Safety Reporting and Pharmacovigilance

Safety reporting and pharmacovigilance are essential components of clinical research. They help identify, evaluate, communicate and manage safety information throughout the development of an investigational product.

Safety responsibilities are shared among investigators, sponsors and other relevant parties. The specific reporting requirements and timelines depend on the nature of the safety information, the clinical trial protocol and applicable regulatory requirements.

Adverse Events and Serious Adverse Events

An adverse event (AE) is an unfavourable medical occurrence in a clinical trial participant that does not necessarily have a causal relationship with the investigational product.

A serious adverse event (SAE) is an adverse event that meets applicable seriousness criteria, such as resulting in death, being life-threatening, requiring or prolonging inpatient hospitalisation, causing persistent or significant disability or incapacity, or meeting another applicable medically important criterion.

Seriousness should be distinguished from severity. Severity describes the intensity of an event, whereas seriousness is based on regulatory criteria and the consequences of the event.

Investigator Safety Reporting

Investigators are responsible for identifying, documenting and appropriately reporting safety information arising during the clinical trial.

All SAEs should generally be reported immediately to the sponsor after the investigator reasonably becomes aware of the event, unless the protocol identifies particular SAEs for which immediate reporting is not required in accordance with applicable regulatory requirements.

The investigator should provide an assessment of causality and submit relevant follow-up information as it becomes available.

For reported deaths, additional information such as terminal medical reports or autopsy reports may need to be provided when available and requested.

Sponsor Review of Safety Information

The sponsor should periodically review relevant accumulated and emerging safety information.

This review may identify new information that affects the known safety profile of the investigational product, participant willingness to continue in the trial, trial conduct or the continued approval or favourable opinion of regulatory authorities or IRBs/IECs.

Important new safety information should be communicated to relevant parties in a timely manner according to applicable requirements.

Safety findings may also lead to updates to the protocol, Investigator’s Brochure, informed consent materials or other trial documentation.

Clinical trial safety responsibilities should be managed in accordance with applicable requirements and the ICH Good Clinical Practice guideline.

Serious, Unexpected and Suspected Adverse Reactions

A Suspected Unexpected Serious Adverse Reaction (SUSAR) is a serious adverse reaction for which there is a reasonable possibility of a causal relationship with the investigational product and whose nature or severity is not consistent with the applicable reference safety information.

SUSARs are particularly important because they may require expedited reporting by the sponsor to regulatory authorities according to applicable requirements.

Expectedness should be assessed against the appropriate reference safety information, such as the relevant information contained in the Investigator’s Brochure or another applicable reference document.

Expedited Safety Reporting

Sponsors should expedite the reporting of SUSARs to regulatory authorities in accordance with applicable regulatory requirements and relevant clinical-safety reporting standards.

Safety communication to investigators, institutions and IRBs/IECs should reflect the urgency of the information and the evolving knowledge of the investigational product’s safety profile.

Urgent safety issues requiring immediate attention or action should be communicated without undue delay to the relevant investigators, IRBs/IECs and regulatory authorities as applicable.

Exact reporting routes and timelines may differ between jurisdictions and should therefore follow applicable regulatory requirements.

Periodic Safety Reporting

In addition to expedited reporting, sponsors may be required to submit periodic safety updates during clinical development.

Periodic reporting provides an integrated assessment of accumulated safety information rather than focusing only on individual expedited cases.

For investigational medicinal products, the Development Safety Update Report (DSUR) provides an internationally harmonised framework for annual reporting during clinical development where applicable.

For a broader overview of safety reporting requirements and concepts, see Safety Reporting in Pharmacovigilance.

Safety Monitoring Throughout the Trial

Safety monitoring is an ongoing process rather than a series of isolated adverse-event reports.

Sponsors should evaluate accumulating safety information for patterns, trends or emerging risks that may affect the benefit-risk assessment of the investigational product or the safe conduct of the trial.

Depending on the trial, safety oversight may also involve an independent data monitoring committee or another appropriately constituted safety-monitoring body.

Related monitoring activities involving investigational product control and documentation are covered in Drug Accountability.

Safety Information and Participant Protection

New safety information may affect how a clinical trial should continue.

When emerging information could influence a participant’s willingness to remain in the study, appropriate communication and updates to informed consent materials may be necessary.

Safety findings may also require changes to the protocol, Investigator’s Brochure, monitoring activities or other risk-control measures.

Participant rights, safety and well-being remain central to all safety-reporting decisions.

Documentation and Data Quality

Safety information should be appropriately documented, reviewed and followed up.

Relevant safety data should be accurate, complete and sufficiently detailed to support appropriate medical and regulatory assessment.

Safety information reported through different trial systems and documents should be appropriately reconciled where necessary to identify important inconsistencies or missing information.

Pharmacovigilance During Clinical Development

Pharmacovigilance during clinical development involves the continuing detection, assessment, understanding and management of safety information associated with investigational products.

It includes individual case evaluation, aggregate safety review, expedited reporting, periodic reporting, signal evaluation and communication of important emerging risks.

These activities continue to evolve as knowledge of the investigational product increases during development.

Importance of Safety Reporting and Pharmacovigilance

Safety reporting and pharmacovigilance help protect clinical trial participants while building an increasingly complete understanding of an investigational product’s safety profile.

Effective safety management requires timely investigator reporting, appropriate sponsor medical assessment, evaluation of cumulative information and communication of important risks to the relevant parties.

Safety reporting should therefore be viewed as an integrated and continuous process throughout clinical development rather than simply as the collection and submission of adverse-event reports.

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