When to start and when to stop? Before answering this question, let’s understand where the confusion relies.
Generally we start recording the adverse event just after singing the informed consent form. It is collected even for those subjects who failed to meet all inclusion criteria after signing the informed consent form.
It is to be noted that as per the ICH (E2A), adverse event can be recorded at or after the first treatment. It does not suggest recording it just after singing the informed consent form.
Definition of adverse event as per ICH:
“Adverse Event (or Adverse Experience) any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have to be a causal relationship with this treatment.
An adverse event (AE) can be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of the medicinal product, whether or not considered related to the medicinal product.”
So ICH excludes the collecting of adverse event before investigational product administration. But many protocols and country specific guidelines mandate to report adverse event before IMP administration and after signing the informed consent form.
Now question comes; how it is useful to record adverse event before IMP administration and just after signing informed consent form. Please see the below list answering this question:
- Sponsor can have a good risk management if they report serious medical events caused by protocol-imposed screening tests or diagnostic procedures.
Few screening procedures may cause potential injury to subjects, for example angiogram in certain cardiovascular studies and biopsies in oncology studies. It is advised to start recording AE just after signing the informed consent form in these cases.
Sponsor may consider collecting adverse event only after IMP administration, if the study contains less invasive and routine procedures only, which does not cause any health risk and considered relatively safe. For example routine X ray, lab assessments etc.
- Sponsor can monitor withdrawal symptoms because of removal of existing treatment (washout period) before starting study IMP.
- Based on the severity and frequency of adverse event during washout period, sponsor can modify the study protocol and study can be halted.
Note: Adverse events which are collected, starting from the Informed consent form singing, can be divided into two parts: A) Treatment emergent AE (TEAE)- Adverse events which occurred after IMP administration. And B) Non-Treatment emergent AE (Non-TEAE)- Adverse events which are collected before IMP administration and after singing the informed consent form.
Now Question arises, when to stop reporting adverse event:
There is no clear guidance on this. It depends mainly on study specific protocol. It is a common practice to continue adverse event reporting even after completion of treatment (follow up period).
The collection of AE largely depends on half life of drug, nature of drug candidate or population (adults or pediatric).
Long term follow up (more than six month) for AE is not quite common.
Reporting of Adverse event for discontinued subjects:
Subject can withdraw informed consent form any time or discontinued from the treatment because of adverse event.
Discontinued subjects may remain in the study and it is very important to collect AE of discontinued subjects till certain period of time which is defined in the protocol (In accordance with regulatory authority and local guidelines).
Note: Any medically important significant findings which are noticed before signing informed consent form, should be captured as Medical history in database