1. Adherence to the Labeling
John Laschinger, M.D.
Medical Officer
FDA/CDRH/ODE/DCD/SHDB

2. I/we have no real or apparent conflicts of interest to report.
John Laschinger, MD
I/we have no real or apparent conflicts of interest to report.

3. Current On Label Indication for Use: SAPIEN THV
SAPIEN is indicated for transfemoral delivery in patients with severe symptomatic calcified native aortic valve stenosis without severe aortic insufficiency and with ejection fraction > 20% who have been examined by a heart team including an experienced cardiac surgeon and a cardiologist and found to either be:
in operable and in whom existing co-morbidities would not preclude the expected benefit from correction of the aortic stenosis; or
be operative candidates for aortic valve replacement , but who have a Society of Thoracic Surgeons predicted operative risk score > 8% or are judged by the heart team to be at a 15% risk of mortality for surgical aortic valve replacement.

4. What is “On-label” Use
FDA Device Clearance or Approval is limited to specific Indications for Use – 3 Components:
Intended Use:
What - What device is designed to do (e.g. Correction of aortic stenosis)
Why – Clinical disease or condition (e.g. Critical AS)
Conditions of Use
Where, who, and how of insertion (e.g. Hybrid suite, heart team, transfemoral access, training, etc)
Target Population
Who – Target patient population (e.g., patient at high or extreme risk for surgery, symptomatic with no AI)
Label Purpose:
Provide information regarding results of evaluation
Transmit applicable warnings and precautions for that indication
Describe potential limitations of the evaluation (e.g., populations not included in studies) or potential performance problems under described circumstances or conditions

5. Why Off-label Use? FDA does not regulate the practice of Medicine
Information provided in the labeling may or may not be applicable depending on how far “off-label”
FDA recognizes other clinical needs/uses not covered by the label may exist
Device has not been evaluated for the Indication
New Intended use
New or lower risk Target Population
The focus of the pivotal trial was inadequate to support a specific marketing approval or clearance for all clinical situations
New Conditions of Use within an approved target population
Higher risk segment of an approved target population
RCT Generally Needed
Targets for Label Expansion

6. A Better Path: Label Expansion
Encourages the collection of additional data needed for the expanded Indications
RCT not always necessary
Early interaction with FDA
Common Goal: least burdensome path
Sponsors – Ability to Market devices appropriately
End-users - Provided with clinically relevant information
Patient - Protection and Early Access

7. Current Initiatives in SHDB with Labeling Implications
Clinical studies based on pre-operative risk stratification (e.g. PARTNER IIA, COAPT)
Initiation of registries to capture real-world use - TVT
Identify how devices are really used
Capture “real world” performance information
Acquire data necessary for expansion of label indications within approved populations
Refine pre-clinical testing requirements to keep up with rapid evolution of devices and materials
Encouraging pre-clinical testing outside of the proposed labeling to help understand potential issues with “off label” use (e.g. valve-in-valve)

8. Progress on Initiatives
TVT Registry active at > 130 sites
FDA has accepted the concept of using single arm study data to support label expansion for approved indications/populations
FDA has approved ACCF/STS sponsored IDE study using data from real-world registries
Alternate Access (non-femoral) in patients inoperable for surgical AVR
TVT registry used for data collection
Data from TVT registry used as comparator

9. John Laschinger, M.D. john.laschinge@fda.hhs.gov
Thank You!
John Laschinger, M.D.

11. On-label
The pre-clinical evaluation was appropriate for the intended use
Testing involved use of the device in accordance with the instructions for use (e.g., preconditioning, sizing)
Clinical information included in the label reflects the intended use

12. Regulation and Off-label Use
FDA regulates interstate commerce of medical devices, not the practice of medicine
FDA encourages appropriate evaluation of devices to allow for modification of the labeling to protect and promote public health
Manufacturers need to do what they can to limit known off-label usage
Restrict distribution/promotion
Modify labeling