search that is not being conducted in accordance with the IRB's requirements or that has been associated with unexpected serious harm to subjects. Any suspension or termination of approval shall include a statement of the reasons for the IRB's action and shall be reported promptly to the investigator, appropriate institutional officials, and the Secretary.1

[46 FR 8386, Jan. 26, 1981; 46 FR 19195, Mar. 27, 1981]

§ 46.114 Cooperative research.

Cooperative research projects are those projects, normally supported through grants, contracts, or similar arrangements, which involve institutions in addition to the grantee or prime contractor (such as a contractor with the grantee, or a subcontractor with the prime contractor). In such instances, the grantee or prime contractor remains responsible to the Department for safeguarding the rights and welfare of human subjects. Also, when cooperating institutions conduct some or all of the research involving some or all of these subjects, each cooperating institution shall comply 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 institutions may use joint review, reliance upon the review of another qualified IRB, or similar arrangements aimed at avoidance of duplication of effort.

(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 actions 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 activities.

(4) Copies of all correspondence between the IRB and the investigators.

(5) A list of IRB members as required by § 46.103(b)(3).

(6) Written procedures for the IRB as required by § 46.103(b)(4).

(7) Statements of significant new findings provided to subjects, as required by § 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 FR 8386, Jan. 26, 1981; 46 FR 19195, Mar. 27, 1981]

§ 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 legally effective informed consent of the subject or the subject's legally authorized representative. An investigator shall seek such consent only under circumstances that provide the prospective subject or the representative sufficient opportunity to consider whether or not to participate and that minimize the possibility of coercion or 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 release the investigator, the sponsor, the institution or its agents from liability for negligence.

(a) Basic elements of informed consent. Except as provided in paragraph (c) 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 explanation of the purposes of the research and the expected duration of the subject's participation, a description of the procedures to be followed, and identification of any procedures which are experimental;

(2) A description of any reasonably foreseeable risks or discomforts to the subject;

(3) A description of any benefits to the subject or to others which may reasonably be expected from the research;

(4) A disclosure of appropriate alternative procedures or courses of treatment, if any, that might be advantageous to the 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 compensation and an explanation as to whether any medical treatments are available if injury occurs and, if so, what they consist of, or where further information may be obtained;

(7) An explanation of whom to contact for answers to pertinent questions about 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 participate will volve 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 informed consent. When appropriate, one or more of the following elements of information shall also be provided to each subject:

(1) A statement that the particular treatment or procedure may involve risks to the subject (or to the embryo or fetus, if the subject is or may become pregnant) which are currently unforeseeable;

(2) Anticipated circumstances under which the subject's participation may be terminated by the 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 subject's decision to withdraw from the research and procedures for orderly termination of participation by the subject;

(5) A statement that significant new findings developed during the 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 subjects involved in the study.

(c) An IRB may approve a consent procedure which does not include, or which alters, some or all of the elements of informed consent set forth above, or waive the requirement to obtain 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 local government officials and is designed to study, evaluate, or otherwise examine: (i) Programs under the Social Security Act, or other public benefit or service programs; (ii) procedures for obtaining benefits or services under those programs; (iii) possible changes in or alternatives to those programs or procedures; or (iv) possible changes in methods or levels of payment for benefits or services under those programs; and

(2) The research could not practicably be carried out without the waiver or alteration.

(d) An IRB may approve a consent procedure which does not include, or which alters, some or all of the elements of informed consent set forth above, or waive the requirements to obtain informed consent provided the IRB finds and documents that:

(1) The research involves no more than minimal risk to the subjects;

(2) The waiver or alteration will not adversely affect the rights and welfare of the subjects;

(3) The 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 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 to provide emergency medical care, to the extent the physician is permitted to do so under applicable Federal, state, or local law.

[46 FR 8386, Jan. 26, 1981; 46 FR 29883, June 3, 1981, as amended at 48 FR 9270, Mar. 4, 1983]

§ 46.117 Documentation of informed consent.

