ICH GCP E6(R2) Definitions

Question 1

Adverse Drug Reaction (ADR)

Answer 1

In the preapproval clinical experience with a new medicinal product or its new usages, particularly as the therapeutic dose(s) may not be established, all noxious and unintended responses to a medicinal product related to any dose should be considered adverse drug reactions. The phrase “responses to a medicinal product” means that a causal relationship between a medicinal product and an adverse event is at least a reasonable possibility, i.e., the relationship cannot be ruled out.

Question 2

Adverse Event (AE)

Answer 2

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 (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product

Question 3

Applicable Regulatory Requirements

Answer 3

Any law(s) and regulation(s) addressing the conduct of clinical trials of investigational products.

Question 4

Approval (in relation to institutional review boards)

Answer 4

The affirmative decision of the IRB that the clinical trial has been reviewed and may be conducted at the institution site within the constraints set forth by the IRB, the institution, good clinical practice (GCP), and the applicable regulatory requirements.

Question 5

Audit

Answer 5

A 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 (SOPs), good clinical practice (GCP), and the applicable regulatory requirement(s).

Question 6

Audit Certificate

Answer 6

A declaration of confirmation by the auditor that an audit has taken place.

Question 7

Audit Report

Answer 7

A written evaluation by the sponsor’s auditor of the results of the audit.

Question 8

Audit Trail

Answer 8

Documentation that allows reconstruction of the course of events.

Question 9

Blinding/Masking

Answer 9

A procedure in which one or more parties to the trial are kept unaware of the treatment assignment(s). Single-blinding usually refers to the subject(s) being unaware, and double- blinding usually refers to the subject(s), investigator(s), monitor, and, in some cases, data analyst(s) being unaware of the treatment assignment(s).

Question 10

Case Report Form (CFR)

Answer 10

A printed, optical, or electronic document designed to record all of the protocol required information to be reported to the sponsor on each trial subject.

Question 11

Clinical Trial / Study

Answer 11

Any investigation in human subjects intended to discover or verify the clinical, pharmacological and/or other pharmacodynamic effects of an investigational product(s), and/or to identify any adverse reactions to an investigational product(s), and/or to study absorption, distribution, metabolism, and excretion of an investigational product(s) with the object of ascertaining its safety and/or efficacy. The terms clinical trial and clinical study are synonymous.

Question 12

Clinical Trial / Study Report

Answer 12

A written description of a trial/study of any therapeutic, prophylactic, or diagnostic agent conducted in human subjects, in which the clinical and statistical description, presentations, and analyses are fully integrated into a single report

Question 13

Comparator (product)

Answer 13

An investigational or marketed product (i.e., active control), or placebo, used as a reference in a clinical trial.

Question 14

Compliance (in relation to trials)

Answer 14

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

Question 15

Confidentiality

Answer 15

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

Question 16

Contract

Answer 16

A written, dated, and signed agreement between two or more involved parties that sets out any arrangements on delegation and distribution of tasks and obligations and, if appropriate, on financial matters. The protocol may serve as the basis of a contract.

Question 17

Coordinating Committee

Answer 17

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

Question 18

Coordinating Investigator

Answer 18

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

Question 19

Contract Research Organization (CRO)

Answer 19

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 20

Direct Access

Answer 20

Permission to examine, analyze, verify, and reproduce any records and reports that are important to evaluation of a clinical trial. Any party (e.g., domestic and foreign regulatory authorities, sponsor’s monitors, and auditors) with direct access should take all reasonable precautions within the constraints of the applicable regulatory requirement(s) to maintain the confidentiality of subjects’ identities and sponsor’s proprietary information

Question 21

Documentation

Answer 21

All records, in any form (including, but not limited to, written, electronic, magnetic, and optical records, and scans, x-rays, and electrocardiograms) that describe or record the methods, conduct, and/or results of a trial, the factors affecting a trial, and the actions taken.

Question 22

Essential Documents

Answer 22

Documents that individually and collectively permit evaluation of the conduct of a study and the quality of the data produced

Question 23

Good Clinical Practice (GCP)

Answer 23

A standard for the design, conduct, performance, monitoring, auditing, recording, analyses, and reporting of clinical trials that provides assurance that the data and reported results are credible and accurate, and that the rights, integrity, and confidentiality of trial subjects are protected

Question 24

Independent Data Monitoring Committee (IDMC)

Answer 24

(Data and Safety Monitoring Board, Monitoring Committee, Data Monitoring Committee)
An independent data monitoring committee that may be established by the sponsor to assess at intervals the progress of a clinical trial, the safety data, and the critical efficacy endpoints, and to recommend to the sponsor whether to continue, modify, or stop a trial.

