Download RSI for Reporting Period

<Identifier e.g. Trial Name>
Development Safety Update Report (DSUR)
Report date <dd-mon-yyyy>
Report Number:
<insert number; sequential,
starting at 1>
For the first DSUR, insert <This is the first DSUR for
the use of <insert IMP/combination> in the <insert
name> trial.
If this is the last DSUR insert <This is the final
DSUR for the use of <insert IMP/combination> in
the <insert name> trial <in the UK>.
IMP(s):
<list trial IMPs (as per CTA)>
Reporting Period:
e.g. 19-May-2011 to 18-May-2012
Report Date:
<insert date of finalised report>
Sponsor:
<enter Sponsor name and address>
Sponsor Ref Number:
<insert number >
EudraCT Number:
<insert number>
REC Reference Number:
<insert number>
Name:
Trial Role:
<Chief Investigator or Clinical Coordinator>
Signature:
Date:
DD / MON / YYYY
This report was prepared by <add name of CI and Co-ordinator> on behalf of the Sponsor and
contains confidential information. For blinded trials also include: <This report includes unblinded
Adverse Event data>
Any correspondence relating to this DSUR should be addressed to:
<<Add trial Co-ordinator’s contact details>>
DSUR Template_V0.2_140617
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<Trial acronym>
DSUR date: dd-mon-yyyy
Executive Summary
This section should provide a concise summary of the important information contained in the report.
Together with the title page, it can serve as a “stand-alone” document suitable for submission to
stakeholders.
This section should be written after all the sections of this report have been completed. Where
possible, keep to 1-2 sides of A4:
IMP(s):
<List trial IMPs (as per CTA)> Include details of mode of action and
therapeutic class. This can be found in the SPC e.g.
Depo-Medrone 40mg/ml sterile, aqueous suspension
Mode of action: a synthetic glucocorticoid. Binds to the glucocorticoid
receptor which in turn up-regulates the expression of anti-inflammatory
proteins
Therapeutic class: anti-inflamatory
<Where an IMP is supplied by the Sponsor, include statement of who
is providing IMP e.g. <supplied by Novartis>>
Treatment Arms:
<insert different treatment arm(s). Include dose, route and
formulation.>
Indication and Population:
<insert indication and population e.g. mild to moderate Carpal Tunnel
Syndrome in adults aged over 18 years>
Estimated Cumulative
Exposure:
<insert details from section 6.1>
Marketing Approval
<insert details from section 2>
Summary and Conclusions:
Include the following.
• A summary of the overall safety assessment (based on Section 18 of the DSUR);
• A summary of the important risks (based on Section 19 of the DSUR);
• Actions taken for safety reasons, including significant changes to RSI;
• Conclusions
DSUR Template_V0.2_140617
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<Trial acronym>
DSUR date: dd-mon-yyyy
Table of contents
All headers must remain as listed. Update page numbers only after completion of report.
Executive Summary .......................................................................................................................... 2
Depo-Medrone 40mg/ml sterile, aqueous suspension .................................................................... 2
Summary and Conclusions: ............................................................................................................. 2
Table of contents ............................................................................................................................... 3
Appendices to the DSUR ................................................................................................................. 5
1. Introduction .................................................................................................................................... 6
Depo-Medrone 40mg/ml sterile, aqueous suspension .................................................................... 6
2. Worldwide Marketing Approval Status ........................................................................................ 7
3. Actions Taken in the Reporting Period for Safety Reasons ..................................................... 7
During Reporting Period .................................................................................................................. 7
Cumulative Listing can be deleted if this is the first DSUR .............................................................. 7
4. Changes to Reference Safety Information (RSI) ........................................................................ 7
RSI for Reporting Period: ................................................................................................................. 8
Changes to the RSI during the reporting period: ............................................................................. 8
Where applicable, include: <RSI for the next reporting period:> ..................................................... 8
5. Inventory of Clinical Trials Ongoing and Completed during the Reporting Period ............... 9
6. Estimated Cumulative Exposure ............................................................................................... 10
6.1 Cumulative Subject Exposure in the Development Programme ............................................. 10
6.2 Patient Exposure from Marketing Experience ......................................................................... 10
7. Data in Line Listings and Summary Tabulations ..................................................................... 10
7.1 Reference Information ............................................................................................................. 10
RSI used to assess expectedness ................................................................................................. 10
7.2 Line Listings of Serious Adverse Reactions during the Reporting Period ............................... 10
7.3 Cumulative Summary Tabulations of Serious Adverse Events ............................................... 10
8. Significant Findings from Clinical Trials during the Reporting Period ................................. 11
8.1 Completed Clinical Trials ......................................................................................................... 11
8.2 Ongoing Clinical Trials ............................................................................................................. 11
8.3 Long-term Follow-up ................................................................................................................ 11
8.4 Other Therapeutic Use of Investigational Drug ....................................................................... 11
