Introduction simplified ASR
According to EU regulation 536/2014 article 43 all clinical trials that lasts more than a year must submit an annual safety report (ASR). The reporting period for the first ASR starts with the approval date of the clinical trial and ends after one full year. The sponsor then has 60 days to prepare and submit the ASR in CTIS. The common standard for ASR is given by the ICH E2F guideline on development safety update report (DSUR).  
For non-commercial sponsors conducting a single clinical trial on IMPs with a MAH in any of the EU/EEA member states and where the SmPC is used as RSI submitting a simplified ASR based on the ICH-E2F may be appropriate. This template gives detailed instructions on what information is expected and what may be omitted in this setting. The simplified ASR should always be written in English. 
Non-commercial sponsors investigating an IMP without a MAH, conducting several trials on the same IMP, or not using the SmPC as RSI are expected to submit a full ASR as of ICH E2F. 
Any sponsor submitting a simplified ASR must still comply with the overall objective of the DSUR which is to present a comprehensive, thoughtful annual review and evaluation of pertinent safety information collected during the reporting period. The focus should be on new (or changed) safety findings that may influence the overall risk benefit of the clinical trial and the sponsors assessment of these findings. In addition, analysis may require or have had required risk mitigations which should be addressed in this simplified ASR too .

Simplified Development Safety Update Report
Title of study		
Investigational Medicinal Product(s) (active substance – brand name – ATC code)
		
 I confirm the IMP(s) is/are authorized and the SmPC is used as RSI.	
DSUR Number 		
Period covered		
Name Sponsor		
Address		
Date of the report		
Relevant study (EU CT number and internal number)		
Note:
-	This DSUR contains safety information about [add number] of active substances belonging to [add number] investigational medicinal product(s) (IMPs) from an investigator initiated clinical trial. The principal investigator has no access to information from other sponsors conducting trials with the same IMP’s.
-	This Development Safety Update Report contains confidential information
-	This report includes unblinded adverse event data, if applicable.	

Abbreviations

AxMP		Auxiliary Medicinal Product
CA		Competent Authority
DMC		Data Monitoring Committee 
DSUR		Development Safety Update Report
IMP		Investigational Medicinal Product
MedDRA 	Medical Dictionary for Regulatory Activities
RSI		Reference Safety Information
SAE		Serious Adverse Event
SAR		Serious Adverse Reaction
SmPC		Summary of Product Characteristics

Executive Summary

Table of Contents

Abbreviations
Executive Summary
1. Introduction
2. Worldwide marketing approval status
3. Actions taken in the reporting period for safety reasons
4. Changes to reference safety information
5. Inventory of clinical trials ongoing and completed during the reporting period
6. Estimated cumulative exposure
6.1. Cumulative subject exposure in the study(ies)
6.2. Patient exposure from marketing experience  Not applicable. The study drug is not marketed by the sponsor.
7. Data in line listings and summary tabulations
7.1. Reference information
7.2. Line listings of serious adverse reactions during the reporting period
7.3. Cumulative summary tabulations of serious adverse events
8. Significant findings from clinical trials during the reporting period
8.1. Completed clinical trials
8.2. Ongoing clinical trials
8.3. Long-term follow-up
8.4. Other therapeutic use of investigational drug
8.5. New safety data related to combination therapies
9. Safety findings from non-interventional studies
10. Other clinical trial/study safety information
11. Safety findings from marketing experience
12. Non-clinical data
13. Literature
14. Other DSURs
15. Lack of efficacy
16. Region-specific information 
17. Late-breaking information
18. Overall safety assessment
18.1. Evaluation of the risks
18.2. Benefit-risk considerations
19. Summary of important risks
20. Conclusions

1. Introduction 

DSUR number:      
Reporting period:      
< Describe shortly:
-	Active substance used as Investigational drug(s) – mode(s) of action, therapeutic class(es), dose(s), route(s) of administration, formulation(s)
-	A brief description of the indication(s) and population(s) being studied; 
-	A short summary of the scope of the clinical trial covered by the report 
-	A brief description and explanation of any information that has not been included in the DSUR (e.g., when written agreements with a partner do not provide for exchange of all safety data); 
-	The rationale for submission of multiple DSURs for the investigational drug, if applicable>
-	Indicate if information on reference IMP (comparator) or AxMP is included

2. Worldwide marketing approval status 
Not applicable.
3. Actions taken in the reporting period for safety reasons
<This section should include a description of significant actions related to safety that have been taken during the reporting period by the sponsor, regulators, data monitoring committees  (DMC) or ethics committees that had an impact on the conduct of a specific clinical trial.  The reason(s) for each action should be provided if known. Relevant updates to previous actions should also be summarised in this section (e.g., resumption of a clinical trial after suspension)> 
OR 

