1. Dartmouth Human Research Protection Program (HRPP) Data Safety Monitoring and Reporting requirements Brown Bag Series: Noon / First Tuesday of the Month April 4th, Auditorium B

2. Updates New initiatives:
AAHRPP update
New initiatives:
Improving the consent process; VoICE; new regulations
Education for new research staff
May: Leigh Burgess – clinical trial.gov; Scientific Review Process update

3. Questions during this session? 
Ann O’Hara and we will try
to respond during our Q&A following the presentation:

4. Reporting : Sponsor FDA Local IRB External IRB OHRP
PI / multi site study
FDA
Local IRB
PI = sponsor
Investigator initiated
IND holder
Institutional
Officials
External IRB
OHRP

5. Monitoring Guidance :
NIH
FDA
GCP – Good Clinical Practice

6. NIH: "a variety of types of monitoring may be anticipated depending on the nature, size, and complexity of the clinical trial. In many cases, the principal investigator would be expected to perform the monitoring function."

7. NIH: Data and safety monitoring is required for all types of clinical trials, including physiologic, toxicity, and dose- finding studies (phase I); efficacy studies (phase II); efficacy, effectiveness and comparative trials (phase III); etc.
Monitoring should be commensurate with risks
Recommend conclusion of the trial when significant benefits or risks have developed or the trial is unlikely to be concluded successfully.
Risk associated with participation in research must be minimized to the extent practical.
Commensurate with size and complexity.

8. Food and Drug Administration
Guidance for Industry
Oversight of Clinical Investigations — A
Risk-Based Approach to Monitoring

9. The regulations are not specific about how sponsors are
to conduct such
monitoring and are therefore compatible
with a range of approaches to monitoring
(see section III)
that will vary depending on multiple
factors (see section IV.C).

10. INTERNATIONAL CONFERENCE ON HARMONISATION OF TECHNICAL
REQUIREMENTS FOR REGISTRATION OF PHARMACEUTICALS FOR HUMAN
USE
ICH HARMONISED TRIPARTITE GUIDELINE
GUIDELINE FOR GOOD CLINICAL PRACTICE (GCP)
E6(R1)

11. 4.11 Safety Reporting
All serious adverse events (SAEs) should be reported immediately to the sponsor except for those SAEs that the protocol or other document (e.g.,
The investigator should also comply with the applicable regulatory requirement(s) related to the reporting of unexpected serious adverse drug reactions to the regulatory
authority(ies) and the IRB/IEC.

12. Adverse events and/or laboratory abnormalities identified in the protocol as critical to safety evaluations should be reported to the sponsor according to the reporting requirements and within the time periods specified by the sponsor in the protocol.
For reported deaths, the investigator should supply the sponsor and the IRB/IEC with any additional requested information (e.g., autopsy reports and terminal medical reports)

13. Reporting to the IRB is a
subset of other
reporting
requirements

14. 46.111 Criteria for IRB approval of research
First: Before any reporting starts –
the IRB is responsible to ensure monitoring is in place :
Criteria for IRB approval of research
(6) When appropriate, the research plan makes adequate provision for monitoring the data collected to ensure the safety of subjects.

15. 45CFR46.103
Reporting - IRB
(5) (i) any unanticipated problems involving risks to subjects or others or any serious or continuing noncompliance with this policy or the requirements or determinations of the IRB;
and (ii) any suspension or termination of IRB approval.

16. Reporting to IRB includes:
Retrospective protocol deviation: RNI
Prospective protocol deviation : modification
Continuing Review

17. Reportable New Information (RNI)
CPHS Reporting Form :
Unanticipated Problems Involving Risks to Subjects or Others (UPRs), Serious Adverse Events (SAEs), and Unanticipated Adverse Device Effects (UADEs)

20. Reporting criteria differs based on whether the occurrence was internal or external.
An internal event is one that involves a Dartmouth site or another CPHS-reviewed site or a Dartmouth research participant (regardless of location of the participant at the time of event).
External events are those that occur at a non-CPHS reviewed site and with participants that are not research participants under CPHS oversight. This also refers to important new information that goes beyond discrete, individual events, such as: IND Safety Report, new animal data, or a black box warning.

22. Timeframe for reporting:
Applies to medical and non-medical problems, and includes potential risks that did not lead to direct harm.
5 calendar days for the temporary or permanent suspension of current activities to avoid potential harm of participants or others.
10 calendar days for both Internal and External Events that meet reporting criteria, but did not lead to suspension.

23. The investigator is reporting this incident to:
☐ CPHS only ☐ Sponsor ☐ Other (e.g., program officer): __________________________
4. Has this event been reported to the FDA, OHRP, and/or others? ☐Yes ☐No*
*If no, does the sponsor intend to do so? ☐Yes ☐No
5. Study location: ☐ Multi-site ☐ Dartmouth Only (sites subject to CPHS review)

24. Is the risk of this event described in the consent form or in the investigator's brochure?
☐ No
☐ Yes, but it has occurred with greater specificity
☐ Yes, but it has occurred with greater frequency
☐ Yes, but it has occurred with greater severity
☐ Yes, but none of the above (this does not meet CPHS reportability criteria,do not report unless study modifications are planned which are directly related to this event/risk). Explain here:

25. Describe the response as a result of this event/problem:
Describe the plan to protect or notify currently enrolled
individuals regarding this event:
Is a modification to the study expected from the sponsor?

26. Thank you for your time.
Questions during this session? 
Ann O’Hara