21 CFR Part 50

Question 1

What does 21 CFR Part 50 cover?

Answer 1

Protection of Human Subjects

Question 2

Clinical Investigation

Answer 2

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

Question 3

Investigator

Answer 3

individual who actually conducts a clinical investigation

Question 4

Sponsor

Answer 4

person who initiates a clinical investigation, but who does not actually conduct the investigation.

Question 5

Sponsor-Investigator

Answer 5

individual who both initiates and actually conducts, alone or with others, a clinical investigation.

Question 6

Human Subject

Answer 6

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

Question 7

Exceptions from informed consent for emergency research

Answer 7

1) subject is in a life-threatening situation and collection of valid scientific evidence is necessary to determine safety and effectiveness of particular interventions.
2) Obtaining consent is not feasible.
3) Participation in the research holds out the prospect of direct benefit.
4) The clinical investigation could not practicably be carried out without the waiver.
5) the treatment plan makes sense and the investigator is doing what he/she can to contact a legally authorized rep.
6) IRB has approved
7) additional protections of the rights and welfare of the subjects will be provided

Question 8

21CFR Part 50 - Elements of informed consent (Mandatory)

Answer 8

1) statement that the study involves research.
2) description of any reasonably foreseeable risks or discomforts to the subject.
3) description of any benefits to the subject or others.
4) disclosure of alternative procedures.
5) statement describing the extent to which confidentiality of records will be maintained
6) statement regarding compensation and medical treatment if any injury occurs
7) who to contact for answers to pertinent questions about research and subjects rights.
8) participation is voluntary.

Question 9

21CFR Part 50 - Additional elements of informed consent (Non-Mandatory)

Answer 9

1) statement that the particular tx may involve additional risk to the subject (or fetus) (which are currently unforseeable).
2) anticipated circumstances under which participation may be terminated.
3) any additional costs.
4) consequences of a subjects decision to withdraw. and procedures for orderly termination of participation
5) statement that significant findings during the research will be provided.
6) approximate number of subjects involved in the study.

Question 10

IRB must require appointment of _______ for each child who is a ward.

Answer 10

an advocate

Question 11

An advocate representing a ward must have these attributes:

Answer 11

▪ Will serve in addition to any other individual acting on behalf of the child as guardian etc.
▪ One individual may serve as advocate for more than one child
▪ Must be an individual who has the background and experience to act in, and agrees to act in, the best interest of the child for the duration of the child’s participation in the clinical investigations
▪ Can’t be associated with the investigation, investigators, or guardian organization

Question 12

A sponsor is arguing informed consent to be waived for a study they wish to perform (non-military). What must the investigator and physician certify to the IRB about the study to justify the waiver? (Hint: emergency use)

Answer 12

1) The subject is confronted by a life-threatening condition which necessitates the use of the test article.
2) Informed consent cannot be obtained from the subject because of an inability to communicate
3) Time is not sufficient to get consent from a LAR
4) There is no alternative method approved or generally recognized that can be used to save the subject

Question 13

True or False: The president may waive prior informed consent for non-military members partaking in a study.

Answer 13

False. The president can waive prior consent for armed forces members in connection with a military operation.

Question 14

Certain types of investigational in vitro diagnostic devices can be deemed feasible for an informed consent waiver. What do these devices typically diagnose and when can consent be waived?

Answer 14

These devices typically identify chemical, biological, radiological or nuclear agents. Consent can be waived if:

1) The subject is confronted with a life-threatening situation necessitating the use of the diagnostic (or it suggests a terrorism/public health event)
2) Time not sufficient to consent subject or LAR without risking subject’s life
3) No alternative available for diagnosing the same target

Question 15

What is required for exception to informed consent for emergency research?

Answer 15

1) The human subject is in a life threatening situation
2) Obtaining informed consent is not feasible
3) Participation in the research holds a prospect of direct benefit to the subject
4) The research could not be carried out without the waiver
5) It is not possible to contact the LAR within the predefined potential therapeutic window and the investigator summarizes efforts made to contact LAR
6) IRB Approval
7) Additional protections have been provided

Question 16

What is required for an IRB to waive informed consent? (non-emergency)

Answer 16

Research involves no more than minimal risk
Waiver will not adversely affect the rights and welfare of subjects
Research could not be carried out without the waiver
Subjects will be provided with additional pertinent information after participation

Question 17

What is a short form written consent document?

Answer 17

The informed consent is presented orally to subject or LAR. There must be a witness present for this. IRB approves a written summary of what should be said which is signed by the witness and consenter. The short form is signed by the witness and the subject. The subject receives a copy of both the short form and summary.

Question 18

True or false: IRB approval is required for any update to the informed consent form.

Answer 18

True.

Question 19

The ____ can waive prior consent requirement for military personnel administration of IND if:

Answer 19

President.
-It’s not feasible to get consent
-Consent is contrary to the best interests of the military
-Safety/effectiveness of IND is acceptable
-Without the IND, military operation at substantial risk and could result in death or serious/life-threatening injuries
-No available alternatives
-IRB approved protocol
-If refusing the IND could seriously affect the safety/health of military members/mission

Question 20

Under what conditions can an IRB waive assent for a clinical trial?

