A BEGINNER’S GUIDE TO SAFETY REPORTING IN CLINICAL TRIALS By William Ray - Drug Safety Expert
So, you’ve managed to work your way into a role in drug safety and you’ve started with your case processing - you’ve even created a Council for International Organizations of Medical Sciences (CIOMS) form. But do you know what happens next with the distribution of the case? I’ve come across quite a few people who know a great deal about pharmacovigilance (PV) but have less of an idea of what happens when it comes to the distribution of cases and beyond. It’s useful to know and is an important step. “What is the process then?”, I hear you ask. “You just send an email, right?” Well, I’m getting to that!
can differ from territory to territory, so robust regulatory intelligence is a must, along with internal processes that ensure all ICSRs are suitably assessed, and periodic reports scheduled. Even within European Medicines Agency members, there are differences in reporting requirements for SUSARs: some RAs wanting all SUSARs from within the trial and others only wanting to be made aware of ones occurring in their country. This also highlights not just the need for external regulatory intelligence, but also for PV to be fully integrated into the sponsor clinical trial team, so PV is fully aware of all the countries that a study is operating in.
I am going to describe the process for clinical trials as this is what I am most familiar with, but there are similar processes for post marketing too. Classification of reports There are a few things we need to know about the classification of case reports before we go any further. There are many types of report that are received and generated throughout clinical trials, with their own associated reporting requirements and formats. In general, report types in clinical trials can be split into two categories: expedited and periodic.
Along with being able to accurately identify what reports are required for submission, companies should also be aware of timelines and where they may differ from industry ‘norms’ (i.e. a 15 day SUSAR to be reported to the US FDA requires submission within 14 days to Argentina).
Expedited Reports The bread-and-butter of clinical trial PV is the receipt and processing of serious adverse events (SAEs). Certain SAEs will require expedited reporting to regulatory authorities (RAs), ethics committees (ECs) and investigators involved in the study. For example, Suspected Unexpected Serious Adverse Reactions (SUSARs), would routinely require reporting. Some non-SUSAR ICSRs which, nonetheless, are considered to affect the benefit-risk balance of a study may also require reporting in an expedited manner.
Finally, at this stage, sponsors will need to identify if there are any additions needed to the report to meet local reporting requirements. For example, SUSARs reported to the US FDA will also need an accompanying analysis of similar events (AOSE) and those occurring in Spain require the case narrative to be translated into Spanish for the submission to the Spanish RA. Where studies are blinded, there will usually be the need to unblind ICSRs before reporting, so there not only needs to be a level of regulatory intelligence to identify which parties may be the exception to this rule, but also internal processes to ensure no inadvertent unblinding of other study team members or investigators.
Periodic Reports Periodic reports can also be termed aggregate reports and contain grouped information to be submitted at defined intervals, rather than triggered by specific events. Periodic reports include annual Development Safety Update Reports (DSURs) or more simple line listings of SAEs or serious adverse reactions (SARs).
Submission methods for reports
For both expedited and periodic reporting, requirements
Once a report has been identified for submission, along 39
