45 part 46 - Protection of Human Subjects

Question 1

45 part 46?

Answer 1

Protection of human subjects

Question 2

45 part 46 part A?

Answer 2

Basic HHS policy for protection of human subjects research

Question 3

To what does the 45 part 46 part A policy apply?

Answer 3

All research involving human subjects conducted supported or otherwise subject to regulation by any federal department or agency

Question 4

When research is conducted in foreign countries procedures normally followed to protect human subjects may differ from those set forth in 45 part 46 part A policy. What happens in this situation?

Answer 4

If a dept or head agency determines that the procedures prescribed by the institution afford protections that are at least equivalent to those provided in the policy, the dept or head agency may approve the substitution of the foreign procedures in lieu of the procedural requirements in this policy

Question 5

The following categories of human subjects research are exempt from Basic HHS Policy for Protection of Human Research Subjects

Answer 5

(1) Research, conducted in established or commonly accepted educational settings, that specifically involves normal educational practices that are not likely to adversely impact students’ opportunity to learn required educational content or the assessment of educators who provide instruction. This includes most research on regular and special education instructional
strategies, and research on the effectiveness of or the comparison among instructional techniques, curricula, or classroom management methods.
(2) Research that only includes interactions involving educational tests (cognitive, diagnostic, aptitude, achievement), survey
procedures, interview procedures, or observation of public behavior (including visual or auditory recording)
(3)(i) Research involving benign behavioral interventions in conjunction with the collection of information from an adult subject through verbal or written responses (including data entry) or audiovisual recording if the subject prospectively agrees to the
intervention and information collection
(4) Secondary research for which consent is not required
(5) Research and demonstration projects that are conducted or supported by a Federal department or agency
(6) Taste and food quality evaluation and consumer acceptance studies:
(7) Storage or maintenance for secondary research for which broad consent is required: Storage or maintenance of
identifiable private information or identifiable biospecimens for potential secondary research use if an IRB conducts a limited IRB
review and makes the determinations required by §46.111(a)(8).
(8) Secondary research for which broad consent is required: Research involving the use of identifiable private information or
identifiable biospecimens for secondary research use,

Question 6

(a) The Secretary of HHS has established, and published as a Notice in the FEDERAL REGISTER, a list of categories of research
that may be reviewed by the IRB through an expedited review procedure. The Secretary will evaluate the list at least every _______ years
and amend it, as appropriate, after consultation with other federal departments and agencies and after publication in the FEDERAL
REGISTER for public comment. A copy of the list is available from the Office for Human Research Protections, HHS, or any
successor office.

Answer 6

8

Question 7

What is 46.110

Answer 7

Expedited review procedures for certain kinds of research involving no more than minimal risk, and for minor
changes in approved research.

Question 8

An IRB may use the expedited review procedure to review the following

Answer 8

(i) Some or all of the research appearing on the list described in paragraph (a) of this section, unless the reviewer determines
that the study involves more than minimal risk;
(ii) Minor changes in previously approved research during the period for which approval is authorized; or
(iii) Research for which limited IRB review is a condition of exemption under §46.104(d)(2)(iii), (d)(3)(i)(C), and (d)(7) and (8).
(2) 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 that the reviewers may not disapprove the research. A research activity may
be disapproved only after review in accordance with the nonexpedited procedure set forth in §46.108(b).
(c) Each IRB that uses an expedited review procedure shall adopt a method for keeping all members advised of research
proposals that have been approved under the procedure.
(d) The department or agency head may restrict, suspend, terminate, or choose not to authorize an institution’s or IRB’s use
of the expedited review procedure.

Question 9

What is 46.111

Answer 9

Criteria for IRB approval of research.

Question 10

In order to approve research covered by this policy the IRB shall determine that all of the following requirements are
satisfied:

Answer 10

(1) Risks to subjects are minimized
(2) Risks to subjects are reasonable in relation to anticipated benefits
(3) Selection of subjects is equitable
(4) Informed consent will be sought from each prospective subject or the subject’s legally authorized representative
(5) Informed consent will be appropriately documented or appropriately waived in accordance with §46.117.
(6) When appropriate, the research plan makes adequate provision for monitoring the data collected to ensure the safety of
subjects.
(7) When appropriate, there are adequate provisions to protect the privacy of subjects and to maintain the confidentiality of
data.

