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.
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.
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.
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.
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).
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.
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.
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.
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Last Updated November 12, 2014