Constitution
of the
UCH Clinical and Translational Research Center
Study Monitoring Committee
Drafted: November 2009
Approved by UCH Scientific Advisory and Review Committee
Last Amended:
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Glossary of terms:
CCTSI
Colorado Clinical Translational Science Institute
CTRC
Clinical and Translational Research Center
COMIRB
Colorado Multiple Institutional Review Board
DSMB
External Data and Safety Monitoring Board
DSMP
Data and Safety Monitoring Plan
FDA
Federal Food and Drug Administration
ME
Monitoring Event
NIH
National Institute of Health
RSA
Research Subject Advocate
SARC
Scientific Advisory and Review Committee
SMC
Study Monitoring Committee
SO
Safety Officer
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Constitution of the UCH Clinical and Translational Research Center
Study Monitoring Committee
The Study Monitoring Committee (SMC) is accountable to the Scientific Advisory and Review
Committee (SARC) and derives its authority from SARC. The SMC has the authority to provide
recommendations but only SARC has the authority to take appropriate action.
Article I. Purpose and Goals
The purpose of the UCH Clinical and Translational Research Center (CTRC) SMC is to oversee the
safety of studies conducted within the CTRC. The SMC is charged to prospectively review the
Data and Safety Monitoring Plans (DSMP) of all studies and review studies that are active. The
goals of the CTRC SMC are to:
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Provide independent monitoring to assure study safety and study integrity of active studies
on the CTRC
Educate and support investigators to develop detailed and effective data and safety
monitoring plans for their study
Ensure that there is appropriate oversight for significant risk studies (in conformity with
NIH guidelines)
Provide SARC with updates on the progress of current studies on the CTRC as needed
Improve communication between the investigator, the CTRC and SARC
Ensure that new literature or research information is considered by on-going studies and
revised appropriately
Review safety reports from other safety bodies and ensure that recommendations have been
appropriately addressed
Oversee and liaise with safety officers
Act as a resource for DSMBs, safety officers, investigators, SARC, COMIRB, and the
CTRC
Article II. Membership
Section 1
The SMC will consist of 4-5 SARC members as follows: (1) one CTRC Research Subject
Advocate, (2) one statistician, (3) one physician, and (4) one senior research scientist.
All conflicts of interest should be disclosed before becoming a committee member:
Financial connections with sponsor or investigators
Professional or institutional affiliations
Section 2
The Chair will be selected by unanimous vote of the members of the CTRC SMC.
The Chair should have:
 Past experience on Data and Safety Monitoring Committees
 Knowledge and leadership skills
 The ability to facilitate focused discussion
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Section 3
A quorum shall be defined as the presence of 3 voting members but must include one physician and
one statistician, and one Research Subject Advocate.
Section 4
The SMC will meet at least monthly and the agenda of the meeting will include:
 Review of Unanticipated Events reported to COMIRB
 Review of Monitoring Event reports
 Review of independent DSMB reports and safety officer reports
 Review of independent DSMB charters and safety officer charters
 Review of documentation presented to COMIRB as part of the protocols continuing
review.
Section 5
Materials to be reviewed are made available on a web based collaboration site for the committee.
All members should review the material prior to the meeting and disclose any potential conflicts of
interest at the beginning of the meeting. At that time, the potential conflict of interest will be noted
in the minutes and a determination will be made as to how the conflict of interest will be managed.
Either the potential conflict will be determined to be acceptable or the member will be recused for
that discussion and this will be noted in the minutes.
Section 6
Minutes of each meeting will include members present, protocols discussed, follow-up
action required, if any, and by whom. Minutes will be recorded by one of the RSAs.
Copies of the minutes shall be made available on a web based collaboration site for the committee.
Minutes are to be followed-up and formally approved at the next meeting of the SMC.
Article III. Study Monitoring
Active studies on the CTRC shall undergo at least annual review by the SMC for safety based on
risk assessment.
Section 1
Study monitoring requirements will vary depending on the nature and structure of the study to be
undertaken. Minimal or low risk studies as determined by SARC can be monitored appropriately
for safety by the investigator. Moderate and high risk studies require a level of oversight other than
can be provided by the investigator. These studies will utilize, in addition to the investigator,
additional monitoring such as a safety officer or DSMB.
