Data Safety Monitoring - Saint Louis University

Revised 04/04/07, 12/1/07, 8/1/11, 03/01/12
Saint Louis University
Institutional Review Board (IRB)
A. Introduction
Ethical considerations and specific guidelines promulgated by Federal agencies
dictate criteria that must be met before approval and at the annual review of research.
Among those criteria are that risks are minimized and that when appropriate, the research
plan makes adequate provisions for monitoring data collected to ensure the safety of
subjects (See CFR 45.46 and 21.56 111(a)(1) & (6)). In cases of federally funded or
industry-sponsored multicenter research, clinical trial monitors and the establishment of
and efforts by external Data Safety Monitoring Committees (DSMCs) typically provide
some degree of oversight. This situation is addressed in Section C.3 of these guidelines.
The remaining guidelines below should be used to determine whether research subject
monitoring carried out by individuals not directly affiliated with the protocol is needed, and
what type of oversight would be appropriate for any particular study. IRB requirements for
data safety monitoring are covered in Section D.
B. Determination of Whether Research Subject Data Safety Monitoring Is Required
1. No safety monitoring plan will be required if the proposed research:
 is a descriptive study and does not involve vulnerable populations nor presents
risks to subjects in the event of loss of confidentiality;
 does not use a drug or device in an unapproved manner and does not involve a
new investigational procedure; or
 reviews retrospective data or is a non-interventional follow up such that subjects
are not likely to be placed at risk of physical, psychological, financial or other
When a research proposal involves a clinical intervention and is considered to pose
greater than minimal risk to subjects (as described below), the principal investigator will
provide a data safety monitoring plan, which must include predetermined safety
considerations with “decision points”, and either a Data Safety Monitor (DSM) or a Data
Safety Monitoring Committee (DSMC).
2. A Data Safety Monitor (DSM) will likely be required in any of the following
The study is a pilot study of a novel treatment, such that there is little prior
information on clinical safety; or
The study, of any phase, is one in which there is evidence that the protocol raises
concerns about the potential for serious end organ irreversible toxicity; or
The study involves vulnerable populations, or
The study presents significant risks to subjects in the event of a loss of
confidentiality; or
Revised 04/04/07, 12/1/07, 8/1/11, 03/01/12
The study is a single center trial utilizing high-risk interventions (e.g. gene therapy,
cancer treatments, AIDS treatments).
3. A Data Safety Monitoring Committee (DSMC) (sometimes known as Data
Safety Monitoring Board or DSMB) will likely be required when the protocol
presents greater than minimal risk to subjects, and entails any of the following
situations. The study is a:
Multicenter phase 3 study using investigational new drugs (IND) or devices (IDE),
which evaluate interventions intended to prolong life or reduce the risk of major
adverse health outcomes such as cardiovascular events or recurrent cancer; or
Multicenter trial in which mortality or major morbidity is a primary or secondary
endpoint; or
Multicenter trial in which any group is at relatively high risk of death or morbidity
due to their underlying conditions, and where a medical intervention with subjects
might increase such risk or cause unanticipated adverse events; or
Multicenter or single center study performed in an emergency (life threatening)
setting in which informed consent has been waived (see 21 CFR 50.24(a)(7)(iv)).
C. Requirements for a Data Safety-Monitoring Plan
1. All plans should include each of the following elements, as appropriate:
A determination of the appropriate interval for safety review; and
A mechanism for review of safety; and
Specific predetermined criteria for stopping the study (predetermined “decision
points”) should that become necessary; and
Identification of the individual and their credentials or a listing of the committee
members credentials, who will review the study’s data to evaluate study safety.
The members of the DSMC should not be affiliated with the protocol (i.e., they
must be free of any financial interest that could be affected by the outcome of the
trial, and they may not receive financial benefit from it, apart from that provided in
exchange for the time and effort in conducting the review and evaluation), nor
should they be included on any research publication resulting from the research);
[the IRB may require that the individual responsible for reviewing safety data be
independent of the study]; and
A description of how the data will be assessed to determine that there are no
significant new interventions, procedures, or safety concerns that would affect the
subjects’ willingness to participate; and
Where applicable, a mechanism to immediately notify all study sites regarding
findings relevant to the safety of study participants.
For guidelines and a sample of a generic monitoring plan, see the following
Revised 04/04/07, 12/1/07, 8/1/11, 03/01/12
2. Additional Requirements for a Local DSMC
When a local DSMC is required, the investigator will be responsible for establishing
such a Committee. The DSMC must meet all of the following requirements:
be composed of no less than three members possessing the qualifications and
expertise to supervise the study; and
have one member who is a biostatistician; and
have no members affiliated with the study; and
produce an annual (at minimum) report for the IRB.
