ICH Harmonized Guideline for Good Clinical Practice (E6)

Question 1

What is the ICH?

Answer 1

International Council for Harmonisation.

Question 2

ICH Harmonised Guideline for Good Clinical Practice

Answer 2

finalized in November 2016 – the Good Clinical Practices document describes the responsibilities and expectations of all participants in the conduct of clinical trials, including investigators, monitors, sponsors and IRBs.

Question 3

What does GCP cover?

Answer 3

Aspects of monitoring, reporting and archiving of clinical trials and incorporating addenda on the Essential Documents and on the Investigators Brochures which had been agreed earlier through the ICH process.

Question 4

What is GCP?

Answer 4

An international ethical and scientific quality standard for designing, conducting, recording, and reporting trials that involve the participation of human subjects.

Question 5

What is the objective of this ICH GCP?

Answer 5

To provide a unified standard for the European Union, Japan, and the United States to facilitate the mutual acceptance of clinical data by the regulatory authorities in these jurisdictions.

Australia, Canada, Nordic countries (Iceland, Norway, Sweden, Denmark and Finland) and WHO’s GCP were also taken into consideration

Question 6

Adverse Drug Reaction

Answer 6

All noxious and unintended responses to a medicinal product related to any dose should be considered adverse drug reactions.

Question 7

Adverse Event

Answer 7

Any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product.

Question 8

Audit

Answer 8

Systematic and independent examination of trial-related activities and documents to determine whether the evaluated trial-related activities were conducted and the data were recorded, analyzed, and accurately reported according to the protocol, sponsor’s standard operating procedures, GCP, adn the applicable regulatory requirements.

Question 9

Comparator (Product)

Answer 9

An investigational or marketed product, or placebo, used as a reference in a clinical trial.

Question 10

Compliance

Answer 10

Adherence to all the trial-related requirements, good clinical practice requirements, and the applicable regulatory requirements.

Question 11

Confidentiality

Answer 11

Prevention of disclosure, to other than authorized individuals, of a sponsor’s proprietary information or of a subject’s identity.

Question 12

Coordinating Committee

Answer 12

A committee that a sponsor may organize to coordinate the conduct of a multicenter trial.

Question 13

Coordinating Investigator

Answer 13

An investigator assigned the responsibility for the coordination of investigators at different centers participating in a multicenter trial.

Question 14

Contract Research Organization (CRO)

Answer 14

A person or an organization (commercial, academic, or other) contracted by the sponsor to perform one or more of a sponsor’s trial-related duties and functions.

Question 15

Direct Access

Answer 15

Permission to examine, analyze, verify, and reproduce any records and reports that are important to evaluation of a clinical trial.

Question 16

Inspection

Answer 16

The act by a regulatory authority of conducting an official review of documents, facilities, records, and any other resources that are deemed by the authorities to be related to the clinical trial and that may be located at the site of the trial, at the sponsor’s and/or contract research organization’s facilities, or at other establishments deemed appropriate by the regulatory authorities.

Question 17

Name the 13 principles of ICH GCP

Answer 17

1) Should be done in line with declaration of Helsinki and consistent with GCP
2) Risks and inconveniences should be weighed against the benefit to the individual or society. Should only be continued if justified.
3) Rights, safety and well-being of subjects is the most important consideration.
4) The nonclinical and clinical information on the investigational product (IP) should support the proposed trial.
5) Should scientifically sound and described clearly
6) Trial must be conducted in line with the IRB approved protocol
7) Medical care takes priority
8) Those conducting the trial must be qualified by education, training, and experience
9) Freely given informed consent should be obtained prior to participation
10) All trial information should be recorded and stored to allow for accurate reporting
Addendum
11) Identifiable information must remain confidential
12) IP must be manufactured in accordance with GMP. And should be used in accordance with the protocol
13) Quality control should be implemented for the study

Question 18

What year did the ICH develop GCP guidelines?

Answer 18

1996

Question 19

According to ICH GCP, what general information should be included in the clinical trial protocol?

Answer 19

Protocol title, identifying number and date
Name and address of the sponsor and monitor
Name and title of person authorized to sign the protocol
Investigator’s name and title
Name, title, address and phone for qualified physician/dentist and medical expert
Name and address of clinical laboratories being used

Question 20

According to ICH GCP, what type of background information should be included in the clinical trial protocol?

Answer 20

Name and description of investigational product
Data from nonclinical studies
Known risks and benefits
Justification and description for route of administration, dosage, dosage regimen and treatment periods
Statement that the trial will be conducted in compliance with the protocol, GCP, and regs
Population to be studies
Any relevant references to literature and data

Question 21

According to ICH GCP, what types of information should be included in the clinical trial protocol?

Answer 21

General trial information and background information
Trial objectives and purpose
Trial design
Selection and withdrawal of subjects
Treatment of subjects
Safety and Efficacy info
Statistical methods
Access to source data/documents and data handling
QA/QC information
Ethics
Financing and Insurance information
Publication policy

Question 22

According to ICH GCP, what info should be included in the trial design section of the trial protocol?

Answer 22

Statement of primary and secondary endpoints
A description of the type of design to be conducted (placebo-controlled, parallel, etc.) with a diagram
Measures used to minimize bias (Randomization or blinding)
Description of treatments, dosage, etc. and what the investigational product looks like
Description of stopping rules or discontinuation criteria
Accountability procedures
Randomization codes and procedures
Data to be included in CRFs

Question 23

What types of subject withdrawal information are typically included in the trial protocol?

Answer 23

When and how to withdraw subjects
Type and timing of the data collected from withdrawn subjects
Whether and how subjects are to be replaced
Subject follow up following withdrawal

Question 24

What types of information regarding statistical methods are typically included in the trial protocol?

Answer 24

Timing of any planned interim analyses
Number of subjects to be enrolled (at each site if multicenter) and justification for that number
Level of significance to be used
Criteria for trial termination
Procedure for accounting for missing, unused and spurious data
Procedures for any deviations from original statistical plan

Question 25

What is the Investigator’s Brochure (IB) and what is its purpose?

Answer 25

The IB is a collection of clinical and nonclinical data on the investigational product relevant to the study. Its purpose is to provide investigators and other in the trial information necessary to comply with the protocol and understand the purpose for the trial.

Question 26

According to ICH GCP, how often should the IB be reviewed?

Answer 26

At least annually and revised as necessary with compliance to sponsor’s written procedures.

Question 27

Who is responsible for keeping an up-to-date IB?

Answer 27

The sponsor.

Question 28

What sections should make up the IB?

Answer 28

Table of Contents
Summary
Introduction
Physical, chemical and pharmaceutical properties / formulation
Nonclinical studies
Clinical data
Summary of data and Investigator guidance

Question 29

According to ICH GCP, what constitutes a Serious Adverse Event (SAE) or a Serious Adverse Drug Reaction (Serious ADR)?

Answer 29

Any untoward medical occurrence that:

Results in death
Is life threatening
Requires inpatient hospitalization or prolongation of existing hospitalization
Results in persistent or significant disability/incapacity
Is a birth defect

Question 30

According to ICH GCP, what is an Unexpected Adverse Drug Reaction?

Answer 30

Adverse reaction the nature or severity of which is not consistent with the applicable product information (Not in investigator’s brochure)