Question 25

Impartial Witness

Answer 25

A person, who is independent of the trial, who cannot be unfairly influenced by people involved with the trial, who attends the informed consent process if the subject or the subject’s legally acceptable representative cannot read, and who reads the informed consent form and any other written information supplied to the subject.

Question 26

Independent Ethics Committee (IEC)

Answer 26

An independent body (a review board or a committee, institutional, regional, national, or supranational), constituted of medical professionals and non-medical members, whose
responsibility it is to ensure the protection of the rights, safety and well-being of human subjects involved in a trial and to provide public assurance of that protection, by, among other things, reviewing and approving/providing favorable opinion on the trial protocol, the suitability of the investigator(s), facilities, and the methods and material to be used in obtaining and documenting informed consent of the trial subjects.

Question 27

Informed Consent

Answer 27

A process by which a subject voluntarily confirms his or her willingness to participate in a particular trial, after having been informed of all aspects of the trial that are relevant to the subject’s decision to participate. Informed consent is documented by means of a written, signed, and dated informed consent form.

Question 28

Inspection

Answer 28

The act by a regulatory authority(ies) of conducting an official review of documents, facilities, records, and any other resources that are deemed by the authority(ies) 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 (CROs) facilities, or at other establishments deemed appropriate by the regulatory authority(ies).

Question 29

Institution (medical)

Answer 29

Any public or private entity or agency or medical or dental facility where clinical trials are conducted.

Question 30

Institutional Review Board (IRB)

Answer 30

An independent body constituted of medical, scientific, and nonscientific members, whose responsibility is to ensure the protection of the rights, safety and well-being of human subjects involved in a trial by, among other things, reviewing, approving, and providing continuing review of trial protocols and amendments and of the methods and material to be used in obtaining and documenting informed consent of the trial subjects

Question 31

Interim Clinical Trial / Study Report

Answer 31

A report of intermediate results and their evaluation based on analyses performed during the course of a trial.

Question 32

Investigational Product

Answer 32

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.

Question 33

Investigator

Answer 33

A person responsible for the conduct of the clinical trial at a trial site. If a trial is conducted by a team of individuals at a trial site, the investigator is the responsible leader of the team and may be called the principal investigator. (See also Subinvestigator.)

Question 34

Investigator’s Brochure

Answer 34

A compilation of the clinical and nonclinical data on the investigational product(s) that is relevant to the study of the investigational product(s) in human subjects

Question 35

Legally Acceptable Representative

Answer 35

An individual or juridical or other body authorized under applicable law to consent, on behalf of a prospective subject, to the subject’s participation in the clinical trial.

Question 36

Monitoring

Answer 36

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, standard operating procedures (SOPs), GCP, and the applicable regulatory requirement(s).

Question 37

Monitoring Report

Answer 37

A written report from the monitor to the sponsor after each site visit and/or other trial-related communication according to the sponsor’s SOPs

Question 38

Multicenter Trial

Answer 38

A clinical trial conducted according to a single protocol but at more than one site, and therefore, carried out by more than one investigator.

Question 39

Nonclinical Study

Answer 39

Biomedical studies not performed on human subjects.

Question 40

Opinion (in relation to Independent Ethics Committee)

Answer 40

The judgment and/or the advice provided by an Independent Ethics Committee (IEC).

Question 41

Protocol

Answer 41

A document that describes the objective(s), design, methodology, statistical considerations, and organization of a trial. The protocol usually also gives the background and rationale for the trial, but these could be provided in other protocol referenced documents. Throughout the ICH GCP Guidance, the term protocol refers to protocol and protocol amendments.

Question 42

Protocol Amendment

Answer 42

A written description of a change(s) to or formal clarification of a protocol.

Question 43

Quality Assurance (QA)

Answer 43

All those planned and systematic actions that are established to ensure that the trial is performed and the data are generated, documented (recorded), and reported in compliance with GCP and the applicable regulatory requirement(s).

Question 44

Quality Control (QC)

Answer 44

The operational techniques and activities undertaken within the quality assurance system to verify that the requirements for quality of the trial-related activities have been fulfilled.

