GLOSSARY. ICH E6 (R3) Guideline on good clinical practice (GCP) Step 5

Adverse Events and Adverse Reaction-related definitions:

Adverse Event (AE): Any unfavourable medical occurrence in a trial participant administered the investigational product. The adverse event does not necessarily have a causal relationship with the treatment.

Adverse drug reaction (ADR):

In the pre-approval clinical experience with a new investigational product or its new usages
(particularly as the therapeutic dose(s) may not be established): unfavourable and unintended responses, such as a sign (e.g., laboratory results), symptom or disease related to any dose of a medicinal product where a causal relationship between a medicinal product and an adverse event is a reasonable possibility. The level of certainty about the relatedness of the adverse drug reaction to an investigational product will vary. If the ADR is suspected to be medicinal product- related with a high level of certainty, it should be included in the reference safety information (RSI) and/or the Investigator’s Brochure (IB).
For marketed medicinal products: a response to a drug that is noxious and unintended and that occurs at doses normally used in humans for prophylaxis, diagnosis or therapy of diseases or for modification of physiological function.

(See ICH E2A Clinical Safety Data Management: Definitions and Standards for Expedited Reporting.)

Serious Adverse Event (SAE): Any unfavourable medical occurrence that is considered serious at any dose if it:

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

(see ICH E2A)

An important medical event that may not be immediately life-threatening or result in death or hospitalisation, that may jeopardise the participant or that may require intervention to prevent serious outcomes (see ICH E2A and E19) should generally be considered as serious.

Suspected Unexpected Serious Adverse Reaction (SUSAR): an adverse reaction that meets three criteria: suspected, unexpected and serious.

Suspected: There is a reasonable possibility that the drug caused the adverse drug reaction.
Unexpected: An adverse reaction, the nature or severity of which is not consistent with the
applicable product information (e.g., Investigator’s Brochure or alternative documents according to applicable regulatory requirements; see RSI).
Serious: See above for SAE.

Agreement

A document or set of documents describing the details of any arrangements on delegation or transfer, distribution and/or sharing of activities and, if appropriate, on financial matters between two or more parties. This could be in the form of a contract. The protocol may serve as the basis of an agreement.

Applicable Regulatory Requirement(s)

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

Assent

Affirmative agreement of a minor to participate in clinical trial. The absence of expression of agreement or disagreement should not be interpreted as assent.

Audit

A systematic and independent examination of trial-related activities and records performed by the sponsor, service provider (including contract research organisation (CRO)) or institution to determine whether the evaluated trial-related activities were conducted and the data were recorded, analysed and accurately reported according to the protocol, applicable standard operating procedures (SOPs), Good Clinical Practice (GCP) and the applicable regulatory requirement(s).

Audit certificate

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

Audit Report

A record describing the conduct and outcome of the audit.

Audit Trail

Metadata records that allow the appropriate evaluation of the course of events by capturing details on actions (manual or automated) performed relating to information and data collection and, where applicable, to activities in computerised systems. The audit trail should show activities, initial entry and changes to data fields or records, by whom, when and, where applicable, why. In computerised systems, the audit trail should be secure, computer-generated and time stamped.

Blinding/Masking

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 participant(s) being unaware, and double-blinding usually refers to the participant(s) and investigator(s) and, if appropriate, other investigator site staff or sponsor staff being unaware of the treatment assignment(s).

Case Report Form (CRF)

A data acquisition tool designed to record protocol-required information to be reported by the investigator to the sponsor on each trial participant (see Data Acquisition Tool).

Certified Copy

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 as the original, including relevant metadata, where applicable.

Clinical Trial

Any interventional investigation in human participants 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.

Clinical Trial/Study Report (CSR)

A documented description of a trial of any investigational product conducted in human participants, in which the clinical and statistical description, presentations and analyses are fully integrated into a single report (see ICH E3 Structure and Content of Clinical Study Reports).

Comparator

An investigational or authorised medicinal product (i.e., active control), placebo or standard of care used as a reference in a clinical trial.

Compliance (in relation to trials)

Adherence to the trial-related requirements, GCP requirements and the applicable regulatory requirements.

Confidentiality

Prevention of disclosure to other than authorised individuals of a sponsor’s proprietary information or of a participant’s identity or their confidential information.

