Developing a Comprehensive Yet Concise DMC Charter

Per FDA, data monitoring committees (DMCs), also referred to as Data and Safety Monitoring Committees (DSMCs) or Data and Safety Monitoring Boards (DSMBs), should operate off of a documented DMC charter.

What is a DMC Charter?

Data Monitoring Committees (DMCs) are independent groups typically comprised of clinicians and biostatisticians who review accumulating data from one or more clinical trials on a regular basis. DMCs then advise sponsors regarding the continuing safety and validity of these trials.

As an independent group that has access to unblinded clinical trial data and a relatively strong voice in whether a trial continues, DMCs must be carefully planned and managed. To assist with this, FDA recommends that each DMC establish a trial-specific charter with clear operating procedures.

“Charters act as an instruction guide or mini protocol specifically for the DMC,” PharPoint’s Sr. Project Specialist and experienced DMC coordinator Victoria Elder, M.S., explains.

An effective charter must define the purpose, responsibilities, and operations of a DMC in a way that is both comprehensive and concise.

“They shouldn’t be overly complex,” Victoria says, “but it should have a good amount of information in there so that DMC members aren’t questioning anything.”

 

Authoring An Effective DMC Charter

So, what should an effective DMC charter look like?

Generally speaking, PharPoint often sees effective charters land somewhere around 20 pages, appendices included – but length can certainly vary.

“It just depends on the complexity of the study itself, the study design,” Victoria notes. “Maybe studies are broken up into two parts, so Part A and Part B, or maybe it’s got a SAD/MAD design. Those are a little bit more complex, and so we would have to go into a little bit more detail [within the charter]. It really just depends.”

While a DMC charter could be written by Sponsors themselves, Victoria also spoke about the value of bringing in an experienced, independent party to help author a charter – especially if maintaining independence between the Sponsor and DMC is a priority for the study. Independence is advised for finding experience participants for the DMC composition.

PharPoint maintains a robust database of experienced DMC members who hold expertise across a variety of therapeutic areas and indications. PharPoint often helps Sponsors narrow down a list of candidates for inclusion within a committee and can author charters on their behalf.

 

“The composition of a committee can benefit from being supported by someone who knows the study well enough to pull members who are experts in their field. This person would be able to offer a lot of good expertise on conducting the DMC to fit the study’s unique needs,” Victoria shares.

“It’s really important to review any conflicts of interest so [committee members] are able to make recommendations that don’t have any bias to them.”

 

What Content Should be Included within a DMC Charter?

Draft guidance released by FDA in February 2024 recently provided an updated and more in-depth look at what the agency suggests, at a minimum, within a DMC charter.

The guidance includes the following:

  • Committee Composition, including:
    • Criteria and rationale for selection of committee members
    • Outline and clarification of roles of committee members, including voting and nonvoting members
    • Procedures for assessing financial and intellectual conflicts of interest for potential DMC members
    • Procedures for adding or removing members when appropriate or for disbanding the DMC

 

  • Meeting Information, Schedule, and Format, including:
    • Planned frequency of meetings, when additional meetings might be scheduled, and the preferred platform for communications and conditions for convening ad hoc meetings
    • Who may attend open and closed portions of DMC meetings and whether any members will not attend full meetings
    • Who will create specific reports and have access to them, where reports will be stored, what reports will be generated in the course of the clinical trial and how they will be transmitted within and outside of the DMC
    • Handling of meeting minutes for open and closed portions
    • Definition of a quorum of DMC members

 

  • Planned Analyses by Committee and Protection of Data, if applicable, including:
    • Schedule and basis of planned interim analyses identified in the protocol and/or statistical analysis plan
    • Analyses associated with prespecified safety considerations

 

  • Maintaining Confidentiality of Data, including:
    • How unblinded analyses will be prepared (e.g., by an independent statistician) for the DMC and at what frequency
    • How blinding of the trial will be maintained for sponsors, investigators, and subjects
    • What procedures will be followed to maintain confidentiality of interim comparative data in communications between the DMC, the sponsor, and outside parties
    • What strategies will be used for maintaining blinding and confidentiality when preparing reports for the DMC open sessions
    • Who, besides the DMC and independent unblinded statistician, will have access to interim data and reports to the DMC chair

 

Conclusion

By establishing clear guidelines for the composition, responsibilities, and operational procedures of Data Monitoring Committees, sponsors can safeguard the safety of trial participants and the validity of trial outcomes.

Ultimately, adherence to a well-crafted DMC Charter, informed by FDA guidance and best practices, supports the ethical and effective management of clinical trials, benefiting all stakeholders involved.

 

About PharPoint

PharPoint Research is a US-based, client-focused contract research organization (CRO) that helps sponsors meet their study goals.

As part of PharPoint’s data monitoring committee services, we act as an independent partner to Sponsors that can support committee members and manage logistical challenges. Our services also include DMC charter development, authoring, and review.

 

For more information about how PharPoint can support your data monitoring committee, visit our DMC Services page or schedule a call with our team.

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