The CRT of EFS Where We’ve Been and Where We’re Going Andrew Farb, MD and Dorothy Abel, BSBME Andrew.Farb@fda.hhs.gov and Dorothy.Abel@fda.hhs.gov Division of Cardiovascular Devices Center for Devices and Radiological Health (CDRH) Food and Drug Administration FDA Town Hall CRT 2016 Washington, DC February 23, 2015

Conflict of Interest No conflicts of interest to report.

Considering the past Recent efforts To the future

EFS @ CRT in Review 2012 Draft EFS guidance Introduction of the EFS pilot program 2013 Just-in-Time testing and the Device Evaluation Strategy (DES) in depth Initial EFS lessons learned Revisions to the draft guidance 2014 Finalized guidance CDRH EFS Strategic Priority Progress (approved IDEs) and challenges 2015 EFS Program update: Process and resources

From the Beginning Efforts focused on device innovation and bringing potentially beneficial devices to the US earlier High interest level Interaction is critical Constantly refining the process: Learn-as-you-go

EFS IDE Progress CDRH Office of Device Evaluation * Through 6/30 of each FY

The CDRH EFS Program is under the direction of Owen Faris, Clinical Trials Director Carla Wiese, Policy Analyst in the Clinical Trials Program Focusing on EFS, is the primary point of contact (Carla.Wiese@fda.hhs.gov)

Recent Efforts CDRH Learn Modules available Device Evaluation Strategy module coming soon; others to follow http://www.fda.gov/Training/CDRHLearn/ CDRH teams established to discuss EFS non- clinical cross-cutting issues Biocompatibility Sterility Animal studies Outreach to CMS to discuss Category A/B IDE studies

CMS Category A Device: Experimental Category B Device: Non-experimental/investigational Open to discussions regarding the appropriate coverage, particularly for studies addressing unmet clinical needs For Category A EFS IDE devices, may consider coverage reasonable and necessary study costs But does not include coverage for the cost of the device Category A (Experimental) device refers to a device for which “absolute risk” of the device type has not been established (that is, initial questions of safety and effectiveness have not been resolved) and the FDA is unsure whether the device type can be safe and effective. Category B (Non-experimental/investigational) device refers to a device for which the incremental risk is the primary risk in question (that is, initial questions of safety and effectiveness of that device type have been resolved), or it is known that the device type can be safe and effective because, for example, other manufacturers have obtained FDA premarket approval or clearance for that device type.

Division of Cardiovascular Devices (DCD) EFS Plans Translate EFS successes (particularly for trans-catheter valves and aortic endografts) into processes across DCD Continue internal and external DCD training

Translating Success Effective interactions Communicate justification for study initiation through use of: DES Just-in-time testing Understanding the use of appropriate leveraging from: Information in the public domain Testing done on prototype devices

Broadening Our Thinking The links between compassionate use and EFS

Compassionate Use (or Single Patient/Small Group Access) Access to an investigational device under or outside of an IDE (Expanded Access provisions) Criteria: Serious disease or condition No alternative Prior FDA approval required before compassionate use can occur

Justification for Compassionate Use (1) A description of the patient's condition and the circumstances necessitating treatment A discussion of: Why alternatives therapies are unsatisfactory; and Why the probable risk of using the investigational device is no greater than the probable risk from the disease or condition

Justification for Compassionate Use (2) Describe patient protection measures, for example: informed consent concurrence of IRB chairperson clearance from the institution independent assessment from uninvolved physician authorization from the IDE sponsor (if applicable) If applicable, identify any deviations in the approved clinical protocol that may be needed to treat the patient

From Compassionate Use (CU) to EFS CU can be viewed as belonging to the continuum of expanded access for a small select group of no-option patients to potentially beneficial devices considering (like EFS): the clinical context; addressing unmet needs; and benefit-risk  CU incorporates additional patient protection measures as compared to other investigational device uses. This approach is also used in EFS IDEs via the inclusion of enhanced risk mitigation strategies.

From CU to EFS If information is adequate to support CU, there could be adequate evidence to build a case for an EFS Ideally, efforts to pursue initial compassionate uses to help individual patients should be done in parallel with developing an EFS that builds the foundation to serve larger groups of patients. However, a series of CU cases should not be used by either sponsors or FDA as a substitute to an EFS, which have the rigor of a clinical investigation.

We Still Need Your Input Please share: Your DCD EFS experiences (good and bad) Training needs Comments and questions EFS contacts for the Division of Cardiovascular Devices: Dorothy Abel and Andrew Farb