Development Safety Update Report 				
{Insert Report No. & Year}					EudraCT Number: XXXX-XXX-XXX
Welcome to the DSUR template.

The red text in this document is instructional and should be removed prior to the submission of your report.

Note: Please refer to the following link for the ICH E2F Guidance document which contains detailed information and description of the ‘contents’:
http://www.ich.org/products/guidelines/efficacy/efficacy-single/article/development-safety-update-report.html 

Note: The Sponsor will make the submission to the MHRA.
For more information on submission to the MHRA please refer to:
http://www.mhra.gov.uk/Howweregulate/Medicines/Licensingofmedicines/Clinicaltrials/Safetyreporting-SUSARsandASRs/index.htm

Note: The Sponsor delegates the REC submission of the DSUR to the Chief Investigator and their team.
For information on submission to NRES please refer to:
http://www.nres.npsa.nhs.uk/

DEVELOPMENT SAFETY UPDATE REPORT

Report Number:	I.e.: 1, 2, 3… etc	
Trial Title:		
Period Covered:		
IMP:		
Sponsor:		
Address:		
Date:		

Signature of CI:
		
Date:

Signature of Sponsor Representative:
		
Date:

This Development Safety Update Report contains CONFIDENTIAL information.
The DSUR also contains UNBLINDED information {delete if not applicable}
In the case of double blinded Trials the CI and team must be kept blinded and therefore some information may not be available.

EXECUTIVE SUMMARY

To be completed by the CI/PI. Provides a concise summary of important information and should include the following information (can be used as a standalone document):
•	Report Number and reporting period
•	IMP(s) – modes of action, indication, therapeutic areas, dose, route and formulation.
•	Cumulative exposure of IMP to trial subjects
•	Marketing Approval (If available)
•	Summary of overall safety evaluation (based on section 18)
•	Summary of important Risks(based on section 19)
•	Actions taken for safety reasons including significant changes to IB
•	Conclusions

TABLE OF CONTENTS
1.	Introduction
2.	Worldwide Marketing Approval Status
3.	Actions Taken in the Reporting Period for Safety Reasons
4.	Changes to e Reference Safety Information
5.	Inventory of Clinical Trials Ongoing and Completed during the Reporting Period
6.	Estimated Cumulative Exposure
6.2.	Cumulative Subject Exposure in Development Programme
6.3.	Patient Exposure from Marketing Experience
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 Finding 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

Appendices

1. INTRODUCTION
To be completed by the CI/PI.
Development International Birth Date (DIBD):	Either CTA approval date or date given by the Sponsor	
Reporting Period:		
DSUR Number:		
IMP:		
Mode of Action:		
Indication:	Brief description of the Indication/ patient population. State is used out of indication.	
Dosage Form, Route of Administration:	Inc. formulation	
Supplier:	Give Details of supplier of IMP(s) or state Hospital Stock	
IMP Previously Authorised:		
Scope:	Short summary of all CTIMPs trials covered in the report.
 If covered as separate DSURs provide rationale:
Due to the nature of investigator led academic, non commercial trials it is impractical to attempt to include more than one trial in this report.	

2. Worldwide Marketing Approval Status
Use:
This section of the Development Safety Update Report is not applicable as all the trials sponsored by Papworth Hospital NHS Trust are non-commercial academic trials.
Or:
To our knowledge…  (If the information is readily available it should be possible to find it on the IMP boxes)

3. Actions Taken in the Reporting Period for Safety Reasons
To be completed by the CI/PI. Please provide information on urgent safety measures that may have been taken in the reporting period. Or state “No actions necessary for safety reasons in this reporting period”.
Urgent Safety Measure:	What was the urgent safety measure?
	
Rationale:	Why was it necessary?
	
Further Action Taken:	Was any further action required to finally resolve the issue? (i.e.: Changes to the PIS or Protocol etc).	

Urgent Safety Measure:		
Rationale:		
Further Action Taken:		

Urgent Safety Measure:		
Rationale:		
Further Action Taken:		

4. Changes to Reference Safety Information
To be completed by the CI/PI. Please detail changes to the Summary of Product Characteristics/ Investigator Brochure that may have occurred during the reporting period.
Revision of SmPC /IB:	Record change here inc. version numbers 	
Date of Revision:	Date that the new SmPC or IB was issued for use	
Impact on Trial:	If any alterations to the protocol/ Trial conduct were necessary as a result of the updated information on the SmPC or IB please reference it here.	

