Data Safety Monitoring Boards Facilitate Ethical Research

In clinical trials, the safety of research participants is paramount. An organization conducting or sponsoring clinical research can ensure participant safety by convening a data safety monitoring board (DSMB), sometimes called a data monitoring committee (DMC) or independent safety monitoring board (ISMB). This group of impartial experts reviews patient safety and treatment efficacy during a trial. They determine whether the trial should continue, be modified, or be closed.

A DSMB is generally needed for trials involving high risk and studies utilizing blinding for Phase III clinical trials and for multicenter clinical trials. A DSMB’s ultimate objective is to safeguard both the participants and the study’s scientific validity. These two principles are essential to ethical research conduct.

DSMB Members

The size and composition of a DSMB varies with a trial’s type and complexity. Most DSMBs include three to seven members. Members have individual expertise in the condition and/or intervention being studied, in statistics, and/or in clinical trial design and conduct. Bioethicists and patient representatives often participate as well. A DSMB is typically chaired by a member experienced in monitoring clinical trials. The board may also include a non-voting member who serves as an executive secretary.

To maintain their objectivity, DSMB members should not have any financial and/or scientific stake in the outcome of the trial. Regulatory guidance from the U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA) indicates members should be independent of the team developing the investigational intervention and of the regulatory officials evaluating it. Members are asked to confirm they have no conflict of interest potentially influencing or appearing to influence their decisions.

The clinical trial sponsor is generally responsible for selecting potential DSMB members. The independent DSMB administrator will typically present members to the sponsor for evaluation and selection. The principal investigator or research institution may also suggest candidates. Candidates are approved by the research team and the sponsor before being invited to participate. Members typically serve for the duration of a trial.

Monitoring Study Data and Participants

A DSMB has key responsibilities. First, the expert members on the DSMB review the protocols and safety monitoring plans for the study and approve the DSMB charter and associated statistical analysis plan (SAP). These collectively outline the safety criteria the DSMB will use to evaluate the ongoing trial data.

Once the trial is underway, the DSMB periodically monitors study data for participant safety, futility, and early signals of efficacy. The board specifically seeks to address any unexpected change in adverse events arising during study conduct, or early indications of futility, in order to protect research participants. The DSMB may also conduct or review the planned interim analyses of the currently available data to determine if changes to the trial are needed at pre-determined points in the trial design.

The DSMB uses safety data and the results of interim analyses to make recommendations for study continuation, modification, or early termination. The board may recommend modification or early termination if they have serious concerns about patient safety, if evidence suggests a lack of efficacy for the intervention, and/or if the trial appears to have little chance of yielding informative results. The DSMB is responsible for communicating its recommendations to the research sponsor.

Defining the Board’s Charter

DSMBs use a charter to outline their scope and specifications. A DSMB charter is reviewed and agreed upon by board members and the sponsor, with approval typically coming before the trial is initiated. A professional third party DSMB administrator will hold an organizational meeting to ensure all parties are on the same page prior to the start of the trial.

The charter creates shared expectations among stakeholders as to how the board will accomplish its objectives. Typical components include:

• Purpose and responsibilities of the DSMB, as described above
• Qualifications and roles of the individual members
• Meeting, reporting, and communication procedures
• Confidentiality and conflict of interest guidelines
• Content of the DSMB SAP and associated tables, listings, and figures (TLFs), which will summarize aggregate trial data for the members to evaluate

Because of the nature of the information they handle, DSMBs maintain strict confidentiality. All of their materials, discussions, and proceedings are kept private. DSMBs also maintain autonomy from the research team and sponsor, avoiding the appearance of conflicts of interest that could be seen to compromise their objectivity. Neither the board nor the DSMB administrator, should be involved in trial activities, and members should not discuss the trial with the research team outside of DSMB meetings.

Effective DSMB Operations

To help achieve the objectives defined in its charter, a DSMB can implement best practices in several areas.

Maintain Independence and Avoid Conflicts of Interest

All DSMB members should sign a certification confirming they have no financial or other ties to any organizations involved in the study or vested interests in a specific outcome. Sponsors and research teams should endeavor to identify and train new candidate DSMB members to expand the pool of participants.

Balance Safety and Confidentiality Concerns

The DSMB might need access to “unmasked” data during the course of a trial to make appropriate recommendations. Such access should be explicitly referenced in DSMB policies. All physical and electronic communications should be secured to avoid unauthorized disclosure of confidential information.

Communicate Effectively with Stakeholders

The DSMB charter should include a list of reports the DSMB provides to stakeholders, including the sponsor and the research team. Verbal reports, meeting minutes, summaries, action reports, and recommendations are normally specified.

Adapt to Changing Study Requirements and Emerging Safety Issues

Once a trial is underway, new information or circumstances may necessitate changes to study conduct or identify or create new safety risks. DSMBs should be flexible and responsive when addressing such emerging issues. Their recommendations can include pausing the trial to allow for analysis and deliberation.

Future of DSMBs

Protecting the safety of trial participants and the integrity of scientific data by monitoring trial results is imperative in the ethical conduct of clinical research. DSMBs fulfill these goals by considering the validity of a clinical trial, the potential utility of its results, and the risks to current and future patients. These considerations inform their recommendations for continuing, modifying, or terminating the trial. DSMBs are integral to responsibility in clinical research, but face certain challenges in achieving their purpose. As the research landscape continues to evolve, DSMBs must adjust their practices to meet these challenges.

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