8.5 New Safety Data Related to Combination Therapies .............................................................. 12
9. Safety Findings from Non-interventional Studies .................................................................... 12
10. Other Clinical Trial/Study Safety Information ......................................................................... 12
11. Safety Findings from Marketing Experience .......................................................................... 12
12. Non-clinical Data ....................................................................................................................... 12
13. Literature .................................................................................................................................... 13
14. Other DSURs .............................................................................................................................. 13
15. Lack of Efficacy ......................................................................................................................... 13
16. Region-Specific Information .................................................................................................... 13
Cumulative summary tabulation of Serious Adverse Reactions .................................................... 13
17. Late-Breaking Information ........................................................................................................ 13
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<Trial acronym>
DSUR date: dd-mon-yyyy
18. Overall Safety Assessment ...................................................................................................... 14
18.1. Evaluation of the Risks ......................................................................................................... 14
18.2 Benefit-risk Considerations .................................................................................................... 15
19. Summary of Important Risks ................................................................................................... 15
19.1 Previously Identified Risks ..................................................................................................... 16
20. Conclusions ............................................................................................................................... 16
Appendices to the DSUR ................................................................................................................ 18
DSUR Template_V0.2_140617
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<Trial acronym>
DSUR date: dd-mon-yyyy
Appendices to the DSUR
The order and nomenclature of the appendices are as per the DSUR guideline. Some appendices are
contained in the main body of the report.
Appendix 1: Current and any revisions to the Reference Safety Information (refer to section 4)
Appendix 2: Cumulative Table of Important Regulatory Advice (refer to Section 3)
Appendix 3: Status of Ongoing and Completed Clinical Trials (refer to Section 5)
Appendix 4: Cumulative Summary Tabulations (refer to Section 6)
Appendix 5: A line listing of all Serious Adverse Reactions
Appendix 6: A cumulative tabulation of all Serious Adverse Events
Appendix 7: Scientific Abstracts (if relevant)
Appendix 8: A cumulative tabulation of Serious Adverse Reactions
DSUR Template_V0.2_140617
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<Trial acronym>
DSUR date: dd-mon-yyyy
1. Introduction
Copy sections from Title Page and Executive Summary where applicable
Refer to section 3.1 of ICH E2F
Report Number:
<insert number; sequential,
starting at 1>
For the first DSUR <This is the first DSUR for the
use of <insert IMP/combination> in the <insert
name> trial.>
If this is the last DSUR insert <This is the final
DSUR for the use of <insert IMP/combination> in
the <insert name> trial <in the UK>.
Reporting Period:
e.g. 19-May-2011 to 18-May-2012
Report Date:
<insert date of finalised report>
CTA Approval Date:
<CTA date: insert date of competent authority approval. If the trial is
conducted in multiple countries this should be the first approval received>
IMP(s):
<list trial IMPs (as per CTA)> Include details of mode of action and
therapeutic class e.g.
Depo-Medrone 40mg/ml sterile, aqueous suspension
Mode of action:
Therapeutic class: anti-inflamatory
<Where an IMP is supplied by the Sponsor, include statement of who is
providing IMP e.g. <supplied by Novartis> or <sourced locally via Trust
Pharmacy>>
Treatment Arms:
<insert different treatment arm(s). Include dose, route and formulation.>
Indication and
Population:
<insert indication and population e.g. mild to moderate Carpal Tunnel
Syndrome in adults aged over 18 years>
Scope:
This DSUR covers the <insert name of trial> trial
The following may apply where other DSURs have been referenced, e.g.
when information has been obtained from the Sponsor or in the rare
circumstance that there are multiple DSURs per trial (international studies):
<The above trial forms the scope of this DSUR and other relevant DSURs
are referenced in section 14.>
In most cases the following statement may apply unless data is contractually provided by a third party.
The University of Keele does not hold the Manufacturing or Marketing Authorisations for the IMP(s)
listed in this DSUR and therefore the <insert trial team> does not have access to some of the
requested data. Where information is not available the response ‘Data not available’ or ‘Not
applicable’ is provided.
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<Trial acronym>
DSUR date: dd-mon-yyyy
2. Worldwide Marketing Approval Status
Refer to section 3.2 of ICH E2F
This section should provide a brief narrative overview including: date of first approval, indication(s),
approved dose(s), and where approved, if applicable.
<IMP> has a Marketing Authorisation, but the University of Keele are not the MA holder and therefore
the <insert trials team> are not aware of the worldwide approval status
3. Actions Taken in the Reporting Period for Safety Reasons
Refer to section 3.3 of ICH E2F
This section should include a description of significant actions related to safety that have been taken
during the reporting period.
For example: Refusal to authorise a clinical trial for ethical or safety reasons; Partial or complete
clinical trial suspension or early termination of an ongoing clinical trial; Recall of investigational drug or
comparator; Failure to obtain marketing approval for a tested indication including voluntary withdrawal
of a marketing application; Protocol modifications due to safety or efficacy concerns (e.g., dosage
