Chicken Soup for the
Busy Coordinator
Aug 2009
Case Study
Scenario:
• Aim: Randomised, double-blind, phase III clinical trial to
compare the safety and efficacy of an investigational antiinflammatory agent and placebo for management of chronic
back pain.
• Problem: Subject ABC was randomised into the clinical trial
on 1 Apr 2009 and developed a severe abdominal pain one
month after randomisation. He was diagnosed with gastric
ulcer and was hospitalised for a week and discharged well. The
investigator felt that the gastric ulcer was related to the
investigational product.
• Study Documents: The protocol, investigator’s brochure and
informed consent document for the study indicated that the
there was a 10% chance of developing mild to moderate
abdominal pain.
Questions & Answers:
Q1. How should the investigator classify this adverse
event in terms of diagnosis, onset date, end date,
relationship to the investigational product, severity and
expectedness?
A1. The investigator should classify the adverse event as
follows:
• Diagnosis : Gastric Ulcer
• Onset Date : 1 May 2009
• End Date : 8 May 2009
• Relationship to the investigational product : Possible
• Severity : Severe
• Expectedness : Unexpected (since it was not
mentioned in any of the study documents)
Questions & Answers:
Q2. Is this event considered a Serious Adverse Event
(SAE)?
A2. Yes. The adverse event should be considered as a
Serious Adverse Event since the subject was
hospitalised. Furthermore, it also meets the criteria for
Unanticipated Problems Involving Risks to Subjects or
Others (UPIRTSO).
Questions & Answers:
Q3. Who should the investigator notify about this event
and what are the timelines for notification?
A3. The event meets the criteria for expedited safety
reporting since it is serious, unexpected and related to
the investigational product.
The investigator must notify the Sponsor, IRB / IEC and
Regulatory Authority (HSA) about the event within the
required timelines as follows:
(a) Sponsor : 24 hrs from becoming aware of the event
(b) IRB / IEC : 7 calendar days from becoming aware of
the event
(c) HSA : 15 calendar days from becoming aware of the
event.
Questions & Answers:
NB: Please note that only SAEs that meet the expedited safety
reporting criteria need to be reported to HSA.
If the investigational product is an unregistered drug in
Singapore, local and overseas adverse drug reactions that are
both serious and unexpected must be reported to HSA
(including other protocols of the same study drug).
If the investigational product was a locally registered product
in Singapore, only local and overseas adverse drug reactions
that are both serious and unexpected and arising from the
clinical trial protocol that is studied in Singapore must be
submitted to HSA.
Questions & Answers:
Q4. If the investigator had unblinded the study drug
assigned to the subject as part of his medical care, what
should the investigator do?
A4. The investigator should notify the Sponsor, IRB / IEC
and the Regulatory Authority (i.e. HSA) about the
unblinding within required timelines as mentioned in the
answer for question [3].
The Sponsor should use the online Expedited Safety
Reporting (ESR) form or email to report the unblinding
to HSA.
Questions & Answers:
Q5. When does expedited safety reporting start and
end?
A5. Expedited safety reporting should start upon the
submission of CTC application and end upon Last Patient
Visit (LPV)*.
* Please refer to specific study protocol as safety reporting
period may vary amongst protocols.
References
Please refer to the regulations:
• Singapore GCP Guidelines:
Sections 1.50, 1.60, 4.11, 5.16 and 5.17
• ICH Harmonized Tripartite Guideline E2A
http://www.ich.org/cache/compo/276-254-1.html
Click here 
• HSA Regulatory Guidance on Safety Reporting Requirements for
Clinical Trials – Sep 2007
http://www.hsa.gov.sg/publish/hsaportal/en/health_products_regulation/clinical
_trials/guidelines/serious_adverse_events.html
Click here 
Contributed By:
Ms Sumitra Sachidanandan
Clinical Trials Branch
Health Products Regulation
Health Sciences Authority
For More Information
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free to write to us through:
• Email: [email protected]
• Snail mail:
Clinical Research Coordinator Society (CRCS)
c/o Research & Development Office
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#04-01/02 GMTI Building
Singapore 149547