Transcript No Slide Title

Community Clinical
Oncology Program (CCOP)
Role of
Data Safety
Monitoring Board (DSMB)
Mira Shah, CIM, CCRP
March 2011
Updated: July 2006
Disclaimer

The views expressed in this
presentation are the views of the
speaker and do not necessarily reflect
the views or policies of The U.T. M. D.
Anderson Cancer Center (UTMDACC).
Presentation Outline
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Introduction of DSMB
Necessity of DSMB
Conduct of meetings
Processes involved with DSMB
Conclusions
Acronyms
CCOP
CNPE
DSMB
DMC
IRB
NCI
PI
Community Clinical Oncology
Program
Closed to New Patient Entry
Data Safety Monitoring Board
Data Monitoring Committee
Institutional Review Board
National Cancer Institute
Principal Investigator
What is a DSMB?
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DSMB is a formally appointed
independent group of individuals with
scientific expertise and lay
representation that reviews accumulated
research data from an ongoing clinical
trial.
Need for DSMB
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All clinical trials require safety
monitoring but not all trials require
monitoring by a DSMB.
All Phase III randomized comparative
trials.
Other higher risk trials.
Large multiple site trials.
Options for Data Monitoring
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Federal regulations require that IRB
determine requirement for DSMB.
PI or project manager may monitor Phase
I and II trials.
A group of Sponsor’s representatives may
monitor trials.
Monitoring should commensurate with
risks. 1998 NIH policy statement
Points to consider
Some government agencies have
required DSMB monitoring for selected
trials.
 If the trial is accruing very quickly,
would a DSMB be practical?
 Current FDA regulations impose no
requirements for the use of a DSMB
except under 21 CFR 50.24*
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(*exception from IC requirements for emergency research where human subjects
may be in a life-threatening situation)
Trials monitored by DSMB
at MDACC
Randomized and/or blinded
 Non-randomized but referred by IRB
 High risk trials
 Community Clinical Oncology Program
(CCOP) trials
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Issues to be Addressed at
DSMB meeting
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Should the study be stopped?
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Inadequate accrual
Increased safety concerns
Have they met the stopping rule
Apparent outcome differences
Futility
Is there a need to change the study
design?
Is additional data needed for adequate
review to be completed?
Timing of the next review of the study.
UTMDACC DSMB Policy
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Per UTMDACC policy, a DSMB will
monitor:
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(1) all randomized studies that originate at
MDACC or that are coordinated or analyzed by
the MDACC and are not being monitored by
another Data Safety Monitoring Board, unless
exempted by the MDACC IRBs; and
(2) any other non-randomized studies
referred by the MDACC IRBs to the DSMB.
(HSRM
17.070 DSMB By-Laws)
Protocol Selection for MDACC DSMB
DSMB oversight may be requested by:
 PI
- Single UTMDACC study
- UTMDACC PI of consortium study
 IRB
 CCOP
DSMB oversight waived if:
 PI sends waiver request to IRB and may be
approved if determined to be low risk.
Committee Membership of
MDACC DSMB
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No more than 15 members
Includes physicians to interpret toxicity and
outcome differences
Statisticians to evaluate methodology and
interpret probability statements (p-values)
Lay members as participant advocates
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50% of members from outside UTMDACC to
prevent bias
Review Frequency
at MDACC
 Annual review is required
 Review frequency may increase
based on:
 Accrual
 Reporting requirements in the trial
 Level of risk to the subject/s
How the DSMB review
process works at MDACC
Pre Meeting
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Eight weeks prior to meeting the PI and
biostatistician are notified of trial
presentation
PI provides data to Biostatistician
Biostatistician analyzes data and completes
the report
One week before the meeting, the
biostatistician provides the report to DSMB
only
Biostatistical Report
Report prepared by biostatistician and presented to
DSMB for review include
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Accrual rates
Patient
Characteristics
Eligibility and
Evaluability
Efficacy
Toxicities
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Adverse Events
Treatment Related Deaths
Maximum Toxicity
Special Toxicity Monitoring
Secondary Malignancies
Biostatistical Report
Biostatistical Report
Biostatistical Report
Biostatistical Report
Confidential
 Not available to the PI or other
investigators
 PI is made privy to trial results and
analyses only after the DSMB officially
releases those results to the PI
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DSMB Meeting
(DSMB Meets Every Other Month)
PI & biostatistician present study
& answer committee questions
PI asked to leave the room
Biostatistician discusses data and outcomes by treatment arm
Biostatistician asked to leave the room
After Discussion,
Motion made & voted on by members
Common Outcomes
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Appropriate to continue study.
Additional information from PI or
biostatistician is requested.
DSMB recommends revisions/
amendments.
CNPE for safety/efficacy concerns.
Closure due to futility.
Post Meeting
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DSMB provides memo to PI and
biostatistician regarding protocol outcome
DSMB provides memo to IRB listing
outcome for each protocol presented
All Revisions/Amendments of
DSMB Designated Protocols
PI revises protocol
DSMB Designee/Scientific Editor
reviews revision(s)
APRPOVED
Moves to IRB review
REJECTED
Revision not appropriate per
DSMB Designee/Editor and is returned.
PI notified of changes required.
PI requests to the DSMB
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Close trial to new patient entry
Request to stop the trial
Cease monitoring the trial and release trial
results
Release interim results to the PI or
department chair for planning of future trial
Release interim results for publication
These requests can be addressed anytime and are not
restricted to scheduled meeting times.
PI responsibilities
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PI needs to request permission from the
DSMB to publish Interim results for a trial
Copies of manuscripts or abstracts that are
to be published must be submitted to
DSMB
The DSMB plays no role in developing publications but may make
recommendations
DSMB Conclusions
Protects patient’s interests and
scientific integrity of trial/s.
 Uses statistical analyses to provide
expert guidance.
 May serve as scientific reviewer for
trial/s.
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DSMB Resources
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FDA Guidance for Clinical Trial Sponsors – Establishment and
operation of Clinical Trial Data Monitoring Committees (March 2006 –
June 30, 2012):
http://www.fda.gov/downloads/RegulatoryInformation/Guidances/ucm127073.pdf
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NIH Policy for Data and Safety Monitoring (June 10, 1998):
http://grants.nih.gov/grants/guide/notice-files/not98-084.html
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NIH Further Guidance on a Data Safety Monitoring for Phase I and
Phase II Trials (June 5, 2000):
http://grants.nih.gov/grants/guide/notice-files/not-od-00-038.html
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OHSR Information Sheet: Guidelines for NIH Intramural Investigators
and Institutional Review Boards on Data and Safety Monitoring
(December 2006):
http://ohsr.od.nih.gov/info/sheet18.html
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MDACC Human Subject Research Manual
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(17.070 Appendix E DMC By-laws)
Contact Information
Mira D. Shah, CIM, CCRP
The University of Texas
M.D. Anderson Cancer Center
713-563-5437
[email protected]