Question 45

Randominzation

Answer 45

The process of assigning trial subjects to treatment or control groups using an element of chance to determine the assignments in order to reduce bias.

Question 46

Regulatory Authorities

Answer 46

Bodies having the power to regulate. In the ICH GCP guidance, the expression “Regulatory Authorities” includes the authorities that review submitted clinical data and those that conduct inspections (see 1.29). These bodies are sometimes referred to as competent authorities.

Question 47

Serious Adverse Event (SAE) or Serious Adverse Drug Reaction (ADR)

Answer 47

Any untoward medical occurrence that at any dose:

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

Question 48

Source Data

Answer 48

All information in original records and certified copies of original records of clinical findings, observations, or other activities in a clinical trial necessary for the reconstruction and evaluation of the trial. Source data are contained in source documents (original records or certified copies).

Question 49

Source Document (or Original Medical Record)

Answer 49

Original documents, data, and records (e.g., hospital records, clinical and office charts, laboratory notes, memoranda, subjects’ diaries or evaluation checklists, pharmacy dispensing records, recorded data from automated instruments, copies or transcriptions certified after verification as being accurate copies, microfiches, photographic negatives, microfilm or magnetic media, x-rays, subject files, and records kept at the pharmacy, at the laboratories and at medico-technical departments involved in the clinical trial).

Question 50

Sponsor

Answer 50

An individual, company, institution, or organization that takes responsibility for the initiation, management, and/or financing of a clinical trial.

Question 51

Sponsor-Investigator

Answer 51

An individual who both initiates and conducts, alone or with others, a clinical trial, and under whose immediate direction the investigational product is administered to, dispensed to, or used by a subject. The term does not include any person other than an individual (e.g., it does not include a corporation or an agency). The obligations of a sponsor-investigator include both those of a sponsor and those of an investigator.

Question 52

Standard Operating Procedures (SOPs)

Answer 52

Detailed, written instructions to achieve uniformity of the performance of a specific function.

Question 53

Subinvestigator

Answer 53

Any individual member of the clinical trial team designated and supervised by the investigator at a trial site to perform critical trial-related procedures and/or to make important trial-related decisions (e.g., associates, residents, research fellows)

Question 54

Subject / Trial Subject

Answer 54

An individual who participates in a clinical trial, either as a recipient of the investigational product(s) or as a control

Question 55

Subject Identification Code

Answer 55

A unique identifier assigned by the investigator to each trial subject to protect the subject’s identity and used in lieu of the subject’s name when the investigator reports adverse events and/or other trial-related data.

Question 56

Trial Site

Answer 56

The location(s) where trial-related activities are actually conducted

Question 57

Unexpected Adverse Drug Reaction

Answer 57

An adverse reaction, the nature or severity of which is not consistent with the applicable product information (e.g., Investigator’s Brochure for an unapproved investigational product or package insert/summary of product characteristics for an approved product). (

Question 58

Vulnerable Subjects

Answer 58

Individuals whose willingness to volunteer in a clinical trial may be unduly influenced by the expectation, whether justified or not, of benefits associated with participation, or of a retaliatory response from senior members of a hierarchy in case of refusal to participate. Examples are members of a group with a hierarchical structure, such as medical, pharmacy, dental, and nursing students, subordinate hospital and laboratory personnel, employees of the pharmaceutical industry, members of the armed forces, and persons kept in detention. Other vulnerable subjects include patients with incurable diseases, persons in nursing homes, unemployed or impoverished persons, patients in emergency situations, ethnic minority groups, homeless persons, nomads, refugees, minors, and those incapable of giving consent.

Question 59

Well-being

Answer 59

The physical and mental integrity of the subjects participating in a clinical trial.

Question 60

Certified Copy

Answer 60

A copy (irrespective of the type of media used) of the original record that has been verified (i.e., by a dated signature or by generation through a validated process) to have the same information, including data that describe the context, content, and structure, as the original.

Question 61

Monitoring Plan

Answer 61

A document that describes the strategy, methods, responsibilities, and requirements for monitoring the trial.

Question 62

Validation of Computerized Systems

Answer 62

A process of establishing and documenting that the specified requirements of a computerized system can be consistently fulfilled from design until decommissioning of the system or transition to a new system. The approach to validation should be based on a risk assessment that takes into consideration the intended use of the system and the potential of the system to affect human subject protection and reliability of trial results.