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Funding & Research

Monitoring Boards for Data and Safety (INTERIM POLICY)

National Heart, Lung, and Blood Institute
National Institutes of Health


Purpose

The Data and Safety Monitoring Plan (DSM Plan) will specify when a Monitoring Board will be used. This determination should ideally be made in conjunction with NHLBI and in advance of submitting a grant application or contract proposal, so the appropriate budget can be included. Any grant, cooperative agreement, or contract that includes a clinical research study that uses a Monitoring Board must include administrative and budgetary provisions for the Board. Funds for the Monitoring Board are restricted for this purpose and cannot be re-budgeted to other uses without prior NHLBI approval. If a Board will be used, the required areas of expertise must be noted in the grant application; however, no members’ names should be included. The following is general guidance:

  • For Phase III clinical trials, a Data and Safety Monitoring Board (DSMB) is required. This can be a DSMB convened by the NHLBI, or by the local institution, depending on the study, the level of risk and the funding mechanism.
  • For a Phase II trial, A DSMB may be established depending on the study, but in most cases a DSMB appointed by the funded institution may suffice.
  • For a Phase I trial, monitoring by the PI and the local IRB usually suffices. However, a novel drug, device or therapy with a high or unknown safety profile may require a DSMB.
  • For an Observational Study, a Monitoring Board (OSMB) may be established for large or complex observational studies. This will be determined on a case-by-case basis by NHLBI.

Scope

This policy applies to all Monitoring Boards, established by either NHLBI or the grantee Institution as specified in this policy.

Background

NHLBI supports clinical research trials and observational studies that vary widely in size and complexity. As the sponsor, NHLBI must ensure that study participants are not unduly exposed to unreasonable or unnecessary research risks. Monitoring Boards are an important component of the overall process of ensuring subject safety and data quality.

Definitions

Clinical Research: Clinical Research is research conducted with human subjects (or on material of human origin such as tissues, specimens and cognitive phenomena) for which an investigator (or colleague) directly interacts with human subjects. Excluded from this definition are in vitro studies that utilize human tissues that cannot be linked to a living individual. Examples of clinical research include:

  • mechanisms of human disease
  • therapeutic interventions
  • clinical trials
  • development of new technologies
  • epidemiologic and behavioral studies
  • outcomes and health services research.

Clinical Trial: A Clinical Trial is a prospective biomedical or behavioral research study of human subjects that is designed to answer specific questions about biomedical or behavioral interventions such as: drugs, treatments, devices, or new ways of using known drugs, treatments, or device.

NOTE: For additional information contact the designated NHLBI Program Director or Clinical Trial Specialist in your study or area of interest. http://dir-intranet.NHLBI.nih.gov/staff-directory/

Responsibilities

NHLBI Program Staff is responsible for adherence to this policy including but not limited to:

  • Ensuring that the monitoring activities occur in adherence to the approved DSM Plan
  • Responding to recommendations made to the Institute by the monitoring activities
  • Assuring that the Investigators are responsive to the recommendations from the monitoring activities

NHLBI management staff are responsible for ensuring that program staff adheres to this policy.

NHLBI Office of Clinical Research (OCR) is responsible for the maintenance of this policy and its revisions and interpretations.

Policy

1.0  Responsibilities of Monitoring Boards

1.1  Each Monitoring Board is an independent advisory group to NHLBI’s Office of the Director with the responsibility of providing recommendations concerning starting, continuing, and/or stopping the clinical research study under review.

1.2  The Monitoring Board’s recommendations are based on:

1.2.1        Safeguarding the interests of study participants

1.2.2        Assessing the safety and efficacy of study procedures

1.2.3        Monitoring the overall conduct of the study. 

1.3  Each Monitoring Board member must complete the standard protection of human subjects education certification requirements for researchers conducting human subjects research. http://ohsr.od.nih.gov/.

1.4 In addition, the Monitoring Board is asked to make recommendations regarding:

1.4.1        Participant Safety

1.4.2        Efficacy of the study intervention (DSMB only)

1.4.3        Benefit/risk ratio of procedures and participant burden

1.4.4        Selection, recruitment, and retention of participants

1.4.5        Adherence to protocol requirements

1.5.6        Data and Statistical Analysis plan

1.547        Adequacy of measured and collected data

1.4.8        Amendments to the study protocol and consent forms, only if cannot be influenced by knowledge of interim outcomes data (DSMBs only);

1.4.9        Performance of individual centers and core labs

2.0  Monitoring Boards appointed by Participating Institutions

2.1  For investigator-initiated studies that do not meet criteria for an NHLBI-appointed DSMB, the need for a DSMB appointed by the funded institution will be determined by the NHLBI in consultation with the Principal Investigator, preferably before a grant application is submitted, and described in the DSM Plan in the grant application.

2.2  The Principal Investigator must provide to the NHLBI an IRB-approved protocol that includes the DSM Plan for review prior to award. 

2.3  The NHLBI's agreement to make the award will constitute the Institute's approval of the DSMP.

2.4  DSMB independence from the study investigators

2.5  An individual from an institution other than the Principal Investigator should be the Board’s ES, particularly if the study is randomized and/or blinded. 

2.6  If this is not feasible, the ES should be from a different department than the study investigators.  If appropriate, the study statistician may serve as the ES.  Participating institutions must also establish and maintain an appropriate written policy on conflicts of interest.

2.7  DSMBs appointed by Participating Institutions, NHLBI staff will serve as ex officio members and will monitor Board activities.

2.7.1         Attendance at Board meetings by the NHLBI program staff will be at their discretion and will typically depend on the issues to be discussed and the nature and stage of the study.

