Heather Bristol, MS, is the Vice President of Informatics at Clinipace. Manejeh Yaqub, MD, is the CEC Consulting Expert.
Thank you to everyone who attended our webcast “Clinical Events Adjudication in the Digital Age.” In the presentation, we discussed when clinical events committees (CECs) are needed, CEC structures, CEC processes, what to look for when outsourcing CEC services and benefits of technology-enabled CEC processes.
During the webcast, we received a number of great questions from the audience. Therefore, we would like to share answers to those questions with you in a series of blog posts. In previous posts, we discussed how to handle therapeutic areas where standard definitions are unavailable as well as several considerations in relation to CEC structure. Today, we’ll dive into a handful of questions about the CEC process. Check back Thursday for our final blog post of this series, in which we’ll discuss the difference between electronic adjudication and traditional adjudication.
If you have any additional thoughts or questions for our experts, please share your comments below.
Q: Are all members of the CEC unblinded to study treatment?
A: It depends on the study. If the study protocol calls for blinded treatment for patients and the sponsor is blinded, the CEC will also likely remain blinded. However, if it’s an open-label study, there is no way to blind members of the CEC because they are actually reviewing the chart from the source level. There may be other study designs where it’s not possible to blind CEC members, so it really follows the protocol blinding criteria.
Q: Can efficacy data be part of a CEC?
A: Yes, efficacy data can be part of a CEC; there are no limitations. Typically we utilize CECs for interpretation of safety results, but some endpoints are both safety as well as efficacy driven. However, you could also involve CECs in efficacy-driven results if it makes sense for a study. For example, if you had an endpoint that was purely core lab driven, you probably wouldn’t want it adjudicated by the CEC, but you would want it adjudicated by the core lab or an imaging lab. On the other hand, if there was one that was core lab driven but had a clinical component to it, we would recommend utilizing a CEC for adjudication (e.g., an endpoint like imaging read in-stent restenosis that is symptomatic and requires intervention).
Q: During the adjudication process, if the chair becomes involved because of discrepant results, does the chair have the ability to discuss results with the committee members, as you would during a traditional meeting?
A: It depends on the setup of the committee. The chair typically adjudicates events after viewing member adjudication results to understand where the discordance lies. Then the chair provides their agreement to one or reviews independently with a result that may then be discordant between members and the chair. In such a situation, a meeting would be necessary to arrive at final results. In either case, to arrive at a final adjudication result, there needs to be agreement between at least two members of a three-member committee.
Q: Does data management edit events before or after CEC adjudication?
A: It depends on how you set up the study. Typically, while data management does not edit events, they can issue a query that either comes from the study safety monitor or from some other entity within a study from the sponsor side. Data management or sponsors typically do not have access to edit data CEC members have entered. Within a study site, only a study site or the principal investigator (PI) can edit site-reported data. Similarly, when a CEC member enters data, only that CEC member can edit their adjudication results. Data managers, at the most, can issue queries, which the appropriate CEC member can go back and answer and then edit their results if the query is accepted.
Q: Is a site investigator made aware when their event diagnosis is changed by a CEC?
A: This also depends on the various practices. Yes, study PIs are made aware of CEC adjudication results through a mapping system, although not all events are adjudicable. The results of adjudicable events, as a good practice, should be provided to site investigators so they are aware of how the CEC assessed the event and they have the opportunity to either update their results, provide the CEC with more information or just keep their assessment unaltered. The investigator’s assessment can remain distinct and independent of the CEC. However, although it would be a good practice for the sponsor to state the final assessment on an event in case of a discrepancy, the CEC adjudication results prevail over any investigator/medical monitor assessment(s).
Q: Do you provide the draft charter to the FDA for all studies? Does the FDA always request a copy?
A: Whenever we convene a CEC, we do provide the draft charter to the FDA. In fact, we also provide the FDA with any updates made to the charter as it is important to let the FDA know of any changes, especially if we are updating definitions, so that when study results are interpreted, the FDA knows exactly how these were defined. So, yes, it is standard practice to provide the FDA with the draft charter, typically with the initial submission and the protocol, and then any updates or finalized versions of the charter.