Coordinating Investigator

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

Computerised Systems Validation

A process of establishing and documenting that the specified requirements of a computerised 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 trial participant protection and the reliability of trial results.

Contract Research Organisation (CRO)

See Service Provider.

Data Acquisition Tool (DAT)

A paper or electronic tool designed to collect data and associated metadata from a data originator in a clinical trial according to the protocol and to report the data to the sponsor.

The data originator may be a human (e.g., the participant or trial staff), a machine (e.g., wearables and sensors) or a computer system from which the electronic transfer of data from one system to another has been undertaken (e.g., extraction of data from an electronic health record or laboratory system).

Examples of DATs include but are not limited to CRFs, interactive response technologies (IRTs), clinical outcome assessments (COAs), including patient-reported outcomes (PROs) and wearable devices, irrespective of the media used.

Data integrity

Data integrity includes the degree to which data fulfil key criteria of being attributable, legible, contemporaneous, original, accurate, complete, secure and reliable such that data are fit for purpose.

Direct Access

Permission to examine, analyse and verify records that are important to the evaluation of a clinical trial and may be performed on-site or remotely. Any party (e.g., domestic and foreign regulatory authorities, sponsor’s monitors and auditors) with direct access should take reasonable precautions within the constraints of the applicable regulatory requirement(s) to maintain the confidentiality of participants’ identities and their data and sponsor’s proprietary information.

Essential Records

Essential records are the documents and data (and relevant metadata), in any format, associated with a clinical trial that facilitate the ongoing management of the trial and collectively allow the evaluation of the methods used, the factors affecting a trial and the actions taken during the trial conduct to determine the reliability of the trial results produced and the verification that the trial was conducted in accordance with GCP and applicable regulatory requirements (see Appendix C).

Good Clinical Practice (GCP)

A standard for the planning, initiating, performing, recording, oversight, evaluation, analysis and reporting of clinical trials that provides assurance that the data and reported results are reliable and that the rights, safety and well-being of trial participants are protected.

Impartial Witness

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 participant or the participant’s legally acceptable representative cannot read, and who reads the informed consent form and any other documented information supplied or read to the participant and/or their legally acceptable representative.

Independent Data Monitoring Committee (IDMC)

An independent data monitoring committee (e.g., data safety monitoring board) that may be established by the sponsor to assess at intervals the progress of a clinical trial, the safety and relevant efficacy data, and to recommend to the sponsor whether to continue, modify or stop a trial.

Informed Consent

A process by which a participant or their legally acceptable representative voluntarily confirms their willingness to participate in a trial after having been informed and been provided with the opportunity to discuss all aspects of the trial that are relevant to the participant’s decision to participate. Varied approaches to the provision of information and the discussion about the trial can be used. This may include, for example, providing text in different formats, images and videos and using telephone or video conferencing with investigator site staff. Informed consent is documented by means of a written (paper or electronic), signed and dated informed consent form. Obtaining consent remotely may be considered when appropriate.

Inspection

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 accessed at the investigator site, at the sponsor’s and/or service provider’s (including CRO’s) facilities, or at other establishments deemed appropriate by the regulatory authority(ies). Some aspects of the inspection may be conducted remotely.

Institution

Any public or private entity or agency or medical or dental organisation in whose remit clinical trials are conducted.

Institutional Review Board (IRB)/Independent Ethics Committee (IEC)

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 participants involved in a trial and to provide public assurance of that protection by, among other things, reviewing and approving/providing favourable opinion on the trial protocol, the suitability of the investigator(s), the facilities, and the methods and material to be used in obtaining and documenting informed consent of the trial participants. The legal status, composition, function, operations and regulatory requirements pertaining to IRBs/IECs may differ among countries but should allow the IRB/IEC to act in agreement with GCP as described in this guideline.

Interim Clinical Trial/Study Report

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

Investigational Product

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 authorisation 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. Investigational products should be considered synonymous with drugs, medicines, medicinal products, vaccines and biological products.

Investigator

A person responsible for the conduct of the clinical trial, including the trial participants for whom that person has responsibility during the conduct of the trial. If a trial is conducted by a team of individuals, the investigator is the responsible leader of the team and may be called the principal investigator. Where an investigator/institution is referenced in this guideline, it describes expectations that may be applicable to the investigator and/or the institution in some regions. Where required by the applicable regulatory requirements, the “investigator” should be read as “investigator and/or the institution.”

