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DSMB Standing Charter

The Standing Data and Safety Monitoring Board (DSMB) is an independent group of experts whose members serve in an individual capacity and provide their expertise and recommendations for clinical studies. The primary responsibilities of the DSMB are to:

  • review the research protocol, informed consent documents and plans for data and safety monitoring;
  • if applicable, advise the sponsor on the readiness of the study staff to initiate recruitment;
  • evaluate the progress of the trial, including periodic assessments of data quality and timeliness, recruitment, accrual and retention, participant risk versus benefit, performance of the trial sites, and other factors that can affect study outcome;
  • consider factors external to the study when relevant information becomes available, such as scientific or therapeutic developments that may have an impact on the safety of the participants or the ethics of the trial;
  • review study performance, make recommendations and assist in the resolution of problems reported by the Principal Investigator;
  • protect the safety of the study participants;
  • if applicable, report to sponsor and on the safety and progress of the trial;
  • make recommendations to the Sponsor, the Principal Investigator, and, if required, to the Food and Drug Administration (FDA) concerning continuation, termination or other modifications of the trial based on the observed beneficial or adverse effects of the treatment under study;
  • if appropriate, review interim analyses in accordance with stopping rules, which are clearly defined in advance of data analysis and have the approval of the DSMB;
  • ensure the confidentiality of the study data and the results of monitoring; and,
  • if applicable, assist the sponsor by commenting on any problems with study conduct, enrollment, sample size and/or data collection.

The DSMB will discharge itself from its duties when the last participant completes the study.

The DSMB should review each protocol for any major concern prior to implementation. During the trial, the DSMB should review cumulative study data to evaluate safety, study conduct, and scientific validity and integrity of the trial. As part of this responsibility, DSMB members must be satisfied that the timeliness, completeness, and accuracy of the data submitted to them for review are sufficient for evaluation of the safety and welfare of study participants. The DSMB should also assess the performance of overall study operations and any other relevant issues, as necessary.

Items reviewed by the DSMB include:

  • Interim/cumulative data for evidence of study-related adverse events;
  • Interim/cumulative data for evidence of efficacy according to pre-established statistical guidelines, if appropriate;
  • Data quality, completeness, and timeliness;
  • Performance of the UTMB site in multi-site studies;
  • Adequacy of compliance with goals for recruitment and retention, including those related to the participation of women and minorities;
  • Adherence to the protocol;
  • Factors that might affect the study outcome or compromise the confidentiality of the trial data (such as protocol violations, unmasking, etc.); and,
  • Factors external to the study such as scientific or therapeutic developments that may impact participant safety or the ethics of the study.

DSMB Charter

  • Confidentiality

    Confidentiality must always be maintained during all phases of DSMB review and deliberations. Usually, only voting members of the DSMB should have access to interim analyses of outcome data by treatment group. Exceptions may be made when the DSMB deems it appropriate. The reason and to whom the exceptions for access to interim analyses is granted will be documented in the Closed Session Report. DSMB members must maintain strict confidentiality concerning all privileged study results provided to them.

  • Membership

    The voting membership of the DSMB should reflect the disciplines and medical specialties necessary to interpret the data from the clinical trial and to fully evaluate participant safety. The number of DSMB members depends on the phase of the trial, range of medical issues, complexity in design and analysis, and potential level of risk but generally consists of three to seven members including, at a minimum:

    • Expert(s) in the clinical aspects of the disease/patient population being studied;
    • Bioethicist;
    • One or more biostatisticians; and,
    • Investigators with expertise in current clinical trials conduct and methodology.
    • Ad hoc specialists may be invited to participate as non-voting members at any time if additional expertise is desired.
    • Ex-officio members are non-voting members of the board.

    The Chair is appointed by the Associate Vice President for Research Regulations and Compliance to serve as the Chairperson and is responsible for

    • Convening DSMB Meetings;
    • Providing minutes of the meeting and recommendations based upon committee deliberations;
    • Providing info to the PI for IRB review;
    • Communicating the views of the DSMB to the PI and to the sponsoring or funding agency (if required);
    • Documenting that DSMB Members have received training.