changes, changes in study inclusion/exclusion criteria, intensification of subject monitoring, limitation
in trial duration); Restrictions in study population or indications; Changes to the informed consent
document relating to safety issues; Formulation changes; Addition by regulators of a special safetyrelated reporting requirement; Plans for new studies to address safety issues.
For marketed products (if known): Failure to obtain a marketing approval renewal; Withdrawal or
suspension of a marketing approval; New post-marketing study requirement(s) imposed by regulators.
During Reporting Period
Insert <No actions taken.> or <The following actions were taken for safety reasons.> and insert table
below.
Action
Reason (if known)
<include summary and by which
body (e.g. REC, DMC)>or<Not
applicable>
Update
<if resolved, say so>
List all issues ongoing/resolved from previous reports in the table below. Once an action has been
taken during the course of the trial it must be included in the Cumulative Listing table.
Cumulative Listing can be deleted if this is the first DSUR
Action
Reason (if known)
<include summary and by which
body (e.g. REC, DMC> or<Not
applicable>
Update
<if resolved, say so>
4. Changes to Reference Safety Information (RSI)
Refer to section 3.4 of ICH E2F
This section should list any significant safety-related changes to the RSI within the reporting period.
Such changes might include information relating to exclusion criteria, contraindications, warnings,
precautions, SARs, AEs of special interest, interactions, and any important findings from non-clinical
studies (e.g., carcinogenicity studies). Specific information relevant to these changes should be
provided in the appropriate sections of the DSUR.
Attach current and any revisions to the RSI as an appendix.
DSUR Template_V0.2_140617
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<Trial acronym>
DSUR date: dd-mon-yyyy
RSI for Reporting Period:
Note: the RSI in effect at the start of the reporting period serves throughout the entire reporting period
<insert document ((sections of) SmPC) name; version number and date>
<add lines if more than one document>
Changes to the RSI during the reporting period:
At present, the guidelines indicate that no changes to the RSI should be made during the reporting
period. For this section therefore insert <No changes to the RSI were made during the reporting
period.>.If changes were made include <The following significant changes were made to the
<(sections of) IB/SmPCs> during the reporting period> and insert table.
Where applicable, include: <RSI for the next reporting period:>
The RSI needs updating should the safety information as embedded in the IB or SmPC have changed
over the last year in such a way that the expectedness of adverse reaction has changed as well. In
this case a substantial amendment would need to be submitted at the time of submitting the DSUR.
This section is to reflect the need of a change in the RSI. Include the following:
<The RSI has now been revised and the following document(s) will form the RSI for the next reporting
period (on approval from the competent authority)>
<insert document (IB/SmPC) name; version number and date>
<add lines if more than one document>
<add <IMP> IB supplied by <company>> where applicable
Delete this section if the RSI is to remain the same
DSUR Template_V0.2_140617
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<Trial acronym>
DSUR date: dd-mon-yyyy
5. Inventory of Clinical Trials Ongoing and Completed during the Reporting
Period
Refer to section 3.5 of ICH E2F
List for the trial included in this DSUR only.
EudraCT
No.
Phase
Phase IV
Status
<Ongoing or Complete>
Country
UK
Trial title
Trial
design
Regimen
and dose
<Abbreviated title>
<e.g. randomised, blinded, uncontrolled>
<list regimen and dose IMPs>
Trial
population
<Age, sex, indication>
Date of
clinical
start (First
Visit First
Patient)
First visit first patient
Planned
enrolment
<Total number of patients needed>
Subject
exposure
(No.
recruited
patients)
Number patients recruited
DSUR Template_V0.2_140617
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<Trial acronym>
DSUR date: dd-mon-yyyy
6. Estimated Cumulative Exposure
6.1 Cumulative Subject Exposure in the Development Programme
Refer to section 3.6.1 of ICH E2F
For the trial included in this DSUR only
Cumulative exposure for the <insert name of trial> is summarised below:
Treatment
Number of subjects <registered/randomised> to treatment arm
<insert treatment arm 1>
<no. patients registered/randomised>
<insert treatment arm 2>
<no. patients registered/randomised>
Total
<no. patients registered/randomised>to trial
6.2 Patient Exposure from Marketing Experience
Refer to section 3.6.2 of ICH E2F
The following statements may apply:
For a licensed IMP/Combination of IMPs: <IMP> has a Marketing Authorisation, but the University of
Keele are not the MA holder and therefore the <insert trials team> are not aware of the worldwide
approval status
7. Data in Line Listings and Summary Tabulations
7.1 Reference Information
Refer to section 3.7.1 of ICH E2F
Coding document used to record Adverse Events
<e.g. National Cancer Institute Common
Terminology Criteria for Adverse Events
(CTCAE) version 4.0>
RSI used to assess expectedness
Note: the RSI in effect at the start of the reporting period serves throughout the entire reporting period
Effective from:
Effective to:
<insert document (IB/SmPC) name; version
number and date>
<add lines if more than one document>
7.2 Line Listings of Serious Adverse Reactions during the Reporting Period
Refer to section 3.7.2 of ICH E2F
See Appendix 5.
Causality and expectedness were assessed as defined in the trial protocol effective at the time of the
event (see <insert reference to relevant section and version of the protocol>).
List any SARs that are excluded from this table in the DSUR and where necessary reference where
this data is summarised. SARs that are excluded from this table in the DSUR (refer to protocol)
7.3 Cumulative Summary Tabulations of Serious Adverse Events
Refer to section 3.7.3 of ICH E2F
See Appendix 6.
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<Trial acronym>
DSUR date: dd-mon-yyyy
Causality and expectedness were assessed as defined in the trial protocol effective at the time of the
event (see <insert reference to relevant version and section of protocol>).
List any SAEs that are excluded from this table in the DSUR (e.g. disease related death) and where
necessary reference where this data is summarised. For example:
Please Note: The following events are excluded from the line listing of SAEs included in Appendix 5:


Disease related death as this data forms the primary end point for the trial. Appendix 9 lists
patients who have died during the reporting period
<insert other and explain why excluded>
8. Significant Findings from Clinical Trials during the Reporting Period
Refer to section 3.8 of ICH E2F
8.1 Completed Clinical Trials
Refer to section 3.8.1 of ICH E2F
The following statement may apply:
<Not applicable; no relevant completed trials are included within this DSUR>.
8.2 Ongoing Clinical Trials
Refer to section 3.8.2 of ICH E2F
If the Sponsor is aware of clinically important information that has arisen from ongoing clinical trials
(e.g., learned through interim safety analyses or as a result of unblinding of subjects with adverse
events), this section should briefly summarise the issue(s). It could include information that supports
or refutes previously identified safety issues, as well as evidence of new safety signals.
This information should be based on the one trial for which the DSUR is prepared. This section needs
to be brief and can include recommendations from the DMC. If no clinically important information has
arisen from the trial, include the following statement:
<No clinically important information has arisen from the trial during this reporting period>
8.3 Long-term Follow-up
Refer to section 3.8.3 of ICH E2F
Where applicable, this section should provide information from long-term follow-up of subjects from
clinical trials of investigational drugs, particularly advanced therapy products (e.g., gene therapy, cell
therapy products and tissue engineered products).
This information should be based on the long term follow-up as defined in the protocol for the trial for
which the DSUR is prepared. This section needs to be brief and can include recommendations from
the DMC.
If no long-term follow up for the trial <Not applicable as there is no long term follow up in this trial>
Or
<At present, patients are not subject to long-term follow-up>
Or
<Patients will be followed for <x> years however this trial is still open to recruitment and there are no
results available from long-term follow-up>
8.4 Other Therapeutic Use of Investigational Drug
Refer to section 3.8.4 of ICH E2F
This section of the DSUR should include clinically important safety information from other
programmes conducted by the Sponsor that follow a specific protocol (e.g., expanded access
programmes, compassionate use programmes).
The following statement may apply:
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<Trial acronym>
DSUR date: dd-mon-yyyy
<Not applicable; this DSUR has been prepared for the trial described in the scope (section 1).>
8.5 New Safety Data Related to Combination Therapies
Refer to section 3.8.5 of ICH E2F
The following statement may apply:
<This DSUR has been prepared for the trial described in the scope (section 1); other relevant DSURs
are referenced to in section 14.>
9. Safety Findings from Non-interventional Studies
Refer to section 3.9 of ICH E2F
This section should summarise relevant safety information from non-interventional studies that
became available to the Sponsor during the reporting period (e.g., observational studies,
epidemiological studies, registries and active surveillance programmes).
The following statement may apply:
<No information from non-interventional studies has become available to the <insert trial team> during
this reporting period.
10. Other Clinical Trial/Study Safety Information
Refer to section 3.10 of ICH E2F
This section should summarise relevant safety information from any other clinical trial/study sources
that became available to the Sponsor during the reporting period (e.g., results from pooled analyses
or meta-analyses of randomised clinical trials, safety information provided by co-development
partner).
It is not expected that additional information is actively sought from external sources. But, information
available to the TMG should be summarised.
<No information from clinical trials/studies has become available to the trials team during this
reporting period.>
11. Safety Findings from Marketing Experience
Refer to section 3.11 of ICH E2F
If the investigational drug has been approved for marketing in any country, this section should include
a concise summary of key safety findings that have arisen from marketing experience and that
became available to the Sponsor during the reporting period, particularly if the findings resulted in
changes to the product labelling, Investigator’s Brochure, informed consent document or amendments
to the product’s risk management plan. This includes not only safety findings relating to approved use
but also off-label use, administration to special populations (e.g., pregnant women), medication errors,
overdose and abuse.
It is not expected that additional information is actively sought from external sources. But, information
available to the TMG should be summarised.
The following statement(s) may apply:
<No information regarding safety findings from marketing experience has been brought to the
