All of us in the clinical research world know just how important it is to properly document and report adverse events that occur during clinical trials. The regulations for doing so vary slightly depending on whether a drug or device is being studied, but the general principle is the same. Unfortunately, history is full of examples of ill effects suffered by human subjects exposed to drugs or devices that are being tested – most times these adverse events are unexpected by those conducting the study. It’s actually one of the two pillars of why any study is conducted at all: safety and effectiveness. At current day, reviewing the adverse events that occur during a trial is the primary method of ensuring subject safety. Investigators who agree to conduct research justly and ethically are legally bound to discontinue an investigation if it becomes know that the object under investigation presents a serious adverse event that was not previously known or expected (21 CFR 312.56(d) and 21 CFR 812.46(b)(2)). The Declaration of Helsinki drives this concept home when it states “the subject’s welfare must always take precedence over the interests of science and society.”
When I was a research coordinator, I always thought understood this concept fairly well and did my best to accurately collect information about adverse events experienced by the research subjects I worked with. From there, we had a system in place where each adverse event was then reviewed by our Principal Investigator (and sometimes Co-Investigators if he was unavailable to do so in a timely fashion). They would use their medical expertise to make judgments as to whether or not each adverse event was expected and/or related. Once this was determined, we as research coordinators knew who to report the adverse event to and how fast we needed to do so. To be honest, it was somewhat stressful at times to meet the deadlines. I could always rest easy though once I accomplished my duty of reporting that adverse event (at least until another one occurred). In my mind, my job was done. Perhaps it was the demanding nature of the job of a research coordinator, or maybe I was just plain naive, but I never really stopped to think of what happened after that. What happens to that information once I notify the sponsor and my IRB? Surely they review it, but then what? And why does the sponsor keep asking me questions about it? And why are they always on my case to report it within what seems like an unreasonably short amount of time? I mean…don’t they realize I have to 10 more patients to see today?
It wasn’t until I became a monitor and began working closely with sponsors that the light bulb went off in my head. You mean, you (the sponsor), also have what sometimes seems like an unreasonable deadline to report the adverse event information on to the FDA that I just reported to you? Aha, now I see why you wanted me to inform you about them so quickly. Because, if it turns out that adverse event is an unanticipated adverse device effect, you have to report it to FDA and all the other reviewing IRBs within 10 working days (21 CFR 812.150(b)(1). And if it turns out that it’s not, then you have to compile that information and send it off to be reviewed by a data safety and monitoring board (DSMB) or clinical events committee (CEC) to be sure. And then you need to summarize it in your annual progress report to FDA. Now I get it!
The FDA is the ultimate decider of whether or not a drug or device is safe to use in humans before it can be marketed in the United States. They are in the unique position of having available to them all the information about the adverse events reported by multiple investigators across multiple studies conducted by multiple sponsors. So one adverse event that is reported to you as a research coordinator may seem insignificant, and may only be reported to you once by 1 out of 100 subjects during the course of the entire trial, could actually turn out to become a pattern of adverse events that occur more frequently at different sites, in different populations, in different locations. By promptly reporting adverse events to your IRB and the sponsor as a research coordinator, you are a very important step in the process. So please continue to do your part and strive to meet all the reporting requirements for adverse events to which you are bound. Human subjects depend on it!
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