ICH Harmonised Guideline for Good Clinical Practice E6 (R2)

Question 1

When was the ICH guideline finalized under step 4

Answer 1

November 2016

Question 2

The guidance was developed with consideration of the current good clinical practices of the
_________________________________

Answer 2

European Union, Japan, and the United States, as well as those of Australia, Canada, the
Nordic countries, and the World Health Organization.

Question 3

What is
E2A
E3
E7
E8
E9
E11

Answer 3

Clinical safety data management

clinical study reporting

geriatric populations

General considerations for clinical trials

Statistical principles

pediatric populations

Question 4

This ICH GCP Guidance Integrated Addendum provides a unified standard for the ____________________ to facilitate the mutual acceptance
of data from clinical trials by the regulatory authorities in these jurisdictions.

Answer 4

European
Union, Japan, the United States, Canada, and Switzerland

Question 5

In the event of any conflict between the E6(R1) text and the E6(R2) addendum text, the ______ addendum text should take priority.

Answer 5

E6(R2)

Question 6

What are the principles of ICH GCP

Answer 6

2.l Clinical trials should be conducted in accordance with the ethical principles that
have their origin in the Declaration of Helsinki, and that are consistent with GCP
and the applicable regulatory requirement(s).
2.2 Before a trial is initiated, foreseeable risks and inconveniences should be weighed
against the anticipated benefit for the individual trial subject and society. A trial should
be initiated and continued only if the anticipated benefits justify the risks.
2.3 The rights, safety, and well-being of the trial subjects are the most important
considerations and should prevail over interests of science and society.
2.4 The available nonclinical and clinical information on an investigational product
should be adequate to support the proposed clinical trial.
2.5 Clinical trials should be scientifically sound, and described in a clear, detailed protocol.
2.6 A trial should be conducted in compliance with the protocol that has received prior
institutional review board (IRB)/independent ethics committee (IEC)
approval/favorable opinion.
2.7 The medical care given to, and medical decisions made on behalf of, subjects
should always be the responsibility of a qualified physician or, when appropriate, of
a qualified dentist.
2.8 Each individual involved in conducting a trial should be qualified by education,
training, and experience to perform his or her respective task(s).
2.9 Freely given informed consent should be obtained from every subject prior to
clinical trial participation.
2.10 All clinical trial information should be recorded, handled, and stored in a way that
allows its accurate reporting, interpretation, and verification.

Question 7

ADDENDUM
This principle applies to all records referenced in this guidance, irrespective of the type of
media used.

Answer 7

2.11 The confidentiality of records that could identify subjects should be protected,
respecting the privacy and confidentiality rules in accordance with the applicable regulatory
requirement(s).

2.12 Investigational products should be manufactured, handled, and stored in accordance with
applicable good manufacturing practice (GMP). They should be used in accordance with the
approved protocol.

2.13 Systems with procedures that assure the quality of every aspect of the trial should
be implemented.

Question 8

T or F: An IRB/IEC should safeguard the rights, safety, and well-being of all trial
subjects. Special attention should be paid to trials that may include vulnerable
subjects.

Answer 8

t

Question 9

The IRB/IEC should obtain the following documents:

Answer 9

1. Trial Protocol amendments
2. ICF and ICF updates
3. Recruitment procedures
4. Written info to be provided to subjects
5. Investigational Brochure
6. Safety Info
7. Compensation
8. Investigators CV

Question 10

The IRB/IEC should review a proposed clinical trial within a reasonable time and
document its views in writing, clearly identifying the trial, the documents reviewed
and the dates for the following:

Answer 10

Approval/favorable opinion;
- Modifications required prior to its approval/favorable opinion;
- Disapproval/negative opinion; and
- Termination/suspension of any prior approval/favorable opinion.

Question 11

The IRB/IEC should consider the qualifications of the investigator for the proposed
trial, as documented by ____________ and/or by any other relevant
documentation the IRB/IEC requests.

