E2A Clinical Safety Data Management: Definitions and Standards for Expedited Reporting — Step 4 (final); 27 October 1994 — II.A.2
In the pre-approval 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 products” 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.
Regarding marketed medicinal products, a well-accepted definition of an adverse drug reaction in the post-marketing setting is found in WHO Technical Report 498 [1972] and reads as follows: A response to a drug which is noxious and unintended and which occurs at doses normally used in man for prophylaxis, diagnosis, or therapy of disease or for modification of physiological function. The old term “side effect” has been used in various ways in the past, usually to describe negative (unfavourable) effects, but also positive (favourable) effects. It is recommended that this term no longer be used and particularly should not be regarded as synonymous with adverse event or adverse reaction.
E2B(R3) EWG/IWG Implementation Guide for Electronic Transmission of Individual Case Safety Reports (ICSRs). Data Elements and Message Specification — Version 5.02; 10 November 2016 — Glossary of Terms
In the pre-approval clinical experience with a new medicinal product or its new usages, particularly as the therapeutic dose(s) cannot 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, e.g. the relationship cannot be ruled out.
Regarding marketed medicinal products: a response to a drug which is noxious and unintended and which occurs at doses normally used in man for prophylaxis, diagnosis, or therapy of diseases or for modification of physiological function (See the ICH Guideline for Clinical Safety Data Management:
Definitions and Standards for Expedited Reporting).[ICHE6(R1)] E2D Post-Approval Safety Data Management: Definitions and Standards for Expedited Reporting — Step 4 (final); 12 November 2003 — 2.2
Adverse drug reactions, as established by regional regulations, guidance, and practices, concern noxious and unintended responses to a medicinal product.
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 (refer to the ICH E2A guideline). A reaction, in contrast to an event, is characterized by the fact that a causal relationship between the drug and the occurrence is suspected. For regulatory reporting purposes, if an event is spontaneously reported, even if the relationship is unknown or unstated, it meets the definition of an adverse drug reaction.
E6(R2) Good Clinical Practice (GCP) — Step 4 (final); 9 November 2016 — Glossary
In the pre-approval 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.
Regarding marketed medicinal products: a response to a drug which is noxious and unintended and which occurs at doses normally used in man for prophylaxis, diagnosis, or therapy of diseases or for modification of physiological function (see the ICH Guideline for Clinical Safety Data Management: Definitions and Standards for Expedited Reporting)
E6(R3) EWG Good Clinical Practice (GCP) — Step 2 (draft); 19 May 2023 — Glossary
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), symptoms 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).
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