Chicken Soup for the Busy Coordinator Aug 2009

Scenario: Aim: Randomised, double-blind, phase III clinical trial to compare the safety and efficacy of an investigational anti- inflammatory 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. Case Study

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 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)*. Questions & Answers: * 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 Click here  HSA Regulatory Guidance on Safety Reporting Requirements for Clinical Trials – Sep l_trials/guidelines/serious_adverse_events.html Click here 

Contributed By: Ms Sumitra Sachidanandan Clinical Trials Branch Health Products Regulation Health Sciences Authority

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