Handling and Use of Information Received from Data Monitoring Committees:

Points to Consider

October 30th, 2007

Jon Haddad

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Agenda

• What types of recommendations can be received

• Appropriate internal recipients

• Is it ‘actionable’

• Some examples for discussion

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Types of Recommendations

• Continue without modification

• Stop for safety concern

• Stop the study for futility

• Stop for success

• Change sample size

• Modify the trial

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Internal Recipients

• Evaluate potential impact (in advance!)

• Look at your organization specifically (Wyeth and Synta are not the same)

– Is there another geographic location/operating unit that is sufficiently removed

– Is it realistic to expect recommendation to remain undisclosed

• What is the ‘real’ need to know?– How does the Sponsor evaluate the recommendation– Is the recommendation automatic based on pre-defined/agreed criteria– Can one do anything with the information once it’s known

• Remember, the goal of the DMC is to add independence to risk:benefit evaluation and to avoid comprising the study team with inappropriate information

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Internal Recipients, cont.

• Define internal procedures– What data will be made available– Who will have access to these data– What protections will be implemented to contain the information

within the company

• Data Flow and Release procedure– Covers internal and external release of the information– Some companies (e.g., Lilly) have entire departments for release

of clinical trial information– Sarbanes/Oxley!

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Is it ‘Actionable’?

• Continue without modification– Is a press release necessary– Does it tell one anything? Anything ‘material’?

Check with your lawyers…

• Stop the study– Do you have to accept a DMC recommendation– How do you know if the DMC recommendation is justified– Who will make this assessment

• Steering Committee• Internal, non-project staff/committee• Independent agent for sponsor• Input from regulators

Check with your lawyers…

• Continue with modifications Assess impact See above…

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Some Examples for Discussion

• Continue without modification– Will have to be disclosed to the operational study team

• Modify sample size– Clearly gives some indication of how things are going

– A precise number may be revealing too much

– Pre-define incremental blocks (25-50; 51-100, etc)

• Stop for efficacy– How in-depth is the sponsor’s review

– How can this be done without team unblinding

– If Sponsor decides to keep going, how to protect study from bias going forward

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Wrap up

• Pre-Consider the potential recommendations that may be received

• Decide and document a process for handling recommendations a priori

• Take great care in protecting the study team from information that may introduce bias/appearance of bias

• Consider carefully the appropriate way to communicate (or not) to the public domain