Transcript THE ROLE OF DSMB’s in CLINICAL RESEARCH

THE ROLE OF DSMB’s in
CLINICAL RESEARCH
Data and Safety
Monitoring
Data and Safety Monitoring
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NIH Policy
Each Institute/Center should have a
system for the appropriate oversight and
monitoring of the conduct of clinical trials
Must ensure the safety of participants and
Should protect the validity and integrity of
the data for all NIH-supported/conducted
trials
DATA and SAFETY MONITORING
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Clinical Trials have a relationship between
participants and investigators
Both must fulfill certain obligations
Data and Safety Monitoring
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Participants:
Must be fully informed of the study
requirements throughout the study
Should comply with the rigors of the
research protocol or be allowed to
withdraw from participation
Data and Safety Monitoring
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Investigators:
Must protect the health and safety of
participants
Inform participants of information relevant
to their continued participation
Pursue the research objectives with
scientific diligence
Data and Safety Monitoring
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1979
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
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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
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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
Data and Safety Monitoring
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Principles of monitoring data and safety in
studies include:
Physiologic, toxicity, and dose-finding
studies—Phase I
Efficacy studies—Phase II
Efficacy, effectiveness and comparative
trials—Phase III
Data and Safety Monitoring
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Monitoring should be commensurate with the
degree of risk involved
A data and safety monitoring committee should
determine safe and effective conduct and
Recommend conclusion of the trial when
significant benefits or risks have developed or
The trial is unlikely to be concluded successfully
Data and Safety Monitoring
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Risk associated with participation in
research must be minimized to the extent
practical
Size and complexity will determine if a
single person or a committee is needed to
oversee the study
Data and Safety Monitoring
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Performance of Data and Safety Monitoring
Is to protect the integrity of the system for
monitoring trial data and participant safety
Monitoring must be performed on a regular
basis
Conclusions of the monitoring must be
reported to the IRB and the Research Subject
Advocate Committee (RSA) on the GCRC
Data and Safety Monitoring
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IRB/RSA responsibilities
May direct who shall perform the
monitoring activities
May direct the composition of the
monitoring group including that:
the PI is not to chair the Data and Safety
Monitoring Board nor be the single person
doing the monitoring
Data and Safety Monitoring Plan
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All protocols receiving GCRC support are
required to have a Data and Safety
Monitoring Plan which
Monitors the progress of the research
study and the safety of participants
Plans for assuring compliance with
requirements for reporting adverse
events
Data and Safety Monitoring Plan
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Plans for assuring that any action
resulting in a temporary or permanent
suspension of the clinical trial is reported
to all responsible parties
Plans for assuring protocol compliance
and data accuracy
Data and Safety Monitoring Plan
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The plan should include the following:
Committee chair and members
Frequency of evaluation
Method of detecting adverse events
How adverse events will be scored
Data and Safety Monitoring Plan
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Adverse event reporting requirements
A description of interim efficacy analysis
if appropriate
Distribution of Data and Safety
Monitoring Board (DSMB) reports—must
go to GCRC RSA for review
Data and Safety Monitoring Plan
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Specifics of the plan will depend upon the
nature, size, complexity and risk of the
clinical trial
A monitoring committee is required to
determine safe and effective conduct
Or to recommend conclusion of the trial
when significant benefits or risks have
developed
Data and Safety Monitoring Plan
and Board
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Single individual—if trial is small with little
risk
IU GCRC has decided that the Principal
Investigator cannot be the chair of the
DSMB and cannot be the only monitor of a
research study in order to eliminate any
potential conflict
Data and Safety Monitoring Plan
and Board
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A description of the plan and the
composition of the monitoring board are
required at the time of the GCRC
submission.
This description should be included in
Section G of the GCRC application
Data and Safety Monitoring Plan
and Board
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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
Data and Safety Monitoring Plan
and Board
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Adverse event reporting requirements
A description of interim efficacy analysis
if appropriate
The distribution of DSMB reports
Significant Risk Protocols
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Definition of Risk is a complex sum of
individual contributors to the overall risk of
participation in the study
Significant Risk Protocols
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Risk to study subjects may be thought of as
encompassing aspects of:
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Study design
2.
Potential for loss of confidentiality
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And the nature of the study population
involved
Significant Risk Protocols
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The risk of the intervention is a function
of the potential for adverse events (AE)
and the severity of adverse events
The potential for adverse events includes the expected
frequency of adverse events
When the frequency of AEs is unknown or identifying
the frequency of AEs is one of the endpoints of the
trial such as Phase I trials, the risk is higher
Significant Risk Protocols
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The severity of adverse events should
also be considered independent of the
frequency of AEs
Study procedures which are not expected to lead to
frequent AEs, but include the possibility of severe AEs,
confer higher risk
Significant Risk Protocols
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The amount of experience with the study
intervention also affects the risk, since the
risk of AEs may not be fully defined.
Significant Risk Protocols
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Study Population
Participation of vulnerable subjects
confers greater risk than non vulnerable
populations
Examples include children under 18, prisoners, and
employees of the workplace
Significant Risk Protocols
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Normal volunteer populations require
special consideration since any
intervention confers greater risk than
would be experienced by subjects not
participating in a study
Significant Risk Protocols
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The gravity of loss of confidentiality
Loss of confidentiality for study participants in genetic
studies, studies of stigmatized conditions, or studies
where loss of confidentiality could lead to social harms
may be considered high risk
Significant Risk Protocols
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Physical, emotional and psychosocial
harms
Example: a genetic study which might lead to a
diagnosis of or identify a predisposition for a serious
disease in study participants would be considered high
risk such as Huntington’s disease
A study including known illegal drug users could be
considered high risk since loss of confidentiality of study
participants could lead to great social harm
Significant Risk Protocols
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Significant Risk may be conferred by the degree
of severity of a single consideration or the
combined weight of several considerations
By mandate, all studies using GCRC facilities or
resources which are considered to be of
significant risk will be required to establish an
independent data safety monitoring board
Significant Risk Protocols
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Independent Data and Safety Monitoring
Board
Is made up of at least one member who is not directly
involved with the study
Should not be a member of the PIs or co-PIs division
within a given department
If the PI is a division director, then the DSMB cannot be
made up of more junior members of his or her division
Significant Risk Protocols
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Studies requiring an Independent DSMB
Early clinical trials
All Phase I studies
Phase II studies unless they involve low risk
interventions
Studies of devices or invasive techniques with which the
PI or the community has little experience
Gene Therapy trials
Significant Risk Protocols
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Genetic Studies
Studies that examine more than 20 genetic loci
Studies which seek to examine stigmatized conditions
Lethal or disabling diseases for which no treatment is
available
Or conditions where loss of confidentiality within the
study could lead to serious emotional, psychological, or
social consequences.
Significant Risk Protocols
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Studies in vulnerable populations
Children under 18
Prisoners
Decisional-impaired subjects involving more than
minimal risk
Studies that involve administering agents
manufactured on campus
The Role of DSMB’s in Clinical
Research
Produced and Presented by
Carole Weir, RN, MSN
[email protected]
Directors
Edward Liechty, MD
[email protected]
Peter Schwartz, MD
[email protected]
The Research Subject Advocate Committee