1. Benefits of US EFS: A Clinical Perspective
Ron Waksman, MD, FACC,FSCAI
Professor of Medicine, Georgetown University
Director, Cardiovascular Research Advanced Education
MedStar Heart Institute, Washington DC

2. Ron Waksman, MD Consulting: Biotronik, Inc. Abbott Laboratories
Boston Scientific Corporation
Medtronic, Inc.
Merck and Company, Inc.
Honoraria:
Abbott Laboratories,

3. Objectives
Rational for new pathways within FDA for investigational new device evaluation for the US population
FIM Trial Status
EFS status
What is still needed from FDA

4. Medical Device Innovation
Meeting unmet clinical needs
Improving diagnostic strategies and treatments
Advantages for the device development process with US clinical studies (including FIH and early feasibility studies) of innovative devices
Opportunity for close contact between developers and investigators
Early access to promising novel technology
Continuity of clinical investigations
Safer
More predictive
More effective
Less invasive
More accurate
Simpler to use

5. What is First-In-Man Study?
FIM is the culmination of the pre-clinical device development “ecosystem”
A FIM trial tests the new device in humans for the first time
Generally, these trials are small in size and in very select patient populations (eg: stable patients with de novo lesions, etc.)
Bench Testing
Animal Safety Testing
Pre-clinical Animal Studies
First-in-Man Clinical Trial

6. Status of FIM Trials in the US
Average Time By Stage For PMA Product
Average per month Expenditure By Stage For PMA Product
FDA Impact on U.S. Medical Technology Innovation: A Survey of Over 200 Medical Technology Companies • November 6

7. Status of FIM Trials in the US
Although device innovation continues to emerge from the US the initiation of the device development has moved to non-US sites
Why?
FDA’s requirements can be an impediment to early clinical testing of new devices
FIM trials need the same rigorous IDE application as a pivotal trial (average time to IDE approval is 14 months)
The cost associated with obtaining an IDE are very high
Implications!
These new devices will either not become available to the US public or emerge into the US market much later than the rest of the global market
FDA Impact on U.S. Medical Technology Innovation: A Survey of Over 200 Medical Technology Companies • November 7

8. FDA response to the call for new pathways…
Initiated a pilot Early Feasibility Study program on December 12 ,2011
Accepted 9 devices into this pilot program
This pilot program will continue until May 8, 2013 for these 9 sponsors
Success of this program, however, is to come

9. What is an EFS?
Clinical investigation of a small number of subjects (generally fewer than 10 initial subjects)
Device early in development, typically before the device design has been finalized, for a specific indication, e.g.,
Innovative device for a new or established intended use
Marketed device for a novel clinical application
Does not necessarily involve the first clinical use of a device
Intended to provide proof of principle and initial clinical safety data

10. Purpose of Early Feasibility Studies
To obtain initial insights into:
the safety of the device-specific aspects of the procedure;
whether the device can be successfully delivered, implanted or used;
operator technique challenges with device use;
human factors (e.g., difficulties in comprehending procedural steps);
patient characteristics that may impact device performance (e.g., anatomical limitations); and
therapeutic parameters (e.g., energy applied, sizing, dose released) associated with device use.

11. Key Principles of the EFS
An EFS may be appropriate when:
Nonclinical testing methods are not available or
Adequate to provide the information needed to advance the developmental process; and
Clinical experience is necessary.
An EFS must be justified by an appropriate benefit/risk analysis and adequate human subject protection measures.
FDA approval of an EFS IDE application may be based on less nonclinical data than would be expected for a traditional feasibility or a pivotal study.

12. Pros and Cons of EFS Pros Cons
Enabling to start a clinical investigation early while the pre-clinical and bench data is on going
Patient populations are very limited (~10)
allows for iterations to progress during clinical testing
Does not address:
FIM trials in US
Devices that have a lot of OUS clinical data
Creating transparency, trust and open discussion with FDA
Early assess to cutting edge device for the US patient population

13. MedStar Cardiovascular Research Network IST FIM Experience
Therapeutic Device:
Vascular Brachytherapy for renal denervation
Evaluation Option 1: Outside the US
Conduct safety animal study
Submission protocol to local EC of collaborator
Approval to start investigation within a short time period
Advantage: Shorten time to study initiation
Disadvantages: soliciting OUS investigators, foreign regulatory agency, language, etc
Evaluation Option 2: US
Submission IDE
Approval to start investigation within 30 days (hopefully!!)
Advantage: PI and patients from US
Disadvantages: Time and costs of required application elements

14. What is still needed?

15. First-in-the-US Investigation
What is it?
A proposed track for devices already tested outside the US (with or without OUS approval) that established relatively safe profiles
Investigations would be limited to up to 100 patients at no more than 5 experienced US centers 15

16. First-in-the-US Investigation
Intended Users?
This proposed track would be available only to sponsors that intend to complete an IDE submission for a pivotal trial or pursue an PMA 16

17. First-in-the-US Investigation
Brief Requirements:
Required to have prior human experience (minimum 100 patients) with at least 6 months follow up
Minimum requirements to initiate this Investigation will be less than a traditional IDE
Completion of current IDE requirements may be submitted throughout First-in-the-US Investigation 17

18. First-in-the-US Investigation
Implication on Patients:
US patients will have an opportunity to be a part of early novel device evaluation
Patients will be fully informed of the potential additional risk involved in being a part of such early device investigations 18

19. First-in-the-US Investigation
Implication on Sponsors:
Motivate sponsors to return to the US for early clinical investigations
Streamline the US human subject investigation into the pivotal trial
Allow for streamlining US track milestones to be reached (eg first patient in US, entering US market)
Allows for data combination from both this track and pivotal trials for the PMA application 19

20. First-in-the-US Investigation
Implication on Agency:
The agency would gain earlier insight into the feasibility and safety of devices in the US population
Utilized these data to help better design the pivotal trials 20