Answer 11

a current curriculum vitae

Question 12

3.1.4 The IRB/IEC should conduct continuing review of each ongoing trial at intervals
appropriate to the degree of risk to human subjects, ____________

Answer 12

at least once per year

Question 13

T or F: The IRB/IEC should review both the amount and method of payment to subjects to
assure that neither presents problems of coercion or undue influence on the trial
subjects. Payments to a subject should be prorated and not wholly contingent on
completion of the trial by the subject.

Answer 13

t

Question 14

The IRB/IEC should consist of a reasonable number of members, who collectively
have the qualifications and experience to review and evaluate the science, medical
aspects, and ethics of the proposed trial. It is recommended that the IRB/IEC should
include:

Answer 14

(a) At least five members.
(b) At least one member whose primary area of interest is in a nonscientific area.
(c) At least one member who is independent of the institution/trial site.
Only those IRB/IEC members who are independent of the investigator and the sponsor
of the trial should vote/provide opinion on a trial-related matter.
A list of IRB/IEC members and their qualifications should be maintained.

Question 15

or f: Only members who participate in the IRB/IEC review and discussion should
vote/provide their opinion and/or advice.

Answer 15

t

Question 16

t or f:The investigator may provide information on any aspect of the trial, and should
participate in the deliberations of the IRB/IEC or in the vote/opinion of the IRB/IEC.

Answer 16

f should not participate in the deliberations of the IRB/IEC or in the vote/opinion of the IRB/IEC.

Question 17

The IRB/IEC should establish, document in writing, and follow its procedures, which
should include:

Answer 17

3.3.1 Determining its composition (names and qualifications of the members) and the
authority under which it is established.

3.3.2 Scheduling, notifying its members of, and conducting its meetings.

3.3.3 Conducting initial and continuing review of trials.

3.3.4 Determining the frequency of continuing review, as appropriate.

3.3.5 Providing, according to the applicable regulatory requirements, expedited review and
approval/favorable opinion of minor change(s) in ongoing trials that have the
approval/favorable opinion of the IRB/IEC.

3.3.6 Specifying that no subject should be admitted to a trial before the IRB/IEC issues
its written approval/favorable opinion of the trial.

3.3.7 Specifying that no deviations from, or changes of, the protocol should be initiated
without prior written IRB/IEC approval/favorable opinion of an appropriate
amendment, except when necessary to eliminate immediate hazards to the subjects
or when the change(s) involves only logistical or administrative aspects of the trial
(e.g., change of monitor(s), telephone number(s)) (see section 4.5.2).

3.3.8 Specifying that the investigator should promptly report to the IRB/IEC:
(a) Deviations from, or changes of, the protocol to eliminate immediate hazards to
the trial subjects (see sections 3.3.7, 4.5.2, 4.5.4).
(b) Changes increasing the risk to subjects and/or affecting significantly the conduct
of the trial (see section 4.10.2).
(c) All adverse drug reactions (ADRs) that are both serious and unexpected.
(d) New information that may affect adversely the safety of the subjects or the
conduct of the trial.

3.3.9 Ensuring that the IRB/IEC promptly notify in writing the investigator/institution concerning:
(a) Its trial-related decisions/opinions.
(b) The reasons for its decisions/opinions.
(c) Procedures for appeal of its decisions/opinions.

Question 18

The IRB/IEC should retain all relevant records (e.g., written procedures, membership lists,
lists of occupations/affiliations of members, submitted documents, minutes of meetings, and
correspondence) for a period of at least _________ years after completion of the trial and make
them available upon request from the regulatory authority(ies).

Answer 18

3

Question 19

Before initiating a trial, the investigator/institution should have written and dated
approval/favorable opinion from the IRB/IEC for the:

Answer 19

trial protocol,
written informed
consent form,
consent form updates,
subject recruitment procedures (e.g.,advertisements),
any other written information to be provided to subjects.