< When no actions were taken you can state the following>
We have taken no actions for safety reasons during the reporting period of this DSUR, and have received no requests that place limitations on our study. 
4. Changes to reference safety information
As reference safety information (RSI)  the Summary of Product Characteristics (SmPC) is used, which was in effect at the beginning of the reporting period. This version dated [add version date] is provided in Appendix 1. 
<This section should list any significant safety-related changes to the SmPC within the reporting period>
No changes to RSI were made during the reporting period of this DSUR.
<OR> 
The following changes were made to the RSI during the reporting period of this DSUR:
The new RSI version dated [add version date] is provided in Appendix 1.
5. Inventory of clinical trials ongoing and completed during the reporting period

< This section should provide a brief overview of the ongoing clinical trial , with detailed information presented in a table see example below>
Overview of the ongoing Study [Study Drug]
EU CT number 	Internal protocol number	Country/
Countries 	Study design (including randomisation ratio) 	Study population 	Start date 	Planned enrolment 	Subject 
exposure **	

**Based upon total number of patients recruited as of [date] and applied randomisation schemes	

6. Estimated cumulative exposure 
6.1. Cumulative subject exposure in the study(ies)
Treatment	Number of subjects	
Drug		
Comparator		
Placebo		

6.2. Patient exposure from marketing experience
 Not applicable. The study drug is not marketed by the sponsor.
7. Data in line listings and summary tabulations
7.1. Reference information
If available use the Medical Dictionary for Regulatory Activities (MedDRA) version [add version] for the coding of adverse events.  The SmPC dated [add date] served as reference document for determination of “expectedness” for all adverse events.

7.2. Line listings of serious adverse reactions during the reporting period
<This section should provide key information on all SARs (blinded and unblinded) reported from the sponsor’s clinical trials during the reporting period.>

Case ID/ 
Subject number*	Country 
Gender 
Age	Serious adverse drug reactions (SARs) 	Expected/unexpected	Date of onset**
Time to onset**	Outcome	Suspect Drug 	Daily dose 
Route 
Formulation 	Dates of treatment 
Treatment duration	 Comments	

*Study/Center/subject
**Primary SAR only
	
7.3. Cumulative summary tabulations of serious adverse events 
<This section should provide a cumulative summary tabulation of SAEs reported in the sponsor’s clinical trial, from the trial authorization to the data lock point of the current DSUR.> 
The table below presents the number of SAEs that have been reported during this clinical trial organized by system organ class. 
System organ Class		
Preferred term	Study drug	Placebo	Active comparator	Code unbroken	
Cardiac disorders
-	Atrial fibrillation
-	Atrial flutter	3
2
1	1
0
1	2
2
0	0
0
0	

					

8. Significant findings from clinical trials during the reporting period
8.1. Completed clinical trials
Not applicable.
8.2. Ongoing clinical trials
<Add significant findings from the ongoing study. This DSUR contains safety information from this investigator initiated clinical trial and it is ongoing. If applicable, add safety information from other relevant ongoing trials. Please fill in this section.>
8.3. Long-term follow-up
Not applicable.  
8.4. Other therapeutic use of investigational drug
Not applicable. 
8.5. New safety data related to combination therapies 
Not applicable.
9. Safety findings from non-interventional studies
Not applicable.
10. Other clinical trial/study safety information
If applicable.
11. Safety findings from marketing experience
If applicable.
12. Non-clinical data
If applicable.
13. Literature 
A full review of the scientific, peer-reviewed literature was conducted during for the duration of the current reporting period. In the searches performed [no] new relevant safety findings for [name study drug] were reported in published scientific literature or unpublished manuscripts.
14. Other DSURs 
If applicable. 
15. Lack of efficacy
<Describe lack of efficacy for IMP(s) intended to treat serious or life-threatening illnesses, that could reflect a significant risk to clinical trial subjects or ‘Not applicable’.>
16. Region-specific information 
<The information in this section can be used to comply with national or regional requirements and can be provided in appendices to the DSUR> 
17. Late-breaking information 
<This section should summarize information on potentially important safety findings that arise after the data lock point but while the DSUR is in preparation, if applicable.>
18. Overall safety assessment
<This section should be a concise, integrated evaluation of all new relevant clinical, non-clinical, and epidemiologic information obtained during the reporting period relative to previous knowledge of the investigational drug. It  should provide an interpretation of the information and its implications for the clinical trial population.> 
Based on the information described in this DSUR we do not have new safety concerns.
<OR> 
The main changes to the overall safety assessment during this reporting period are greater concern regarding [add newly identified/potential risks].
18.1. Evaluation of the risks
<This section should evaluate the newly identified risks, if applicable. >

18.2. Benefit-risk considerations
<This section should provide a succinct statement on the perceived balance between risks that have been identified from cumulative safety data and anticipated efficacy/benefits and should note whether there have been any changes in this balance since the previous DSUR. This section is not intended to be a full benefit-risk assessment of the investigational drug. >
19. Summary of important risks 
<This section should provide a concise, cumulative, issue-by-issue list of important identified and potential risks. It should focus on the risk specific to the study.>
20. Conclusions 
We conclude that the information obtained in this reporting period justifies continuation of this investigator initiated study without any modification.

<OR>
During this DSUR reporting period some new safety concerns are addressed. The following actions [have been/will be taken] to address emerging safety issues during this investigator initiated trial.