Clinical Trial Activities 2

Question 1

When can the enrolment of subjects begin?

Answer 1

They must receive approval from EC (ethics committee) /IRB approval (institutional review board) and after site initiation

Question 2

Who carries out the subject recruitment?

Answer 2

PI (principle investigator), Co-Investigator

The clinical investigator has primary responsibility of recruiting subjects, ensuring that only eligible subjects are enrolled in the study and obtaining and documenting the informed consent of each subject

Question 3

What does the CRC do in terms of Informed Consent for the paitent?

Answer 3

They explain the IC and documenting process, they DO NOT sign the ICF the clinical investigator is in charge of that

Question 4

Who revises the I/E ?

Answer 4

IRB institutional review board/ HSA (singapore)

Question 5

How do we check the eligibility of the subjects? How do we define the study population?

Answer 5

using the I/E criteria, the patient must not meet any exclusion criteria

Criteria for clinical trial eligibility defining the study population by:
1. Defining diseases

2. Excluding subjects likely to suffer from adverse effects from the experimental therapy and attempting to ensure the outcome can be measured
3. Determining who is the population that the potential study patients will be selected from

Question 6

What is the significance of the inclusion/ exclusion criteria? How does it affect the study?

Answer 6

Eligibility criteria must be carefully reviewed at the planning stage

Once trial is initiated they must be strictly adhered to

The stricter the I/E criteria, the smaller the study population

Enrolment of ineligible subjects interferes with the credibility of the results
leads to invalid results- patient dropout

Question 7

What are the 3 conditions to be satisfied when we consider an informed consent process is properly conducted?

Answer 7

• decision is voluntary (not influenced by anyone or convinced/ no persuasion)
• an appropriate understanding of the circumstances (they must comprehend the circumstances)
• patient’s choice is deliberate; patient has carefully considered all of the expected benefits, burdens, risks, adverse events and reasonable alternatives

Question 8

Define investigational product (IP):

Answer 8

“study drug”

A pharmaceutical form of an active ingredient or placebo being tested or used as a reference in a clinical trial, including a product with a marketing authorization when used or assembled (formulated or packaged) in a way different from the approved form, or when used for an unapproved indication, or when used to gain further information about an approved use

-in other words

Pharmaceutical form of an active ingredient or placebo/ drug used as a reference in a clinical trial

includes a product with a marketing authorization when used or assembled in a different way from the approved form or use for an unapproved indication, or when used to gain further information about an unapproved use

Question 9

How are Investigational Products handled?

Answer 9

Quality of the investigational product is assured by compliance with Good Manufacturing Practice (GMP) and by handling and storing the product according to the manufacturing specifications and the study protocol

Question 10

Who controls the access to the IP, within GCP?

Answer 10

GCP requires that sponsors control access to the investigational product :

• control access
• quantity produced
• whom product is shipped
• disposition of unused supplies

Question 11

What is included in the study records?

Answer 11

Study records documenting each trial-related activity provide critical verification that the study has been carried out in compliance with the protocol

Question 12

How should research be conducted?

Answer 12

Research should be conducted according to the approved protocol and applicable regulatory requirements

Question 13

Safety management, Who is responsible for alerting the sponsor and the IEC/IRB to adverse events?

Answer 13

The clinical investigator has primary responsibility for alerting the sponsor and IEC/IRB to adverse events, particularly serious/life-threatening unanticipated events, observed during the course of the research

CRC also supports this role however Clinical Investigator has the primary responsibility

Question 14

Site response report includes:

Answer 14

-treat all AE (adverse event)/ SAE (serious adverse event) until resolution

Question 15

Who should you report to in the event of SAE (serious adverse event)?

Answer 15

Sponsor

IRB (institutional review board)

SAE (serious adverse event) referring to an adverse event not listed in the IB (investigator brochure)

Question 16

What is the role of the sponsor once they have been alerted of an SAE (serious adverse event)?

Answer 16

The sponsor, in turn has primary responsibility for reporting of study safety to regulatory authorities and other investigators ongoing global safety assessment of the investigational product

A data and safety monitoring board (DSMB) may be constituted by the sponsor to assist in overall safety management (they may terminate the study/ continue/ change study design

Question 17

What is the definition of study monitoring?

