Data Safety Monitoring Boards

DSMBs, also known as Data Monitoring Committees (DMCs), provide independent, objective oversight of regulatory submission studies, such as Phase II/III IND studies for pharmaceuticals and IDE studies for medical devices. DSMBs operate under relevant FDA guidance to monitor subject safety and to ensure that the trial is being conducted in a manner that is consistent with the FDA approved study protocol.

The DSMB will typically consist of physicians that are subject matter experts in the clinical domains that are relevant to the clinical trial, and an independent biostatistician with experience in clinical trials and relevant statistical methodologies. The members of the DSMB may not have any fiduciary association with the study sponsor or competing interests, nor have any operational role in the conduct of the study, thus avoiding any potential conflict of interest in maintaining an objective oversight role.

There will typically be ongoing DSMB meetings, which consist of separate "open" versus "closed" components. The closed or executive part of the meeting for the DSMB members only, will enable the DSMB to review and discuss content that may not be apropos for the open part of the meeting, where sponsor or other representatives, who may have operational roles in the conduct of the study, are present. This approach preserves the confidentiality of the DSMB discussions to avoid, even inadvertently, affecting the conduct of the study due to exposure to that knowledge.

In this role, operating under a formally defined DSMB Charter for the study, I collaborate with the independent subject matter expert physicians, to support key ongoing discussions that can include:

• • Pre-study reviews of the protocol and relevant discussions with the sponsor.
  • Reviews of ongoing DSMB reports prepared by a designated statistician that can contain blinded and/or unblinded interim results, as apropos for the study. Modifications to the content of the DSMB report can also occur over time, as the study evolves and questions arise.
  • Reviews of study enrollment status to monitor whether or not the study is proceeding according to expected accrual rates.
  • Reviews of overall and site-specific study conduct, including topics such as protocol deviations, premature withdrawals, treatment compliance and cross-overs, and related activities, to ensure that the integrity of the study is being maintained in accordance with the approved study protocol.
  • Reviews of subject safety presentations, to assess the impact of adverse events, especially any treatment related, device related and/or unexpected serious adverse events, that may raise concerns as to the safety of the subjects in the study.
  • Reviews of interim efficacy data that, in combination with the safety data presentations, ensure that the risk/benefit balance for the study subjects is being maintained as the study progresses.
  • If the study should have pre-defined stopping rules for safety, efficacy and/or futility, these rules will be evaluated against the ongoing interim analyses, including the consideration of any relevant trends, given the decision making framework for the DSMB that has been defined.

Within the context of the ongoing DSMB meetings, and the reviews of the data that are presented, the DSMB is in a position to therefore make recommendations to the study sponsor, which can include continuing the study "as is", make recommendations for protocol modifications that may require a formal amendment process, and/or make a recommendation to stop the study in the presence of formally pre-specified stopping rules or other concerns predicated upon relevant interim findings.