Question 20

The investigator may implement a deviation from, or a change in, the protocol to
eliminate an immediate hazard(s) to trial subjects without prior IRB/IEC
approval/favorable opinion. As soon as possible, the implemented deviation or
change, the reasons for it, and, if appropriate, the proposed protocol amendment(s)
should be submitted:

Answer 20

(a) To the IRB/IEC for review and approval/favorable opinion;
(b) To the sponsor for agreement and, if required;
(c) To the regulatory authority(ies).

Question 21

Prior to the beginning
of the trial, the investigator should have the IRB/IEC’s written approval/favorable
opinion of the ___________________________________

Answer 21

written informed consent form and any other written information to be
provided to subjects

Question 22

Nontherapeutic trials may be conducted in subjects with consent of a legally
acceptable representative provided the following conditions are fulfilled:

Answer 22

(a) The objectives of the trial cannot be met by means of a trial in subjects who can
give informed consent personally.
(b) The foreseeable risks to the subjects are low.
(c) The negative impact on the subject’s well-being is minimized and low.
(d) The trial is not prohibited by law.
(e) The approval/favorable opinion of the IRB/IEC is expressly sought on the inclusion
of such subjects, and the written approval/ favorable opinion covers this aspect.

Question 23

Essential documents should be retained until at least __________ after the last approval of a marketing application in an ICH region and until there are no pending or contemplated marketing applications in an ICH region or at least ___________ years have elapsed since the formal discontinuation of clinical development of the investigational product. These documents should be retained for a longer period, however, if required by the applicable regulatory requirements or by an agreement with the sponsor. It is the responsibility of the sponsor to inform the investigator/institution as to when these documents no longer need to be retained (see section 5.5.12).

Answer 23

2 years,2

Question 24

The _______ should submit written summaries of the trial’s status to the IRB/IEC
annually, or more frequently, if requested by the IRB/IEC.

Answer 24

investigator

Question 25

5.2.1 A sponsor may transfer any or all of the sponsor’s trial-related duties and functions to a _______, but the ultimate responsibility for the quality and integrity of the trial data always resides with the _________
The CRO should implement quality assurance and
quality control.

5.2.2 Any trial-related duty and function that is transferred to and assumed by a CRO should be _______

Answer 25

CRO
sponsor.
specified in writing.

Question 26

If the sponsor discontinues the clinical development of an investigational product
(i.e., for any or all indications, routes of administration, or dosage forms), the
sponsor should maintain all sponsor-specific essential documents for at least _______
after formal discontinuation or in conformance with the applicable regulatory
requirement(s).

Answer 26

2 years

Question 27

The sponsor should obtain the investigator’s/institution’s agreement:

Answer 27

(a) To conduct the trial in compliance with GCP, with the applicable regulatory
requirement(s) (see section 4.1.3), and with the protocol agreed to by the sponsor
and given approval/favorable opinion by the IRB/IEC (see section 4.5.1);
(b) To comply with procedures for data recording/reporting;
(c) To permit monitoring, auditing, and inspection (see section 4.1.4); and
(d) To retain the trial- related essential documents until the sponsor informs the
investigator/institution these documents are no longer needed (see sections 4.9.4
and 5.5.12).

Question 28

t or f: The sponsor is responsible for supplying the investigator(s)/institution(s) with the
investigational product(s).

Answer 28

t

Question 29

The Investigator’s Brochure (IB) is a compilation of the clinical and nonclinical data on
the investigational product(s) that are relevant to the study of the product(s) in human
subjects

Answer 29

t

Question 30

What should the IB include?

Answer 30

Title page
2. Confidentiality statement
3. Summary
4. Introduction
5. Physical, Chemical and Pharmaceutical Properties and Formulation
6. Nonclinical studies ( Pharmocokinetics and product metabolism in animals, toxicology)
7. Effects in humans (6.1 Pharmacokinetics and Product Metabolism in Humans, Safety and Efficacy, Marketing Experience)
8. Summary of data and guidance for the investigator