Minimal Risk
Defined in the federal statutes as: “The probability and magnitude of harm or discomfort anticipated
in the research are not greater in and of themselves than those ordinarily encountered in daily life or
during the performance of routine physical or psychological examinations” (45 CFR 46.102)
Examples: routine physical tests – phlebotomy, normal bloods, routine X-rays, DEXAs, routine
psychological examinations or tests when low risk for confidentiality; use of surveys or
questionnaires when low risk to confidentiality; non-invasive radiology or imaging studies;
observational studies; nutritional studies that do not involve radioactive isotopes; behavioral studies;
survey/questionnaire studies.
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Monitoring frequency: Annually
Low risk
Involves a minor increase over minimal risk- the intervention or procedure presents experiences that
are reasonably commensurate with those inherent in actual or expected medical, dental,
physiological, social or educational situations (45 CRF 46.406).
Examples: studies of normal volunteers using well described research procedures such as
intravenous infusions of non-vasoactive drugs, euglycemic clamp, indirect calorimetry, muscle and
fat biopsy, or low risk exercise tests.
Monitoring frequency: Annually
Moderate risk
Risks are reasonable in relation to anticipated benefits, if any, to subjects and the importance of the
knowledge that may reasonably be expected to result. Risks are recognized as being greater than
low, but are not considered as serious as high risk, and their surveillance and protections are
adequate to identify adverse events promptly and keep their effects minimal (45 CFR 46.111).
Examples: participants treated with placebo for a recognized disease or a multi-arm study where
there is the potential for increased risk in one or more arms; disease orientated participants exposed
to non-FDA approved drug or drug combinations; reasonable level of baseline knowledge from
which feasible to extrapolate risk of adverse events; only anticipated mild/moderate adverse events
or low probability of SAE ; substantial risk, > 5%, of SAEs, originating from underlying condition
of enrolled subject; microneurography in normal participants.
Monitoring frequency: Semi-annually or Annually
High Risk
Involves greater than minimal risk with no prospect of direct benefit to individual subjects, but is
likely to yield generalized knowledge about the disorder or condition studied. Studies that are of
high levels of risk may result in permanent physical and/or mental changes, hospitalization, and/or
death (45 CRF 46.406). In situations where the prospect of direct benefit to the study participant
exists, the risks associated with study procedures are considered substantial.
Examples: interventions or invasive procedures that involve substantial risk (may result in
permanent physical and/or mental changes, hospitalization, and/or death); blinded Phase I and II
trials; studies involving the manufacturing of agents on campus or use of a chemical/drug/device for
which there are little or no human toxicology data; gene transfer studies or research involving
recombinant DNA; investigator-initiated phase III or multi-center clinical trials; studies where
consent is waived such as in emergency circumstances or in populations unable to give informed
consent (e.g., mentally incapacitated); potential anticipated for serious AE or frequent AE
associated with the research requiring medical intervention; investigator initiated new drug trial;
implantation of device with an IDE; a gene therapy study or research involving recombinant DNA
molecules (gene transfer); Category III radiation risk (HE (mrem) > 5000 mrem or organ limit of HT
> 750/WT); phase I or II studies with no available safety data in humans .
Monitoring frequency: There is a formally established independent Data Safety Monitoring Board
that has specific oversight of the safety monitoring of the study (such as company-sponsored). In
the event an independent DSMB is not established, a local DSMB is needed. All correspondence
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from the Data Safety Monitoring Board will be submitted to the IRB and to the UCH CTRC
Research Subject Advocate. All serious adverse events will be promptly reported by the PI to the
DSMB, the IRB, the study sponsor, and the UCH CTRC Research Subject Advocate. In addition,
all changes in protocol procedures will be submitted for approval to the IRB and the UCH CTRC
before being implemented on the CTRC.
Section 2
The extent of SMC monitoring for UCH CTRC studies will be based upon a risk assessment.
Factors to be taken into account include the following:
 Risk
 Investigator experience
 Multicenter vs single site investigator initiated studies
 Inclusion of normal, healthy subjects
 Inclusion of special populations
 Continued oversight of DSMB
 Continued SAE and AE monitoring
See appendix A.