Investigator’s Brochure (IB)

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 participants (see Appendix A).

Investigator Site

The location(s) where trial-related activities are conducted and/or coordinated under the investigator’s/institution’s oversight.

Legally Acceptable Representative

An individual or juridical or other body authorised under applicable law to consent, on behalf of a prospective participant, to the participant’s participation in the clinical trial. When a legally acceptable representative provides consent on behalf of a prospective participant, activities related to the consenting process (and re-consent, if applicable) and, where relevant, activities associated with the withdrawal of consent described in this guideline are applicable to the participant’s legally acceptable representative.

Metadata

The contextual information required to understand a given data element. Metadata is structured information that describes, explains or otherwise makes it easier to retrieve, use or manage data. For the purpose of this guideline, relevant metadata are those needed to allow the appropriate evaluation of the trial conduct.

Monitoring

The act of overseeing the progress of a clinical trial and of ensuring that the clinical trial is conducted, recorded and reported in accordance with the protocol, SOPs, GCP and the applicable regulatory requirement(s).

Monitoring Plan

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

Monitoring Report

A documented report following site and/or centralised monitoring activities.

Multicentre Trial

A clinical trial conducted according to a single protocol but at more than one investigator site.

Nonclinical Study

Biomedical studies not performed on human participants.

Protocol

A document that describes the objective(s), design, methodology, statistical considerations and organisation 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 Guideline, the term “protocol” refers to protocol and protocol amendments.

Protocol Amendment

A documented description of a change(s) to a protocol.

Quality Assurance (QA)

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).

Quality Control (QC)

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

Randomisation

The process of deliberately including an element of chance when assigning participants to groups that receive different treatments in order to reduce bias.

Reference Safety Information (RSI)

Contains a cumulative list of ADRs that are expected for the investigational product being administered to participants in a clinical trial. The RSI is included in the Investigator’s Brochure or alternative documents according to applicable regulatory requirements. Refer to ICH E2F Development Safety Update Report for more information about RSI.

Regulatory Authorities

Bodies having the power to regulate, including those that review submitted protocols and clinical data and those that conduct inspections. These bodies are sometimes referred to as competent authorities.

Service Provider

A person or organisation (commercial, academic or other) providing a service used by either the sponsor or the investigator to fulfil trial-related activities.

Signature

A unique mark, symbol or entry executed, adopted or authorised by an individual, in accordance with applicable regulatory requirements and/or practice to show expression of will and allow authentication of the signatory (i.e., establish a high degree of certainty that a record was signed by the claimed signatory). A signature may be physical or electronic.

Source Records

Original documents or data (which includes relevant metadata) or certified copies of the original documents or data, irrespective of the media used. This may include trial participants’ medical/health records/notes/charts; data provided/entered by trial participants (e.g., electronic patient-reported outcomes (ePROs)); healthcare professionals’ records from pharmacies, laboratories and other facilities involved in the clinical trial; and data from automated instruments, such as wearables and sensors.

Sponsor

An individual, company, institution or organisation that takes responsibility for the initiation, management and arrangement of the financing of a clinical trial. A clinical trial may have one or
several sponsors where permitted under regulatory requirements. All sponsors have the responsibilities of a sponsor set out in this guideline. In accordance with applicable regulatory requirements, sponsors may decide in a documented agreement setting out their respective responsibilities. Where the documented agreement does not specify to which sponsor a given responsibility is attributed, that responsibility lies with all sponsors.

Sponsor-Investigator

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 participant. The term does not include any person other than an individual (e.g., the term 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.

Standard Operating Procedures (SOPs)

Detailed, documented instructions to achieve uniformity of the performance of a specific activity.

Sub-investigator

Any individual member of the clinical trial team designated and under the oversight of the investigator to perform significant trial-related procedures and/or to make important trial-related decisions (e.g., associates, residents, research fellows).

Trial Participant

An individual who participates in a clinical trial who is expected to receive the investigational product(s) or as a control. In this guideline, trial participant and participant are used interchangeably.

Trial Participant Identification Code

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

Vulnerable Participants

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 participants may include 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.

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