Considerations for Establishing a DSMB
DSMB Charter and Meeting Schedule
DSMB Charter
The DSMB Charter is a guiding document for the DSMB that includes well-defined standard operating procedures.7 A well-developed charter allows for structured consideration of critical concepts, improves effectiveness, and bolsters trial integrity. The best practice is to use a standard template modified for individual studies.
The DSMB Charter should define:
The responsibilities of the DSMB.
Its membership.
The purpose and timing of its meetings’ conduct and documentation.
A clear decision-making process.
How the DSMB will make its recommendations.
Procedures for ensuring confidentiality.
Guidelines for proper sponsor communication.
An outline of the data packet the DSMB should receive before each data review meeting.
Unlike the protocol and statistical analysis plan, which study teams must strictly follow with documentation of any deviations, the DSMB Charter should be a succinct document that outlines a set of guiding principles for the conduct of the DSMB. While aligned with the protocol, the charter should refrain from rigidity since it is impossible to anticipate and address all potential scenarios that could emerge during an ongoing trial.17 The DSMB Charter should provide guidelines, not rules, for data review and making recommendations.18
Lastly, the DSMB Charter is a living document that is reviewed and approved before study initiation, typically at the DSMB Orientation meeting, and should be revised at least annually. If it is necessary to amend a charter during the study, the changes must be reviewed and accepted by the DSMB members. The DSMB should document the acceptance in the minutes of the meeting in which the new charter was discussed and approved and file all versions of the charter for regulatory documentation.
Additional note: The FDA may request the sponsor to submit the charter well before the performance of any interim analysis and, ideally, before the initiation of the trial.7 The need for finalization of the charter before the First Patient In is also due to the possibility of having a Serious Adverse Event right after a patient signs the ICF or a Suspected Unexpected Serious Adverse Drug Reaction right after the first dose of the study drug, either of which may trigger an ad hoc DSMB meeting.
After establishing a DSMB, all parties involved – the DSMB, the sponsor, and the CRO – must attend an orientation meeting to familiarize the DSMB members with the study, their roles, and responsibilities and to discuss and approve the DSMB Charter. An essential part of the agenda is determining the DSMB data review meetings’ schedule and format. If the charter is not finalized and approved during this initial meeting, such as because of comments and suggestions that will take time to implement, the board must finalize it as soon as possible.
The frequency of DSMB meetings depends on the study design, the expected accrual and event occurrence rate, and the perceived risk of the experimental and control interventions.7 DSMBs may set the meeting schedule based on time increments or study-related milestones or events. For example, meetings may be held quarterly, on an annual or bi-annual basis, or based on milestones such as a certain percentage or number of patients enrolled or treated or the number of study-related events.7 Most frequently, we see a combination of these approaches.
Each DSMB data review meeting typically consists of an “open” and “closed” session. The ”open session” is attended by an extended circle of people, including DSMB members, the sponsor, and the CRO, while closed sessions are for the DSMB members only.
At an open session, attendees update the DSMB on the study conduct and overall safety experience in the study of interest and other completed and ongoing trials with the same study drug. After each open session, a draft of the meeting minutes is prepared, reviewed, and revised by the entire DSMB, then approved.
At the closed session, the DSMB discusses unblinded data. Following their comprehensive review, the DSMB will send their recommendations.
Meetings may be held either in a face-to-face format or via teleconference or web-based conferencing.17
Ad hoc meetings may be called in case of an unexpected event, often called a “safety signal,” requiring immediate review and decision. For example, if a hemophilia clinical trial has a stopping rule of a fatal cerebrovascular accident related to the study drug, the DSMB must have an ad hoc meeting as soon as possible once such an event is reported.
The two main challenges with DSMB meetings are:
1. Arranging all participants for the meeting while managing scheduling conflicts and other duties, especially when the meeting needs to be conducted within a narrow time frame.
2. Preparing high-quality meeting minutes with clear, concise details for the sponsor(s) and other parties.
Sponsors can address both with a dedicated team whose main task is DSMB management. At PSI, we have a DSMB Support Group that includes experienced DSMB Coordinators who track DSMB members’ availability and the study meetings’ schedule and arrange meetings without delays. They are also responsible for preparing, finalizing, and filing the meeting minutes. In doing so, we keep the process of DSMB management consistent, transparent, and predictable throughout our studies.
Next up: Final Thoughts
