Conducting a Study

Question 1

What must be included in an IND application?

Answer 1

1. Clinical Protocol (Protocols for subsequent studies not submitted with the original IND application can be submitted at a later time as Protocol Amendments).
2. Investigator’s Statement form 1572 (for all investigators participating in the study)
3. Financial Disclosure forms 3454 (certification) and 3455 (disclosure)

Question 2

What should a Protocol contain?

Answer 2

1. General Information
2. Background Information
3. Trial Objectives and Purpose
4. Trial Design
5. Selection and withdrawal of subjects
6. Treatment of subjects
7. Assessment of efficacy
8. Assessment of safety

Question 3

Safety Reporting

Answer 3

*Promptly report information about significant new adverse events, new information or risks with respect to the investigational product or investigation to FDA and investigators.

• If the Sponsor determines the investigational product presents an unreasonable and significant risk to study subject the sponsor must:
  -Discontinue all studies that present the risk
  -Notify FDA, all investigators involved in the study and the IRBs
  -Assure return and accounting for all investigational products, its return to the Sponsor (or on-site destruction).

Question 4

What are the criteria for registering a trial in ClincalTrials.gov?

Answer 4

-The trial has one or more sites in the United States
-The trial is conducted under the FDA investigational new drug application or investigational device exemption
-The trial involves a drug, biological, or device product that is manufactured in the United States or its territories and is exported for research

Question 5

Who is responsible for registering the trials and submitting the results?

Answer 5

-The sponsor of the clinical trial as defined in 21 CFR 50.3 or
-The principal investigator (PI). The PI is responsible for conducting the trial, has access to and control over the data from the clinical trial, has the right to publish the results of the trial, and can meet all the requirements for the submission of the clinical trial information.

Question 6

Who is responsible for reporting adverse events during a study?

Answer 6

Investigator

(21 CFR 312.64)

Question 7

What does ALCOA-C stand for?

Answer 7

Attributable, legible, contemporaneous original, accurate, and complete.

Question 8

How should corrections be made?

Answer 8

*single line through error, enter correct information, initial and date change, provide explanation if needed; do not obliterate the error, no erasures, no white-out

Question 9

What is a risk-based approach?

Answer 9

Focuses oversight activities on preventing or mitigating important and likely risks to data quality and to processes critical to human subject protection and trial integrity.

Question 10

How is monitoring conducted?

Answer 10

1. On-site Monitoring: Periodic site visits by a clinical research associate conducted in person
2. Remote Monitoring: replace on-site with remote activity
3. Centralized Monitoring: electronic data capture involving analytical evaluation

Question 11

What is a medical monitor?

Answer 11

They provide medical expertise and oversite to ensure clinical integrity and safety accountability, and respond to subject safety and trial management for example: inclusion, exclusion criteria, unblinding procedure

Question 11

What are Data Safety Monitoring Boards

Answer 11

An independent group that conducts periodic reviews and evaluates study data for patient safety, study conduct, and progress has initiated “event triggers” prior study start

Question 12

What are the monitor’s responsibilities?

Answer 12

1. They facilitate communication between the sponsor and investigator.
2. They follow organizational SOPs for monitoring and protocol-specific requirements
3. They comply with the clinical monitoring plan, including compliance with the risk evaluation and mitigation strategy plan

Question 13

Who is responsible for verifying the following:
-Investigator qualifications
-Appropriate product storage, handling, and accountability
-Investigator compliance with the protocol, regulations, and GCP guidelines

Answer 13

The Monitor

Question 14

Who is responsible for performing Site Initiation Visits (SIV) with the site investigator and study team (IRB is not required)

Answer 14

The monitor

Question 15

What should each monitoring visit include?

Answer 15

Complete written reports of the following:
-Investigator’s name and site location
-Date of the visit
-Monitor’s name
-Site personnel contacted
-Summary of what information was reviewed
-Significant findings and corrective actions

Question 16

Other responsibilities for the monitor?

Answer 16

Review and follow-up by the sponsor on corrective actions should be documented.

Question 17

What does the IRB have authority over?

Answer 17

1. Approve
2. Require Modification
3. Disapprove research

Question 18

Appropriately constituted group that has been formally designated to review and monitor biomedical research involving human subjects

Answer 18

IRB

Question 19

What is the purpose of and IRB

Answer 19

To assure, both in advance and by periodic review the appropriate steps to protect the rights, safety, and welfare of humans participating as subjects in the research.

Question 20

The IRB must have at least what members?

Answer 20

1. One scientific member
2. One nonscientific member
3. One unaffiliated member

Question 21

To approve research what does the IRB need to determine?

