Skip Navigation

Microbiology and Infectious Diseases Clinical Research Policies, Guidance, and Tools

Skip Content Marketing
  • Share this:
  • submit to facebook
  • Tweet it
  • submit to reddit
  • submit to StumbleUpon
  • submit to Google +

Safety Oversight

Safety Oversight Committee refers to a committee of experts, independent of the trial investigators, pharmaceutical sponsor (if any), and funding agency, that periodically reviews the conduct and results of the clinical trial and recommends continuation without change, continuation with change, or termination of the trial. The Division of Microbiology and Infectious Diseases (DMID) convenes a Data and Safety Monitoring Board (DSMB) for randomized, multi-center trials that are large Phase II, are Phase III, or are Phase IV. DMID also utilizes another type of committee, a Safety Monitoring Committee (SMC), which is an independent group of experts that advises DMID and the study investigators for many Phase I and smaller Phase II trials. The primary responsibility of the SMC is to monitor participant safety.

The DSMB or SMC is convened by authority of DMID and is advisory to DMID and the study team. The DSMB/SMC Charter serves as the standard operating procedure and defines the primary responsibilities of the DSMB/SMC, its membership, the purpose and timing of its meetings, data to be reviewed and procedures for ensuring confidentiality and proper communication. The Charter will be finalized following the Organizational meeting and will be updated or revised as indicated. Revisions to the Charter will be reviewed and approved by the DSMB/SMC. When there is another party other than DMID supporting the conduct of the study, such as an industrial collaborator, the party will participate in the DSMB/SMC activities according to the guidelines in the contract, grant, or Clinical Trial Agreement (CTA) with DMID, as applicable.

For Phase I and II clinical trials, DMID requires that an Independent Safety Monitor (ISM) be identified for each trial site prior to trial enrollment. The ISM should be a physician local to the site, have relevant expertise to evaluate the subject, and be able to do so in a timely manner. Under special circumstances, an ISM may be asked by DMID to examine the subject and provide an ad hoc medical assessment.

For trials other than Phase I and II, DMID may determine that ISMs are not required based on the trial design and projected enrollment rate. This would be determined prior to the start of the clinical trial. The investigator at each site will then be responsible for identifying a physician with relevant expertise to provide an ad hoc medical evaluation of a safety event, if requested by DMID.

Conflict of Interest

DMID, in consultation with the study team, identifies DSMB/SMC members and will assess their eligibility based on Conflict of Interest (COI) disclosure. The sources of these conflicts may be financial, scientific or regulatory in nature. DMID is responsible for deciding whether consultancies or the financial interests of the members materially affect their objectivity. Members will notify DMID promptly if a change occurs that may create a potential conflict of interest.

Membership

The DSMB/SMC consists of at least three voting Members. A DSMB will include a biostatistician experienced in statistical methods for clinical trials and a clinician with relevant expertise; and although not required, a biostatistician may also be included in the SMC. Representatives of other clinical or laboratory specialties, bioethics, and the affected community are often critically important. When selecting DSMB/SMC Members, DMID should consider: clinical trials experience, relevant scientific expertise, prior DSMB/SMC service, and potential significant conflicts of interest. If needed, consultants may be invited to provide needed expertise, as ad-hoc members, and will not vote. NIAID employees will not serve as Members of the DSMB/SMC. Individuals who are directly involved in the conduct of the clinical trial will not be Members. Members will not be under the supervision of any of the investigators involved in the conduct of the clinical trial. Typically, the DSMB/SMC membership is for the duration of the clinical trial. If any Members leave the DSMB/SMC during the course of the trial, DMID will promptly appoint their replacement. If, in the judgment of DMID, a Member is not participating as needed in the DSMB/SMC activities, DMID will ask the Member to resign and will appoint a replacement. Membership in DMID DSMBs and SMCs is strictly voluntary as these positions do not receive compensation.

Responsibilities of the DSMB/SMC and DMID

The DSMB/SMC will be responsible for safeguarding the interests of the clinical trial subjects and for monitoring the overall conduct of the clinical trial.

DSMB/SMC members
  • Sign a Conflict of Interest certification at the time they are asked to participate and notify DMID promptly of any potential conflict of interest
  • Provide contact information to the DMID DSMB/SMC support contractor
  • Protect the confidentiality of the trial data and DSMB/SMC discussions
  • Review the protocol, sample informed consent and plans for data safety and monitoring prior to initiation of the study
  • Approve the Charter and review materials provided prior to the DSMB/SMC meetings
  • Periodically review and evaluate the accumulated study data for participant safety, study conduct and progress, and, when appropriate, efficacy
  • Review and evaluate ad hoc safety issues concerning the study at the request of DMID
  • Make recommendations to the DMID Medical Monitor (MM) and Clinical Project Manager (CPM) concerning continuation, termination, or modification of the study based on the observed beneficial or adverse effects of the study
  • Participate in safety oversight for the period of the study up until notification is received from DMID that their service is complete
  • Ensure review materials are kept secure; at the completion of the DSMB/SMC service, the members will verify by email that the materials have been destroyed.
The DSMB/SMC Chair
  • Serves as the point of contact for the DSMB/SMC and facilitates meetings and discussions
  • Communicates DSMB/SMC Recommendations to DMID and members of the project team
  • Reviews, approves, and signs Final Recommendations and meeting summaries
  • Works directly with the DMID DSMB/SMC support contractor (SOCS), which serves as the DSMB/SMC executive secretary, to document recommendations and meeting summaries as well as provide signatures for these documents
  • Is available to DMID for consultation regarding potential safety or study-related issues

DMID Clinical Project Manager (CPM) and Medical Monitor (MM)

The DMID Clinical Project Manager (CPM) is the DMID primary point of contact responsible for the coordination and management of DMID-supported clinical research throughout the life cycle of the protocol. The DMID CPM will notify the DSMB/SMC Members, through the DMID DSMB/SMC support contractor, when their service is complete. The DMID Office of Clinical Research (OCRA) will assign a Medical Monitor (MM) to provide input on safety considerations during development of protocol and associated documents, and safety oversight throughout the life cycle of the clinical research including evaluation, assessment and monitoring of safety events and protocol deviations; participates in safety oversight committees, and consults with Independent Safety Monitors (ISMs).