    A safety officer maybe identified at the first meeting and is typically the Chair unless this individual is not a physician. In this case another member of the DSMB is appointed as the safety officer. The safety officer will be the contact person for serious adverse event reporting. Procedures for notifying the Chair of the DSMB and the sponsor or funding Program Official will be discussed and agreed upon and documented at the first meeting for the clinical study.

  • Conflict of Interest

    No member of the DSMB should have direct involvement in the conduct of the study. Furthermore, no member should have financial, proprietary, professional, or other interests that may affect impartial, independent decision-making by the DSMB. Letters of invitation to prospective DSMB and ad hoc members should include the following: "Acceptance of this invitation to serve on the UTMB DSMB confirms that I do not have any financial or other interest with any of the collaborating or competing pharmaceutical firms or other organizations involved in the study that constitute a potential conflict of interest." In addition, all DSMB and ad hoc members will sign a Conflict of Interest certification to that effect at the time they are asked to participate. At the beginning of every DSMB meeting, the Chair will reconfirm that no conflict of interest exists for DSMB members. Interests that may create a potential conflict of interest should be disclosed to the DSMB prior to any discussion. The DSMB will determine how to handle any such potential conflict. The DSMB can require that a member with a potential conflict abstain from voting or take other means deemed appropriate. The Chair may dismiss a member of the DSMB in the event of unmanageable potential conflict or appearance of conflict.

  • Meetings

    The DSMB may meet a minimum of once monthly but should convene as often as necessary. An emergency meeting of the DSMB may be called at any time by the Chair should participant safety questions or other unanticipated problems arise related to a study.

    The DSMB will discuss protocols, suggest modifications, and establish guidelines for study monitoring by the Board for each study. The DSMB Chairperson in consultation with the Principal Investigator and the Sponsor, if applicable, will prepare the agenda to address the review of study materials, modifications to the study protocol and informed consent document, initiation of the trial, appointment of a safety officer, as needed, reporting of adverse events, statistical analysis plan including interim analysis and stopping rules, etc.

    The DSMB examines the accumulated safety and enrollment data, review study progress, and discuss other factors (internal or external to the study) that might impact continuation of the study as designed. A DSMB meeting may be requested by DSMB members, Sponsor, Industry Collaborator, IRB, or study Principal Investigator at any time to discuss safety concerns. Decisions to hold ad hoc meetings will be made by the DSMB Chair. Meetings may be held by conference calls or videoconferences or as face-to-face meetings. In the event a DSMB member cannot attend a meeting, he/she may receive a copy of the closed session DSMB report (see below) and either participate by conference call or provide written comments to the DSMB Chair for consideration at the meeting.

    Meetings are closed to the public because discussions may address confidential participant data. Meetings are attended by the Principal Investigator and members of his/her staff.

  • DSMB Meeting Format

    The recommended meeting format consists of three sessions: Open Session, Closed Session, and Closed Executive Session.

    A. Open Session: Issues relating to the general conduct and progress of the study are discussed including adverse events and toxicity issues, accrual, demographic characteristics of enrollees in aggregate, disease status of enrollees (if relevant), comparability of groups with respect to baseline factors, protocol compliance, site performance, quality control, and timeliness and completeness of follow-up. Any data provided must be presented without grouping by treatment assignment or otherwise by preserving the masking of all subjects. Outcome results are not generally discussed during this session. DSMB members, voting and ex officio members, PI and key members of the study team, ad hoc experts and the study biostatistician attend this session in order to present results and respond to questions. This session is open to study investigators, coordinating center staff, representatives for industry collaborators, representatives from the Food and Drug Administration (FDA) and other regulatory agencies (DOD, NIH, etc., if applicable, and sponsors.

    B. Closed Session: Grouped safety data and, if appropriate, efficacy data are reviewed with the study statistician(s) available for consultation at this session. Grouped data should be presented by coded treatment arm. This session is normally attended only by voting members. This final session involves only DSMB voting members to ensure complete objectivity as they discuss outcome results, make decisions, and formulate recommendations regarding the study. If treatment codes have been made accessible to the DSMB, then the DSMB may unmask the data based on procedures identified in advance.

