21 CFR 812.3(m)), the institution shal} identify the drug or device in the certification. The institution shall also state whether the 30-day interval required for investigational new drugs by 21 CFR 312, (a) and for significant risk devices by 21 CFR $12.30 has elapsed, or whether the Food and Drug Administration has waived that requirement. Ef the 30-day interval has expired, the institution shall State whether the Food and Drup Administration has requested that the Sponsor continue to withhold or testrict the use of the drug or device in human subjects. If the 30-day interval has not expired, and a walver has not been received, the institution shall send a stttement to the Department upon expiration of the imerval. The Department will not consider 3 certification acceptable until the institution has submitted a statement that the 30-day interval has elapsed, and the Pood and Drag Administration bas not requested it to limit the use of the drug or device, or that the Food and Drug Administration has waived the Ad-day interval, $46,122) Use of Federal funds. Federal funds administered by the Department may not be expended (or research involving human subjects unless the requirement of these NE RSS ERG ETS ER OE regulations, including all subparts of these regulations, have been satisfied. § 46.123 Earty termination of research funding; evaluation of subsequent applications and proposals. (a) The Secretary may require that Department funding for any project be terminated or suspended in the manner prescribed in applicable program requirements, when the Secretary finds an institution has materially failed to comply with the terms of 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 requiremenis and program criteria, factors such as whether the applicant has been subject to a termination or suspension under paragraph (a) of this section and whether the 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 responsibility for the Protection of the rights and welfare of human subjects (whether or not Department fuads were involved), § 46.124 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 Secretary's judgment additional conditions are necessary for the Protection of human subjects. Subpart B--- Additional Protections Pertaining to Research Development, and Related “Activities Involving Fetuses,° Pregnant Women, and Human tn Vitro Fertilization’ Source, 40 FR 3828, Aug. 8, 1975, 43 FR H7S8, January £1, 1978, 44 ER 31559. November 3, 197K 846.201 Applcahitity, {a) The regulations in this subpart are applicable to aif Department of Health, Education, and Welfare Approved For Release 2000/08/08 : CIA-RDP96-00788R001700250001-7