Answer 21

1. Risks to participants are minimized
2. Risks to participants are reasonable about the anticipated benefits and to the importance of the expected knowledge to be gained
3. Equitable selection of participants
4. Informed consent will be obtained and the consent forms will include all required elements and be written in language that is understandable to the participants
5. Provisions for obtaining and documenting informed content are appropriate
6. Privacy and confidentially are adequately protected
7. DSM Plan adequate
8. Additional safeguards are in place to protect the rights and welfare of vulnerable populations

Question 22

What are the ethical principles of the IRB criteria to approve research?

Answer 22

1. Beneficence
2. Justice
3. Respect for persons

Question 23

What encompasses beneficence?

Answer 23

• Study Design
  *Risk/Benefits
  *Data Safety Monitoring
  *Qualifications of researchers and staff

Question 24

What encompasses Justice?

Answer 24

*Selection of subjects
*Inclusion/exclusion
*Recruitment
*Fair distribution

Question 25

What encompasses Respect for Persons

Answer 25

*Privacy and confidentiality
*Vulnerable populations
*Informed consent/assent/permission

Question 26

What are the three levels of IRB from the lowest level of risk to the highest?

Answer 26

1. Exempt (45 CFR 46)
2. Expedited
3. Full Board

Question 27

Study deviations/changes?

Answer 27

No deviations or changes can be initiated without written IRB approval of the amendment unless the change eliminates an immediate hazard to the subject

ICH GCP guideline: Changes involving only logistic or administrative aspects of the trial, e.g.-change in the monitor, and telephone numbers) maybe implemented without prior IRB approval

Question 28

What is category 1 allowable research with children?

Answer 28

Research not involving greater than minimal risk

ex the mag of harm or discomfort is those encountered during physical exams etc.

must have the assent of children and parent/guardian

Question 29

What is category 2 allowable research with children?

Answer 29

Research involving greater than minimal risk but presenting the prospect of direct benefit to the individual subjects

Must include assent of children and parent/guardian

Question 30

What is category 3 allowable research with children?

Answer 30

Research involving greater than minimal risk and no prospect of direct benefit to individual subjects is likely to yield generalizable knowledge about the subject’s disorder or condition.

Must include assent of children and both parents/guardian

Question 31

What is category 4 allowable research with children?

Answer 31

Research not otherwise approvable which presents an opportunity to understand, prevent, or alleviate a serious problem affecting the health or welfare of children.

Question 32

What are the safeguards for children -Assent?

Answer 32

21 CFR 50.55 (a); 45 CFR 46.408 (a)

Assent means a child’s affirmative agreement to participate in a clinical investigation. Mere failure to object should no, absent affirmative agreement, be construed as assent.

“Adequate provisions are made for soliciting the assent of children WHEN the children are capable of providing assent.

Question 33

Category 1 research with children

Answer 33

Research not involving greater than the minimal risk

Question 34

Category 2 research with children

Answer 34

Research involving greater than minimal risk but presenting the prospect of direct benefit to the child

Question 35

Category 3 research with children

Answer 35

Research involving greater than minimal risk and no prospect of direct benefit to the child, but likely to yield generalizable knowledge about the child’s disorder or condition

Question 36

Category 4 research with children

Answer 36

Research not otherwise approved that presents an opportunity to understand, prevent, or alleviate a serious problem affecting the health or welfare of children

Question 37

When is the signature of the other parent not required?

Answer 37

-If the other parent is deceased
-The other parent is unknown
-The other parent is incompetent
-The other parent is not reasonably available

Question 38

When can pregnant women participate in research?

Answer 38

45 CFR 46 Subpart B

• Preclinical studies have been conducted and provide data for assessing potential risks to pregnant women and fetuses
  -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;
  -Has prospect of direct benefit (mother/fetus/both) or no more than the minimal risk

Question 39

When is the consent of the pregnant woman enough?

Answer 39

When the research holds out the prospect of direct benefit to the pregnant woman, the prospect of direct benefit both to the pregnant woman and the fetus or no prospect of benefit for the woman nor the fetus when the risk to the fetus is not greater than minimal and the purpose o the research is the development of important biomedical knowledge that cannot be obtained by any other means, her consent is obtained

Question 40

When do you need both the father and pregnant woman to consent?

Answer 40

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, 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

Question 41

A subject has been enrolled in a study and was randomized to the non-treatment arm. The protocol
outlines study procedures for all subjects to be performed within one week of enrollment. Which of the
following statements about this case is correct?

Answer 41

This subject should undergo all study procedures as outlined in the protocol

Question 42

Informed consent documents must contain which of the following?

Answer 42

An explanation of the purpose of the investigation

Question 43

Concerning IRB/IEC membership, both the FDA and the ICH require that

Answer 43

At least one member’s primary area of interest is in a nonscientific area

Question 44

Which of the following is the proper way to make a correction to a CRF?

Answer 44

Add the initials of the person making the change, the date of the change, and, if necessary, a brief explanation of the change

Question 45

The purpose of monitoring clinical trials is to verify that:

Answer 45

The rights, safety, and well-being of human subjects are protected