View Presentation - Cleveland Clinic

Focusing on the “Big Picture”
Getting to Clinical Utilization
Dorothy Abel, BSBME
Division of Cardiovascular Devices Center for Devices and Radiological Health (CDRH) [email protected] Stent Summit; The Future – How will the unmet clinical needs best be met?
September 16, 2014
Worldwide Device Development: the Perception
1 Design device or identify a new use
2 Do preliminary bench testing
3 Initiate clinical use outside of the US
Conduct additional bench testing
4 Initiate animal studies in the US
Get CE Mark and market outside of the US
5 Initiate feasibility study in the US
6 Conduct clinical study in the US
Complete pre-clinical testing (e.g., durability)
7 Market the device in the US
2
Ideally
•  Patients in the U.S. have access to highquality, safe, and effective medical devices
of public health importance first in the
world
•  The US would participate in all phases of
clinical evaluation
3
Worldwide Device Development: the Goal
1 Design device or identify a new use
2 Do bench and animal testing to justify FIH or
early feasibility study (EFS)
3 Initiate EFS
Conduct additional bench testing and animal
studies to support a larger clinical study
4 Initiate pivotal study
Complete pre-clinical testing (e.g., durability)
5 Market worldwide
4
Worldwide Device Development Premise
The data requirements to support the initiation of
various phases of clinical evaluation and to support
market approval should be universal.
5
Worldwide Device Development
1 Design device or identify a new use
2 Do bench and animal testing to justify FIH or
early feasibility study (EFS)
3 Initiate EFS
Conduct additional bench testing and animal
studies to support a larger clinical study
4 Initiate pivotal study
Complete pre-clinical testing (e.g., durability)
5 Market worldwide
6
EFS Data Requirements
•  Approval of an EFS may be based on less
nonclinical data than would be needed to
support the initiation of a larger clinical study of a
more final device design
–  Early feasibility studies enroll highly selected patients
who receive individualized care and monitoring
–  An early feasibility study incorporates enhanced risk
mitigation strategies and patient protection measures
as compared to a pivotal study
7
Just-In-Time Testing (JITT)
•  Recognize that comprehensive testing during
early phases of device development may add
cost without return
–  Testing could have limited future applicability if the
device is modified
–  Time-consuming, non-informative testing delays
access to the device for patients who may have
limited treatment alternatives
•  Acknowledge that it may be acceptable to defer
some nonclinical testing until the device design
has been finalized for use in a pivotal study
8
Report of Prior Investigations
Device Evaluation Strategy (DES)
•  Identify the device-related and procedurerelated functions that may be affected by
each modification and develop a DES
focusing on these functions
•  An assessment of whether the device may
be placed in a different in vivo
environment should be considered in
identifying the functions that may be
9
affected and the testing needed
Worldwide Device Development
1 Design device or identify a new use
2 Do bench and animal testing to justify FIH or
early feasibility study (EFS)
3 Initiate EFS
Conduct additional bench testing and animal
studies to support a larger clinical study
4 Initiate pivotal study
Complete pre-clinical testing (e.g., durability)
5 Market worldwide
10
Early Feasibility Study (EFS)
•  Small number of subjects
•  Device may be early in development, typically before
the device design has been finalized
–  Does not necessarily involve the first clinical use of a
device
•  May involve a new intended use for a device that has
already been in clinical use
•  Needed when the information to further the
development cannot practically be provided through
additional nonclinical assessments or appropriate
nonclinical tests are unavailable
•  May be done concurrently or in conjunction with nonUS studies
11
Purpose of Early Feasibility Studies
operator
technique
challenges
human
factors
safety
device
failures
whether the device
performs its intended
purpose
OBTAIN INSIGHTS
patient characteristics that may
impact device performance
therapeutic
parameters
12
Value Added with US EFS
Review team familiarity with
the technology throughout the
product development process
Method for identifying
appropriate data
requirements that can be
applied at each phase of
device development
Better quality
submissions
Address
unmet
clinical
needs
FDA
Clinicians
Direct
collaboration
Sponsors
Earliest access to
potentially
beneficial medical
devices
Patients
Improved
treatments and
diagnostics
Innovators
Smoother transitions between Information relevant to US
population
phases of clinical evaluation
13
Other EFS Information
•  An EFS may be sponsored by a
manufacturer or a sponsor-investigator
•  Future sponsors should contact DCD staff
dedicated to EFS as a first step
Co-‐Leaders Andrew Farb, M.D.
