Community Clinical Oncology Program
(CCOP)
Updated: July 2006
Role of
Data SafetyMonitoring Board (DSMB)
Mira Shah, CIM, CCRP
March 2011
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
Introduction of DSMB Necessity of DSMB Conduct of meetings Processes involved with DSMB Conclusions
Acronyms
CCOP Community Clinical Oncology Program
CNPE Closed to New Patient EntryDSMB Data Safety Monitoring Board DMC Data Monitoring CommitteeIRB Institutional Review BoardNCI National Cancer InstitutePI Principal Investigator
What is a DSMB?
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 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
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* (*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
Issues to be Addressed at DSMB meeting
Should the study be stopped? 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
Per UTMDACC policy, a DSMB will monitor: (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
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 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
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
Pre Meeting
Biostatistical Report
Accrual rates Patient
Characteristics Eligibility and
Evaluability Efficacy Toxicities
Report prepared by biostatistician and presented to DSMB for review include
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
DSMB Meeting(DSMB Meets Every Other
Month)PI & biostatistician present study
& answer committee questions
Biostatistician discusses data and outcomes by treatment arm
After Discussion, Motion made & voted on by members
PI asked to leave the room
Biostatistician asked to leave the room
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.
Common Outcomes
DSMB provides memo to PI and biostatistician regarding protocol outcome
DSMB provides memo to IRB listing outcome for each protocol presented
Post Meeting
All Revisions/Amendments of DSMB Designated
ProtocolsPI revises protocol
DSMB Designee/Scientific Editorreviews revision(s)
Moves to IRB review
APRPOVED REJECTED
Revision not appropriate per DSMB Designee/Editor and is returned.
PI notified of changes required.
PI requests to the DSMB 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 publicationThese requests can be addressed anytime and are not restricted to scheduled meeting times.
PI responsibilities 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.
DSMB Resources 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
NIH Policy for Data and Safety Monitoring (June 10, 1998): http://grants.nih.gov/grants/guide/notice-files/not98-084.html
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
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
MDACC Human Subject Research Manual (17.070 Appendix E DMC By-laws)
Contact Information
Mira D. Shah, CIM, CCRP
The University of Texas M.D. Anderson Cancer Center