Revision of SmPC /IB:		
Date of Revision:		
Impact on Trial:		

Revision of SmPC /IB:		
Date of Revision:		
Impact on Trial:		

5. Inventory of Clinical Trials Ongoing and Completed during the Reporting Period
This information will be completed for those trials Sponsored by CUH or CUH in partnership with the University of Cambridge by the Sponsor representative.
Clinical Trial Short Term	Clinical Trial Full Title	EudraCT No.	Phase	IMP regimen & Comparators (inc. dose)	Study Population	Study design	Trial Start Date	Ongoing/ Completed	Trial Stop Date	

										

6. Estimated Cumulative Exposure
To be completed by the CI/PI. Provide if possible (i.e.: If demographic data is collected in the CRF) Please present demographic data by treatment group for age, sex, ethnicity etc.
Or use text:
Study remains blinded and the numbers of patients exposed is based on the randomisation scheme. Given that the trial is blinded we cannot provide demographic data by treatment group, for the study as a whole:  XX% are male, XX% are aged Y, XX% are caucasian etc
6.1 Cumulative Subject Exposure in Development Programme
Estimated Cumulative subject Exposure by age and gender:
Example table
	Number of Subjects	
Age (Yr)	Male	Female	Total	
40 – 50				
51 – 60				
61 – 70				
71 – 80				
>80				
Total				

Estimated Cumulative subject Exposure by ethnic origin:
Example table
Ethnic Origin	Number of Subjects	
Caucasian		
Black		
Oriental		
Other		
Total		

6.2 Patient Exposure from Marketing Experience
This section is not applicable for the trials sponsored by Papworth Hospital NHS Trust.

7. Data in Line Listings and Summary Tabulations
7.1 Reference Information
To be completed by the CI/PI. State how events are being coded and assessed – eg: MedDRA coding, CTCAE coding etc.
7.2 Line Listings of Serious Adverse Reactions during the Reporting Period
Please refer to the Serious Adverse Reactions Line Listing at the end of this Document (Appendix XX)
7.3 Cumulative Summary Tabulations of Serious Adverse Events
Please refer to the Serious Adverse Events Cumulative Summary table at the end of this Document (Appendix XX)

8. Significant Findings from Clinical Trials during the Reporting Period
The sponsor will provide a summary of ongoing and completed trials with the same IMP if necessary, if any of the sections below are not applicable please state: “This section is not applicable as no relevant information has been received during the reporting period.”
8.1 Completed Clinical Trials
Briefly summarise clinically important emerging efficacy and safety findings from clinical trials completed in the reporting period. It should include information that supports or refutes previously identified safety issues, as well as evidence of new safety signals.
8.2 Ongoing Clinical Trials
Briefly summarise clinically important emerging efficacy and safety findings from clinical trials ongoing in the reporting period. It should include information that supports or refutes previously identified safety issues, as well as evidence of new safety signals.
8.3 Long-Term Follow Up
Briefly summarise clinically important emerging efficacy and safety findings from clinical trials ongoing in the reporting period. It should include information that supports or refutes previously identified safety issues, as well as evidence of new safety signals.
8.4 Other Therapeutic Use of Investigational Drug
This section is not applicable for the trials sponsored by Papworth Hospital NHS Trust.
8.5 New Safety Data Related to Combination Therapies
This section is not applicable for the trials sponsored by Papworth Hospital NHS Trust.

9. Safety Finding from Non-interventional Studies
This section is not applicable for the trials sponsored by Papworth Hospital NHS Trust.
The Sponsor will complete this section ONLY if the sponsor becomes aware of any epidemiological studies using the IMP.

10. Other Clinical Trial/Study Safety Information
This section is not applicable for the trials sponsored by Papworth Hospital NHS Trust.

11. Safety Findings from Marketing Experience
This section is not applicable for the trials sponsored by Papworth Hospital NHS Trust.

12. Non-clinical Data
This section is not applicable for the trials sponsored by Papworth Hospital NHS Trust.
However if new information is made available to the Trial team from the manufacturer or supplier detailing recent animal study information please include the information in this section and remove the N/A statement.

