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What are regulatory expectations for distribution of amended Informed Consent Form to the sites?
Dr Chandru Advani
An amended Informed Consent Form (ICF) should be distributed to clinical sites/investigators as soon as it has received a favourable opinion from the Ethics Committee(s). An unjustified substantial delay, which affects patients’ rights, between the favourable opinion/ approval and the distribution (e.g. several weeks) is considered unacceptable. Cases where an outdated ICF missing important new information was signed by participant at enrolment, or a delay to obtain re-consent to participate in a clinical trial on a new ICF, are considered GCP non-compliance, i.e. the trial participant was not (adequately) informed.
What is the purpose of the Reference Safety Information section of an Investigator’s Brochure for clinical trials and what should it contain?
Dr Bharat Kulkarni
The Reference Safety Information (RSI) is used for the assessment of the expectedness of all ‘suspected’ serious adverse reactions (SARs) that occur in clinical trials. Hence the Reference Safety Information is a list of expected serious adverse reactions, which are classified using Preferred Terms (PTs) according to the Medical Dictionary for Regulatory Activities (MedDRA). The Reference Safety Information should include the nature, frequency, and severity of the expected serious adverse reactions. An expectedness assessment is required to be conducted by the sponsor on each ‘suspected’ serious adverse reaction to determine expedited reporting of ‘suspected unexpected serious adverse reactions (SUSARs), and for the identification of SUSARs in the cumulative summary tabulation of ‘suspected’ serious adverse reactions in the Development Safety Update Report (DSUR).
The content of the RSI should include a clear list of ‘expected serious adverse reactions’ to the IMP(s). These ‘expected serious adverse reactions’ should be restricted to ‘suspected’ serious adverse reactions that were previously observed where, after a thorough assessment by the sponsor, reasonable evidence of a causal relationship between the event and the IMP exists. This confirmation should be based for example on the comparative incidence of ‘suspected’ serious adverse reactions in all previous and ongoing clinical trials and/or on a thorough evaluation of causality from individual case reports.
‘Suspected’ serious adverse reactions that have occurred once cannot usually be considered expected, unless there is a very strong plausibility of a causal relationship with the IMP and a robust justification based on medical judgement is provided. Fatal and life-threatening serious adverse reactions should usually be considered unexpected even if previous fatal and life-threatening serious adverse reactions have occurred.
Dr Arun Bhatt is a Consultant - Clinical Research & Development,
Mumbai. Readers can send their queries at:arun_dbhatt@hotmail.com
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