Transcript Class II - CRTOnline

Peripheral Vascular Devices - Appropriate Global Studies for DrugCoated Balloons and Stents
Points To Consider in the Review of Endovascular
Treatment Devices: US Regulatory View
Donna C. Buckley, MS, MD
Medical Officer
Peripheral Interventional Devices Branch
Division of Cardiovascular Devices
Office of Device Evaluation
Food and Drug Administration
February 20, 2017
Disclosure Statement of Financial Interest
I, Donna Buckley, DO NOT have a financial
interest/arrangement or affiliation with one or
more organizations that could be perceived
as a real or apparent conflict of interest in the
context of the subject of this presentation.
CDRH Mission
The mission of the Center for Devices and Radiological Health
(CDRH) is to protect and promote the public health.
• Assure timely and continued access to safe, effective, and highquality medical devices
• Provide understandable and accessible science-based
information about the products
• Facilitate medical device innovation
http://www.fda.gov/AboutFDA/CentersOffices/OfficeofMedicalProductsandTobacco/CDRH/ucm300639.htm
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CDRH Mission
Identify the best treatment option for a
patient or population.
Design Products.
Fund Clinical Research.
http://www.fda.gov/AboutFDA/CentersOffices/OfficeofMedicalProductsandTobacco/CDRH/ucm300639.htm
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FDA Device Approval
CLASSIFICATION
MARKETING
APPLICATION
THRESHOLD
FOR APPROVAL
EXAMPLE
Class I
General Controls
most exempt
N/A
Class II
Special Controls
510(k)
(some exempt)
“substantial equivalence”
PTA catheter,
guidewire
Class III
Premarket Approval
PMA
“safety and effectiveness”
DCB, DES
HDE
“safety and probable
benefit”
stethoscope
For general information regarding Device Regulation:
http://www.fda.gov/cdrh/devadvice
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FDA Device Approval
CLASSIFICATION
MARKETING
APPLICATION
THRESHOLD
FOR APPROVAL
EXAMPLE
Class I
General Controls
most exempt
N/A
Class II
Special Controls
510(k)
(some exempt)
“substantial equivalence”
PTA catheter,
guidewire
Class III
Premarket Approval
PMA
“safety and effectiveness”
DCB, DES
HDE
“safety and probable
benefit”
stethoscope
For general information regarding Device Regulation:
http://www.fda.gov/cdrh/devadvice
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FDA Device Approval
• PMA - Premarket Approval Application – marketing of
device in US
– Reasonable assurance of safety and effectiveness
– Probable benefits to health from use of the device for its intended
use outweigh any probable risks
– Based on:
•
•
•
•
Valid scientific evidence
Consideration of indication for use
Patient population
Disease or condition the device will diagnose or treat
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DCB/DES Regulation
Combination Products
• Device + Drug Combination
– dilatation catheter or stent (device) – opens vessel and
delivers drug
– Antiproliferative agent (drug)
• Primary regulatory authority is designated to CDRH
with CDER consultation if no new drug claims
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DCB/DES Regulation
Regulatory Experience
• LE PAD
• Most experience ATK
• Some other peripheral uses (e.g., AV-related stenosis)
General Trial Design Considerations
• Consider patient population and goals of treatment (e.g., Claudication
versus CLI)
• Need robust control; currently recommending active control
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DCB/DES Regulation
Endpoints for Safety and Effectiveness
• Primary endpoints include hypothesis testing for safety (MAE)
and effectiveness data (TLR, patency)
Example – DCB: CLI BTK
»
»
Safety: MALE + POD at 30 days
Effectiveness: Composite of Limb Salvage and Primary Patency at 6 months
• Time of primary assessment depends on goals of treatment – 12
month primary assessment preferred but 6 month primary
assessment considered
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Challenges with DCB/DES Evaluation
Treatment Approach & Selection Criteria
Heterogeneous Treatment Approaches and Patient Population
• Multiple specialties and a lack of robust treatment guidelines result in
variability in treatment algorithms and approaches
• Heterogeneous patient population with multiple medical comorbidities
– Clinical Exclusions - Trials may exclude important patient groups
expected to have poor outcomes (e.g., patients on renal replacement
therapy)
– Technical and Regulatory Exclusions - (e.g., longer lesions, post
atherectomy)
• Limiting patient population to address issues related to clinical trial goals
limits applicability of results to real world patient populations after
approval
www.fda.gov
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Challenges with DCB/DES Evaluation
Multiple Device Use
• Challenging to isolate impact of one particular device - Regulatory
threshold is to demonstrate that particular device is safe and effective,
not that overall treatment is safe and effective
• Imaging outcomes (e.g., patency) support mechanism of action of device
but not always concordant with clinical outcomes; other clinical measures
(e.g., wound, perfusion) not as established and directly relatable to
mechanism of action
• Added clinical benefit of adjunctive therapies (e.g., embolic protection,
atherectomy, scoring) may be difficult to discern given that not typically
driving clinical/imaging outcomes
www.fda.gov
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Challenges with DCB/DES Evaluation
Single Arm Trials
• Impact of known and unknown covariates result in
difficulties in interpreting single arm data
– Other factors may drive outcome more than DCB/DES
(e.g., wound care)
– Variability in other characteristics may significantly
impact outcome (e.g., lesion length, calcification, wound
care, glycemic control, uremic control, age, gender,
occlusions)
www.fda.gov
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Summary
• Global studies are important and FDA is working to harmonize efforts to
improve the quality/utility of global data to meet regulatory criteria
• Continuing to identify differences between patients and the care of patients
globally
• Consistency of endpoints and definitions essential
• Discrepancies between clinical trial populations and real world populations
• Challenges with isolating the impact of new device on outcome and
interpreting single arm data
• Device evaluation doesn’t stop with completion of the premarket study
• Real-world data are likely needed to fully evaluate novel technologies and
combinations of treatments
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Thank you
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