Trial complexity a headache for IRBs
Interested parties have previously complained to the US Food and Drug Administration (FDA) that the rising number of adverse event reports submitted to IRBs is hindering their ability to protect patients.
To alleviate this problem the FDA recommends that the trial’s sponsor receives adverse event information from all study sites and analyses the significance of this information. If an “unanticipated problem” is detected this can then be sent to an IRB.
The guidance states that IRBs have been receiving individual, unanalysed adverse events from local investigators, which often contain little detail or context. Being sent large numbers of these uninformative reports is hindering IRBs’ ability to protect patients, according to the guidance.
Another aspect of the problem is the lack of understanding regarding what adverse events should be considered as unanticipated problems, which have to be reported to the IRB.
In its guidance the FDA seeks to clarify the situation, stating that for an adverse event to be classed as an unanticipated problem it must be unexpected, serious and have implications for the conduct of the study.
The guidance states that an event has implications for the study when, for example, it would result in: “a significant, and usually safety-related, change in the protocol such as revising inclusion/exclusion criteria or including a new monitoring requirement, informed consent, or investigator’s brochure.”
It is the FDA’s belief that the majority of adverse events do not meet these criteria as they are isolated cases and consequently their implications for the study cannot be understood.
However, if an aggregate analysis of a series of adverse events found the occurrence rate to be higher in patients receiving the investigational drug than those in the control group this would be considered an unanticipated problem.
The exception to this general rule is in cases of serious, uncommon adverse events that are strongly associated with drug exposure, for example angioedema, agranulocytosis or anaphylaxis.
A copy of the complete guidance can be found here.
