NHLBI Policy for Data and Safety Monitoring
Extramural Clinical Studies
National Heart, Lung, and Blood Institute
National Institutes of Health
The purpose of this document is to outline the National
Heart, Lung, and Blood Institute (NHLBI) policy for data and
safety monitoring of clinical studies for all human subjects
research funded in whole or in part by the NHLBI. The NIH
requires the monitoring activities of all NIH-sponsored or
-conducted clinical studies to be commensurate with their risks,
nature, size, and complexity. This policy complies with the NIH
mandate by making the NHLBI responsible for oversight of data
and safety monitoring to ensure that an appropriate monitoring
system is in place for all NHLBI-supported trials and that the
Institute is informed in a timely manner of all recommendations
emanating from monitoring activities. It does not usurp the role
of Institutional Review Boards (IRBs) or other regulatory and
monitoring bodies; the policy simply makes clear that the role
of the NHLBI is to ensure that appropriate approvals have been
obtained. Release of funds for human subjects research
activities is contingent upon compliance with this policy. This
policy supersedes NHLBI’s Data Safety Monitoring Policy (2008),
and Data Monitoring Boards for Data and Safety - Interim Policy
Refer to NHLBI Clinical Research Guide Glossary for additional
terms not identified.
The NIH requires all extramural research involving human
subjects or identifiable human specimens to be reviewed by an
Institutional Review Board (IRB) before NIH funds are released
to conduct that research. The NIH further requires documentation
of an IRB-approved data and safety monitoring plan for all
interventional trials and the appointment of a Data and Safety
Monitoring Board (DSMB) for all clinical trials that involve:
- investigation of a research question having direct
implications for clinical care and/or public health (including
all Phase III trials), and/or
- a high-risk intervention, and/or
- a highly vulnerable patient population.
In addition to the NIH requirements outlined above, the NHLBI
also requires an IRB-approved data and safety monitoring plan
prior to study initiation for all human subjects research that
involves greater than minimal risk to participants (as
determined by the IRB).
- For multi-center trials, research networks, and for other
clinical trials performed under a contract or a cooperative
agreement, the NHLBI will usually appoint a DSMB and provide an
executive secretary for it.
- For all other clinical trials, a DSMB will be appointed by the
- For epidemiologic studies and registries involving multiple
sites and/or conducted under a contract or cooperative
agreement, the NHLBI may appoint an Observational Study
Monitoring Board (OSMB) or may ask the institution to appoint
Data and Safety Monitoring Plans:
- Data and safety monitoring plans, when required, must:
- Identify the entity that will monitor the study. Monitoring
may be conducted in various ways or by various individuals or
groups -- depending upon the size and scope of the research
effort, it may be performed by the Principal Investigator (PI),
an independent monitoring group, a DSMB, or an OSMB. For studies
with low risk, monitoring by the PI and the IRB may suffice; for
higher risk studies, a DSMB may be required.
- Describe the procedures for
- monitoring study safety
- minimizing research-associated risk
- protecting the confidentiality of participant data, and
- identifying, reviewing, and reporting adverse events and
unanticipated problems to the
- For multi-site studies, describe the procedures for ensuring
compliance with the monitoring plan and requirements for
reporting across study sites.
Data and Safety Monitoring Plan Checklist)
- Certification of IRB approval(s) of a protocol with its data
and safety monitoring plan must be sent (preferably
electronically) to the NHLBI Grants Management Officer (GMO)
before a proposed human subjects research project may begin at a
site. For multi-site studies, the Data Coordinating Center (DCC)
and study sites initiating a protocol must submit certification
of IRB approval as well as assurance that IRB approvals have
been obtained from all study sites, are on file, and are
available to the NHLBI upon request.
- PIs must submit annual progress reports that:
- Confirm adherence to the data and safety monitoring plan.
- Include a summary of any data and safety monitoring issues
that occurred since the previous reporting period.
- Describe any changes in the research protocol or the data and
safety monitoring plan that may or does affect risk.
- Provide all new and continuing IRB approvals.
If an IRB-approved data and safety monitoring plan is
not received for a study that, in the opinion of the program
official (PO), requires a data and safety monitoring plan,
the NHLBI may request certification by an appropriate
official of the awardee institution that its IRB has
concluded that the proposed research is neither a clinical
trial nor a study that involves greater than minimal risk to
Monitoring Board Operations for DSMBs and OSMBs
Monitoring Board Principles:
- NHLBI monitoring boards
- Are convened to protect the interests of research subjects and
ensure that they are not exposed to undue risk.
- Operate without undue influence from any interested party,
including study investigators or NHLBI staff.