DMID will identify DSMB/SMC Members and approve them based on their Conflict of Interest (COI) disclosure. The DMID Clinical Project Manager (CPM) and Medical Monitor (MM) will
  • Review and approve the DSMB/SMC Charter
  • Determine the purpose for each meeting and ensure appropriate review materials are prepared for the DSMB/SMC for each meeting
  • Review and approve Open session reports intended for all meeting participants.
  • Review the DSMB/SMC Recommendations and recommend actions for implementation by the study team, as applicable.
  • Review and approve Open session meeting summaries

Meetings

DSMB/SMC committee meetings are primarily conducted via teleconference. Three types of meetings are convened:
  • Organizational Meeting: An initial meeting of the DSMB/SMC will be held prior to any participant enrollment in order for the members to review the Charter, form an understanding of the protocol and definitions used, establish a meeting schedule, review the halting rules, and finalize format and protocol-specified statistical methods to be used in reports to be considered by the DSMB/SMC. The review of the protocol does not constitute participation in the trial design, but rather gives the DSMB/SMC an opportunity to communicate to DMID that major issues and concerns need to be addressed. In this case, the DSMB/SMC will provide DMID a detailed list of specific issues that need to be resolved before the DSMB/SMC will assume oversight responsibilities.
  • Data Review Meeting: DSMB/SMC meetings will be held to review and discuss study data. The purpose of the data review is safety evaluation, and the study may be stopped because of significant safety concerns. Emerging efficacy data may be considered by the DSMB/SMC when evaluating the potential risks and benefits of the treatment under study. Data Review Meetings consist of open and closed session discussions.

    The Open Session is open to members of the study team, coordinating/data center staff, NIAID staff, and representatives of industry collaborators or representatives from government agencies. The Open session provides the DSMB/SMC an opportunity to query the study team about issues that have arisen during the review of the data.

    The Closed session is attended only by the DSMB/SMC members, the independent biostatistician who generated the closed reports, and the executive secretary. The DSMB/SMC may request unblinding of the treatment assignments for individual subjects or by group if they feel it is necessary to adequately assess the safety data presented. In this case, treatment assignments are provided in the Closed session meeting.

  • Ad Hoc Meeting: An ad hoc meeting is an unplanned meeting that is called for a specific purpose. The meeting can be requested by any party with the responsibility of overseeing the trial (such as the PI, ISM, DSMB/SMC, DMID, industry collaborator). The DSMB/SMC may request special reports on an as-needed basis. These requests will be made to DMID, biostatistics, and SOCS, as appropriate. The Chair, in collaboration with DMID and SOCS, will schedule any unplanned meetings. Significant safety events that may need review include, but are not limited to, the following:
    • A death or life-threatening condition sustained by a participant, regardless of causality
    • An unexpected serious safety issue newly identified during the development program that could expose participants to unnecessary risks
    • Any other concern regarding participant safety raised by the DSMB/SMC, DMID, or member of the study team
  • Final Meeting and End-of-Service At the conclusion of the final scheduled meeting, SOCS will confirm with the DSMB/SMC Members and DMID that no additional meetings are necessary. This will indicate the end-of-service for the DSMB/SMC Members; however, this does not preclude contacting the Members to request the scheduling of an Ad hoc meeting should a safety concern arise. SOCS will confirm with the DMID CPM that end-of-service activities should proceed, notify the DSMB/SMC Members that their service is complete, provide them with Certificates of Appreciation on behalf of DMID, and request confirmation that they have destroyed all study-related documents.

Recommendations

At each meeting of the DSMB/SMC during the conduct of the trial, the DSMB/SMC will make a recommendation if the study should continue, be modified, or terminated. The DSMB/SMC may also provide recommendations relating to selection, recruitment and retention of subjects, their management, improving adherence to the protocol and procedures for data management and quality control. Immediately following the Closed session, a brief teleconference will be held between the DSMB/SMC Chair and the DMID CPM and MM to discuss the Recommendations of the DSMB/SMC. SOCS will prepare a brief written summary of the DSMB/SMC Recommendations. The Recommendations will be approved by the Chair and then forwarded to the DMID CPM and MM for their review and inclusion of action items for implementation, as indicated. If DMID determines not to implement a recommendation, a response with rationale will be provided to the DSMB/SMC. The final, signed Recommendation form will be distributed to the investigator(s), DSMB/SMC, DMID, and others as designated on the contact list upon receipt of signatures and will be posted on the DMID-CROMS Document Library.

Electronic Data Review

DSMB/SMC members may be asked to review data electronically and provide their assessment through email. Electronic reviews are conducted similarly to closed sessions in that electronic communications are limited to the members.

Safety Oversight Coordination Support (SOCS) is DMID contractor that facilitates DSMB/SMC meetings and related activities. SOCS serves as the executive secretary for the DSMB/SMC and supports the DSMB/SMC Chair with meeting conduct and documentation. SOCS may be contacted via email: SOCS@DMIDCROMS.com ; telephone 301-897-7455 or by fax: 800-275-7619. For international faxes, please use 301-897-1710.

DMID Policies

DMID Guidance and Tools

Additional Information

back to top

Last Updated November 12, 2014