Why Does The FDA Catch Findings After A Site Has Already Been Monitored?
Today I got a question from someone who asks, “Dan, all drug and device clinical trials are monitored, yet the FDA still finds significant GCP (Good Clinical Practice) violations which should theoretically be detected and corrected by study monitors. Any ideas as to why this occurs?”
So, there are a couple of reasons for this. First of all, Sponsors rarely audit sites. Yes, they send out study monitors on regular monitoring visits, but rarely do they conduct a full sponsor audit in the same way that the FDA would do an audit. I myself have participated in probably over a hundred trials, and I can remember maybe a dozen Sponsor audits. So to quantify that would be about 12%. Realistically, around 10–15% of the time you’ll get a sponsor audit which is a very thorough audit much like an FDA audit would be. However, there is a lot less pressure because you are not being audited by a regulatory agency — it’s just one of your customers so to speak.
Another reason, I believe, is because CRAs are either overworked (most of the time) or lazy (some of the time), or they are not given enough resources to do an adequate and thorough monitoring job. What do I mean by that? Let’s go one at a time. First, the lazy monitors. We’ve all seen them if you’ve been in this business long enough. You’ve seen them coming in late and leaving really early. I’ve seen a monitor stay for only two hours once and then leave. This is not good for my business either because we don’t get paid unless they review the data. So it’s obvious how a lazy monitor can miss certain things in their monitoring process if they’re actually not on site that often. Granted, the vast majority of monitors do not fall into this category. Secondly, you have overworked monitors going to very busy, high-enrolling sites that enroll something like 30 patients in a study. They don’t even have time, all they’re doing is playing catch up every time they go to the site so they don’t even have time to look over the regulatory binder. I’ve seen this at my own sites because some of my sites are high-enrolling. What many monitors do when they visit these sites is look over the data and the most recent patient visits since their last monitoring visit. Maybe if they happen to have time they might take a look at the action items from their last visit to see if hopefully they’ve been completed. To compound this problem, the CRO industry is flushed with CRA turnover so having a replacement monitor trying to figure out where the previous CRA left off is frustrating to say the least. In theory, the CROs should send someone to help the CRAs go through everything in these cases. But oftentimes this doesn’t happen because the CROs are in the business to make profit just like all of us, so it’s kind of a way of cutting corners. Another issue is there’s no real standard in the industry other than GCP which is pretty vague. It’s not that thorough so it leaves a lot open to interpretation and to the discretion of sites and CROs which may not always align with what the FDA thinks should be done. That’s three possible reasons why the FDA may catch findings after a site has already been monitored. There are probably hundreds of reasons as to why this happens but those are the three I can provide for you today.