- Are encouraged to review interim analysis of study data in an
unmasked fashion. If a board decides to remain masked for a
certain period of time, rigorous stopping rules should be
outlined at the onset of the study and documented in the board’s
- NHLBI staff who function as Project Scientists for a study
should not be privy to post-randomization data broken down by
treatment group that may be discussed during closed board
- Access to unmasked data must be limited to board members and a
small group of additional individuals who are to be determined
at the onset of the study. Typically the additional individuals
will include DCC staff directly involved in the analyses and
designated NHLBI staff, including NHLBI statistician(s) who are
overseeing the analysis. Details may vary by study.
Monitoring boards are either appointed by the NHLBI and act as
an independent advisory group to the NHLBI Director, or are
appointed locally for investigator-initiated studies. The NHLBI
program office, in consultation with the PI and the respective
institution, will determine if a locally-appointed monitoring
board is appropriate for a given investigator-initiated study.
Generally both types of monitoring boards should function in
accordance with criteria described below, and essential elements
of the board must be included in the data and safety monitoring
- Every board must have an executive secretary who is not
otherwise involved in the study or with the study team.
- For NHLBI-appointed boards, the executive secretary* is either
a NHLBI employee with clinical trial expertise or a contractor.
- For locally-appointed boards, the executive secretary is
usually a member of the monitoring board.
- Each monitoring board must have a chair and members who are
independent of the study and generally have expertise in
biostatistics, epidemiology, clinical trials, bioethics, and key
subject areas involved in the research.
- Defined terms for members of NHLBI-appointed boards.
- In general, members will be appointed for a term that will coincide with the duration of the study or the award. For studies that continue beyond a single award period, board membersí service will be evaluated at the time of the new award, and may be renewed, based on expertise, contributions and participation, and study needs.
- When specialized expertise is needed for a short period of time, ad hoc members can also be appointed to boards with shorter terms of service.
Management of Reports and Other Study Documentation:
- All Monitoring boards must
- Have a charter that has been reviewed and approved by the
board and accepted by the NHLBI program office. (see
Monitoring Board Charter Template (34 KB))
- Approve the study protocol, including the data and safety
monitoring plan, informed consent template, reporting templates
for data to be presented to the board, and anything else the
board may wish to see before a study can begin enrollment.
- Monitoring board meeting minutes must summarize the topics
discussed and list the all recommendations, and must be signed
by the board chair. After each board meeting, throughout the
active phase of a study, the lead investigators must arrange for
a summary of board recommendations to be sent to each
- For NHLBI-appointed boards, minutes must be co-signed by the
executive secretary and submitted to the NHLBI Director for
approval within 14 calendar days. Minutes must be summarized for
investigators and IRBs within 7 calendar days of approval.
- For locally-appointed monitoring boards, minutes or meeting
summaries and the PIs follow-up plans must be submitted to NHLBI
program staff and the board within the timeline specified in the
board charter. Minutes need not be sent to the NHLBI Director
- Conflicts of Interest (COI) for board members must be reviewed
and managed appropriately.
- For NHLBI appointed boards, COIs are reviewed by the executive
secretary and the NHLBI ethics officer.
- For locally appointed monitoring boards, institutions are
expected to have a COI policy and/or plans for management and
monitoring of COIs.
Format of Board Meetings:
Board meetings generally have an Open Session, a Closed Session
(for DSMBs only), and an Executive Session.
- For NHLBI-appointed boards, a board may limit the number of
non-board members in attendance. The number of coordinating
center and NHLBI representatives in attendance should be limited
so as not to overwhelm free and open exchange among board
- For locally-appointed monitoring boards, NHLBI program staff
may participate (but not vote) in the open session unless the
board chair decides that the presence of NHLBI staff may inhibit
free and open discussion, or compromise or appear to compromise
the board’s independence. The issue should be addressed in the
board charter. The NHLBI program official should be informed of
upcoming board meetings at least 1-2 weeks in advance, and
receive the appropriate meeting materials at the same time as
the board members.
- For NHLBI-appointed boards, staff participation in closed sessions when unmasked data will be discussed is restricted to unmasked NHLBI and Coordinating Center staff. For NHLBI, this would usually be the executive secretary and the designated NHLBI study statistician. Additional NHLBI representatives must be approved by the program official in consultation with the executive secretary and the DSMB Chair. However, if other topics are to be discussed in closed session, such as site performance, additional NHLBI staff would participate.
- For locally-appointed boards NHLBI staff participation is at the discretion of the DSMB Chair.
- For NHLBI-appointed boards, NHLBI staff are not required to
attend the Executive Session; however, the DSMB Chair may ask
the executive secretary* to remain in the Executive Session at
their discretion. The DSMB Chair will record
minutes/recommendations during the Executive Session, when the
executive secretary is not present.
- For locally-appointed boards NHLBI staff participation is at
the discretion of the DSMB Chair.
*An executive secretary, in consultation with the DSMB Chair,
can appoint a delegate to assist with note-taking.