DMID Clinical Research Policies and Standard Procedure Documents
Safety Oversight
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Introduction
Data and Safety Monitoring Board (DSMB)
Clinical trials requiring DSMB oversight are randomized, multi-center trials that are large Phase II, are Phase III, or are Phase IV, plus all Division of Intramural Research (DIR) randomized, double-blind trials regardless of size or phase of trial. The NIAID Division Directors, Clinical Director or IRB may designate other trials for DSMB or SMC oversight for specific programmatic reasons.
Safety Monitoring Committee (SMC)
The Division of Microbiology and Infectious Diseases (DMID) Safety Monitoring Committee (SMC) is an independent group of experts that advises DMID and the study investigators for many Phase I and smaller Phase II trials.
Independent Safety Monitor (ISM)
ISMs will be identified for study sites participating in DMID-supported clinical trials using the following criteria:
- For Phase I and II clinical trials, DMID will require that an 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 committee members and approves them regarding their Conflict of Interest (COI) eligibility. 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.
Safety Committee Operations
The DSMB and SMC are convened by authority of DMID and are advisory to DMID and the study team. The Committee Charter serves as the standard operating procedure and defines primary responsibilities of the DSMB/SMC, its membership, the purpose and timing of meetings, data to be reviewed and procedures for ensuring confidentiality and proper communication. The Charter is finalized following the DSMB/SMC organizational meeting and is 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, Clinical Terms of Award or Letter of Amendment with DMID, as applicable.
Responsibilities of the DSMB/SMC
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 periodically thereafter.
- Provide contact information to the DMID DSMB/SMC support contractor.
- Protect the confidentiality of the trial data and DSMB/SMC discussions.
- Review the protocol, informed consent documents, 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.
- 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.
- Participate in safety oversight for the period of the study up until notification is received from DMID that their service is complete.
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, 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.
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 DMID-CROMS SOCS, as appropriate. The Chair, in collaboration with DMID and DMID-CROMS 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.
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.
A safety oversight committee support contractor, Safety Oversight Committee Support (SOCS), facilitates committee 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: 1-800-275-7619. For international faxes, please use 301-897-1710.
Conflict of Interest (COI) Forms
Policies and Safety Guidelines
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