Question 11

What is 46.113

Answer 11

Suspension or termination of IRB approval of research

Question 12

An IRB shall have authority to suspend or terminate approval of research 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 _________________

Answer 12

investigator, appropriate institutional officials, and the department or agency head.

Question 13

(a) Cooperative research projects are those projects covered by Basic HHS Policy for Protection of Human Research Subjects that involve___________

Answer 13

more than one institution

Question 14

Any institution located in the United States that is engaged in cooperative research must rely upon approval_______________ for that portion of the research that is conducted in the United States. The reviewing IRB will be identified by the Federal
department or agency supporting or conducting the research or proposed by the lead institution subject to the acceptance of the
Federal department or agency supporting the research

Answer 14

single IRB

Question 15

The following research is not subject to cooperative research

Answer 15

(i) Cooperative research for which more than single IRB review is required by law (including tribal law passed by the official
governing body of an American Indian or Alaska Native tribe); or
(ii) Research for which any Federal department or agency supporting or conducting the research determines and documents
that the use of a single IRB is not appropriate for the particular context.
(c) For research not subject to paragraph (b) of this section, an institution participating in a cooperative project may enter into
a joint review arrangement, rely on the review of another IRB, or make similar arrangements for avoiding duplication of effort.

Question 16

46.115 (a) An institution, or when appropriate an IRB, shall prepare and maintain adequate documentation of IRB activities, including
the following:

Answer 16

(1) Copies of all research proposals reviewed, scientific evaluations, if any, that accompany the proposals, approved sample
consent forms, 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 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, including the rationale for conducting continuing review of research that otherwise
would not require continuing review as described in §46.109(f)(1).
(4) Copies of all correspondence between the IRB and the investigators.
(5) A list of IRB members in the same detail as described in §46.108(a)(2).
(6) Written procedures for the IRB in the same detail as described in §46.108(a)(3) and (4).
(7) Statements of significant new findings provided to subjects, as required by §46.116(c)(5).
(8) The rationale for an expedited reviewer’s determination under §46.110(b)(1)(i) that research appearing on the expedited
review list described in §46.110(a) is more than minimal risk.
(9) Documentation specifying the responsibilities that an institution and an organization operating an IRB each will undertake
to ensure compliance with the requirements of this policy, as described in §46.103(e).

Question 17

(b) The records required by Basic HHS Policy for Protection of Human Research Subjects shall be retained for at least ____ years, and records relating to research that is conducted
shall be retained for at least ____ years after completion of the research.

Answer 17

3,3

Question 18

What are basic elements of informed consent

Answer 18

(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 that 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 that 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;
(8) 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 or loss of benefits to which
the subject is otherwise entitled; and
(9) One of the following statements about any research that involves the collection of identifiable private information or
identifiable biospecimens:
(i) A statement that identifiers might be removed from the identifiable private information or identifiable biospecimens and that,
after such removal, the information or biospecimens could be used for future research studies or distributed to another investigator
for future research studies without additional informed consent from the subject or the legally authorized representative, if this
might be a possibility; or
(ii) A statement that the subject’s information or biospecimens collected as part of the research, even if identifiers are
removed, will not be used or distributed for future research studies.

Question 19

Additional elements of informed consent.

Answer 19

(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) that are currently unforeseeable;
(2) Anticipated circumstances under which the subject’s participation may be terminated by the investigator without regard to
the subject’s or the legally authorized representative’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 that may relate to the subject’s
willingness to continue participation will be provided to the subject;
(6) The approximate number of subjects involved in the study;
(7) A statement that the subject’s biospecimens (even if identifiers are removed) may be used for commercial profit and
whether the subject will or will not share in this commercial profit;
(8) A statement regarding whether clinically relevant research results, including individual research results, will be disclosed
to subjects, and if so, under what conditions; and
(9) For research involving biospecimens, whether the research will (if known) or might include whole genome sequencing
(i.e., sequencing of a human germline or somatic specimen with the intent to generate the genome or exome sequence of that
specimen).

