What is a Data Monitoring Committee?
Clinical trials receive a lot of oversight from regulatory agencies, as well as independent committees reviewing different aspects of the trial. Depending on the nature of the trial, the independent committees involved may include:
- Institutional review boards (IRBs)
- Institutional biosafety committees (IBCs)
- Scientific review committees (SCRs)
- Endpoint adjudication committees (EACs)
- Data monitoring committees (DMCs)
In particular, IRBs are likely the most well-known of the independent oversight committee functions. While IRBs are also known as research ethics boards (REBs), ethics committees (ECs), or independent ethics committees (IECs), we will refer to this committee as an IRB in this blog.
Each committee plays an important role in providing trial oversight. They aim to keep participants and research staff safe, and help the IRB determine if a trial has an adequate safety monitoring plan as required by Food and Drug Administration (FDA) regulation 21 CFR 56.111(a)(6).
In this blog we look at the specific role DMCs play in overseeing research, and how IRBs rely on the independent DMC’s oversight of interim trial data to ensure an adequate safety monitoring plan is in place.
What Is an Independent DMC?
A DMC is an independent group of experts who conduct a periodic review of accumulated interim data during a clinical trial. DMCs are strenuously recommended for certain clinical trials by both U.S. FDA and EU European Medicines Agency (EMA) guidelines.
Particularly in trials with a blind or placebo control, the DMC’s purpose is to review unblinded trial data as it is collected to detect and report safety concerns, early evidence of benefit or harm, and futility of the treatment, using criteria outlined in the clinical trial protocol.
DMCs are typically comprised of five to six members, including biostatisticians and clinicians. All must be independent of the trial sponsor.
Sponsors are responsible for creating the DMC for a trial, or engaging an independent firm to create and administer the DMC on the sponsor’s behalf.
Many sponsors use independent administrators to support DMC separation and independence as an independent oversight committee.
The DMC typically operates under a detailed charter outlining what data the committee will review, how members are selected and vetted for conflicts, and other operational considerations governing how the committee runs. This includes the format for reporting and providing recommendations back to the sponsor.
What’s the Difference Between a DMC and a Data Safety Monitoring Board?
In short, both FDA and EMA use “data monitoring committee” to describe the group, independent of the sponsor, who is charged with looking at the data to determine when trial endpoints and other milestones are met.
In North America, these groups are also referred to as data safety monitoring boards (DSMBs). In other parts of the world, they are also known as data and safety monitoring committees (DSMCs), independent data monitoring committees (IDMCs), and other similar titles.
Regardless of the name, the concept and purpose of these committees are the same: providing independent oversight of certain aspects of the study. In blinded research, DMCs evaluate unblinded study results to determine if endpoints and other milestones have been met.
When is a DMC Needed?
FDA guidelines outline when the agency expects a data monitoring committee to be created. However, sponsors may engage independent DMCs for other types of studies, and on occasion, the IRB may determine there is a need for a DMC as part of the clinical protocol’s overall data safety monitoring plan.
In brief, the FDA recommends sponsors consider using a DMC when:
- The trial is blinded or has endpoints, such that an independent group must evaluate unblinded data to determine if the study has met pre-determined endpoints, futility, or other stopping rules and should be terminated early
- There are other reasons for a safety concern (e.g., a particularly invasive procedure)
- There is prior information suggesting the possibility of serious toxicity where interim analysis of adverse event data is necessary to determine if toxicity endpoints are met
- The trial is large, or of long duration, and multicenter, where a single group in needed to evaluate and analyze the consolidated interim study data
Most commonly, DMCs are created for later phase, randomized, drug and device studies. In these studies, there is a need for an independent committee to evaluate interim study data for emerging participant safety issues and to determine if stopping rules have been met.
The DMC is advisory to the sponsor and provides an opinion, based on interim analysis, as to whether the trial should continue as it has been, receive changes to the trial design, or be stopped early. Most DMC charters give the committee the power to make recommendations only. Unlike the IRB, which under the FDA regulations has authority to disapprove or terminate approval for research (21 CFR 56.113), the DMC only plays an advisory role to the sponsor.
Where Does a DMC Fit With IRB Review?
U.S. FDA regulations stipulate IRBs must determine that “where appropriate, the research plan makes adequate provision for monitoring the data collected to ensure the safety of subjects.” (21 CFR 56.111(a)(6))
The IRB must determine if an appropriate plan is in place to adequately monitor data to ensure participant safety. This is typically referred to in the clinical protocol document as the data safety monitoring plan (DSMP).
One of the primary ways a sponsor satisfies this regulatory requirement is to utilize an independent DMC as part of the plan. The IRB will typically view a monitoring plan, which incorporates an independent DMC as “adequate provision” to ensure data is monitored for safety.
During the trial, as part of the required continuing review process, the IRB typically requests copies of the DMC’s recommendations to the sponsor. In this way, the IRB can leverage the work of an independent DMC and its recommendations in a few different ways. They can determine if there is any new information which may impact the IRB’s decision to approve the research to continue, require alterations to the research, inform participants of potential new risk information, or not approve the research to continue (21 CFR 56.109(f)).
DMC and IRB Relationship
IRBs do not see unblinded study data and are not in a position to know unilaterally if trials have met stopping rules. They must rely on independent DMC review, and other oversight committees, to work collaboratively to protect clinical trial participants.
As an example, at Advarra, our IRB diligently reviews each trial’s data safety monitoring plan to ensure it is adequate to satisfy the FDA regulatory criteria. Many times, the safety monitoring “plan” will include an independent DMC. In these circumstances, the IRB routinely verifies if the DMC recommends stopping the trial early or making any changes to reduce participant risk.
The DMC and IRB are two committees, with different roles and focuses, both working together to independently oversee a clinical trial and the safety of the participants.
Note: This article was originally published on July 1, 2021, and has been updated to include new and clarifying information.