    C. Closed Executive Session:  Executive sessions are an option if there is a sponsor involved. If necessary, an executive session will be attended by voting DSMB members and the sponsor staff and / or their representatives. The executive session will be held to identify and discuss the DSMB’s recommendations to the sponsor. The study staff may be present, at the request of the DSMB, during the executive session.

    A brief summary that describes the individual findings, overall safety assessment and DSMB recommendations will be the responsibility of the Chair. Each meeting must include a recommendation to continue, pause, or to terminate the study and whether the DSMB has any concerns about participant safety made by a formal DSMB majority or unanimous vote. Should the DSMB decide to issue a termination recommendation, the full vote of the attending DSMB members is required. In the event of a split vote, majority vote will rule, and a minority report should be appended. The DSMB Chair provides the tiebreaking vote in the event of a 50-50 split vote.

    A recommendation to terminate the study may be made by the DSMB at any time by majority vote. The Chair should provide such a recommendation to the sponsor immediately by telephone and email. After the sponsor makes a decision about whether to accept or decline the DSMB recommendation to terminate the study, the PI is immediately informed about his decision.

  • Voting

    A quorum, as defined by the DSMB in the initial meeting, must be present either in person, on video or by conference call. After a thorough discussion of DSMB members' opinions and rationale and an attempt to reach clarity regarding individual recommendations, the final recommendations of each DSMB member should be solicited during the Closed Session. A consensus opinion or recommendation among members is not required; each member may have individual opinions. The final recommendations are recorded and either identified as majority or minority positions or are accompanied by actual vote tallies for each divergent recommendation, i.e., as number of votes for or against a particular action, such as continuing or terminating a study, etc.

  • Study Reports for DSMB Meetings

    It is the responsibility of the PI to ensure that the DSMB is apprised of all new safety information relevant to the study product and the study. This includes providing the DSMB with a copy of the Clinical Investigator’s Brochure (CIB) in advance as well as promptly providing all CIB revisions and all safety reports issued by the Investigational New Drug (IND) sponsor and manufacturer. Summary safety and enrollment data should be forwarded periodically to the DSMB as described in the Study Charter. The DSMB should receive all protocol revisions and may receive other documents relating to the study.

    Reports are prepared by the study statistician(s). The study statistician should provide suggested formats or templates for data presentation for the initial meeting of the DSMB. The DSMB must review and approve the data elements to be presented. At subsequent meetings, additions or modifications to these reports may be directed by the DSMB on a one-time or continuing basis. Written reports should be sent to DSMB members prior to the meeting at a time specified in the Study Charter and should allow sufficient time for review.

    Reports for meetings of the DSMB consist of two separate parts: Open Session Report and Closed Session Report. Open Session reports are distributed to DSMB members and other appropriate persons as directed by the DSMB at least one week prior to a scheduled meeting. Closed Session reports are distributed on the same schedule but only to DSMB members and others as designated by the DSMB Chair. The data presented in the reports must reflect both the need for the fullest possible information on study results and the need to assure reliability and accuracy of the information included.

    A. Open Session Report: This report provides information on study conduct, as outlined above in Section III, such as accrual, appropriate demographic representation, baseline characteristics, protocol compliance, site performance, quality control, and currency of follow-up. General (ungrouped) adverse events and toxicity issues are also included in the open report.

    B. Closed Session Report: This report may contain data on study outcomes, including safety data and, depending on the study, efficacy data coded by group. It may also contain data from the Open Session report but presented separately for each study arm. Interim analyses of efficacy data are presented only when planned in advance and appropriate statistical criteria for assessing evidence of efficacy have been clearly addressed. The Closed Session reports should be destroyed at the conclusion of the meeting. If the meetings are held by telephone, printed copies of the closed reports should be destroyed immediately following the meeting. If a study has an interim analysis, it is also discussed in the closed session.

    If an exception has been made to provide the Closed Session Report to non-voting members, the reasons and recipients will be clearly explained. Supplemental information may need to be furnished immediately after the meeting if the DSMB decides that such follow-up is needed in order to conclude their deliberations.

