THE ROLE OF DSMB’s in
CLINICAL RESEARCH
Data and Safety
Monitoring
Data and Safety Monitoring



Every clinical trial should have provision
for data and safety monitoring
The size of the monitoring committee
depends upon the nature, size, and
complexity of the clinical trial
The Principal Investigator was expected to
perform the monitoring function but may
have had others to help
Data and Safety Monitoring


1994
It was recommended that every clinical
trial, even those that pose little likelihood
of harm have an external monitoring body
Data Safety Monitoring Boards



1998
Establishment of Data Safety Monitoring
Board (DSMB) is required for multi-site
clinical trials involving interventions that
entail potential risk to the participants
The functions and oversight of such
activities are distinct from the requirement
for study review and approval by an IRB
A DSMB is your Friend
Not your Enemy
Definitions

Data Safety Monitoring
Plan (DSMP)


describes how the study
investigators plan to
oversee research subject
safety and how adverse
events will be characterized
and reported
The intensity and
frequency of monitoring
should be tailored to fit the
expected risk level,
complexity, and size of the
particular study

Data and Safety
Monitoring Board
(DSMB/DMC)


A group of individuals with
pertinent expertise that
review on a regular basis
accumulating data from
ongoing an clinical trial
Advises sponsor regarding
safety of current and future
participants and validity
and scientific merit of the
trial
DSMBs perform 3 fundamental
functions



Review accumulating clinical data relating
to the efficacy and safety of the
investigational product (drug, biologic
and/or device).
Conduct interim analysis of the clinical
data to determine whether the study
needs to be terminated for safety reasons.
Ensure the continued scientific validity and
merit of the study
Roles of a Data Safety
Committee

Monitor adverse events



Monitor enrollment



Is Risk:Benefit is not altered
Does Informed Consent need to be changed
Is study meeting target? Can it be Completed?
Potentially monitor subject outcomes
Monitor new information relative to the study
To be effective
1.
2.
3.
Monitoring must be performed on a regular
basis
Conclusions should be discussed with PI if
he/she not part of the committee
Conclusions of the monitoring must be
reported to the IRB
Specifics of the plan will depend
upon the nature, size, complexity
and risk of the clinical trial





Observation Study, no intervention
Observation study, non-randomized
intervention
Randomized Controlled Trial using
approved drugs/devices
IND/IDE Studies
Multi-center RCTs
Observation Study, no
intervention



PI and 1-2 others
Meet annually
Report to IRB – enrollment status,
recommendation to continue
Observation study, nonrandomized intervention




2-4 Members, PI not Chair, at least 1
member not involved with the study
If low Risk, meet annually
Report enrollment, Adverse Events.
Review SSS and ICS for needed changes
Randomized Controlled Trial
using approved drugs/devices







2-4 members, PI should not be a member but may
attend meetings at discretion of chair
 Consider a biostatistician as member
No member should be involved (Co-I) on study
Meet semiannually depending on enrollement pace
Report enrollment, Adverse Events.
Review SSS and ICS for needed changes
Review group outcome differences, if large may need to
break blind in executive session
May need to recommend discontinuation if:


One group has significantly better outcomes
Adverse events serious and mostly in one intervention
IND/IDE Studies and/or
Multi-center RCTs

Require a formally constituted Data Safety
Monitoring Board (DSMB)





No conflicts of interest
Formal Stopping rules
Regular scheduled meetings
Reports to IRB and FDA
Generally set up by the study sponsor
Data and Safety Monitoring Plan
and Board

A description of the plan and the
composition of the monitoring board are
required at the time of the IRB
submission.
SECTION IX: DATA SAFETY
MONITORING PLAN

For all research that is greater than
minimal risk, a Data Safety Monitoring
Plan (DMSP) must be developed. This is a
plan to assure the research includes a
system for appropriate oversight and
monitoring of the conduct of the study to
ensure the safety of subjects and the
validity and integrity of the data.
Monitoring Plan Checklist





□ N/A. The research is minimal risk.
□ The DSMP is contained in the protocol. State where in
the protocol the description is located:
 NOTE: Ensure that all points outlined below are
addressed in the description in the protocol. If any
points are not addressed, within the protocol, they
should be addressed below.
□ The DSMP is NOT contained in the protocol; however,
this is a repository/database protocol and the primary
risk is that of loss of confidentiality; thus, I do not need
to complete this section.
□ The DSMP is NOT contained in the protocol.
Complete the questions below.
Section IX – A

Who will be responsible for the data
and safety monitoring?


Examples include: a DSMC or DSMB, medical
monitor, investigator, independent physician)
Clarify if this individual or committee
is independent from the sponsor
and/or investigator.
Section IX –B
What will be monitored

Examples include: data quality, subject
recruitment, accrual, and retention,
outcome and adverse event data,
assessment of scientific reports or
therapeutic development, results of
related studies that impact subject safety,
procedures designed to protect the privacy
of subjects
Section IX-C

What are the procedures for analysis
and interpretation of data, the
actions to be taken upon specific
events or endpoints, the procedures
for communication from the data
monitor to the IRB and site, and
other reporting mechanisms
Section IX – D

What is the frequency of monitoring?

The appropriate frequency of data and safety
monitoring will be dependent on the nature
and progress of the research; however,
monitoring must be performed on a regular
basis (e.g, at least annually).
Section IX – E

What information will be reported to the
IRB?



IRB requires the following information at the time of
continuing review:
 1) frequency and date(s) of monitoring;
 2) summary of cumulative adverse events;
 3) assessment of external factors (i.e. scientific
reports, therapeutic developments, results of
related studies) that impacted the safety of
subjects;
4) summary of subject privacy and research
data confidentiality outcomes; and
5) any changes to the risk-benefit ratio.
Data and Safety Monitoring Plan
and Board

1.
2.
3.
4.
Description should include:
DSMB chair and members
How frequently the study will be
evaluated
The method of detecting adverse events
How events will be scored
Translational Research Ethics
Consultation
Service (TREX)


Available to researchers to help clarify and address
ethical issues that arise in planning, carrying out, and
analyzing human subjects research.
Areas for possible consults include but are not limited
to:
o Recruitment and informed consent issues
o Vulnerable, pediatric, or impaired research
subjects
o Data sharing with research subjects or a broader
community
o Biobank construction and governance
o Data Safety Monitoring Plans or Boards
TREX





Free of charge, offered by the IU Center the Bioethics
(IUCB) as a service of the Bioethics and Subject
Advocacy Program (BSAP), a part of the Indiana
Clinical and Translational Sciences Institute (CTSI).
Confidential and anonymous when appropriate.
Conclusion of the consult is a memo issued as advice
to the requestor.
Researchers can request a consult by emailing Dr.
Peter Schwartz (phschwar@iupui.edu), Director of
TREX, or Dr. Eric Meslin (emeslin@iupui.edu),
Director of IUCB.
To learn more about the IUCB and BSAP go to
www.bioethics.iu.edu/bsap