Considerations for Writing and Submitting DSURs for MRCTs

Asymchem Clinical (Clin-Nov)

Considerations for Writing and Submitting Development Safety Update Reports (DSURs) for Multi-Regional Clinical Trials (MRCTs)

Abstract: This article explores key considerations in writing and submitting Development Safety Update Reports (DSURs) for Multi-Regional Clinical Trials (MRCTs).

Introduction

The primary purpose of the Development Safety Update Report (DSUR) is to provide a comprehensive annual review and assessment of safety information collected during the reporting period for an investigational or marketed drug. Typically, the start date for the annual DSUR should align with the date the drug's first clinical trial was approved anywhere in the world—known as the Development International Birth Date (DIBD).

The first DSUR submission should be completed within 60 calendar days following the first DIBD after global clinical trial approval. Subsequent submissions should also follow the DIBD timeline.

If the drug has already received marketing authorization in any country, the sponsor may choose to base the DSUR on the International Birth Date (IBD)—the date of first marketing approval, if appropriate. In such cases, the reporting period for the first submission should not exceed one year.

Key Content Requirements

According to ICH E2F guidelines [1], the Overall Safety Assessment section of the DSUR should emphasize the aggregation and analysis of serious adverse events (SAEs) and other important safety information. It should also address risk assessment, risk minimization measures, and risk communication strategies. This section is critical to ensuring patient safety during the course of clinical development.

Additionally, if further clinical studies continue after marketing approval, the DSUR should also incorporate data from post-marketing studies.

Regional Annexes

The DSUR should be accompanied by region-specific annexes in line with local regulatory requirements. These may include:

  ●  A cumulative summary table of serious adverse reactions (SARs),

  ●  A list of subjects who died during the reporting period,

  ●  A list of subjects who withdrew from the study, and more.

All relevant safety data should be included, covering studies conducted globally. For example, when submitting a DSUR to the National Medical Products Administration (NMPA) in China, data from studies conducted outside of China must also be included. These data support the regulatory authority in evaluating the safety and efficacy of the investigational drug and in making decisions on its approval or rejection.

Key Considerations for MRCT DSURs

Differences in Region-Specific Requirements

Each country or region may have its own regulatory requirements regarding DSUR content. For instance, in China, the Center for Drug Evaluation (CDE) issued an announcement on July 27, 2018, to standardize DSUR preparation procedures [2]. When drafting the Region-Specific Information section, it is essential to comply with local regulations—for example, Article 12 of the Guidelines for the Management of Development Safety Update Reports [3] in China.

Collection and Integration of Global Safety Data

MRCTs typically involve multiple research sites across two or more countries. While this approach provides diverse safety data, it also presents challenges in aggregating and standardizing information across sites.

Ensuring consistency and accuracy during data integration is essential. Pharmacovigilance personnel must maintain timely and effective communication with data providers to verify the completeness and reliability of submitted information. A robust data collection and review process enhances risk identification, facilitates appropriate mitigation strategies during the study design phase and supports the overall integrity of the trial.

Submission Strategies and Regional Coordination

DSURs for MRCTs must be submitted in all participating countries, in accordance with each region’s regulations. This involves translation, validation, and review procedures tailored to the local context. Therefore, local pharmacovigilance or regulatory staff are often best positioned to manage these submissions.

For example, DSURs submitted in China should ideally be prepared and submitted by local personnel familiar with NMPA requirements. Similarly, local project teams in other regions should handle submissions in line with their national regulatory frameworks.

Conclusion

Writing and submitting DSURs for MRCTs involves careful consideration of global harmonization alongside regional regulatory nuances. Understanding and incorporating region-specific requirements, maintaining accurate global data aggregation, and coordinating local submissions are essential steps in ensuring regulatory compliance and safeguarding patient safety throughout clinical development.

Reference：

1.  International Conference on Harmonization, ICH E2F: ICH E2F Development safety update report - Scientific guideline.

2.  Announcement of the State Drug Administration on Adjusting the Procedures for Review and Approval of Clinical Trials of Drugs, National Medical Products Administration, Announcement No. 50 of 2018.

3.  Guidelines for the Management of Development Safety Update Report (for Trial Implementation), No. 7 of 2020.