Section 3
Safety Officer (SO):
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A SO should be an expert in the field but independent of the study. He or she should be
recommended by the investigator and approved by the SMC.
The charter outlining the role of the SO in the study should be written by the investigator in
conjunction with the SO and submitted to the SMC for review. This charter should include
appropriate individual and study stopping criteria for safety.
Specific monitoring events (ME) may be identified for the study. Investigators will be
requested to submit an ME form to the RSAs for each event that occurs as outlined in the
DSMP and reported to the SO in a timely manner. See appendix B.
A written SO report should be sent to COMIRB and the RSAs as predetermined by the
DSMP and SO charter and will be protocol specific. This report will be reviewed at the next
scheduled SMC, and any follow-up requests by the SMC will be communicated to the
investigator and SO in a timely manner. When appropriate, the report will be forwarded to
SARC with accompanying recommendations from the SMC with regard to possible action
to be taken.
Section 4
Local DSMB:
A local DSMB may be constituted for single site high-risk studies, which, as determined by SARC
and the SMC, cannot be effectively and/or appropriately monitored by a Safety Officer.
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Membership of the DSMB will include at least 3 individuals who are independent of the
investigators and have no financial, scientific, proprietary, or other conflict of interest with
the study. The remaining members should have relevant study expertise, and may include
physicians, scientists, ethicists, and patient advocates.
A formal meeting of the DSMB shall be held prior to the PI meeting to establish a working
charter for the study. At the initial meeting the members of the DSMB, in conjunction with
the principal investigator and the research team, should write the charter outlining the
specific monitoring role of the DSMB in the study. This charter should include individual
and study stopping criteria for safety and efficacy as appropriate. Once the DSMB charter
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has been approved by all its members, then DSMB charter must be reviewed and approved
by the SMC.
A written DSMB report shall be compiled after each meeting. This report will be noted at
the next scheduled SMC. Any recommendations by the SMC will be communicated to the
investigator in a timely manner. When appropriate the report will be forwarded to SARC
with accompanying recommendations from the SMC with regard to possible action to be
taken.
External DSMB:
All multi-site CTRC studies considered by SARC to be ‘significant’ risk studies are required to
have an independent DSMB. Any exception to this stated policy must be approved by the SMC and
SARC.
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The constitution and membership of any external DSMB must be provided by the
investigator for review by the SMC.
A written DSMB report should be sent to the RSAs as predetermined by the DSMP and this
will be protocol specific. This report will be reviewed at the next scheduled SMC. The
written report will be reviewed by the SMC and any follow-up requests by the SMC will be
communicated to the investigator in a timely manner. When appropriate the report will be
forwarded to SARC with accompanying recommendations from the SMC with regard to
possible action to be taken.
Section 5
A mechanism is in place on the UCH CTRC for overseeing the safety of all patients admitted to the
CTRCs as a function of the CTRC's provisions of services whereby unanticipated problems
resulting from a function of the CTRC are monitored, managed and reported to COMIRB.
Monitoring event forms describing risks related to the provision of services on the CTRC are
submitted to the RSAs from CTRC staff, a PI or a PI's study staff. These reports are then included
in the agenda of the next monthly SMC meeting. The SMC reviews all monitoring event forms and
recommends a management plan for risks associated with the unit (as opposed to individual
protocols). The management plan for the specified risk must include the frequency of monitoring
by the SMC as well. Unanticipated problems related to administration of CTRC services, including
a SMC developed management plan, will be reported to COMIRB by the RSAs.
Article IV. Reporting to SARC
If an unanticipated event occurs on the CTRC that the RSAs determine requires comprehensive
review before the study can continue then the information should be reported to the SMC members
for a determination to put the study on hold until a formal evaluation can take place. This requires
consensus of all available SMC members within 24 hours of the request being made. This request
and determination must then be promptly communicated to the SARC co-chairs, the UCH CTRC
Medical Director, and investigators with a request for the study to be put on hold until an
investigation and report are completed. A ruling on the status of the study should be provided by the
available SARC chairs or UCH CTRC Medical director within 48 hours of the request and then a
strategy agreed upon by all parties as to how to proceed. At the discretion of the SARC co-chairs,
the plan may then be submitted to SARC at the next meeting for their consideration.
