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FDA-Industry Communication
How to Get the Most Out of Your Courtship with FDA
-An FDA Reviewer’s Perspective
Society For Clinical Trials May 20, 2013
Phyllis M. Silverman, M.S. Biostatistics Team Leader
FDA/CDRH
Menu
• Venues of Communication
• Be Prepared to Discuss………..
• Top Ten Communication Crimes
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Venues of Communication Non Verbal
• IDE’s, 510(K)’s, PMA’s, HDE’s
• Modular PMA’s
• Q-Sub (formally Pre-IDE), Pre-PMA’s
• Email correspondence
• eCopy
• Electronic Data Submission
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Venues of Communication (cont’d)
Verbal
• Face to face meetings
– After pre-IDE review
– During IDE review cycle
– During PMA review cycle
• Teleconferences
Always have someone take minutes at meetings and telcons
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Tips for Pre-IDE and IDE Meetings
• Submit protocol to FDA in advance
• Make it clear if your study is a feasibility or pivotal study and if the claim will be for superiority or NI
• Prepare an agenda or list of specific questions for FDA sent in advance
• Bring the necessary experts to the meeting, such as the statistical consultant
• Let FDA know if you are bring a
statistician so we can invite ours
For an IDE Pivotal Study Be prepared to discuss………..
• Sample size justification, assumptions, and rationale
• Hypotheses to be tested
• Appropriateness of the control
• Statistical methods that will be used
• Primary analysis cohort
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Be prepared………..
• Important covariates and how they will be handled
• Randomization scheme
• Futility boundaries
• For Non-Inferiority claim: What advantage does the new device have that could justify a slightly lower success rate?
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Have a Plan For………..
• Interim analyses including Type 1 error adjustment if necessary
• Subgroups analyses
• Handling multiplicity
• Minimizing lost to follow-up
• Handling missing data
• Appropriate simulations if Bayesian or adaptive design
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Pre-PMA and PMA Meetings
• Pre-PMA – Brief FDA on highlights of study results and
anything unusual that might have happened
– Can occur before data analysis is complete
• Possibly even before the blind is broken
– Get FDA feedback on presentation of data tables and summaries
• Show table templates
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For PMA Meetings Topics of Discussion……..
• Patient accountability
• Analysis cohorts
• Adjustment for multiplicity
• Clinical meaningfulness
of the results
• Protocol violations
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PMA Topics of Discussion……
• Was there a physician or operator
learning curve?
• Patient compliance to treatment regimen
• Loss to Follow-up
• Potential biases
• Success of the masking
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More possible topics……….
• Justification of pooling across sites
or countries
• Appropriateness of statistical assumptions
• Sensitivity analysis on missing values
• Robustness of the statistical inference
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Top Ten Communication Crimes
1. Spending too much time at a meeting giving an overview of the device or clinical study
2. Spending too much time at a meeting discussing a single issue
3. Failure to address all FDA concerns
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Top Ten Crimes
4. Not successfully communicating the study objective and statement of hypotheses
5. Not having someone oversee the clinical report to check for consistency and accuracy
6. Providing voluminous tables of computer printout without summary tables
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Top Ten Crimes
7. Having poorly labeled tables without units, sample sizes, or analysis cohort
8. Conveying results in lengthy text rather than using tables or graphs
9. Failure to submit electronic data and software codes
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Drum Roll………………..
10. Not coming in early to talk to FDA!
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Don’t Hesitate - Communicate!
It’s the best way
to get FDA to say
to your proposal.
