1. The Adjudicators: Role and Responsibility of the CEC
Donald E. Cutlip, MD
Beth Israel Deaconess Medical Center
Harvard Clinical Research Institute
Harvard Medical School

2. I have no real or apparent conflicts of interest to report.
Donald E. Cutlip, MD
I have no real or apparent conflicts of interest to report.

3. Outline Roles and Responsibilities of CEC Physician (Adjudicator)
Management of the adjudication process
CEC Operations – Key Points
Case Examples

4. Role of CEC Physician (Adjudicator)
Apply specific clinical trial definitions to determine if suspected events meet criteria for endpoint.
Expert (clinical area and specific study protocol)
Independent (Sponsor, Investigators, Competitors)
Limit Bias (blinded to treatment assignment and other related information – investigator, clinical site, treating physicians etc)
Consistent (in decision making)

5. Event Adjudication Process Purpose and Management
Complete and accurate reporting of events
Limit Bias in Event Reporting
Consistency of Adjudication Results

6. Event Adjudication Process Purpose and Management
Complete and accurate reporting of events
Verification that all confirmed events meet pre- specified criteria
Establish processes for determination of event when minimum data not available
Systematic reporting of events (and their absence) by clinical centers
Find unreported events

7. Event Adjudication Process Purpose and Management
Limit Bias in Event Reporting
Especially important in open label or unblinded trials
Ensure events reported by different investigators are of similar severity – uniform definitions/consistent application
Site monitoring and review of adjunctive data needed to assure all potential events are captured (supplement investigator reports)

8. Event Adjudication Process Purpose and Management
Consistency of Adjudication Results
Exercise clinical judgment but think like an adjudicator (apply the rules)
Keep track of committee judgment decisions and rationale (adjudicate next similar case the same)
It may be more important to be consistent that right

9. Management of CEC Operations
Identification of Potential Events (cast a wide net)
Begins with design of the study and case report forms (capture the absence of event at specific intervals)
Investigator reports (always limited)
Laboratory data
AE and SAE reviews
Clinical site monitors

10. Management of CEC Operations
Adjudication Methods
Independent review
2 physicians with 3rd review for discordance
1 physician with referral to others as needed
Consensus panel
Full panel review of each event
Face-to-face
Web or telephone conference

11. Case Examples Missing Required Data Suspected MI
Protocol definition- Total CK > 2 times normal with elevated CKMB
Patient experiences dissection and transient abrupt closure. Review of lab data indicates CK and CKMB not obtained. Troponin elevated >10 time normal.
How should this event be adjudicated?
How does it affect future similar cases?

12. Case Examples Role of Clinical Judgment Suspected MI
Protocol definition- New symptoms with total CK > 2 times normal with elevated CKMB
Patient presents after a fall at home and reports chest pain in addition to other symptoms.
Review of lab data shows total CK >5 times normal with CKMB 1.1 times normal (relative index <2); Troponin not elevated.
How should this event be adjudicated?
How does it affect future similar cases?