1. THE ROLE OF DSMB’s in CLINICAL RESEARCH
Data and Safety
Monitoring

2. Data and Safety Monitoring
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

3. DATA and SAFETY MONITORING
Clinical Trials have a relationship between participants and investigators
Both must fulfill certain obligations

4. Data and Safety Monitoring
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

5. Data and Safety Monitoring
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

6. Data and Safety Monitoring
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

7. 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

8. 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

9. Data and Safety Monitoring
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

10. Data and Safety Monitoring
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

11. Data and Safety Monitoring
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

12. Data and Safety Monitoring
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

13. Data and Safety Monitoring
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

14. Data and Safety Monitoring Plan
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

15. Data and Safety Monitoring Plan
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

16. Data and Safety Monitoring Plan
The plan should include the following:
Committee chair and members
Frequency of evaluation
Method of detecting adverse events
How adverse events will be scored

17. Data and Safety Monitoring Plan
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

18. Data and Safety Monitoring Plan
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

19. Data and Safety Monitoring Plan and Board
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

20. 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 GCRC submission.
This description should be included in Section G of the GCRC application

21. Data and Safety Monitoring Plan and Board
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

22. Data and Safety Monitoring Plan and Board
Adverse event reporting requirements
A description of interim efficacy analysis if appropriate
The distribution of DSMB reports

23. Significant Risk Protocols
Definition of Risk is a complex sum of individual contributors to the overall risk of participation in the study

24. Significant Risk Protocols
Risk to study subjects may be thought of as encompassing aspects of:
Study design
Potential for loss of confidentiality
And the nature of the study population involved

25. Significant Risk Protocols
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

26. Significant Risk Protocols
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

27. Significant Risk Protocols
The amount of experience with the study intervention also affects the risk, since the risk of AEs may not be fully defined.

28. Significant Risk Protocols
Study Population
Participation of vulnerable subjects confers greater risk than non vulnerable populations
Examples include children under 18, prisoners, and employees of the workplace

29. Significant Risk Protocols
Normal volunteer populations require special consideration since any intervention confers greater risk than would be experienced by subjects not participating in a study

30. Significant Risk Protocols
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

31. Significant Risk Protocols
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

32. Significant Risk Protocols
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

33. Significant Risk Protocols
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

34. Significant Risk Protocols
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

35. Significant Risk Protocols
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.

36. Significant Risk Protocols
Studies in vulnerable populations
Children under 18
Prisoners
Decisional-impaired subjects involving more than minimal risk
Studies that involve administering agents manufactured on campus

37. The Role of DSMB’s in Clinical Research
Produced and Presented by
Carole Weir, RN, MSN
Directors
Edward Liechty, MD
Peter Schwartz, MD
The Research Subject Advocate Committee