Adverse Events & Serious Adverse Events
- What is the time frame for SAE reporting to sponsor? Is it within 24 hours from the event or within 24 hours from awareness of event?
All SAEs should be reported to the Sponsor within 24 hours from awareness of the event.
- After a patient completes the study treatment period of a trial there is often a follow-up visit scheduled for some time later. Are there any guidelines as to the length of time non-serious Adverse Events should be collected?
There are no strict guidelines for the collection of non-serious Adverse Event information after the study treatment period, and the approach will be very much dependent on the disease and drug characteristics. The phase of the trial will also have an influence, Phase II trials prompting a much closer monitoring of such events. For example, a good rule of thumb to employ is that of a follow-up period of at least five half lives of the compound under investigation, but whatever the decision it should be made very clear in the protocol what the requirements for the timescale of reporting are and what categories of events should be considered during this period
- When should we start collecting safety information on patients, and when should adverse event reporting start?
In general, information on a patient’s medical condition(s) should be collected from the date of informed consent, and a medical history should be taken at screening. During wash-out and baseline periods, any changes in the health of the patient should be recorded as a change in medical status or medical history. Such information becomes adverse event data when the patient has taken the first dose of trial medication, and therefore adverse event data should be collected from the date of first dose. However this does vary greatly depending on the design of the trial, and can be dependent on terminology when interpreting the ICH guidelines.
- Is it the responsibility of the investigator or the company to provide regular listings of serious adverse events to the Ethics Committee?
This can vary depending on the logistics of the situation. For example, if the serious adverse event information is only available at the investigator site it must be the investigator’s responsibility to circulate it as necessary. If the sponsor has the information as is often the case, they would be the source and the relevant information can be circulated to the investigator and the Ethics Committees as required and agreed. Listings are generally only provided if the Ethics Committee have specifically requested them. However all unexpected serious adverse drug reactions that require reporting to regulatory authorities within documented timelines must also be forwarded to the Ethics Committees via the investigator.
- Reporting serious adverse events (SAE) to ethics committees - where does the sponsor company responsibility end?
Investigators are responsible for all communication with the ethics committee. However, in multicenter trials the investigator will (probably) be dependant on the sponsor for information on SAEs, and it could therefore be argued that the sponsor's responsibility ends when they have given information to the investigator. For some studies where SAEs occur frequently, it is common practice for the sponsor to prepare the information to meet the ethics committee reporting requirements and send it to both the ethics committee and investigator - with the prior agreement of both parties. It is preferable to have a receipt for the SAE information from the ethics committee.
- Is it acceptable for the patient to be asked to report only those adverse events related to the study drug?
No. Patients cannot be asked to assess causality; this should be the Investigator's decision. Also, it is generally agreed that all adverse events must be recorded; to give the complete picture of each subject and also since causality may not be apparent until analysis of all study data.
- What is the definition of hospitalization with regard to SAEs?
The useful definition of hospitalization is an unplanned overnight stay. Note however that the patient must be formally admitted – waiting in outpatients or A&E would not count (even though this can sometimes be overnight). Prolongation of an existing hospitalization also qualifies as a SAE. Thus planned hospital stays would not be counted as SAEs, nor would stays in hospital for “social reasons” (e.g. respite care, the fact that there is no-one at home to care for the patient). Also, if patients had a day-case operation, this would not qualify as hospitalization. However, if a planned operation was brought forward because of worsening symptoms, this would be considered as an SAE. Similarly, if patients were brought into hospital for observation (but not necessarily intervention). It is important to have a clear statement in your SOPs and/or protocol as to which events would be regarded as hospitalization and which would not.