This monthly feature presents a variety of questions from clinical trial professionals with answers from WCG Clinical’s expert staff. This month features two WCG pharmacovigilance experts, WCG Vigilare Vice President Angela Pittwood and Jim Bannon, president of the scientific and regulatory review division of WCG Clinical.

Question:

How, and how frequently, should I look at aggregate data to ensure patient safety?

Answer:

Pittwood: I believe that it’s important to be looking at the data all the time. Even with small clinical trials, I think it’s important to know what’s happening. The first part of any kind of risk management is the safety physician who sees these safety reports coming in.

As the individual cases are being processed, that’s your first line of defense, so to speak. And then, as you work through the protocol and as you work through the different studies, I think it’s important to start to look at any kind of adverse events of special interest — anything that is in the protocol or in the class of product that you might want to make sure is being addressed as it happens. Maybe there are certain events that may occur that you want to make sure are not happening on a frequent basis.

Looking at the data as it comes in is one thing, but then looking at it as it accumulates each month, each quarter leads into your aggregate reports or your study reports. That’s when you’re going to be looking at that data more clearly and looking to see what assessments you’ve been making along the way. There definitely are more formal ways of doing this, but I think the first part of that is let me just take a look every month and see what’s coming in, from a safety physician perspective.

Bannon: Signal detection does begin with the individual case, and having the same medical reviewer look at all the data is a key step in understanding the safety profile that is developing.

Question:

Do you have any tips on getting PIs to comply with best practices in reporting safety problems? Without regulations, some can be difficult to persuade.

Answer:

Pittwood: Well, I think it boils down to education and training when the protocol starts. Those investigator kickoff meetings are very important so that the sponsor can go over the expectations and what it is that we need the investigators to do and be responsible for.

The investigators need to be informed about what is needed. When you’re starting a study you need to know what your institution requires you to do and how often the IRBs and the ethics committees need you to forward these reports to them as well. It’s really about being informed.

A lot of site coordinators can do a lot to help in that regard. Basically, they’re mostly the eyes and ears of the investigator, who sometimes might need some reminding: “This is something you need to look at” or “This is something you need to know.” I think it’s about having good communication on a regular basis, not only within the site, but also between the sponsor and the investigators, to make sure that they are performing the task for which they’ve been recruited.

Bannon: A principal investigator has clear responsibilities, but if we don’t really interact and communicate in the best and most efficient way with the investigator, we’re creating a burden at that level that could sometimes be perceived as noncompliance, when it’s really just not organizing the communication properly and not organizing that through the appropriate use of the properly trained people.

The interactions that I think go best at the site level, at the investigator level, are those that are completed by healthcare practitioners — nurses, pharmacists, physicians, etc. — who have a clear understanding of what it’s like to be in practice, a clear understanding of what it means and what the right questions are to ask, and then in addition to that, to have drug safety experience. I think having that as criteria for the individuals speaking to the sites and organizing the questions, to make sure that the most informative information to help delineate the case is collected up front, is appropriate, is really an important aspect of compliance.