1. Insights from the Melody Pulmonic Transcatheter Valve Panel

2. Disclosure Slide Thomas Armitage is an employee of Medtronic, Inc.
I just had knee surgery (hence the crutches, knee brace and blue jeans)

3. Melody Overview Melody Transcatheter Pulmonary Valve (TPV)
Melody Valve:
Bovine jugular venous valve segment
Platinum-iridium stent
Ensemble Catheter Delivery System
22 Fr crossing profile
Balloon-in-balloon

4. FDA Advisory Panels

5. What is an FDA Advisory Panel?
FDA Advisory Panels
Committees of experts to provide an independent assessment
Make recommendations
Circulatory System Devices Advisory Panel
Physicians and scientists
Consumer and industry representative
Executive Secretary (FDA employee)

6. What is an FDA Advisory Panel?
Panel meetings sometimes referred to as “running the gauntlet”
. . .a form of punishment in which the culprit was made to run stripped to the waist between two rows of men who whipped and beat him as he passed by. These beatings were extremely severe and the victims often died as a result - and many of those that didn't may well have wished they had.
Yeah, that sounds right

7. Panel Prep Timeline
Elapsed Prep Time: 2 Months

8. Key Considerations for Melody Panel
Primary Considerations
Alignment with FDA
Presentation and Presenters
The Risk / Benefit Equation
Secondary Consideration
The open public session
Media Interest

9. Key Considerations for Panel
Alignment with FDA
Reach agreement with the FDA, or at least agree to disagree, before the Panel
Don’t force a Panel meeting unless necessary. This is a tactic of desperation.
The FDA’s concerns re your technology are reflected by their questions to the Panel members
Make it a point to address the FDA’s questions in your presentation

10. Key Considerations for Panel
Presentation
Anticipate
Being surprised or confused at a Panel meeting can change votes. Anticipate all questions.
Be prepared with any materials to answer any question
Prepare
Mock Panels are valuable. Hire uninvolved experts to critique your presentation

11. Key Considerations for Panel
Presentation
Melody Backup Preparation:
Backup Slides: 554 (1.8 GB)
Anticipated Questions: 199
Questions asked by Panel: 30
Questions requiring new slides: 2

12. Melody Panel Presenters
Takeaway Messages
Panel meetings are almost always about the clinical data:
Let the clinicians do the talking
Select the right clinicians
Respected, calm, not easily provoked
De-emphasize the sponsors role in the discussion
Let the sponsors presenter(s) play quarterback

13. Melody Panel Presenters
Tom Armitage, MD
John Cheatham, MD
William Hellenbrand, MD
James Lock, MD
10 Clinicians / 1 Medtronic Person
Additional Experts:
Prof Philipp Bonhoeffer, MD
Robert Padera, MD, PhD
Patrick O’Leary, MD
Anjan Batra, MD
Marshall Jacobs, MD
John Mayer, MD
Joseph Massaro, PhD

14. The Risk / Benefit Equation
Risk / Benefit Background
FDA Draft Guidance on Risk / Benefit

15. The Risk / Benefit Equation
Risk / Benefit Background
FDA Draft Guidance on Risk / Benefit
A reasonable assurance of safety occurs when “it can be determined, based upon valid scientific evidence, that the probable benefits … outweigh any probable risks.” The evidence of which is demonstrated by establishing, “the absence of unreasonable risk of illness or injury associated with the use of the device for its intended uses and conditions of use.” (21 CFR 860.7(d)(1).
Similarly, a reasonable assurance of effectiveness occurs when “it can be determined, based upon valid scientific evidence … the use of the device for its intended uses … will provide clinically significant results.” (21 CFR 860.7(e)(1)). The evidence of which is demonstrated principally through “well-controlled investigations” (see 21 CFR 860.7(e)(2)) as defined in 21 CFR 860.7(f)

16. The Risk / Benefit Equation
Opportunities with the Melody Program
In the absence of an RCT, the risk/benefit analysis may need to be made using two different technologies with different risks:
Melody
Risk of reintervention vs
Surgical Conduit Replacement
Risk of the Surgery
Risk of Right Heart Failure 2○ to delayed surgical intervention

18. Melody FDA Panel Recommendation for Approval
Panel unanimously recommends approval with conditions (12-0)

19. Thank You