Development safety update reports

What is a Development safety update report (DSUR)?

A DSUR is a safety document that is submitted annually for investigational drugs. The DSUR is a comprehensive document that details all of the safety data collected during the clinical development of an investigational drug. These reports play a key role in the evolving safety profile of an investigational drug, and facilitate sponsors, regulators, and stakeholders to make appropriate risk assessments and decisions over the course of an investigational drug’s clinical development lifecycle.

Not discussed as part of this deep-dive is the Periodic Safety Update Report (or PSUR), which is a pharmacovigilance document used to monitor the safety and risk-benefit profile of approved and marketed medicinal products.

What are the main requirements of a full DSUR?

The key requirements for developing a DSUR include:

1. Cumulative safety summary
The safety summary provides an integrated assessment of all the safety information, which includes known risks, emerging safety patterns, and any new safety concerns collected up to the data lock point (DLP). Adverse event data across all ongoing and completed clinical studies as well as any pertinent changes to the risk-benefit profile will also be detailed in the safety summary.

The DLP is a pre‑determined date at which data is deemed complete for a specific reporting period.

2. Clinical and non-clinical trial data
Clinical trial data can include final or interim safety results and any notable serious adverse reactions or laboratory abnormalities, while non-clinical data can include any new relevant animal or in vitro studies conducted within a defined reporting period.

3. Risk-benefit assessment
This section details new risks or changes in risk severity, including if the risk-benefit is favourable at defined doses or for specific patient populations. Recommendations for any clinical trial amendments or risk mitigation strategies may also be discussed.

4. Overview of ongoing and completed studies
This overview contains a list of any ongoing, completed, or terminated studies within the designated reporting period. Protocol amendments, if applicable, would also be detailed here, as well as any reasons for study discontinuation.

5. Important safety findings from other relevant sources
Other relevant safety data may include information from relevant literature reviews, compassionate use programmes, spontaneous reports, or even data from comparable marketed products.

6. Summary tabulations of serious adverse events (SAEs), serious unexpected serious adverse reactions (SUSARs), and narrative summaries of significant cases
These sections typically include tabulations of serious safety events, including SAEs and SUSARs, as well as any reporting rates and patterns of severity. Certain SUSARs could also warrant detailed explanations that may highlight new safety signals.

7. Summary of safety signals and ongoing evaluation
This section summarises any new safety signals, updates on previously identified risks, how safety signals are assessed, or if current safety signals are still being evaluated or confirmed.

The final report will include qualitative and quantitative data, and the overall investigational drug’s safety profile will be assessed. Any implications for ongoing drug development or if drug development should be modified based on novel safety signals will also be stated.

How are DSURs used within the regulatory framework?

DSURs serve as key documents for regulators to monitor the safety of an investigational drug during the clinical development lifecycle. They align with the International Council of Harmonisation (ICH) E2F guidelines and serve as a harmonised document across multiple regions. DSURs are provided to regulators, such as the US Food and Drug Administration, European Medicines Agency, Medicines and Healthcare products Regulatory Agency, and Japanese Pharmaceuticals and Medical Devices Agency. Regulators then use the DSUR to assess safety and emerging risks and determine if clinical trial continuation is justified, or if any further regulatory actions are required.

What source materials are needed to write a DSUR?

To develop comprehensive DSUR, the following documents are generally required:

Clinical trial data: safety narratives, safety listings, clinical study protocols (CSPs), and CSRs
Safety databases
Pharmacovigilance data
Non-clinical study data
Previous regulatory submissions: previous DSURs, risk management plans, and Investigator’s Brochures
Any related literature or publications
Other materials for appendices

What is the general timeframe/timeline for writing a DSUR?

A DSUR is updated annually and is based on the Development International Birth Date (DIBD), which is the date of the sponsor’s first authorisation to conduct a clinical trial with an investigational drug. The DIBD at Day 0 is the same as the DSUR DLP, and there is a 60-day window from the DLP to submit the DSUR to the relevant regulatory authority to ensure on-time delivery. This short window means that medical writers must have timely and efficient project management to write, review, and finalise the DSUR prior to submission.

Overview of the development of a DSUR

Graphic showing an overview of the development of a DSUR

Abbreviations: DLP = data lock point; DSUR = Development Safety Update Report.

Alchemy’s top tips and tricks for writing and/or submitting a DSUR?

My top tip for authoring DSURs is to create a clear actionable timeline in collaboration with the client and project manager. Given the tight turnaround time based on the DIBD, it is essential to ensure that client expectations are managed from the get-go concerning draft writing, internal review, finalisation, and final quality control checking prior to regulatory submission. Prior to the DLP, it is always helpful to ask the client for word and PDF copies of previous DSUR iterations and request any available sources required to help expedite the draft writing process.

Mark Stuart, Medical Writer II