DSUR in Clinical Trials

ICH E2F: Development Safety Update Report (DSUR)

The Development Safety Update Report, commonly known as DSUR, is a reporting instrument (internationally standardized by the ICH) used to provide a summary highlighting the safety profile associated with an investigational drug during its development (i.e., through clinical trials, prior to its approval).¹ An important function of this tool is to ensure that clinical trial participant safety is maintained throughout trial phases, by supporting external oversight/monitoring and evaluation of any potential risks as data comes in. Simultaneously, it also serves as means to communicate between regulatory bodies and sponsoring organizations or pharmaceutical firms.

The sponsor of a clinical trial - whether a sponsor or a pharmaceutical company - is responsible for submitting the DSUR. The DSUR includes information about how many participants there are, records of adverse events, measures to reduce risks during the clinical trial, and updates about the investigation. In addition, the document provides a brief summary of the benefit-risk assessment of the drug based on the available safety data.

A brief history of the DSUR and what it replaces

The DSUR was developed in order to harmonize annual safety reporting requirements, and has been mandatory in the EU since 2011. Regulatory bodies in both the EU and the US consider that DSURs fulfill the regional and national requirements for annual safety reporting, which were previously fulfilled by the Annual Safety Report in the European Union and the IND Annual Report in the U.S.²

DSUR timelines and DIBD

In clinical research, DIBD stands for Development International Birth Date, which is the date of first authorization for a clinical trial anywhere in the world.

The submission deadline for the DSUR is set to one year from the DIBD. Sponsors are required to submit the DSUR annually until all clinical investigations are finished.

Scope and objectives of DSURs

The key objective of a DSUR is to provide an internationally harmonized and comprehensive review of the safety profile for an investigational drug currently under study. Investigational drugs currently in any phase of clinical development (including any post-marketing studies) are subject to DSUR requirements.

The DSUR can be used to verify the consistency of new safety information with older data from previous reports, thus allowing continuous monitoring. The DSUR details any safety concerns that could negatively impact clinical trial participants, provides a summary of potential hazards, and reports on developments in the progress of the clinical trial program in general.³ Importantly, the report should act as a summary - it is not the appropriate place for disclosing new safety concerns for the first time.

DSUR Guidance

Since the DSUR is crucial for regulatory compliance and for ensuring patient safety, sponsors should be sure to follow appropriate guidance when preparing the annual DSUR. Reliable and accurate guidelines are available on the FDA website (for the US) as well as the European Medicines Agency (EMA) website.⁴,⁵