We were reviewing a study protocol for a maker of medical devices, and there was one provision that just didn’t make sense. The sponsor specified a need for regular data monitoring committee meetings, but we didn’t see the need and couldn’t justify the effort.
It was a short study involving few sites. In all likelihood, it would conclude before the DMC would have any meaningful data to digest. We asked the sponsor why it wrote this provision into the protocol and were told, “We heard that there is a requirement to have a committee, and we thought this was the right one.”
For the record, no such broad requirement exists. But the sponsor was not entirely wrong; in our assessment, it would have benefited from having a clinical endpoint committee (though none was in place).
The sponsor’s confusion is hardly uncommon. Clinical research can be a bewildering alphabet soup of abbreviations: DMCs are also known as DSMBs (data and safety monitoring boards) and IDMCs (independent data monitoring committees). Then there are IRBs (institutional review boards), sometimes called ERBs (ethics review boards). And, of course, CECs — clinical endpoint committees — sometimes known as … (you get the idea).
DMCs and CECs are among the most commonly deployed clinical trial support mechanisms, so let’s look at what they do and why you might consider using one or both.
Data monitoring committees
A DMC’s principal role is providing guidance on continuing, changing, or stopping a clinical trial. Let’s say your trial is forecast to last two or three years. It’s blinded, so you really don’t know to what extent the adverse events you’ve observed are caused by the treatment. The DMC can assess the unblinded data independently from the sponsor, void of any conflict of interest, and issue an impartial judgment on whether to stay the course, modify the protocol, or stop the study because it’s not benefitting the participants or may even be harming them.
Data monitoring committees can also look at things other than safety, such as efficacy, concomitant medications, and lab findings. And they can recommend stopping a study not only for safety’s sake, but also because of futility or because the treatment has been shown so effective that further research is unnecessary.
An illustration of that last scenario is a device company that was aiming to enroll about 300 patients in a non-inferiority trial, and of these obtain 222 available patients. Written into the protocol from the start was an interim data analysis. After 156 patients were enrolled and treated (accounting for 70 percent of the 222 target), the review board determined that the trial had already demonstrated non-inferiority and recommended that the trial end early, saving the sponsor significant time and money.
Do you need a DMC? Start by considering these questions:
- What potential risks are associated with the investigational drug or device?
- Do those risks translate to a potential safety threat, perhaps as a result of an invasive procedure?
- Are your patients already very sick?
- Is the study especially large in terms of patients and/or sites, or of very long duration?
Clinical endpoint committees
The objective of a CEC, in contrast, is to adjudicate any variables that cannot be objectively measured but are subject to interpretation. For example, a chest X-ray may show what one physician assesses to be lung tumors, while another sees benign lymph nodules.
CECs focus on data from sources such as laboratory findings, medical reports, radiological data, and electrocardiograms. They can be especially useful in evaluating devices when the study cannot be blinded. In a study of occlusion devices, we had an adjudication committee assess the endpoints in a blinded manner — something that’s essential, even in an open-label study.
CECs also can be used for enrollment adjudication. In one study that involved highly subjective diagnostic criteria, we sent all of the patient data to an enrollment committee to verify that the patients really had the diagnosis we were looking for.
The clinical endpoint committee’s job is to provide an independent assessment of information that is subject to interpretation. The structure is very simple, with just one meeting and no open and class session. It can even be accomplished without a meeting and can have an e-adjudication.
To learn more about the vital role these committees play in clinical trials, check out our webcast, Decoding The Distinction: DMCs, CECs, And Their Role In Medical Device Research.