attention of trial team during this reporting period.>
12. Non-clinical Data
Refer to section 3.12 of ICH E2F
This section should summarise major safety findings from non-clinical in vivo and in vitro studies (e.g.,
carcinogenicity, reproduction, or immunotoxicity studies) ongoing or completed during the reporting
period. Implications of these findings should be discussed in the Overall Safety Assessment.
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<Trial acronym>
DSUR date: dd-mon-yyyy
It is not expected that additional information is actively sought from external sources. But, information
available to the TMG should be summarised.
The following statement may apply.
<No information from non-clinical studies has become available to the trial team during this reporting
period.>
13. Literature
Refer to section 3.13 of ICH E2F
This section should summarise new and significant safety findings, either published in the scientific
literature or available as unpublished manuscripts, relevant to the investigational drug that the
Sponsor became 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; the Sponsor should provide a copy of the abstract, if possible.
It is not expected that additional information is actively sought from external sources. But, information
available to the TMG should be summarised. This could include information reported through TSC
and DMC reports if relevant.
Attach abstracts as Appendix 7 (if applicable)
OR
<No new literature has become available to the trial team during this reporting period.>
14. Other DSURs
Refer to section 3.14 of ICH E2F
When available, the Sponsor should summarise significant findings from DSURs provided by other
Sponsors conducting clinical trials with the same investigational drug during the reporting period.
An attempt should also be made to obtain a summary of any other DSUR which have been prepared
for a trial a) with both the same Sponsor and which utilises the same IMP(s).
It is not expected that additional information is actively sought from external sources. But, information
available to the TMG should be summarised.
The following statement may be applicable: <<IMP> is manufactured/ marketed by <insert MA
holder> and the <insert the trials team> do not have access to the any other DSUR.
15. Lack of Efficacy
Refer to section 3.15 of ICH E2F
Data indicating lack of efficacy, or lack of efficacy relative to established therapy(ies), for
investigational drugs intended to treat serious or life-threatening illnesses could reflect a significant
risk to clinical trial subjects and should be summarised in this section.
Insert a summary or <Not applicable>.
16. Region-Specific Information
Refer to section 3.16 of ICH E2F
The following regional specific information is required for reports produced for submission to
competent authorities in the EU only. Additional information may be required if the report is submitted
to authorities within other ICH regions.
Cumulative summary tabulation of Serious Adverse Reactions
See Appendix 8 If no SARs have been reported, include <not applicable>
17. Late-Breaking Information
Refer to section 3.17 of ICH E2F
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<Trial acronym>
DSUR date: dd-mon-yyyy
This section should summarise information on potentially important safety findings that arise after the
data lock point but while the DSUR is in preparation. Examples include clinically significant new case
reports, important follow-up data, clinically relevant toxicological findings and any action that the
Sponsor, a DMC, or a regulatory authority has taken for safety reasons. The Overall Safety
Assessment should also take these new data into account.
Insert a summary or <Not applicable>
18. Overall Safety Assessment
Refer to section 3.18 of ICH E2F
The overall safety assessment 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. This assessment should consider cumulative experience, new
information collected in the period covered by the DSUR and, for investigational drugs with a
marketing approval, clinically significant post-marketing data.
It should not summarise or repeat information presented in previous sections of the DSUR, but should
provide an interpretation of the information and its implications for the clinical trial population and the
development programme. If appropriate, separate assessments can be provided by therapeutic area,
route of administration, formulation and/or indication.
Do not enter data here but in sub-sections 18.1 and 18.2. Only include significant issues. Do not list
all. It is not expected that additional information is actively sought from external sources. But,
information available to the TMG should be summarised.
18.1. Evaluation of the Risks
Refer to section 3.18.1 of ICH E2F
In evaluating the risks, particular emphasis should be placed on interpretation of data related to newly
identified safety concerns or providing significant new information relative to previously identified
safety concerns. Relevant points to consider include (where applicable):

