Writing the Annual Safety Report (DSUR) under the EU CTR: Cumulative Safety Assessment focus

The Annual Safety Report (or Development Safety Update Report) is an annual report that summarizes and evaluates the safety of a drug under development to provide an annual review of safety information and identify any new safety issues that could affect the drug's benefit-risk balance. Among all the elements outlined in the ICH E2F guideline, there is one section that gives real purpose to the Development Safety Update Report (DSUR): the cumulative safety assessment. While the EU Clinical Trials Regulation (EU) No. 536/2014 and CTIS define how and where the Annual Safety Report must be submitted, it is ICH E2F that explains what truly matters inside the report. And nothing matters more than showing that the sponsor understands the global safety picture of the Investigational Medicinal Product (IMP). 

The cumulative safety assessment is the point where the DSUR stops being an administrative obligation and becomes a scientific tool. Instead of listing adverse events mechanically, this section asks the sponsor to step back and focus on the entire year of safety data as a whole: what patterns emerged? Which events were unexpected? Did any known risks change in frequency or severity? Is the overall benefit–risk balance still acceptable? 

This perspective is crucial because regulators are not looking for raw numbers—they want insight. ICH E2F stresses that sponsors must integrate all available information: serious adverse events, serious adverse reactions, emerging trends across studies, global exposure data, medical judgment and any signals that may be forming. The goal is not to repeat data already found in line listings, but to transform it into meaningful conclusions about participant safety. 

Under the CTR, this analytical approach becomes even more critical. Since the DSUR is submitted centrally through CTIS and assessed simultaneously by multiple Member States, the narrative must be clear, coherent, and scientifically well-reasoned. A robust cumulative safety assessment enables regulators to reach aligned conclusions and minimises the chance of follow-up questions or assessment of delays. It also strengthens internal decision-making: key choices regarding trial design, monitoring intensity, protocol amendments and updates to the Investigator’s Brochure often depend directly on the insights emerging from this section. 

In practice, delivering a high-quality cumulative safety assessment means understanding the product’s entire development context. It requires accurate exposure estimates, consistent SAE and SAR reconciliation, and continuous dialogue between the clinical and safety teams. But above all, it requires the ability to analyse - not just report - data. 

When sponsors, small companies or non-profit organisations, manage to approach the DSUR in this way, they demonstrate maturity, transparency and readiness to support the safe progress of their clinical development programme within the EU framework. 

Contact us at pv@clinopshub.com to discuss how we can help you strengthen your safety reporting and streamline your regulatory processes.  

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