Question 20

left off on 152-elements of broad consent for the storage

Answer 20

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Question 21

If the
subject or the legally authorized representative is asked to provide broad consent, the following shall be provided to each subject
or the subject’s legally authorized representative:

Answer 21

(2) A general description of the types of research that may be conducted with the identifiable private information or identifiable
biospecimens. This description must include sufficient information such that a reasonable person would expect that the broad
consent would permit the types of research conducted;

(3) A description of the identifiable private information or identifiable biospecimens that might be used in research, whether
sharing of identifiable private information or identifiable biospecimens might occur, and the types of institutions or researchers that
might conduct research with the identifiable private information or identifiable biospecimens;

(4) A description of the period of time that the identifiable private information or identifiable biospecimens may be stored and
maintained (which period of time could be indefinite), and a description of the period of time that the identifiable private information
or identifiable biospecimens may be used for research purposes (which period of time could be indefinite);

(5) Unless the subject or legally authorized representative will be provided details about specific research studies, a
statement that they will not be informed of the details of any specific research studies that might be conducted using the subject’s
identifiable private information or identifiable biospecimens, including the purposes of the research, and that they might have
chosen not to consent to some of those specific research studies;

(6) Unless it is known that clinically relevant research results, including individual research results, will be disclosed to the
subject in all circumstances, a statement that such results may not be disclosed to the subject; and

(7) An explanation of whom to contact for answers to questions about the subject’s rights and about storage and use of the
subject’s identifiable private information or identifiable biospecimens, and whom to contact in the event of a research-related
harm.

Question 22

(3) Requirements for waiver and alteration. In order for an IRB to waive or alter consent as described in this subsection, the
IRB must find and document that:

Answer 22

(i) 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:
(A) Public benefit or service programs;
(B) Procedures for obtaining benefits or services under those programs;
(C) Possible changes in or alternatives to those programs or procedures; or
(D) Possible changes in methods or levels of payment for benefits or services under those programs; and
(ii) The research could not practicably be carried out without the waiver or alteration.

Question 23

Requirements for waiver and alteration. In order for an IRB to waive or alter consent as described in this subsection, the
IRB must find and document that:

Answer 23

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

(ii) The research could not practicably be carried out without the requested waiver or alteration;

(iii) If the research involves using identifiable private information or identifiable biospecimens, the research could not
practicably be carried out without using such information or biospecimens in an identifiable format;

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

(v) Whenever appropriate, the subjects or legally authorized representatives will be provided with additional pertinent
information after participation.

Question 24

(g) Screening, recruiting, or determining eligibility. An IRB may approve a research proposal in which an investigator will
obtain information or biospecimens for the purpose of screening, recruiting, or determining the eligibility of prospective subjects
without the informed consent of the prospective subject or the subject’s legally authorized representative, if either of the following
conditions are met:

Answer 24

(1) The investigator will obtain information through oral or written communication with the prospective subject or legally
authorized representative, or
(2) The investigator will obtain identifiable private information or identifiable biospecimens by accessing records or stored
identifiable biospecimens.

Question 25

(3) The informed consent form must be posted on the Federal Web site after the clinical trial is closed to recruitment, and no later than ____ days after the last study visit by any subject, as required by the protocol.

Answer 25

60

Question 26

(c)(1) An IRB may waive the requirement for the investigator to obtain a signed informed consent form for some or all subjects if it finds any of the following:

Answer 26

(i) That the only record linking the subject and the research would be the informed consent form and the principal risk would be potential harm resulting from a breach of confidentiality. Each subject (or legally authorized representative) will be asked whether the subject wants documentation linking the subject with the research, and the subject's wishes will govern; (ii) 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; or (iii) If the subjects or legally authorized representatives are members of a distinct cultural group or community in which signing forms is not the norm, that the research presents no more than minimal risk of harm to subjects and provided there is an appropriate alternative mechanism for documenting that informed consent was obtained.

Question 27

What is 45 part 46 part B

Answer 27

Additional Protections for Pregnant Women, Human Fetuses and Neonates Involved in Research

Question 28

Pregnant women or fetuses may be involved in research if all of the following conditions are met:

Answer 28

(a) Where scientifically appropriate, preclinical studies, including studies on pregnant animals, and clinical studies, including studies on nonpregnant women, have been conducted and provide data for assessing potential risks to pregnant women and fetuses; (b) The risk to the fetus is caused solely by interventions or procedures that hold out the prospect of direct benefit for the woman or the fetus; or, if there is no such prospect of benefit, the risk to the fetus is not greater than minimal and the purpose of the research is the development of important biomedical knowledge which cannot be obtained by any other means; (c) Any risk is the least possible for achieving the objectives of the research; (d) If the research holds out the prospect of direct benefit to the pregnant woman, the prospect of a direct benefit both to the pregnant woman and the fetus, or no prospect of benefit for the woman nor the fetus when risk to the fetus is not greater than minimal and the purpose of the research is the development of important biomedical knowledge that cannot be obtained by any other means, her consent is obtained in accord with the informed consent provisions of subpart A of this part; (e) If the research holds out the prospect of direct benefit solely to the fetus then the consent of the pregnant woman and the father is obtained in accord with the informed consent provisions of subpart A of this part, except that the father's consent need not be obtained if he is unable to consent because of unavailability, incompetence, or temporary incapacity or the pregnancy resulted from rape or incest. (f) Each individual providing consent under paragraph (d) or (e) of this section is fully informed regarding the reasonably foreseeable impact of the research on the fetus or neonate; (g) For children as defined in §46.402(a) who are pregnant, assent and permission are obtained in accord with the provisions of subpart D of this part; (h) No inducements, monetary or otherwise, will be offered to terminate a pregnancy; (i) Individuals engaged in the research will have no part in any decisions as to the timing, method, or procedures used to terminate a pregnancy; and (j) Individuals engaged in the research will have no part in determining the viability of a neonate

Question 29

(a) Neonates of uncertain viability and nonviable neonates may be involved in research if all of the following conditions are met:

Answer 29

(1) Where scientifically appropriate, preclinical and clinical studies have been conducted and provide data for assessing potential risks to neonates. (2) Each individual providing consent under paragraph (b)(2) or (c)(5) of this section is fully informed regarding the reasonably foreseeable impact of the research on the neonate. (3) Individuals engaged in the research will have no part in determining the viability of a neonate.

Question 30

(b) Neonates of uncertain viability. Until it has been ascertained whether or not a neonate is viable, a neonate may not be involved in research covered by this subpart unless the following additional conditions are met: (1) The IRB determines that:

Answer 30

(i) The research holds out the prospect of enhancing the probability of survival of the neonate to the point of viability, and any risk is the least possible for achieving that objective, or (ii) The purpose of the research is the development of important biomedical knowledge which cannot be obtained by other means and there will be no added risk to the neonate resulting from the research; and (2) The legally effective informed consent of either parent of the neonate or, if neither parent is able to consent because of unavailability, incompetence, or temporary incapacity, the legally effective informed consent of either parent's legally authorized representative is obtained in accord with subpart A of this part, except that the consent of the father or his legally authorized representative need not be obtained if the pregnancy resulted from rape or incest.

Question 31

(c) Nonviable neonates. After delivery nonviable neonate may not be involved in research covered by this subpart unless all of the following additional conditions are met:

Answer 31

(1) Vital functions of the neonate will not be artificially maintained; (2) The research will not terminate the heartbeat or respiration of the neonate; (3) There will be no added risk to the neonate resulting from the research; (4) The purpose of the research is the development of important biomedical knowledge that cannot be obtained by other means; and (5) The legally effective informed consent of both parents of the neonate is obtained in accord with subpart A of this part, except that the waiver and alteration provisions of §46.116(c) and (d) do not apply. However, if either parent is unable to consent because of unavailability, incompetence, or temporary incapacity, the informed consent of one parent of a nonviable neonate will suffice to meet the requirements of this paragraph (c)(5), except that the consent of the father need not be obtained if the pregnancy resulted from rape or incest. The consent of a legally authorized representative of either or both of the parents of a nonviable neonate will not suffice to meet the requirements of this paragraph (c)(5).

Question 32

§46.207 Research not otherwise approvable which presents an opportunity to understand, prevent, or alleviate a serious problem affecting the health or welfare of pregnant women, fetuses, or neonates. The Secretary will conduct or fund research that the IRB does not believe meets the requirements of §46.204 or §46.205 only if:

Answer 32

(a) The IRB finds that the research presents a reasonable opportunity to further the understanding, prevention, or alleviation of a serious problem affecting the health or welfare of pregnant women, fetuses or neonates; and (b) The Secretary, after consultation with a panel of experts in pertinent disciplines (for example: science, medicine, ethics, law) and following opportunity for public review and comment, including a public meeting announced in the FEDERAL REGISTER, has determined either: (1) That the research in fact satisfies the conditions of §46.204, as applicable; or (2) The following: (i) The research presents a reasonable opportunity to further the understanding, prevention, or alleviation of a serious problem affecting the health or welfare of pregnant women, fetuses or neonates; (ii) The research will be conducted in accord with sound ethical principles; and (iii) Informed consent will be obtained in accord with the informed consent provisions of subpart A and other applicable subparts of this part.