newly identified safety issues (detailed description of adverse events or reactions; associated
laboratory values; risk factors; relationship to dose, duration, time course of the treatment;
reversibility; factors that could be useful in predicting or preventing reactions)

meaningful changes in previously identified adverse reactions (e.g., increased frequency or
severity, outcome, specific at-risk populations)

symptoms, signs, and laboratory evidence of newly and previously identified clinically
significant toxicities

deaths that are an outcome of an adverse event

study drug discontinuations because of adverse events, including abnormal laboratory values
or investigations

drug–drug and other interactions

important non-clinical safety findings

manufacturing issues that could affect risk

lack of efficacy where this would place trial participants at risk

any specific safety issues related to special populations, such as the elderly, children, patients
with hepatic or renal impairment, or any other at-risk groups (e.g., slow or fast metabolisers)

pregnancy and lactation exposure and outcomes
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<Trial acronym>
DSUR date: dd-mon-yyyy

safety findings arising from experience with long-term treatment

evidence of clinically significant medication errors

evidence of lack of patient compliance

experience with overdose and its treatment

occurrences of drug misuse and abuse
any safety issues resulting from procedures required by the protocol (e.g., bronchoscopy, biopsy,
central line insertion) or associated with the conduct or design of a particular study (e.g.,
inadequate subject monitoring schedule, excessive period without active treatment)
potential impact of significant new safety issues identified with another drug in the same class
The following statement may apply:
<The <xxx> trial team are not aware of any newly identified safety concerns or significant new
information that would change any previously identified safety risks.>
Or
Include a summary
18.2 Benefit-risk Considerations
Refer to section 3.18.2 of ICH E2F
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.
The following statement may apply:
<The perceived balance between risks and anticipated efficacy/benefits have not changed during the
reporting period.>
OR
Example text:




