Impact of E6R3 on clinical trial pharmacovigilance

Drug safety begins at the conception of drug molecule. Collection of adverse events during clinical development phase plays major role in determining initial safety profile of the drug to be presented in drug labels, which is later on updated by safety data collected in post marketing phase.

ICH E6 guideline provides general framework for Good Clinical Practice to be followed during conduct on an interventional clinical trial. ICH has adopted third revision of the guideline on 06 January 2025 and it is in process to be adopted by major ICH countries. Below are the key impacted/newly added sections in new adopted guidelines:

Section 2 Responsibilities of Investigators, sub section 2.7.2 Safety Reporting

Included language about the reporting of unfavourable medical events occurring in participants before IP administration (e.g., during screening) to the sponsor, if required by the protocol.

Subsection 2.7.2 (a) Adverse events and/or abnormal test results required for safety evaluations (as outlined in the protocol) should be reported to the sponsor according to the reporting requirements and within the time periods specified in the protocol. Unfavourable medical events occurring in participants before investigational product administration (e.g., during screening) should be considered and reported to the sponsor if required by the protocol.

Impact:  Protocol should provide detailed instructions regarding reporting of screening phase adverse events or baseline emergent adverse events for investigators to report such events to Sponsor and other stakeholders.

Appendix A Investigator’s Brochure, sub section A.1.2 and A.3.6 (b)

Added that a list of adverse reactions identified as the reference safety information, including information on their frequency and nature, should be included to determine expectedness of adverse events.

A.1.2 The reference safety information (RSI) contained in the IB provides an important reference point for expedited reporting of suspected unexpected serious adverse reactions (SUSARs) in the clinical trial. This RSI should include a list of adverse reactions, including information on their frequency and nature. This list should be used for determining the expectedness of a suspected serious adverse reaction and subsequently whether reporting needs to be expedited in accordance with applicable regulatory requirements

A.3.6 (b) In cases where a number of clinical trials have been completed, the use of summaries of safety and efficacy across multiple trials by indications in subgroups may provide a clear presentation of the data. Tabular summaries of adverse drug reactions, including information on their frequency and natures for all the clinical trials (including those for all the studied indications) would be useful. Important differences in adverse drug reaction patterns/incidences across indications or subgroups should be discussed.

Impact: Medical writing and safety teams involved in preparation of Investigator’s Brochure should be meticulous in representing safety data in IBs. It will help in accurate assessment and reporting of SAEs during clinical trials, which can have a major impact on overall safety profile of the drug.