(a) Except as provided in paragraph (c) of this section, informed consent shall be documented by the use of a written consent form approved by the IRB and signed by the subject or the subject's legally authorized representative. A copy 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 elements 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 adequate opportunity to read it before it is signed; or

(2) A "short 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 summary, and the person actually obtaining 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 form."

(c) An IRB may waive the requirement for the investigator to obtain a signed consent form for some 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 subject's wishes will govern; or

(2) That the research presents no more than minimal 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 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 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 responsibility; research training grants where the activities 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 submitted to the Department.

§ 46.119 Research undertaken without the intention of involving human subjects. In the event research (conducted or funded by the Department) is undertaken without the intention of involving human subjects, but it is later proposed to use human subjects in the research, the research shall first be reviewed and approved by an IRB, as 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 the subjects and others, and the importance of the knowledge to be gained.

(b) On the basis of this evaluation, the Secretary may approve or disapprove the application or proposal, or enter into negotations to develop an approvable one.

§ 46.121 Investigational new drug or device 30-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 21 U.S.C. 355(i) or 357(d)) or a significant risk device (as defined in 21 CFR 812.3(m)), the institution shall identify the drug or device in the certifica

tion. The institution shall also state whether the 30-day interval required for investigational new drugs by 21 CFR 312.1(a) and for significant risk devices by 21 CFR 812.30 has elapsed, or whether the Food and Drug Administration has waived that requirement. If the 30-day interval has expired, the institution shall state whether the Food and Drug Administration has requested that the sponsor continue to withhold or restrict the use of the drug or device in human subjects. If the 30-day interval has not expired, and a waiver has not been received, the institution shall send a statement to the Department upon expiration of the interval. The Department will not consider a certification acceptable until the institution has submitted a statement that the 30-day interval has elapsed, and the Food and Drug Administration has not requested it to limit the use of the drug or device, or that the Food and Drug Administration has waived the 30-day interval.

§ 46.122 Use of Federal funds.

Federal funds administered by the Department may not be expended for research involving human subjects unless the requirements of these regulations, including all subparts of these regulations, have been satisfied.

§ 46.123 Early 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 requirements 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

§ 46.201 Applicability.

(a) The regulations in this subpart are applicable to all Department of Health and Human Services grants and contracts supporting research, development, and related activities involving: (1) The fetus, (2) pregnant women, and (3) human in vitro fertilization.

(b) Nothing in this subpart shall be construed as indicating that compliance with the procedures set forth herein will in any way render inapplicable pertinent State or local laws bearing 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.

any other officer or employee of the Department of Health and Human Services to whom authority has been delegated.

(b) "Pregnancy" encompasses the period of time from confirmation of implantation (through any of the presumptive signs of pregnancy, such as missed menses, or by a medically acceptable pregnancy test), until expulsion or extraction of the fetus.

(c) "Fetus" means the product of conception from the time of implantation (as evidenced by any of the presumptive signs of pregnancy, such as missed menses, or a medically acceptable pregnancy test), until a determination is made, following expulsion or extraction of the fetus, that it is viable.

(d) "Viable" as it pertains to the fetus means being able, after either spontaneous or induced delivery, to survive (given the benefit of available medical therapy) to the point of independently maintaining heart beat and respiration. The Secretary may from time to time, taking into account medical advances, publish in the FEDERAL REGISTER guidelines to assist in determining whether a fetus is viable for purposes of this subpart. If a fetus is viable after delivery, it is a premature infant.

(e) "Nonviable fetus" means a fetus ex utero which, although living, is not viable.

(f) "Dead fetus" means a fetus ex utero which exhibits neither heartbeat, spontaneous respiratory activity, spontaneous movement of voluntary muscles, nor pulsation of the umbilical cord (if still attached).

(g) "In vitro fertilization" means any fertilization of human ova which occurs outside the body of a female, either through admixture of donor human sperm and ova or by any other

means.

[40 FR 33528, Aug. 8, 1975, as amended at 43 FR 1759, Jan. 11, 1978]

§ 46.204 Ethical Advisory Boards.

(a) One or more Ethical Advisory Boards shall be established by the Secretary. Members of these board(s) shall be so selected that the board(s) will be competent to deal with medi