Sponsors may have different areas to drive the formation and facilitate the DMC work. At NN, DMCs are overseen by the Pharmacovigilance area. A Global Patient Safety Surveillance department representative, hereafter termed ‘DMC advisor’, plays a key role in DMC management and serves as the central point of contact for the DMC. The DMC advisor drives the sponsor assessment for whether a DMC is required and, subsequently, the DMC composition and expertise areas to be included.

The proposal for a DMC is submitted to the internal NN safety committee, which consists of representatives from various functional areas. This committee is the sole body responsible for evaluating the product’s safety profile, benefit-risk balance, and communications related to product safety. The safety committee supports the DMC proposal and considers whether it is advantageous to have a single DMC oversee multiple related trials. Having one DMC monitor several trials within the development program allows for synergy and provides the committee with more data to make informed assessments and recommendations. These decisions should ideally be made early in the trial planning process, since it takes time to identify and contract DMC members and establish the committee.

Typically, DMCs for NN sponsored trials consist of three to six members, including a DMC statistician and a DMC chair, in accordance with guidelines [3, 14, 15]. It is crucial that DMC members are independent of the sponsor, meaning that they cannot be an investigator in one of the sponsor’s trials or part of related committees such as steering or event adjudication committees, and advisory boards. To preclude bias in data assessment, DMC members are prohibited from having any financial, intellectual, or emotional competing interests such as serving on a competitor’s DMC, i.e. within the same indication and the same mode of action or serving on a competitor advisory board. These requirements are contractually binding and detailed in the DMC charter.

When a candidate for a DMC has been identified and cleared from conflicts of interest (COI), the following is obtained: a signed General Data Protection Regulation (GDPR) consent form to comply with EU data legislation, a current curriculum vitae, and documentation of training in Good Clinical Practice. Once a DMC member is contracted, they are subsequently blocked from NN expert directories, preventing members from being approached for other sponsor-related activities during their DMC service. All DMC members are reminded in relation to the data review meetings to disclose any new obligations after contract signing to assess potential COI.

The DMC should be established in parallel with protocol development and must be fully established prior to the treatment of participants. Before finalization, at least one DMC member, preferably the DMC chair, should review the protocol. This ensures that the DMC can provide input to sections related to and impacting the role and responsibility of the DMC. In addition, a DMC charter is required as part of the clinical trial application for some Health Authorities, which underscores the importance of an early DMC establishment.

At NN, two additional roles are assigned to tasks related to the DMC from the Global Safety Surveillance Department. The ‘DMC coordinator’ is responsible for handling the DMCs’ contracting and compliance with external healthcare professional (HCP) and healthcare organization (HCO) regulatory and financial aspects. The second role is a ‘DMC process manager’, who serves as the internal DMC subject matter expert and the go-to person for all DMC-related questions in general. These roles are critical for ensuring consistency and alignment across the various DMCs and as sponsor representatives, they must remain blinded and not have access to unblinded information.

Prior to the trial start date, a DMC kick-off meeting is held to initiate the collaboration between the DMC, sponsor and statistical vendor [3]. At this meeting, the trial protocol, the statistical plans, current knowledge of the product safety profile, and the DMC charter are presented and discussed with DMC members (Fig. 2).

The DMC charter is created based on a sponsor template document and includes a clear description of the roles and responsibilities of the DMC, the sponsor, and the statistical vendor. It documents rules of conduct for data review meetings, minimum data items to be reviewed by the DMC, and the process for providing recommendations to the sponsor. DMC feedback on the charter and on the interim analysis, if applicable, will be discussed at the DMC kick-off meeting. The DMC charter is approved and signed by the DMC chair and sponsor before the first patient’s treatment. Mock table shells for the DMC report should be prepared by the statistical vendor and will be agreed upon at the kick-off meeting. Any updates to table shells during trial conduct will only be discussed in closed meeting sessions to avoid any potential unblinding of the sponsor. Typically, timelines for the first data review meeting will be agreed upon at the kick-off meeting, and the communication line between the DMC, the statistical vendor, and the sponsor will be made clear to everyone.