    The Closed Session Report is confidential, and password protected and marked accordingly. Procedures for securing closed reports distributed to telephone and video conference participants should be specified in advance of the meeting.

  • Other Reports of Study Progress

    Masked safety and enrollment data may be forwarded periodically to all DSMB members or to the member who serves as the Independent Safety Officer. The DSMB receives all protocol revisions and may receive other documents relating to the study, such as annual reports, manuscripts, and newsletters.

    1. Mailings to the DSMB: On a scheduled basis (as agreed upon by the DSMB) blinded safety data could be communicated to all DSMB members or to the designated Safety Officer. The study may provide these data directly to the DSMB, if such communication procedures are requested. If there is a sponsor, approval will have to be granted by the sponsor.

    2. Access to Interim Data: Access to the accumulating endpoint data should be limited to as small a group as possible, such as the statistician. Limiting the access to interim data to the DSMB members relieves the investigator of the burden of deciding whether it is ethical to continue to randomize individuals and helps protect the study from bias in recruitment and/or evaluation.

    3. Interim Analyses: In studies in which an interim analysis is planned, the DSMB will need to review investigators’ plan and advise sponsor (if applicable) on its appropriateness (e.g., after n participants have been accrued). The interim analysis will be reviewed in closed session and may be presented in blinded group A/B format; however, the DSMB may request review of the unblinded data.

    Interim analyses of efficacy data are performed only if they are planned and approved in advance and criteria for possible stopping are clearly defined.

  • Reports from the DSMB

    1. Summary Report: The DSMB will approve written minutes that identify topics discussed by the DSMB and describe its individual findings, overall safety assessment, and recommendations. The rationale for recommendations will be included when appropriate. Minutes will generally not include information that was discussed in the Closed Session.  The DSMB Chair or designee is responsible for drafting, circulating, and obtaining approval from other DSMB members in a prompt manner.   Additional reporting (e.g., IRB) is the responsibility of the study team.  If the study is being conducted under an active IND/ IDE, the IND/IDE sponsor will forward the summary report including routine and nominal findings to the Food and Drug Administration (FDA) and to any other industry collaborators.

    2. Closed Session Report: The DSMB Chair prepares confidential minutes that include a summary of closed session discussions. Meeting minutes are to be held in the custody of the Chair until such time when the study is closed or the DSMB recommends early termination or in the event the minutes are requested by the FDA or other appropriate regulatory agencies (e.g., NIH, DOD) for participant safety reasons or for regulatory purposes.

    A formal report containing the recommendations for continuation or modifications of the study will be prepared by the DSMB Chairperson. The draft report will be sent by email to the DSMB members for review and approval and responses recorded. Once approved by the DSMB members, the report will be forward to the Principal Investigator. It is the responsibility of the Principal Investigator to distribute the DSMB recommendation to all co-investigators. The Principal Investigator will ensure that copies are submitted to all the IRBs associated with the study.

    As previously stated, the formal DSMB report must include a recommendation to continue or to terminate the study. This recommendation should be made by formal majority vote. A termination recommendation may be made by the DSMB at any time by majority vote. The DSMB is responsible for notifying the Principal Investigator of its decision to terminate the study. In the event of a split vote in favor of continuation, a minority report should be contained within the regular DSMB report. The report should not include unblinded data or discussion of the unblinded data.

  • Relationship Between DSMBs and IRBs
    NIH policy has explicitly identified required communications that must occur between DSMBs and Institutional Review Boards (IRBs) (“Guidance on reporting adverse events to IRBs for NIH-supported multicenter clinical trials” dated June 11, 1999). The DSMB should provide feedback at regular and defined intervals to the IRBs. After each meeting of the DSMB, the DSMB’s Executive Secretary or Chair should send a brief summary report to each investigator. The report should document that a review of data and outcomes across all centers took place on a given date. It should summarize the DSMB members’ review of the cumulative toxicities reported from all participating sites without specific disclosure by treatment arm. It should also inform study investigators of the DSMB members’ conclusions with respect to progress or need for modification of the protocol. The investigator is required to transmit the report to his/her local IRB.

Dated: February 8, 2022