Key Definitions in Clinical Trials (ICH E6(R3) and India)

In short: Clinical trial documents use a fixed vocabulary. This guide explains the most-used terms in plain words, based on the glossary of ICH E6(R3) Good Clinical Practice (adopted at Step 4 on 6 January 2025) and the definitions in India’s New Drugs and Clinical Trials Rules, 2019. Use it as a study aid, and read the official glossary for exact legal wording.

Which documents define these terms?

Two sources matter for a trial run in India:

• ICH E6(R3) Good Clinical Practice, which replaced E6(R2) after Step 4 adoption on 6 January 2025. Its glossary is the international reference for GCP terms. Whether and when it applies in a region depends on that region’s adoption, so check with CDSCO for the position in India.
• New Drugs and Clinical Trials Rules, 2019 (NDCT Rules), Rule 2, which gives the legal definitions used by the Indian regulator.

The definitions below are paraphrased, not copied. Where ICH E6(R3) changed a term compared with the older E6(R1)/(R2) text, this is noted. The most visible change is that “subject” became “participant”, “CRF” is now one type of “data acquisition tool”, and “essential documents” became “essential records”.

The trial and the people involved

Clinical trial

A systematic study of an investigational product in human participants to discover or verify its clinical, pharmacological or other pharmacodynamic effects, to identify adverse reactions, or to study its absorption, distribution, metabolism and excretion, so that safety and efficacy can be established. ICH E6(R3) describes it as an interventional investigation. The NDCT Rules (Rule 2(1)(j)) define a clinical trial of a new drug or investigational new drug as a systematic study in human subjects to determine its safety, efficacy or tolerance through clinical, pharmacological or adverse-effect data.

Sponsor

The individual, company, institution or organisation that takes responsibility for starting, managing and arranging the financing of a trial. ICH E6(R3) allows more than one sponsor, with their responsibilities set out in a documented agreement. The NDCT Rules (Rule 2(1)(hh)) describe the sponsor as responsible for initiation and management of the trial.

Investigator, sub-investigator and sponsor-investigator

• The investigator is responsible for the conduct of the trial at the site. In a team, the leader is the principal investigator. The NDCT Rules (Rule 2(1)(t)) use almost the same idea.
• A sub-investigator is a team member designated by, and working under the oversight of, the investigator for significant trial tasks or decisions.
• A sponsor-investigator both starts and conducts the trial and carries the duties of both roles. Only an individual can be one, not a company or agency.

Coordinating investigator

The investigator given responsibility for coordinating investigators at the different sites of a multicentre trial. A multicentre trial follows one protocol at more than one site.

Service provider (CRO)

A person or organisation, commercial or academic, that carries out trial-related activities for the sponsor or investigator. In ICH E6(R3) a contract research organisation (CRO) is a kind of service provider.

Trial participant (trial subject)

Someone who takes part in a trial and is expected to receive the investigational product or serve as a control. ICH E6(R3) uses “participant”; the NDCT Rules use “trial subject” for a patient or healthy person to whom the investigational product is given (Rule 2(1)(jj)).

Vulnerable participants

People whose willingness to join may be unduly influenced by expected benefits, or by fear of retaliation from seniors if they refuse. Examples include students, subordinate hospital or laboratory staff, employees of the pharmaceutical industry, armed forces members and people in detention. Others include patients in emergencies, people in nursing homes, minors and those unable to consent.

Regulatory authority and inspection

Regulatory authorities are bodies with the power to regulate, including those that review protocols and data and those that inspect. An inspection is an official review by such an authority of documents, facilities and records connected with the trial. Some parts may now be done remotely. In India the Central Licencing Authority is the Drugs Controller, India, appointed by the Central Government (Rule 3 of the NDCT Rules); the post is commonly called the DCGI.

Ethics and consent

Ethics committee (IRB/IEC)

An independent body of medical professionals and non-medical members that protects the rights, safety and well-being of participants. It reviews and approves, or gives a favourable opinion on, the protocol, the suitability of the investigator and facilities, and the consent process. Under the NDCT Rules, an Ethics Committee for clinical trials is one constituted under Rule 7 and registered under Rule 8 (Rule 2(1)(o)).

Informed consent

A process, not just a form, by which a participant (or their legally acceptable representative) voluntarily confirms willingness to take part after being given the relevant information. It is documented by a written (paper or electronic), signed and dated consent form. ICH E6(R3) accepts varied ways of giving information, including different formats and remote consent where appropriate. For vulnerable subjects in trials of a new chemical or molecular entity, Indian rules also require an audio-video recording of the consent process.

Legally acceptable representative

A person or body authorised under applicable law to consent on behalf of a prospective participant.

Impartial witness

A person independent of the trial, who cannot be unfairly influenced by those involved in it, and who attends the consent process when the participant or representative cannot read, and reads the consent form and other information.

Assent

Affirmative agreement of a minor to take part. If the minor expresses neither agreement nor disagreement, that silence should not be treated as assent.