Answer 17

The act of overseeing the progress of a clinical trial, and of ensuring that it is conducted, recorded and reported in accordance with the protocol, (SOP) standard operating procedure, (GCP) good clinical practice and the applicable regulatory requirements

Question 18

Who carries out study monitoring?

Answer 18

Sponsor CRA (clinical research associate)

CRO (clinical research organization) CRA (clinical research associate),

Sponsors generally perform site monitoring of a clinical trial to assure high quality trial conduct every 4-6 weeks

Question 19

Extent and nature of monitoring, What does the Sponsor, CRA, CRO check when monitoring?

Answer 19

Ensures the trials are adequately monitored

Determines the appropriate extent (referring to the frequency of the visits) and nature (referring to type such as on-site or remote monitoring) of monitoring

Question 20

What factors increases the frequency visits/ monitoring?

Answer 20

The more complex a study is

The larger patient size

The more end point that we collect

Increases the frequency of the monitoring

Question 21

What is the purpose of trial monitoring?

Answer 21

The purpose of trial monitoring are to verify that:

• the rights and well-being of human subjects are protected (ICF obtain)
• the reported trial data are accurate, complete and verifiable from source documents (medical documents) (AE/SAE)
• the conduct of the trial is in compliance with the currently approved protocol/ amendments(s) , with GCP and with the applicable regulatory requirements

Question 22

What does the Investigator control when it comes to handling the IP? within GCP

Answer 22

Control the receipt, administration (contains dosing record, accountability record, dispose/return) and disposition of the investigational product

Question 23

What is the qualification of a monitor (CRA)?

Answer 23

Should be appropriately trained, and should have the scientific and/or clinical knowledge needed to monitor the trial adequately

His/her qualification should be documented

Question 24

A monitor should be thoroughly familiar with..

Answer 24

• the investigational product(s)
• the protocol
• written informed consent form
• any other written information to be provided to subjects
• the sponsor’s SOP
• GCP trained
• the applicable regulatory requirements

Question 25

What are the different stages that monitoring occurs?

Answer 25

• Before (initial visit)
• During(intermediate visit)
• After (closing visit)

Question 26

What is the significance of managing trial data appropriately?

Answer 26

Assures that the data are complete, reliable and processed correctly and that data integrity is preserved

Question 27

What does

data management include?

Answer 27

Includes all processes and procedures for collecting, handling, manipulating, analyzing and storing/archiving of data from study start to completion

Question 28

Who bears primary responsibility for managing trial data?

What role does the sponsor and investigator share?

Answer 28

Sponsor bears primary responsibility for developing appropriate data management systems

Share the responsibility for implementing such systems to ensure that the integrity of the trial data is preserved

Question 29

How is Quality Assurance verfied?

Answer 29

verifies through systematic, independent audits (not part of study team , crc doesn’t take this job) that existing quality control systems (e.g study monitoring, data management systems) are working and effective

Quality assurance audits may be performed during the course of the clinical trial and/or upon trial completion

Sponsors bear primary responsibility for establishing quality systems and conducting quality assurance audits

Question 30

What must a clinical report include?

Answer 30

Summary of Investigational product results described in an integrated clinical study report containing clinical data and statistical descriptions, presentations and analysis

Should be complete, timely, well-organized, free from ambiguity (peer reviewed) and easy to review

Question 31

Who is responsible for preparation of clinical study reports?

Answer 31

Sponsor (takes about 3 months)

Investigator sends to EC/IRB

Question 32

Describe the aspects of a trial report:

Answer 32

1. A description of ethical aspects of the study
2. An introduction that explains the critical features and context of the study
3. A description of the administrative structure of the study
4. A summary of the study objectives
5. A description of the overall study design and plan
6. A description of any protocol amendments
7. An accounting of all subjects who participated in the study, including all important deviations from inclusion/exclusion criteria and a description of subjects who discontinued after enrolment
   - unblinding info will be