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EVENT ADJUDICATION IN THE DIGITAL AGE AN E-BOOK FROM ICON PLC.


ICON PLC

ELECTRONIC EVENT ADJUDICATION

The Adjudicator’s Job: The Indecisive Need Not Apply CEC members are expected to be independent and unbiased experts in the relevant clinical field. CEC members are presented with the facts surrounding each suspected adverse event or reported outcome, yet remain agnostic to the patient’s treatment assignment. They are then asked to evaluate each event/endpoint in a standardized way (as detailed in an Adjudication Charter) [could we link to a sample?] and to “rule” on the investigator’s original determination.

The Growing Need for Adjudication Increasingly, regulators require drug sponsors to conduct event-driven, or outcomes-based, trials. These are designed to rule out an increased risk of specific events or endpoints for treated patients compared to a control group.

Logically, an adjudicator can either agree with the site investigator’s determination or not. Non-agreement results in the adjudicator either upgrading or downgrading the investigator’s finding to a different clinical classification. More than one Committee Member evaluates each case, and when the reviewers do not agree, there must be some procedure in place to resolve the discrepancy.

To confirm what investigators report, sponsor companies arrange for adjudicators on a Clinical Event Committee (CEC) to review all suspected events and reported endpoints. What’s more, as trials have become global, regional differences have naturally affected how events are identified, diagnosed, and reported. A central review, or adjudication, neutralizes these differences.

CEC

+ -

INVESTIGATOR REPORTED EVENTS

+ -

AGREE

DOWNGRADE

UPGRADE

AGREE

These adjudications must be done in a timely fashion so as not to delay decisions based on emerging safety or efficacy information.

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ICON PLC

ELECTRONIC EVENT ADJUDICATION

Agreeing to Disagree

Your Grandfather’s Adjudication Methodology

How often do adjudicators agree with site investigators? The answer varies significantly across indications and subgroups within trials as seen in this summary of several trials conducted to measure cardiovascular endpoints.

Traditionally, CECs have met face to face every so often to adjudicate several hundred cases in each session. Once convened, members are presented with an Event Adjudication package, typically in a three-ring binder. They then study, discuss, and agree upon how events and endpoints are to be designated, recording their decisions on paper. Later, their findings are transcribed and entered into a system for subsequent reporting to the Safety Monitoring Board or Trial Steering Committee.

Other comparisons have shown that the level of agreement between the CEC and site investigators varies from one region of the world to the next, as would be expected. Because CEC members are blinded to the treatment assignment, apply standardized definitions as they make their diagnoses, and reach consensus, their judgment is considered authoritative.

While this approach gives Committee members the ability to confer with one another in person, that ability comes at a great price—a sacrifice in data quality, delays in bringing safety and efficacy information forward, and added costs.

Drawbacks of Manual Adjudication

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Study

Event

Site Diagnosis

CEC Diagnosis

Agreement

Paragon-B

MI

1736

483

28%

MOST

CV Death

404

363

90%

VALIANT

MI

2159

1360

63%

VALIANT

Stroke

541

492

91%

VALIANT

CHF

3841

2804

73%

Logistical challenges in convening CEC members Potential information gap and time lag for important trial governance decisions –potentially adding to trial costs Costly travel arrangements Laborious, manual process for reviewers, requiring subsequent data entry No visibility to project status & limited auditing ability Reviewers unaware of inconsistencies and incomplete data No immediate access to case data for review (?) Difficulty in ensuring patient confidentiality and document security Is there any point to be made about group think? Isn’t it better to have them make their first determinations independent of one another?

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To learn how ICON’s adjudication services meet your needs, contact us to schedule a meeting today

ICON plc 2800 Kelly Road Warrington, PA 18976 USA

ICON plc Zeltweg 46 CH-8032 Zurich Switzerland

Tel: +1 267-482-6300 Fax: +1 267-482-6301

Tel: +41 44-582-4100 Fax: +41 44-582-4101

iconplc.com

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