Safety terms

The NDCT Rules define adverse event (Rule 2(1)(d)) and serious adverse event (Rule 2(1)(ff)) in similar terms. In India the investigator must report every serious adverse event to the Central Licencing Authority, the sponsor and the Ethics Committee within 24 hours of occurrence (Rule 42(1)); delays must be explained.

An unexpected adverse reaction is one whose nature or severity is not consistent with the reference safety information (RSI), which in ICH E6(R3) is a cumulative list of expected ADRs, normally held in the Investigator’s Brochure or an equivalent document.

Study design terms

• Protocol: the document describing the objectives, design, methodology, statistical considerations and organisation of the trial. A protocol amendment is a documented description of a change to it. The NDCT Rules define the protocol in Rule 2(1)(k).
• Investigational product: a pharmaceutical form of an active ingredient or placebo that is tested or used as a reference in a trial. It includes a marketed product when used or packaged differently from the approved form, for an unapproved indication, or to gain further information on approved use.
• Comparator: an investigational or authorised product, a placebo or standard of care used as a reference.
• Placebo: under the NDCT Rules, an inactive substance visually identical to the drug being tested (Rule 2(1)(bb)).
• Randomisation: deliberately including an element of chance when assigning participants to treatment groups, to reduce bias.
• Blinding (masking): keeping one or more parties unaware of the treatment assignment. Single-blind usually means the participant; double-blind usually means the participant and investigator and, where suitable, other site or sponsor staff.
• Investigator’s Brochure: a compilation of clinical and non-clinical data on the investigational product relevant to its study in humans.
• Independent data monitoring committee (IDMC): an independent group that reviews progress, safety and relevant efficacy data at intervals and advises the sponsor to continue, modify or stop the trial.
• Interim report and clinical study report (CSR): an interim report gives intermediate results from analyses during the trial; the CSR integrates the clinical and statistical description and analysis of the finished trial (see ICH E3).

Quality and oversight terms

Audit also has related terms: an audit certificate confirms an audit took place, and an audit report records its conduct and outcome. To see how audits work in a manufacturing setting, read self-inspection. For the CAPA step that follows findings, see CAPA step by step.

Records and data terms

• Source records (source data and documents): original documents or data, including relevant metadata, or certified copies of them, such as medical records, participant-entered data, laboratory records and data from automated instruments or wearables.
• Certified copy: a copy, on any media, verified by a dated signature or by a validated process to hold the same information as the original, including relevant metadata.
• Case report form (CRF): a tool for recording the protocol-required information to be reported to the sponsor for each participant. ICH E6(R3) treats it as one kind of data acquisition tool (DAT), along with electronic outcome assessments and wearable devices.
• Essential records: the documents and data, with metadata and in any format, that together let the methods, influencing factors and actions of the trial be evaluated, so the reliability of results and GCP compliance can be verified.
• Audit trail: secure, computer-generated, time-stamped metadata showing what was entered or changed, by whom, when and, where applicable, why.
• Metadata: contextual information needed to understand a data element.
• Data integrity: the degree to which data are attributable, legible, contemporaneous, original, accurate, complete, secure and reliable, so they are fit for purpose.
• Direct access: permission to examine, analyse and verify records important for evaluating the trial, on site or remotely, while protecting participant identity and sponsor confidential information.
• Participant identification code: a unique identifier assigned by the investigator to each participant, used in place of the name when reporting trial data.

Trial records are kept as required by the protocol, the regulations that apply and the sponsor’s agreements. For the manufacturing side of GMP records, the site rule is to keep them at least 1 year after the expiry date of the respective product batch (EU GMP Part I Chapter 4 §4.11; 21 CFR 211.180(a)), or longer where local law or the marketing authorisation requires.

Frequently asked questions

Is “clinical trial” the same as “clinical study”?

In ICH GCP usage the terms are used interchangeably. The Indian rules use “clinical trial” for studies of a new drug or investigational new drug, and treat other health research separately as “biomedical and health research” (Rule 2(1)(h)).

What is the difference between an AE and an ADR?

An AE is any unfavourable occurrence during the trial, whether or not the product caused it. An ADR is an adverse event where a causal link to the medicine is at least a reasonable possibility.

What is the difference between “serious” and “severe”?

Seriousness depends on the outcome or action needed, such as death, hospitalisation or disability. Severity describes intensity (mild, moderate, severe). A severe headache may not be serious; a mild event that needs hospitalisation is serious.

Who is responsible for reporting SAEs in India?

The investigator reports to the Central Licencing Authority, the sponsor (or its representative) and the Ethics Committee within 24 hours (NDCT Rules, Rule 42(1)).

Where can I learn what a clinical trial is and how it runs?

Read What Is a Clinical Trial? for the overview and development phases.

References

1. ICH. E6(R3) Guideline for Good Clinical Practice, Step 4, 6 January 2025, Glossary. ich.org.
2. Government of India, Ministry of Health and Family Welfare. New Drugs and Clinical Trials Rules, 2019, Rules 2 (Definitions), 3 and 42, consolidated text as amended by GSR 778(E) dated 14 October 2022, published on cdsco.gov.in.
3. ICH. E2A Clinical Safety Data Management: Definitions and Standards for Expedited Reporting, as referred to in the E6(R3) glossary.