Answer 20

No more than minimal risk
Waiving assent won’t adversely affect the rights/welfare of subjects
Trial can’t be performed without a waiver
Subjects provided with any additional pertinent info after participation

Question 21

True or False. Both parents need to provide consent for a child’s assent?

Answer 21

False. Not required if one parent is deceased, unknown, incompetent, not available or 1 parent has custody.

Question 22

If an investigator uses the test article in an emergency use situation, what must happen afterwards and in what time frame?

Answer 22

The investigator must have an independent physician review the reason for use within 5 working days of use. This documentation must be submitted to IRB within 5 working days of use.

Question 23

If a trial that uses children is greater than minimal risk and presents the prospect of direct benefit, what characteristics of the trial are required for IRB approval?

Answer 23

Risk is justified by the benefits
Benefit is is similar to those presented by available alternatives
Adequate provisions made for getting assent/consent

Question 24

What is the different between assent and consent?

Answer 24

Assent - approval from child.

Consent - approval from adult or parent/guardian

Question 25

If a trial that uses children is greater than minimal risk without the prospect of direct benefit, what characteristics of the trial are required for IRB approval?

Answer 25

Risk is little more than minimal risk
Intervention / procedure is similar in proportion / likelihood to what they would experience with standard of care
Intervention / procedure is likely to yield generalizable knowledge about the condition
Adequate provisions in place for assent / consent

Question 26

21 CFR 50.27(a) requires that a copy of the consent document be given to the person signing the form. Does this copy have to be a photocopy of the form with the subject’s signature affixed?

Answer 26

No. The regulation does not require the copy of the form given to the subject to be a copy of the document with the subject’s signature, although this is encouraged.

Question 27

The informed consent regulations [21 CFR 50.25 (a)(5)] require the consent document to include a statement that notes the possibility that FDA may inspect the records. Is this statement a waiver of the subject’s legal right to privacy?

Answer 27

No. FDA does not require any subject to “waive” a legal right. Rather, FDA requires that subjects be informed that complete privacy does not apply in the context of research involving FDA regulated products.

Question 28

Who should be present when the informed consent interview is conducted? (According to FDA regulations)

Answer 28

FDA does not require a third person to be present during the consent process. It should be the consenter and the consentee.

Question 29

Should the sponsor prepare a model informed consent document?

Answer 29

though not required by the IND regulations, the sponsor provides a service to the clinical investigator and the IRB when it prepares suggested study-specific wording for the scientific and technical content of the consent document. However, the IRB has the responsibility and authority to determine the adequacy and appropriateness of all of the wording in the consent.

Question 30

When should study subjects be informed of changes in the study?

Answer 30

Protocol amendments must receive IRB review and approval before they are implemented, unless an immediate change is necessary to eliminate an apparent hazard to the subjects. Those subjects who are presently enrolled and actively participating in the study should be informed of the change if it might relate to the subjects’ willingness to continue their participation in the study. Reconsenting is not required.

Question 31

If a clinical investigation involving children is not otherwise approvable, it may only proceed if:
Hint: Multiple steps

Answer 31

1) The IRB finds that the clinical investigation presents a reasonable opportunity understand, prevent, or alleviate a serious problem affecting the health and wellfare of children
2) The Commissioner of Food and Drugs, after consultation with a panel of experts and following opportunity for public review and comments determines:
I) Investigation presents a reasonable opportunity to further understanding, prevention, or alleviation of a serious problem affecting health/wellfare of children
II) Investigation will be conducted with sound ethical principles
III) Adequate provisions are made for soliciting assent of children and permission of parents

Question 32

Minimal Risk

Answer 32

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 routine physical/psychological tests

Question 33

How is the prospect of direct benefit to the subject determined?

Answer 33

1) Subject is facing life-threatening situation that necessitates intervention
2) Appropriate animal and other preclinical studies have been conducted, supporting potential for direct benefit
3) Risks associated with investigation are reasonable in relation to what is known about medical condition of potential class of subjects, and risks/benefits of standard therapy, and what is known about risks and benefits of proposed intervention or activity

Question 34

What are examples of additional protections of rights and welfare provided to subjects?
5 examples

Answer 34

I) consultation with reps of communities in which investigation will be conducted
II) Public disclosure to communities in which investigation will be conducted
III) Public disclosure of sufficient information following completion of trial
IV) Establishment of an independent data monitoring committee
V) If obtaining informed consent is not feasible and a LAR is not reasonably available, the investigator will attempt to contact family member who is not a LAR; the investigator will summarize efforts made to contact family members and make this available to IRB at time of continuing review

Question 35

Assent is not necessary to proceed with a clinical investigation if the IRB determines that:

Answer 35

1) Capability of some/all of the children is so limited that they cannot reasonably be consulted
2) Intervention/procedure holds a prospect of direct benefit and is only available in the context of a clinical investigation