3. Information Regarding DSMC on Multicenter Studies
When a DSMC is required for a multi-center study, the SLU Principal Investigator will
be responsible for:
Industry Sponsored trials – Making sure the proposal has a DSMC or equivalent
mechanism and that this information is adequately reflected in the SLU eIRB
NIH Sponsored Cooperative Group protocol – that there is a mechanism for
monitoring safety data in place and that this information is adequately reflected in
the SLU eIRB application. (Note that the requirements for a DSMC in NIH
supported research may exceed those stated above)
Studies sponsored by a granting agency (other than NIH) or by another
investigator – that such agency or investigator has documentation of the existence
of a DSMC and that this information is adequately reflected in the SLU eIRB
D. Additional Study Monitoring
Additional study monitoring by the sponsor may include:
 Monitoring for adherence to the consent process, and monitoring of the data
records and case report forms; and
 Procedures to assure that Serious Adverse Events (SAE’s) will be provided in a
timely manner to appropriate recipient agencies and to the IRB
E. IRB Policy Information
The IRB requires all the information listed in C.1. be included in a protocol, as
appropriate, in sufficient detail to make a determination that criteria for approval have
been met.
At time of initial submission, please ensure that:
 Reporting requirements of the monitoring entity are included in the research
protocol and/or in the Clinical Trial Agreement (CTA).
 The CTA states 1) the timing of safety reviews and how reports will be distributed
to sites or 2) “Sponsor will provide the SLU principal investigator with any findings
from its data and safety monitoring that could affect the safety of subjects or their
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willingness to participate or influence the conduct of the study. Reports of an
urgent nature must be provided within ten (10) business days; routine reports must
be submitted within thirty (30) business days.”
The protocol states the timing of safety reviews and how reports will be distributed
to sites.
The Safety Monitoring Guidelines on the attached tip sheet are followed.
Note: If the plan is to have a Data and Safety Monitoring Board and the charter is not
ready at the time of IRB submission, the study may obtain full approval if sufficient
detail about the plan is included in the protocol (see attached tipsheet), but the charter
will need to be submitted within 90 days on an amendment.
The charter will then be reviewed by a convened board.
If a DSMB charter is not submitted to the IRB within 90 days, justification must be
provided by the investigator/sponsor and approved by IRB staff or the study approval
will be suspended.
At times of continuing review:
The IRB is charged with determining that the criteria for approval are still met and that
no new information is found that would affect the safety of subjects or their willingness
to continue their participation in the study.
At the time of continuing review, a status of the safety must be reviewed with each
continuing review.
The IRB will not review protocols for continuing review that do not have the
required data and safety plan reports or appropriate documentation that there are
no safety issues or no new information that might affect a subject’s willingness to
continue in the study.
Revised 04/04/07, 12/1/07, 8/1/11, 03/01/12
Saint Louis University IRB
Tips for Safety Monitoring Guidelines
Of Research that is Greater than Minimal Risk
Committee Needed
Phase III Clinical Interventions (Or significant risk studies)
Requirements: Data Safety Monitoring Board*
• List of the credentials of those that make up the board/committee?
• How often will the committee meet? (Should be at least semi
annually or justify why it is less)
• When will reports (board determinations) be sent to the site?
Plan Needed
All other research
Requirements: Safety Monitoring Plan**
New Protocols
• How will the study be monitored? Safety monitor MUST
Be an MD
Review safety data as it is reported
Review safety data in aggregate no less often than every 6 months
• How and when will the findings be reported to the IRB?
Continuing Review
• Based on meeting schedule indicated in the protocol, all safety
correspondence from the continuing review period need to be
OR a justification from the sponsor as to why the information in the
protocol has not been followed should be included with the request
for continuing review.
Continuing Review
• All safety correspondence from the continuing review period need to be
included with the request for continuing review as indicated in the
*Data Safety Monitoring Board (or Committee) – a formal board that usually operates from a charter. The board should consist of MD’s and PhD’s
with expertise in the field of study that is not affiliated in any way with the sponsor or study sites. Usually also includes a statistician. These
boards have set meetings, they issue reports, minutes, or determination statements (a statement, memo, or email that indicates the board met,
found no safety problems, and agree the study should continue as planned). The determination statements are all that is required.
**Safety Monitoring Plan – there are many ways to monitor the safety of subjects. Frequently seen plans include either a medical monitor or local
group that review safety data both in real time and aggregate safety data to look for trends. This should be clearly explained in the protocol.
Reports from any type of plan should be reported to the IRB.