At the present stage of development, the risk of VGF-2 seems acceptable in light of its potential
benefit (amelioration of PAD)
With this DSUR, there is stronger evidence of a risk of hepatic injury, and we have made
appropriate changes in the protocol and informed consent, as noted in this report
By excluding subjects with a history of hepatic disease, and monitoring transaminases more
frequently, we hope to detect hepatic transaminase elevations at an earlier stage, and diminish
risk
These risks should be considered in light of the significant morbidity of PAD and VGF-2’s potential
to ameliorate claudication, improve function, and enhance limb salvage
19. Summary of Important Risks
Refer to section 3.19 of ICH E2F
This section should provide a concise, cumulative, issue-by-issue list of important identified and
potential risks, e.g., those that might lead to warnings, precautions, or contraindications in labelling.
Such risks might include, for example, toxicities known to be associated with a particular molecular
structure or drug class, or concerns based on accumulating non-clinical or clinical data. Each risk
should be re-evaluated annually and re-summarised as appropriate, based on the current state of
knowledge. New information should be highlighted. The appropriate level of detail is likely to be
dependent on the stage of drug development. For example, summaries covering drugs in early
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<Trial acronym>
DSUR date: dd-mon-yyyy
development might include information on individual cases, whereas in later development, as more
knowledge and perspective are gained, the information on each risk might be less detailed.
The information in this section could provide the basis for the safety specification of a risk
management plan (ICH E2E).
Risks that have been fully addressed or resolved should remain in the summary and be briefly
described, e.g., findings from toxicology studies or early clinical trials that were not borne out by later
clinical data.
The information can be provided in either narrative or tabular format.
This section should only include the information which relates directly to the trial, the population being
studied and which is over and above the information contained within the RSI.
Example text:
Identified risks are as recorded in the Reference Safety Information. No new risks or potential risks
associated with the IMP have been identified during the reporting period. Previously identified risks
have been evaluated and are not considered to have changed during the reporting period.
19.1 Previously Identified Risks
Depo-Medrone 40mg/ml is not specifically licenced for use in carpal tunnel syndrome, but is both
frequently used in research and through consensus has been established as the drug most commonly
used in practice. Patients are not be put at any higher risk of side effects than if they were to receive
this treatment as a part of standard care. Patients with relevant medical history are excluded from
participation in the trial due to restrictive eligibility criteria.
OR
This section summarises the important identified or potential risks that have been recognised during
the conduct of the trial and identified in the scope of this DSUR. Identified risks will be as recorded in
the Reference Safety Information.
The following have been recognised as important potential risks during the reporting period:
• Nephrotoxicity
• Hepatotoxicity
• Syncope
• Pancreatitis
Additional details are provided below:
Risk
(New or updated risks
are denoted with an *)
Non-clinical data
Clinical data
Actions
20. Conclusions
Refer to section 3.20 of ICH E2F
The conclusion should briefly describe any changes to the previous knowledge of efficacy and safety
resulting from information gained since the last DSUR. The conclusion should outline actions that
have been or will be taken to address emerging safety issues in the clinical development programme.
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<Trial acronym>
DSUR date: dd-mon-yyyy
Example text:
The risks remain consistent with the experience described in our previous DSUR, and we conclude
that the information obtained in this reporting period justifies continuation of the trial, with the
modifications noted in this DSUR.
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<Trial acronym>
DSUR date: dd-mon-yyyy
Appendices to the DSUR
The order and nomenclature of the appendices are as per the DSUR guideline. Some appendices are contained in the main body of the report.
Appendix 1: Current and any revisions to the Reference Safety Information
Appendix 2: Cumulative table of important regulatory advice (refer to Section 3)
Appendix 3: Status of ongoing and completed clinical trials (refer to Section 5)
Appendix 4: Cumulative Summary Tabulations (refer to Section 6)
Appendix 5: A line listing of all Serious Adverse Reactions
Appendix 6: A cumulative tabulation of all Serious Adverse Events
Appendix 7: Scientific abstracts (if relevant)
Appendix 8: A cumulative tabulation of Serious Adverse Reactions
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<Trial acronym>
DSUR date: dd-mon-yyyy
Appendix 1: Current and any revisions to the Reference Safety Information
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<Trial acronym>
DSUR date: dd-mon-yyyy
Appendix 5: A line listing of all Serious Adverse Reactions
Refer to section table 5 of ICH E2F
Include a line listing of all SARs and SUSARs received within the reporting period. List each SAR only once regardless of how many AEs are reported per
SAE
If there have been no SARs include <No Serious Adverse Reactions have been reported during the DSUR reporting period>
If more than one AR has been reported on the SAE Form mention all but list under the most serious reaction term (where possible)
If data has not been collected in the required format then the best available data should be presented (e.g. ‘date last given’ instead of ‘treatment start and end
dates’). Each event reported for an individual subject must be listed as a separate event
Notes:
Can be amended to reflect terminology used in the trial
Can be listed prior to line-listing if consistent throughout trial (e.g. all female subjects, all UK subjects)
Outcome example: resolved; sequelae; ongoing; fatal; improved; unknown
Given for the most serious SAR
Relevant comments may be causality assessment if the sponsor disagrees with the reporter; concomitant medications suspected to play a role in the
reactions directly or by interaction; indication treated with suspect drug(s); dechallenge/rechallenge results if available
Subject clinical
trial
identification
number1
Sponsor’s
adverse
reaction
case
reference
number1
Country2;
Gender2;
Age
SARs
Outcome3
Date and/or
time of
onset 1,
Suspect
drug (if
blinded,
state
‘blinded)
Daily
dose;
Route;
Formulati
on
Dates of
treatment
and/or
best
estimate of
treatment
duration 1
Comments if
relevant 5
<Not applicable>
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<Trial acronym>
DSUR date: dd-mon-yyyy
Appendix 6: A cumulative tabulation of all Serious Adverse Events
Refer to section table 6 of ICH E2F
2 separate reports are required:

