A Development Safety Update Report (DSUR) is the annual safety report for a drug in clinical development. It is defined by ICH E2F, which sets out its purpose plainly: "to present a comprehensive, thoughtful annual review and evaluation of pertinent safety information collected during the reporting period related to a drug under investigation, whether or not it is marketed."
The DSUR replaced two older regional reports. E2F notes that US and EU regulators consider the DSUR "would meet national and regional requirements currently met by the US IND Annual Report and the EU Annual Safety Report," and FDA has adopted E2F as guidance. For a sponsor with an open IND or an authorised trial in Europe, it is a fixed annual deadline.
This guide covers how to plan a DSUR, what goes in each of its 20 sections, and where they most often go wrong. For how the DSUR differs from the post-marketing PSUR/PBRER, see DSUR vs PSUR/PBRER.
The clock: DIBD, data lock point and the 60-day deadline
Three dates drive every DSUR.
- The Development International Birth Date (DIBD). E2F defines it as "the sponsor's first authorisation to conduct a clinical trial in any country worldwide." The DSUR year starts on the month and day of the DIBD, and the same DIBD is used for every country, even when trials start later elsewhere.
- The data lock point. "The data lock point of the DSUR should be the last day of the one-year reporting period." For convenience, a sponsor can use the last day of the month before the DIBD month.
- The submission deadline. "The DSUR should be submitted to all concerned regulatory authorities no later than 60 calendar days after the DSUR data lock point."
Sixty days is not long once you subtract data cleaning, medical review and sign-off. Most teams start drafting the sections that do not depend on the final data (the trial inventory, the RSI history, the regulatory actions) before the lock.
If the drug is also marketed somewhere, E2F allows the DSUR to be aligned to the PSUR's International Birth Date so the two reports can be synchronised, provided the next DSUR period is no longer than a year.
The reference safety information
Before any safety data is assessed, the DSUR has to say what the data are being compared against. E2F section 2.6 says the reference safety information (RSI) in effect at the start of the reporting period should be used, and that usually this is the Investigator's Brochure. For a marketed drug, the local label can serve instead. Section 4 of the DSUR then lists changes to the RSI made during the period.
This is where many DSURs start to go wrong. If the IB was updated mid-period, the expectedness of each serious adverse reaction has to be judged against the RSI that applied at the start, and the change described in section 4. Mixing versions makes the line listings inconsistent.
The 20 sections
E2F asks that "all sections should be completed; when no information is available, this should be stated." The sections are:
| # | Section | What it holds |
|---|---|---|
| 1 | Introduction | Reporting period, drug, indications, scope |
| 2 | Worldwide marketing approval status | Where the drug is approved, if anywhere |
| 3 | Actions taken in the reporting period for safety reasons | Holds, terminations, protocol changes for safety |
| 4 | Changes to reference safety information | RSI updates during the period |
| 5 | Inventory of clinical trials | Ongoing and completed trials in the period |
| 6 | Estimated cumulative exposure | Subjects exposed in the programme, and marketed exposure if any |
| 7 | Data in line listings and summary tabulations | Interval SAR listings and cumulative SAE tabulations |
| 8 | Significant findings from clinical trials | Completed, ongoing and long-term follow-up studies |
| 9 | Safety findings from non-interventional studies | Observational studies and registries |
| 10 | Other clinical trial/study safety information | Pooled analyses, partner data |
| 11 | Safety findings from marketing experience | Post-marketing safety data, if marketed |
| 12 | Non-clinical data | New toxicology or pharmacology findings |
| 13 | Literature | Relevant new publications |
| 14 | Other DSURs | Where a sponsor has several DSURs for one drug |
| 15 | Lack of efficacy | Where it could signal a risk to subjects |
| 16 | Region-specific information | Regional annexes |
| 17 | Late-breaking information | Important findings after the data lock point |
| 18 | Overall safety assessment | Evaluation of risks and benefit-risk considerations |
| 19 | Summary of important risks | Cumulative list of important identified and potential risks |
| 20 | Conclusions | Changes needed to protect trial subjects |
The report opens with a title page (sequential DSUR number, drug, period, date, sponsor, confidentiality statement, and a note if it contains unblinded information) and an executive summary that, with the title page, can stand on its own.
The sections that carry the weight
Section 6: exposure
The denominator for everything else. Section 6.1 covers cumulative subject exposure across the development programme, broken down by trial, treatment arm and where possible by age, sex and race. Sources disagree more often than teams expect: the clinical database, the IRT system and the CROs' reports may give different counts. Pick a source, say which, and reconcile before drafting.
Section 7: line listings and summary tabulations
E2F asks for two different things here, and confusing them is a common error.
- Interval line listings of serious adverse reactions (SARs) for the reporting period: events the investigator or sponsor judged to be related.
- Cumulative summary tabulations of serious adverse events (SAEs) since the DIBD: all serious events, related or not, by system organ class and treatment group.
So the listing is "reactions, this year" and the tabulation is "events, ever." Getting the scope of each right is the single most mechanical, and most error-prone, part of the DSUR. Appendix B of E2F gives example table layouts.
Section 18: overall safety assessment
This is the part regulators read most closely. Section 18.1 evaluates the risks: new findings, changes in the frequency or severity of known risks, and their clinical relevance. Section 18.2 sets out benefit-risk considerations for the trial population. It should be a concise integrated judgement, not a repeat of sections 6 to 17.
Section 19: summary of important risks
A cumulative list of the important identified and potential risks, each with a short explanation of its current status. E2F Appendix C gives worked examples. Carry this forward from the previous DSUR and update it, rather than rewriting it each year, so the history of each risk is visible.
A working plan for the 60 days
- Before the lock: confirm the DIBD and data lock point, the RSI version in effect, the trial inventory, any regulatory actions, and partner data agreements.
- At the lock: freeze exposure data and SAE data; generate section 6 and section 7 tables from the locked data.
- Weeks 1 to 4: draft sections 8 to 17 from study reports, safety review minutes, the literature search and partner inputs.
- Weeks 4 to 6: write sections 18 to 20 with the safety physician; update the executive summary last.
- Weeks 6 to 8: QC every number against the tables, sign off, and submit with any regional annexes.
Common findings
- Section 7 listings that include non-serious events, or tabulations that are interval rather than cumulative.
- Expectedness judged against the latest IB instead of the RSI in effect at the start of the period.
- An exposure figure in section 6 that does not match the denominators in section 7.
- A section 18 that lists events but never says whether the benefit-risk balance for trial subjects has changed.
- Sections left blank instead of stating that no information is available.
Where automation helps
A DSUR is mostly reconciliation and carry-forward: tables built from line listings, exposure reconciled across studies, and last year's risk summary updated with this year's data. Asthra's DSUR AI writing tool drafts the report in the E2F structure from your safety data, RSI and prior DSUR, building the tables from source and citing every figure, so the safety team can focus on sections 18 to 20. Sign-off stays with the sponsor's safety physician.
FAQ
When is the DSUR due? No later than 60 calendar days after the data lock point, which is the last day of the annual period starting on the DIBD.
Does the DSUR replace the US IND annual report? E2F states that US and EU regulators consider the DSUR can take the place of the US IND Annual Report and the EU Annual Safety Report. Check current regional requirements for any additional regional content.
What reference safety information should the DSUR use? The RSI in effect at the start of the reporting period, usually in the Investigator's Brochure. Changes during the period are described in section 4.
What if the drug is already marketed? A DSUR is still required while clinical development continues. E2F allows it to be synchronised with the PSUR's International Birth Date.