Dorothy Abel
[email protected]
[email protected]
EFS Division RepresentaCves Carmen Gacchina Johnson, Ph.D. Anna Schroeder Deborah Castillo, Ph.D. [email protected] [email protected] [email protected] 14
Additional Testing
Additional nonclinical testing could be
completed concurrent with conducting the
EFS if needed to support the conduct of a
traditional feasibility or pivotal study
15
Worldwide Device Development
1
2
Design device or identify a new use
Do bench and animal testing to justify FIH or
early feasibility study (EFS)
3 Initiate EFS
Conduct additional bench testing and animal
studies to support a larger clinical study
3.5 Expand EFS to a traditional feasibility study or
start with a traditional feasibility study
4 Initiate pivotal study
Complete pre-clinical testing (e.g., durability)
16
5 Market worldwide
Traditional Feasibility Study
•  Commonly used to capture preliminary safety and
effectiveness information on a near-final or final device
design to adequately plan an appropriate pivotal study
•  Takes place later in development than an EFS, so more
nonclinical (or prior clinical) data may be needed to
support the initiation of a traditional feasibility study
•  A traditional feasibility study does not necessarily need
to be preceded by an early feasibility study, but EFS
data may support initiation of the traditional feasibility
study
•  May be sponsored by a manufacturer or a sponsorinvestigator
17
Sponsor-Investigator IDEs
•  Contact FDA early and often
•  Preparing an IDE and conducting an IDE
study are not trivial efforts
•  A skilled research staff is required
•  Consultation with the device manufacturer
and physicians who have experience with
the IDE process may be helpful
•  Interaction with FDA through the PreSubmission process is recommended
18
IDE Application
•  The IDE regulations list the information to be included in an IDE application:
•  Sufficient information to justify the proposed study based on:
•  reports of prior investigations of the device,
•  an appropriate investigational plan, and
•  adequate patient protection measures
•  Other required elements of an IDE application address records and reports, study
monitoring, and manufacturing information
•  The SVS is working on a generic IDE template for sponsor-investigators
•  Guidance on the preparation and submission of an IDE:
http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/
HowtoMarketYourDevice/InvestigationalDeviceExemptionIDE/
ucm046164.htm
Pre-Submission
•  Allows for informal discussion and feedback to
address key components that need to be added
or revised in a draft IDE submission
•  Information on the Pre-Submission process may
be found in the guidance “Medical Devices: The
Pre-Submission Program and Meetings with
FDA Staff” at
http://www.fda.gov/downloads/MedicalDevices/
DeviceRegulationandGuidance/GuidanceDocuments/
UCM311176.pdf
20
Worldwide Device Development
1 Design device or identify a new use
2 Do bench and animal testing to justify FIH or
early feasibility study (EFS)
3 Initiate EFS
Conduct additional bench testing and animal
studies to support a larger clinical study
4 Initiate pivotal study
Complete pre-clinical testing (e.g., durability)
5 Market worldwide
21
Pivotal Study
•  Designed to collect definitive evidence of
the safety and effectiveness of a device for
a specified intended use
•  Typically includes a statistically justified
number of subjects
•  It may or may not be preceded by an early
and/or a traditional feasibility study
22
Progress
•  Clinical trial infrastructure improvements
•  Least burdensome clinical study designs
–  Large simple trials
–  Use of performance goals
–  Adaptive trial designs
23
Additional Testing
Additional nonclinical testing could be
completed concurrent with conducting the
pivotal study if needed to support
marketing approval
24
Worldwide Device Development: the Goal
1 Design device or identify a new use
2 Do bench and animal testing to justify FIH or
early feasibility study (EFS)
3 Initiate EFS
Conduct additional bench testing and animal
studies to support a larger clinical study
4 Initiate pivotal study
Complete pre-clinical testing (e.g., durability)
5 Market worldwide
25
Opportunities
•  Expedited Access PMAs
–  Devices intended for unmet medical need for
life threatening or irreversibly debilitating
diseases or conditions
–  Earlier FDA engagement and more interaction
–  Lesser regulatory requirements prior to
marketing
•  Premarket and postmarket balance
26
Summary
•  The goal is worldwide device
development/evaluation
•  There are programs and processes
intended to improve the ability to conduct
clinical studies in the US and to expedite
US approval
•  Close collaboration and communication
are key in getting to clinical utilization
27

Download Report