1. Early Feasibility in the USA –An Academic View
Ron Waksman, MD
Director, Cardiovascular Research and Advanced Education
Associate Chief of Cardiology
MedStar Washington Hospital Center

2. 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

3. What is an EFS?
Clinical investigation of a small number of subjects, usually registry
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

4. 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.

5. 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.

6. EFS Advantages from the Academic View
Allow for the early study of unapproved devices or new intended use of approved device (even if no marketing application planned)
Address unmet clinical needs
Provide patients early access to novel potentially beneficial devices
Provide early options for patients with limited options to life threatening/changing disease

7. Stakeholders of EFS

11. On Going Early Feasibility Study in the US for mitral valve repair (industry sponsor)

12. 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

13. MedStar Cardiovascular Research Network: Sponsor collaborations Experience
Therapeutic Device:
BioFreedom Coronary System – polymer-free drug coated stent
Available data: Outside the US
Animal data
Over 1,000 patients who received the stent outside the US with no alarming safety signal
Question: To bring the stent to the US or not?
Evaluation Option: US
Conduct safety animal study in conjunction with a EFS trial on US patients
Submission IDE
Approval to start investigation within 30 days
Advantage: PI and patients from US, EFS trial has allowed for the additional animal studies to be completed simultaneously and pave the path for the pivotal trial

14. MedStar Cardiovascular Research Network: IST Feasibility Experience
Therapeutic Device:
Low Risk transcatheter aortic valve replacement
Evaluation Option: US
Conduct feasibility study to address the initial safety and operational feasibility of this procedure (any commercially available device) in a low risk (STS < 3) population
Submission IDE
Approval to start investigation within 30 days (or less!)
Advantage: PI and patients from US
Motivated to industry to submit their IDE
Disadvantages: Time and costs.
Few individuals got upset

15. Top 5 Reasons Why Not to Do An Early Feasibility Study
Significant investment with limited return on investment for some products
No guaranteed time to market advantage
Although for complex products may actually shorten development timelines
If study performed a long ways from home = huge disadvantage
Difficulties and cost associated with studies conducted far away from manufacturing
More consideration given for US EFS
Data obtained may not satisfy curiosity
Proper clinical protocol is essential

16. Top 5 Reasons Why to Do An Early Feasibility Study
Obtain data to drive product design refinement
Confirm fitness for use in a controlled situation where bench & animal model testing is inadequate
Physician training & best practice refinement
Gain confidence to proceed to a larger clinical investigation
Understanding patient selection / device use interactions

17. Conclusions
EFS allows investigators to conduct trials at the early phase
It’s upon the investigators and the agencies to demonstrate that the EFS will increase the trial being conducted within the US as well as shorten the time duration to PMA submission
With a successful and robust EFS program more investigators and companies will come to the US with their devices
It is imperative that CMS will be an integral partner in these EFS initiatives by providing reimbursement
Liability remains a threat to dissemination of this EFS initiative
We remain cautiously optimistic
We view addition of new pathways for complex products and a sign of collaboration
“least burdensome” pathways
Reality of making product modifications during EFS – depends upon the modifications and severity of failure?
Do these failures follow the product through its regulatory pathway
Does this actually lengthen approval time by requiring typical feasibility then phase II trial for approval? (3 total)?

18. Thank you for your attention