The SMC must report any concerns arising from active protocols on the unit to the CTRC Medical
Director and SARC in a timely manner.
Article V. Amendments to the Constitution
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All amendments to the CTRC SMC Constitution require consensus of the SMC. Any such
amendments must be approved by the Scientific Advisory and Review Committee at the next
meeting of that committee.
Article VI. Ratification
This constitution shall become effective upon approval by a majority vote of the Scientific Advisory
and Review Committee.
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[Appendix A]
Classification of CTRC Protocols Based on Risk Assessment
Level Risk
Criteria
NA
Minimal
Low
Moderate
High
Subject Evaluation
Population
Vulnerability
Size
PI Evaluation
Level of Experience
Volume of Protocols
Audit History
Staff Levels
COI
Research Evaluation
Procedures
Anticipated Adverse Events
Status of drug/device
Psycho-Social Impacts
Knowledge Base
(Literature)
Gene Therapy
Privacy/Data Security
Consent Issues
Oversight Evaluation
Location of Research
Study Sponsor
Audit History
COI
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[Appendix B]
UCH CLINICAL TRANSLATIONAL RESEARCH CENTER
MONITORING EVENT FORM
Instructions for determining the types of events that should be reported are provided on
page 2 of this document.
Protocol #:
Title of the study:
Principal Investigator:
Submitted by:
Patient ID:
Date
Email:
Email:
Type of Report:
Initial
Expectedness:
Unexpected
Relationship:
Unlikely
Follow-up
Phone:
Phone:
Other ______________
Expected
Possibly
Probably
Definitely
Timeline:
Date Event Started
Date Event resolved
Date PI/study staff became aware of event
Event ongoing? (Yes/No)
Describe Event
Attachments: If applicable, attach all supporting documentation and list attachments here:
Do you recommend changes to the protocol or consent form?
Yes
No
Signature: ___________________________________________________________
RSA Recommendation:
RSA Signature
Date
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UCH Clinical and Translational Research Center
Monitoring Event Form Reporting Requirements
The purpose of the UCH Monitoring Event form is to
 document events which do not meet the criteria for reporting to COMIRB, but result
in a deviation from the approved protocol/consent or standard practice.
 allow for independent monitoring of unanticipated problems related to the provision
of services on the CTRC by the Research Subject Advocates (RSAs) and UCH
CTRC Study Monitoring Committee (SMC) to assure study safety and study
integrity of active studies on the CTRC.
 Identify procedural problems on the unit and facilitate process improvements.
The UCH CTRC Monitoring Event form is to be completed whenever an event occurs that
deviates from the latest approved version of the protocol, consent form, or nursing flow sheet
especially if it causes the study to be aborted. The deviation from the approved protocol or flow
sheet may be in response to a physical event experienced by the participant, or it may be due to predetermined participant stopping criteria, or it may be due to a procedural error on the unit.
Action Required: this form can be completed by the investigator, the PRA or any other member of
the research staff, the nurse who was assisting with the study at the time, the person who responded
to the monitoring event, or any member of the UCH CTRC staff.
The Monitoring Event Form is to be completed and a copy given to the RSAs as soon as
practicable. This form is not to be placed in the participant’s medical records.
COMIRB requirements
Not required by COMIRB
Examples of events to be reported using the Monitoring Event Form can include:
Long and/or unanticipated delays in study
Syncope with procedure
Study aborted
Unexpected abnormalities in vital signs
Problems with diet (missed, cold, wrong foods)
Multiple IV sticks
Participant enrolled in more than one study concurrently
Unable to obtain adequate tissue sample in biopsy
Abnormal labs that result in study termination
Unrelieved pain
Break in sterile technique
Issues with informed consent or hospital consent
Medication errors which do not meet the reporting criteria for COMIRB
Deviations from study flowsheet (e.g., missed blood draw, incorrect
sample processing)
RSA contact information is:
Barbara Hammack, PhD.
720 848-6662
Barbara.hammack@ucdenver.edu
MS B141
David Badesch, MD
720 848-6567
David.badesch@ucdenver.edu
MS C272
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