2.7.2         It is expected that the assigned NHLBI program staff person will be informed of upcoming DSMB meetings or calls well in advance.

2.7.3        Minutes, recommendations, and reports will be forwarded to the assigned NHLBI staff in a timely fashion, who will provide them to the Branch Chief, as needed. 

2.7.4        The annual progress reports (Type 5s) should summarize the implementation of the DSM Plan, including the dates and a brief description of the outcome of DSMB meetings.

3.0  Observational Monitoring Boards (OSMBs)

3.1  The NHLBI may appoint OSMBs for Institute-initiated and investigator-initiated observational studies to help assure the integrity of the study by closely monitoring data acquisition for comprehensiveness, accuracy, and timeliness; and monitoring other concerns such as participant confidentiality. 

3.2  For OSMBs appointed by the NHLBI, an Institute staff member serves as the Board's ES. 

3.3  The general guidance for DSMBs applies to OSMBs. 

3.4  As a general rule, the NHLBI appoints OSMBs for:

3.4.1        Large, long-term Institute-initiated and selected investigator-initiated observational studies, whether multiple or single center in nature. 

3.4.2        Selected smaller Institute-initiated and selected investigator-initiated observational studies or registries.

4.0  Monitoring Boards appointed by NHLBI

4.1  Recommendations are made to the Institute’s Office of the Director.

4.2  An Institute staff member who is not the primary program official serves as the Monitoring Board's Executive Secretary (ES).

4.3  Board members must be approved by NHLBI program staff, in consult with the NHLBI Branch Chief or Division Director, as needed, and NHLBI Ethics Office.

4.4  Proposed Board members must reflect the necessary expertise for the particular study and should exclude individuals who have collaborated extensively with the investigators or are at participating institutions.

4.5  The Institute must be assured that the proposed Board will protect the participants

4.6  Selection and Approval of Members

4.6.1        The Board must be formed as soon as a decision to fund the clinical research study is made, because the Board’s first action will be to accept the protocol.

4.6.2        The number and expertise of Board members is determined by the size and complexity of the clinical trial or observational study. 

4.6.3        Typically, membership consists of three to nine members who collectively provide adequate representation in biostatistics, ethics, clinical trials, and the specific area(s) of research to be studied.

4.6.4        For clinical trials, the chairperson must have clinical trial experience, preferably in the area under study. 

4.6.5        If the Institute had previously convened a Protocol Review Committee (PRC) for the study, some of its members may be eligible to participate on the Monitoring Board.  

4.6.6        NHLBI program staff compiles a proposed slate of members and alternates, for review by the Office of the Director, NHLBI.  Once the slate is approved, support staff begin the process of establishing the Board.

4.6.7        Ad hoc consultants or other individuals may be invited to meetings by the Executive Secretary (ES) as needed for a particular aspect of oversight.

4.6.8        The final appointment of Board members is contingent on the absence of or acceptance by NHLBI of any conflicts of interest.

4.6.8.1   Individuals invited to serve on Monitoring Boards are required to complete and submit a "Conflict of Interest Certification" prior to participating in any meetings and annually thereafter.

4.6.8.2  Potential conflicts are reviewed by NHLBI staff, with the final decision made by the Office of the Director, NHLBI. 

4.6.9        Sources of conflict of interest or the appearance of a conflict of interest include but are not limited to:

4.6.9.1  Financial ties, investments, stocks etc., to any commercial concerns likely to be affected by the outcome of the trial;

4.6.9.2  Consulting activities that provide financial, investment, or other business advice; and

4.6.9.3  Professional or other affiliation that could cause others to question the objectivity of the Board deliberations, such as close scientific collaboration with the study investigators.

4.7  Operating Procedures

4.7.1        The Charter Template (see appendix) provides a detailed overview of the responsibilities, operating procedures, and reporting guidelines for NHLBI-appointed DSMBs and OSMBs. 

4.7.1.1  This template may also be useful to investigators establishing local DSMBs. 

4.7.1.2  The purpose of the Charter is to provide a common understanding between the NHLBI and Board members about shared oversight of clinical research.

4.7.1.3   The Charter should be tailored to each Board, and provided to the Board members for discussion at the first meeting.

4.7.2        Minutes are the official record of the Board’s discussion

4.7.2.1  Prepared according to NHLBI guidelines (see appendix), using the standard template (see appendix). 

4.7.2.2  Minutes are to be submitted to the Office of Director, NHLBI within 14 days after the Board meeting. 

4.7.2.3  The Office of the Director, NHLBI only receives notification of significant or urgent problems/concerns that require immediate action. These would be submitted as soon as possible after the DSMB meeting for approval and action.

4.7.3        Members of Monitoring Boards are eligible for reimbursement of travel expenses, and for compensation for their work consistent with NHLBI policies (embed link to policy).

4.7.4        Reimbursement and compensation are provided by the study Coordinating Center from funds restricted for this purpose. 

4.7.4.1  Government employees serving on Monitoring Boards are not eligible to receive compensation, but may be reimbursed for their travel. 

4.7.4.2  Funds budgeted for the support of the Board will be restricted in such a fashion as to maintain its independent operation.

5.0  Monitoring Boards for Co-Funded Studies

5.1  For studies co-funded with another Institute or Center (IC), the decision to appoint a Monitoring Board would generally be made by the lead IC.

5.2  The oversight plan for the Monitoring Board would be developed collaboratively prior to commencing the study.

References

NIH Policy for Data and Safety Monitoring: http://grants.nih.gov/grants/guide/notice-files/not98-084.html

Inquiries

Office of Clinical Research, nhlbiodocr@nhlbi.nih.gov

Availability

Policy Effective Date: 14 May 2007

Appendices

None

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