Protection of Human Subjects

Question 1

Clinical Investigation

Answer 1

any experiment that involves a test article and one or more human subjects that is either subject to the requirements for prior submission to the FDA or is not subject to those requirements but the results are intended for submission to or held for inspection by the FDA as part of an application

Question 2

Investigator

Answer 2

an individual who actually conducts a clinical investigation ie. under whose immediate direction the test article is administered or dispensed to, or used involving, the subject. In the event of an investigation conducted by a team of individuals, the Investigator is the leader of that team.

Question 3

Sponsor

Answer 3

a person who initiates a clinical investigation but does not actually conduct the investigation. A person other than an individual (eg. corporation or agency) that uses one or more of its own employees to conduct a clinical investigation it has initiated is considered to be a sponsor and the employees are considered to be investigators.

Question 4

Sponsor-Investigator

Answer 4

an individual who both initiates and actually conducts, alone or with others, a clinical investigation. The term only refers to individuals, not corporations or agencies.

Question 5

Human subject

Answer 5

an individual who is or becomes a participant in research, either as a recipient of the test article or as a control.

Question 6

Institution

Answer 6

any public or private entity or agency

Question 7

Institutional Review Board

Answer 7

any board, committee, or other group formally designated by an institution to review biomedical research involving humans as subjects, to approve the initiation of and conduct periodic review of such research.

Question 8

Test article

Answer 8

any drug, medical device for human use, electronic product, food additive, color additive, other article subject to regulation of the FDA

Question 9

Minimal Risk

Answer 9

means that the probability and magnitude of harm or discomfort anticipated in the research are not greater in and of themselves than those ordinarily encountered in daily life or during the performance of routine physical or psychological examinations or tests

Question 10

Legally authorized representative

Answer 10

an individual or judicial or other body authorized under applicable law to consent on behalf of a prospective subject to the subject’s participation in the procedures involved in the research

Question 11

Assent

Answer 11

a child’s affirmative agreement to participate in a clinical investigation. Mere failure to object should not, absent affirmative agreement, be construed as assent

Question 12

When is informed consent NOT required before use of a test article?

Answer 12

Both the investigator and a physician not participating in the clinical investigation certify the following in writing:
1) the human subject is confronted by a life-threatening situation necessitating the use of the test article
2) informed consent cannot be obtained from the subject because of an inability to communicate with, or obtain legally effective consent from, the subject
3) time is not sufficient to obtain consent from the subject’s legal representative
4) there is no alternative method of approved or generally recognized therapy that provides and equal or greater likelihood of saving the life of the subject

This documentation must be submitted to the IRB within 5 working days after use of the test article.

Question 13

If a test article is used in an emergency without prior informed consent, and without prior authorization of emergency use, what happens?

Answer 13

the investigator must make the determination and submit documentation to be reviewed, in writing, by a physician who is not participating in the investigation within 5 working days. This documentation must also be submitted to the IRB within 5 working days after the use of the test article

Question 14

What are the basic elements of informed consent?

Answer 14

1) a statement that the study involves research, explains the purpose of the research, and describes the duration of participation and any procedures to be followed

2) a description of any foreseeable risks or discomforts to the subject

3) a description of any benefits to the subject or others

4) disclosure of alternative procedures or treatments

5) statement describing the extent to which confidentiality will be maintained (and that the FDA may inspect the records)

6) an explanation as to whether any compensation or whether there are any medical treatments for potential injury (for research involving more than minimal risk)

7) who to contact for answers to questions about research, research subjects rights, and whom to contact in event of research-related injury

8) statement that participation is voluntary, that refusal to participate will involve no penalty or loss of benefits to which the subject is entitled, that the subject may discontinue participation at any time

Question 15

What are additional elements of informed consent?

Answer 15

When appropriate, the following items should also be provided to each subject:
1) statement that the treatment or procedure may involve risks to the subject (or embryo/fetus) that are currently unforeseen
2) anticipated circumstances under which the subject’s participation may be terminated by the investigator without regard tot he subjects 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 study which may relate to the subject’s willingness to continue participation will be provided to the subject
6) the approximate number of people involved in the study

Question 16

How should informed consent be documented?

Answer 16

Informed consent shall be documented by the use of a written consent form approved by the IRB and signed and dated by the subject or the subject’s legally authorized representative at the time of consent. A copy of the ICF should be given to the person signing the form.

The ICF must be either of the following:

a) A written consent document that embodies the elements of informed consent. It may be read to the subject or LAR, but the investigator shall give the subject/LAR adequate opportunity to read it before signing.

b) a short form written consent document stating that the elements of informed consent have been presented orally to the subject (or LAR) in the presence of a witness. The IRB must approve a written summary of what will be said. Only the short form itself is to be signed by the subject (or LAR). The witness will sign the short form and the summary. The person obtaining consent will sign the summary. The subject will receive a copy of the short form and the summary.

Question 17

When consenting children, in which situation does only one parent/guardian need to consent?

Answer 17

Only one parent/guardian needs to consent for:

a) Clinical investigations not involving greater than minimal risk, or

b) clinical investigations involving greater than minimal risk but presenting the prospect of direct benefit to individual subjects, or

c) one parent is deceased, unknown, incompetent, or not reasonably available or only one parent has legal responsibility for the care and custody of the child

Question 18

When consenting children, when do both parents need to consent?

Answer 18

In clinical investigations involving greater than minimal risk and no prospect of direct benefit to individual subjects (unless one parent is deceased, unknown, incompetent, or not reasonably available or only one parent has legal responsibility for the care and custody of the child)