A tabulation of all SAEs (including SARs and SUSARs) that have occurred during the course of the trial (appendix 6)

A tabulation of all SARs (including SUSARs) that have occurred during the course of the trial (appendix 8)

Create a summary table as indicated below
o Include all SAEs/SARs (as applicable) reported throughout lifetime of trial
o Amend the number of columns as required to accommodate the appropriate number of treatment arms
o Report by coding terms that are referenced within section 7.1 of this document. If no coding has been used, group by body system as appropriate
o Include a sub-total for each category
Example 1 – for non-blinded trials
The exact detail will be dependent on the events reported.
If no SAEs have occurred, include: <No serious adverse reactions have been reported during the DSUR reporting period.>
CTCAE Category
Adverse Event Term
Number of Serious Adverse Events
<insert treatment arm 1>
<insert treatment arm 2 etc>
<Not applicable>
Sub-total
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<Trial acronym>
DSUR date: dd-mon-yyyy
Appendix 7: Scientific Abstracts
If there are no relevant scientific abstracts <Not applicable>
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<Trial acronym>
DSUR date: dd-mon-yyyy
Appendix 8: A cumulative tabulation of all Serious Adverse Reactions
Refer to section table 6 of ICH E2F
If no SAEs, include: <No serious adverse events have been reported during the DSUR reporting period.>
CTCAE Category
Number of Serious Adverse Reactions
Adverse Event Term
<insert treatment arm 1>
<insert treatment arm 2 etc>
<Not applicable>
Sub-total
Example 2 – for blinded trials
The exact detail will be dependent on the events reported
Reactions should only be listed under the relevant treatment arms where results have been unblinded. All other adverse reactions will be classed as ‘blinded’.
Number of <insert Adverse Events or Adverse Reactions>
CTCAE Category
Eg: Allergy / Immunology
Eg: Blood / Bone Marrow
DSUR Template_V0.2_140617
Adverse Event Term
Unblinded
Blinded
<insert treatment arm 1 >
<insert treatment arm 2 etc>
Allergic reaction/
hypersensitivity
(including drug fever)
1*
3
7
Vasculitis
4
1
7
Sub-total
5
4
14
Platelets
0
2
15
Sub-total
0
2
15
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