Question 33

What is 45 part 46 part C

Answer 33

Additional Protections Pertaining to Biomedical and Behavioral Research Involving Prisoners as Subjects

Question 34

In addition to satisfying the requirements in §46.107 of this part, an Institutional Review Board, carrying out responsibilities under this part with respect to research covered by this subpart, shall also meet the following specific requirements:

Answer 34

(a) A majority of the Board (exclusive of prisoner members) shall have no association with the prison(s) involved, apart from their membership on the Board. (b) At least one member of the Board shall be a prisoner, or a prisoner representative with appropriate background and experience to serve in that capacity, except that where a particular research project is reviewed by more than one Board only one Board need satisfy this requirement.

Question 35

What is 45 part 46 part D

Answer 35

Additional Protections for Children Involved as Subjects in Research

Question 36

HHS will conduct or fund research in which the IRB finds that more than minimal risk to children is presented by an intervention or procedure that does not hold out the prospect of direct benefit for the individual subject, or by a monitoring procedure which is not likely to contribute to the well-being of the subject, only if the IRB finds that:

Answer 36

(a) The risk represents a minor increase over minimal risk; (b) The intervention or procedure presents experiences to subjects that are reasonably commensurate with those inherent in their actual or expected medical, dental, psychological, social, or educational situations; (c) The intervention or procedure is likely to yield generalizable knowledge about the subjects' disorder or condition which is of vital importance for the understanding or amelioration of the subjects' disorder or condition; and (d) Adequate provisions are made for soliciting assent of the children and permission of their parents or guardians, as set forth in §46.408.

Question 37

(a) Children who are wards of the state or any other agency, institution, or entity can be included in research approved under §46.406 or §46.407 only if such research is:

Answer 37

(1) Related to their status as wards; or (2) Conducted in schools, camps, hospitals, institutions, or similar settings in which the majority of children involved as subjects are not wards. (b) If the research is approved under paragraph (a) of this section, the IRB shall require appointment of an advocate for each child who is a ward, in addition to any other individual acting on behalf of the child as guardian or in loco parentis. One individual may serve as advocate for more than one child. The advocate shall be an individual who has the background and experience to act in, and agrees to act in, the best interests of the child for the duration of the child's participation in the research and who is not associated in any way (except in the role as advocate or member of the IRB) with the research, the investigator(s), or the guardian organization.

Question 38

What is 45 part 46 PART E

Answer 38

Registration of Institutional Review Boards

Question 39

When must an IRB be registered?

Answer 39

An IRB must be registered before it can be designated under an assurance approved for federalwide use by OHRP under §46.103(a). IRB registration becomes effective when reviewed and accepted by OHRP. The registration will be effective for 3 years.

Question 40

How must an IRB be registered?

Answer 40

Each IRB must be registered electronically through http://ohrp.cit.nih.gov/efile unless an institution or organization lacks the ability to register its IRB(s) electronically. If an institution or organization lacks the ability to register an IRB electronically, it must send its IRB registration information in writing to OHRP.

Question 41

When must IRB registration information be renewed or updated? (a) Each IRB must renew its registration every ______ years. (b) The registration information for an IRB must be updated within )____ days after changes occur regarding the contact person who provided the IRB registration information or the IRB chairperson. The updated registration information must be submitted in accordance with §46.504. (c) Any renewal or update that is submitted to, and accepted by, OHRP begins a new _______ effective period. (d) An institution's or organization's decision to disband a registered IRB which it is operating also must be reported to OHRP in writing within ________ after permanent cessation of the IRB's review of HHS-conducted or -supported research.

Answer 41

(a) Each IRB must renew its registration every 3 years. (b) The registration information for an IRB must be updated within 90 days after changes occur regarding the contact person who provided the IRB registration information or the IRB chairperson. The updated registration information must be submitted in accordance with §46.504. (c) Any renewal or update that is submitted to, and accepted by, OHRP begins a new 3-year effective period. (d) An institution's or organization's decision to disband a registered IRB which it is operating also must be reported to OHRP in writing within 30 days after permanent cessation of the IRB's review of HHS-conducted or -supported research.

Question 42

What is FDA form 482

Answer 42

Notice of inspection