How long a study participant should be monitored for AE/SAE?
Dr Mohmed Suleiman
The sponsor should describe in the protocol SAEs that it does not plan to report individually in an expedited manner because they are anticipated, along with a plan for monitoring such events.
In a long-term follow-up study e.g. oncology, if a subject is experiencing an ongoing AE beyond the final follow-up visit e.g. 24 months, and if such information is relevant to the investigation and could contribute useful information about the safety profile of a drug, the sponsor should monitor the subject and record the data.
If the event is serious, the investigator should continue to follow the patient, and should always follow if the AE is unexpected. It may not be necessary to follow subjects suffering from non-serious events already listed in the IB.
For an AE that occurs after study completion, it is not usually necessary to collect information. The follow-up period provided for in the protocol is generally considered adequate to capture AE that may be related to the IP. However, if an investigator believes an event occurring after the patient has completed the trial may be related to the IP, the investigator should inform the sponsor. The sponsor should evaluate as it would any other event reported by the investigator.
In an oncology study, neutropenia occurred in a patient and resolved in a week. As the IB did not include this event, it was considered Suspected Unexpected Serious Adverse Reaction (SUSAR). It will take about 3 months for IB to be updated. But neutropenia has recurred. How do we report this event?
Dr Yogesh Chitalia
The initial event neutropenia qualifies for SUSAR reporting. As the IB is not yet updated to include this event, it will remain SUSAR.
The sponsor can expedite inclusion of an unexpected suspected adverse reaction to the IB as an addendum, rather than reissuing the entire IB. This is an acceptable approach for keeping investigators informed of new observations. The sponsor should ensure that any addenda are incorporated into the next full revision of the IB.
When does one record adverse events (AE) - once the subject has signed ICF, but has not yet received the IP or only after the subject has received IP?
The definition of an AE is:
Any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment.
As the subject has not yet received IP, this event could not be considered associated with the use of IP.
If a subject experiences an AE e.g. an illness or condition, infection, headache after the subject signed the EC approved ICF, and passed the screening tests but before administration of IP, this event should not be reported as an AE /serious AE (SAE).
However, as such an event could affect the subject's eligibility/continued eligibility for the study, the event should still be recorded by the study site in the study records, tracked, and be reported to the sponsor. The investigator should also ensure that the subject receives appropriate medical care.
It is recommended that investigators follow EC-approved protocol and consult the sponsor regarding expectations and any questions related to events that occur after a subject has signed ICF, but before they receive any dose of IP.
In an FDA approved global trial, in accordance with FDA regulations, the investigators must promptly report to the IRB all unanticipated problems involving risk to human subjects. Hence, it would be advisable to consult EC to find out if such an event requires reporting to the EC.
Dr Arun Bhatt is a Consultant - Clinical Research & Development, Mumbai.
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