DSUR in Clinical Trials: Avoid Costly Mistakes & Ensure Compliance
- Dr. Catherine Kennedy
- Nov 9
- 5 min read
Clinical trials are conducted as part of the clinical development of investigational drugs to assess their efficacy and safety profiles. As trials progress, it is essential that the drug safety profile is thoroughly mapped to provide a detailed record of the risks to the subjects participating in the trial. This information is required in the form of the annual submission of a regulatory document detailing to regulators and other external parties the results of safety information assessments. The Development Safety Update Report (DSUR) was introduced in 2011 for the reporting of these annual safety assessments of drugs under development. Prior to this, requirements differed between regions. The DSUR is used in clinical trials to provide a common standard across ICH regions and is required by many regulatory authorities, including the FDA (USA), EMA (Europe), MHRA (UK), TGA (Australia), and MedSafe (New Zealand).
Regulatory Framework and Submission Requirements
The DSUR regulatory framework is described by the ICH E2F guidelines. The form of these guidelines has had minimal change since their introduction in 2011, but regional implementation has been updated. Notably, the UK (post-Brexit) and the USA have recently aligned their processes with the DSUR, increasing international regulatory harmonization.
DSUR submission is tightly regulated and mostly harmonized across ICH regions. All regions require DSUR submission annually and specify submission within 60 days of the last day of the yearly reporting cycle (the data lock point). Electronic DSUR submissions are now standard for the majority of regulators, although each uses a separate submission portal and may differ slightly in formatting rules.
DSUR Structure and Essential Content Elements
The ICH E2F guidelines form the basis of the DSUR for clinical trials, providing the necessary information on how to write the report. These guidelines describe the scope, provide a detailed explanation of what to include, and outline the structure. Standard sections include:
Introduction: To include key information on the study and report, including the official start date, report number, what the investigational drug is and how it works, and drug doses and formulations.
Study Status: To include lists of ongoing and completed clinical trials, including info on clinical trial phase and status.
Safety Information: Includes all available clinical and pre-clinical cumulative safety data. Split into several sections, such as ‘Actions taken for safety reasons’, ‘Changes to reference safety information’, ‘Cumulative exposure’, and ‘Serious adverse events’.
Benefit-Risk Considerations: To include a succinct summary of the balance between the risks identified in the safety information and the anticipated benefits, and whether any changes have occurred in this consideration since the previous DSUR.
The ICH E2F guidelines specify 20 different sections forming the full DSUR structure. Detailed information on each of these can be found in the guidelines.
Challenges in DSUR Preparation and How to Overcome Them
The preparation of DSUR in clinical trials is complex, requiring data integration from multiple sources, tight timelines, high accuracy, and cross-team collaboration.
Data integration: Safety data is often compiled from different sources, including separate clinical trials and nonclinical studies. As a result, data stored in different systems and databases by different collaborators (including non-commercial or academic sponsors) must be compiled into a single report in a comprehensive manner while avoiding duplication and filling any information gaps.
Tight timelines: The report must be compiled within 60 days of the data lock point. This gives teams a short timeline to compile data from multiple sources or risk submission delays.
High data accuracy: The data within the report must be highly accurate and comprehensive. Inaccurate or missing data can result in regulatory delays.
Collaboration: Data from multiple sources, including clinical teams, regulatory experts, data management teams, and statisticians, must be compiled into one document. To carry this out effectively, collaboration and communication between all teams are essential.
The failure to address these challenges can risk an incomplete report produced in a rush and lacking essential data. This can result in regulatory compliance failures and subsequent regulatory delays.
How to overcome challenges in DSUR preparation?
Incorporating best practices into the preparation of DSUR for clinical trials can enhance the efficiency of DSUR development and aid in avoiding common pitfalls. Best practices can include:
Early planning: A DSUR project plan should be compiled well in advance of the data lock point.
Use of standardized templates: Using templates ensures consistency across the annual reports, decreases the risk of missing sections, and improves regulatory compliance.
Planning effective communication strategies: Establishing cross-team meetings and routes of communication in advance of DSUR completion can improve collaboration and decrease the risk of content gaps.
Incorporating quality reviews: Implementing expert review processes and regulatory feedback cycles can catch errors, missing content, and formatting mistakes, resulting in a higher quality DSUR. Employing a medical writing company with expertise in regulatory compliance can help streamline DSUR preparation.
DSUR’s Role in Clinical Trial Progression and Decision-Making
The DSUR forms an essential element of clinical trial progression. The compilation of data from multiple sources enables the production of a single comprehensive document that can serve as a source. This source is fully transparent, allowing both investigators and regulators to assess essential information to confirm ongoing patient safety. The annual reports provide updated, cumulative safety information, enabling researchers to better assess the favourability of risk-benefit profiles. Significant changes to safety profiles may warrant trial protocol amendments, the implementation of safety monitoring plans, or potentially trial termination. Therefore, the DSUR provides essential information facilitating regulatory and ethical decision-making and controlling clinical trial progression.
Frequently Asked Questions About DSUR
Q: Does the FDA require DSURs for all investigational drugs?
A: Yes, the FDA has recently replaced its IND Annual Report with a DSUR. All investigational drugs now require a DSUR.
Q: When exactly should a DSUR be submitted during the trial?
A: DSUR submission is required annually and must be completed within 60 days of the data lock point.
Q: What differentiates DSUR from PSUR in ongoing safety monitoring?
A: The DSUR is submitted annually while a drug is in development; a PSUR (Periodic Safety Update Report) is submitted periodically after the drug is approved and on the market to continue to evaluate the benefit-risk profile and maintain pharmacovigilance.
Q: How does DSUR complement the Investigator’s Brochure?
A: The Investigator’s Brochure (IB) provides comprehensive safety data to the investigators. It is not a regulatory document, but instead provides essential information to support the investigators. The DSUR necessitates safety re-evaluations, which can be added to the safety profile in the IB.
Conclusion
DSURs in clinical trials are important regulatory documents that are submitted annually to provide cumulative safety information for investigative drugs. They were introduced to harmonize regulations across IHD regions, forming standardized guidelines. Preparing DSURs can be challenging due to complex data integration, tight timelines, and multi-source data requiring inter-team collaboration. To successfully produce a comprehensive, compliant report, investigators must plan early, use standardized templates, establish inter-team communication pre-year-end, and implement a quality review process.
Planning effectively can minimize the stress of producing the DSUR within the short timeframe and enhance confidence in regulatory compliance.
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ABOUT THE AUTHOR
Dr. Catherine Kennedy Ph.D Medical Writer Catherine undertook an integrated masters in Biosciences (MBiol) before carrying out a Ph.D in Clinical Neurosciences at the University of Cambridge. Her research focussed on the immunology of Parkinson’s disease, specifically looking into the role of Toll-like receptors in the progression of the disease.