13. Literature
IMPORTANT
To be completed by the CI/PI. Please perform a literature search relevant to the disease group and IMP using the period reporting dates. 
Write a concise summary of new and significant safety findings, either published in the scientific literature or available as unpublished manuscripts, relevant to the investigational drug that you become aware of during the reporting period. This section should include information from non-clinical and clinical studies and, if relevant and applicable, information on drugs of the same class. It should also summarise significant new safety information presented at a scientific meeting and published as an abstract.
Add the relevant literature into this table and provide a precise reference. Please attach abstracts to the report as appendix 5.
File a print out of the literature search in the TMF for future reference.
Abstracts for all literary references listed here can be found in appendix 5 of this report.
Title & Journal Reference		
Summary	

	

Title & Journal Reference		
Summary 	

	

Title & Journal Reference		
Summary	

	

14. Other DSURs
The Sponsor will complete this section if known for DSURs submitted for other trials of the same IMP in the reporting period.
Trial 	Date DSUR due	DSUR Reference No.	Date Submitted	

				

15. Lack of Efficacy
To be completed by the CI/PI. Please provide details if applicable, other wise state “Not applicable in this instance”.

16. Region-Specific Information
This section is not applicable for the trials sponsored by Papworth Hospital NHS Trust.

17. Late Breaking Information
To be completed by the CI/PI. Please give details on any significant safety information that may have arisen after the data lock for this report.
Or:
“There has been no significant safety information made available between the data lock for this report and the time of submission.”

18. Overall Safety Assessment
To be completed by the CI/PI, detail any changed safety assessment since the last DSUR (or ASR). Specify the major changes in the overall safety assessment during the reporting period, but take into account any late breaking news.
18.1 Evaluation of the Risks
Evaluation of risks to trial subjects. 
Take into account information regarding Urgent Safety Measures, tests performed as part of the trial, expected adverse events (monitoring in place to capture and resolve). Also data integrity with regards this specific trial, literature searches, changes to safety reference documents and other trial information supplied to you.
 18.2 Benefit-risk Considerations
Present a new risk-benefit assessment.
Take into account information from this specific trial, literature searches, changes to safety reference documents and other trial information available to you.

19. Summary of Important risks
To be completed by the CI/PI. List all specific risks (known side effects) and give details on percentage of patient experiencing these events and how this is being monitored.
I.e.: Hypotension: Acute Hypertension was observed in ….

20. Conclusions

To be completed by the CI/PI. One or two sentences as a conclusion (i.e.: Risks remain the same as previously described/ higher/ lower etc).

Appendices to the DSUR
Documents	Tick or N/A	
1.	 Investigator Brochure or SmPC: if applicable
	(Version and Date)  		
2. 	Cumulative Table of Important Regulatory Advice		
3. 	Line Listing of Serious Adverse Reactions (SARs): (Table)		
4. 	Cumulative Summary Tabulations of Serious Adverse Events 	(SAEs): (Tables)		
5. 	Scientific Abstracts: (Attached)		

Appendix 2: Cumulative Table of Important Regulatory Advice
To be completed by the CI/PI. This could include any serious breaches that may have been reported and any guidance received on implementation of resulting CA/PA, any direct queries to the MHRA and their response, requests for alterations to amendment requests in order to gain further approval.
Date	Query	Regulatory Response	Application to the trial	

				

Or: mark the section as not applicable on the appendix table if there has been no significant regulatory advice applied to the trial, and delete this page from the report.

Appendix 3: Line Listing of Serious Adverse Reactions (SARs): (Table)
To be completed by the CI/PI. For Term please use the MedDRA ‘Preferred Term’ if using MedDRA to code
Example row completed below:
EudraCT no.	Subject ID.	SAE No.	Country of Origin	Age & Sex	Treatment Group	Dose,  Interval & Route of admin.	Date of Onset	Treatment for Event	Term	Outcome	Comments	
XXXX-XXX-XXX	001/001	001	UK	69 male	Arm B	100mg IMP/ daily/ oral 	01/01/2011	Loperamide 2mg	Diarrhoea	Resolved without Sequelae	Event did not require withdrawal of IMP	

Appendix 4: Cumulative Summary Tabulations of Serious Adverse Events (SAEs): (Tables)
To be completed by the CI/PI. Example table
System Organ Class				
Preffered Term	Arm A	Arm B	Control Arm	
Cardiac Disorders				
Atrial Fibrillation				
Vascular Disorders				
Right lower Extremity Ischemia (requiring PTA, STENT, Amputation)				
Hypotension				
Investigations				
Elevated Alanine Transaminase				
Eye Disorders				
Decreased visual acuity