Transcript Module 2 Good Clinical Practice (GCP)

THE UNIQUE ROLES OF IRB
IN MEDICAL DEVICE
CLINICALL TRIAL
Chiu Lin, Ph.D.
CITI, May, 2009
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The World of Medical Device Industry
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Venture Oriented
Diverse
- > 20,000 firms world wide
- Produce > 80,000 brand products
Rapidly Expanding
Becoming very innovative and hightech
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Medical Device Industry
Exponential Growth
Number of Manufacturers by Year
16000
14000
12000
Ophthalmic
Eletromedical
X-Ray
Dental
Surgical
Instruments
Diagnostics
10000
8000
6000
4000
2000
0
1998
1999
2000
2001
2002
2003
2004
Dun & Bradstreet Medical Device Firm Data
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DEVICES ARE NOT DRUGS
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DRUGS ARE DISCOVERED
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DEVICES ARE DESIGNED
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Development of Products Clinical Investigations
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DEVICES (IDE)
( ̴̴ ̴̴20% clinical trials)
- Effectiveness and/or
safety pivotal trial
(one phase)
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DRUGS AND BIOLOGICS
(100% clinical trials) (IND)
- Dose limiting toxicity
(Phase I)
- Safety and efficacy (Phase
II & Phase III)
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The complexity and need for clinical
data is ̴̴growing…
Embolic protection
Daily wear contact
devices
lenses
Vascular
anastomosis devices
CPAP devices
for CABG
for apnea
… ̴̴requiring ̴̴more ̴̴in-depth
assessment of safety and
effectiveness…….
Combination product
Image-guided
bronchoscopes
Glaucoma shunts
Perspectives of Device Clinical
Trials – Compared to Drugs
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Devices vary greatly on type, intended use
population, and risk posed
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FDA device regulation recognizes these
differences by classifying devices into 3
classes: Class I (low risk), Class II
(intermediate risk), and Class III (high risk)
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FDA does not automatically require clinical
trials as part of its approval process for all
devices (only about 20% devices require
clinical trials)
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Premarket Submission
Requirements of Medical Devices
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Premarket Notification [510(k)]
–Class I & Class II
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Premarket Approval (PMA)
– Class III
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PREMARKET
NOTIFICATION 510(K)
Data to demonstrate the new device is
as safe and effective (substantially
equivalent, SE) as a legally market
(predicate) device
Only in few cases, a clinical data is
needed to support SE determination.
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PREMARKET APPROVAL
(PMA)
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The most stringent marketing application
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PMA must contain sufficient information
to reasonably assure the safety and
effectiveness of the proposed device.
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Valid scientific evidence must be provided
to demonstrate that the device is safe and
effective for its intended use.
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Valid Scientific Evidence
(21 CFR 860.7)
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Well-controlled clinical investigation
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Partially controlled clinical studies
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Studies and objective trials without
matched control
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Regulation of Medical Device
Clinical Investigation
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21 CFR Part 812 - Investigational Device
Exemption, IDE (IND – 21 CFR Part 312)
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21 CFR Part 50 - Informed consent
– drugs, devices, and biologics
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21 CFR Part 56 - Institutional Review Boards
(IRB)
– drugs, devices, and biologics
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Clinical Investigations
Subject to IDE Regulation
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To support marketing application [PMA,
or 510(k)]
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Collection of safety and effectiveness
information for unapproved device
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Sponsor-investigator studies
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Clinical Investigation Under IDE
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To determine safety and effectiveness of an
investigational device
No phases in clinical investigation
Distinction between significant risk (SR)
devices and non-significant risk (NSR)
devices in approval process
Different approval procedures for SR and
NSR studies
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Significant Risk (SR) Investigation
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A study that presents a potential for serious
risk to the health, safety, or welfare of a subject
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Require FDA and IRB approval before clinical
investigation can begin
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Examples of SR Devices
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Cardiac catheters
Surgical tissue adhesives
Vascular and arterial graft
protheses
Dental endosseous implants
Cochlear implants
Implantable infusion pumps
Implantable pacemaker
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Examples of NSR Devices
(Require only IRB approval for investigation)
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Bio-stimulation lasers for treatment of pain
Daily wear contact lenses
Glucose monitor
Blood pressure monitor
Magnetic resonance imaging (MRI)
Pulse oximeter
Ob/Gyn diagnostic ultrasound
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Approving Clinical
Investigation of Medical
Devices by IRB
(21 CFR 812 Subpart D – IDE
Regulation)
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IRB Review and Approval
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§ 812.60 – IRB composition, duties, and
function
- An IRB reviewing and approving
investigation shall comply with
requirements of Part 56 in all respects,
including its composition, duties, and
function
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IRB Review and Approval
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§ 812.62 – IRB Approval
- An IRB shall review and have authority to
approve, require modifications, or
disapprove all investigations under IDE.
- If ̴̴FDA ̴̴finds ̴̴that ̴̴an ̴̴IRB’s ̴̴review ̴̴is ̴̴
inadequate, a sponsor should submit an
IDE application to FDA.
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IRB Review and Approval
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§ 812.64 – IRB’s ̴̴Continuing ̴̴Review ̴̴
- The IRB shall conduct its continuing
review of an investigation in accordance
with Part 56.
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Determination of SR/NSR Study
(21 CFR 812.66)
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Sponsor presents protocol to IRB and a
statement why investigation does not pose
significant risk (NSR study)
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If IRB agrees the study is NSR & approves the
study, then, no formal IDE submission for FDA
approval is needed. Investigation can begin
(Abbreviated IDE requirements).
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If IRB disagrees, then, submit IDE application
to FDA for approval (SR Investigation with full
requirements)
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Abbreviated IDE
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No formal FDA IDE approval is needed
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IRB is required to meet all aspects of:
- 21 CFR Part 50 (protection of human subjects) –
Informed consent
- 21 CFR Part 56 (IRB)
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Labeling requirements
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Comparison Between Device
and Drug/Biologics Trials
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Regulatory Distinctions
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Device Classification – risk based
- Class I
- Class II
- Class III
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Drug and Biologics
- All high risk
- No Class I, II, and III classification
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Regulatory Distinctions
* ̴̴ ̴̴Devices: ̴̴“Investigator ̴̴agreement” ̴̴generated ̴̴
by the sponsor [per 21 CFR 812.43(c)]
* ̴̴ ̴̴Drugs: ̴̴“Statement ̴̴of ̴̴Investigator” ̴̴- Form
1572
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Regulatory Distinctions
Adverse Events
 Devices: investigators shall submit the
adverse effect report to the sponsor and
IRB [21 CFR 812.150(a)(1)]
 Drugs/Biologics: investigators shall
submit the adverse effect report to the
sponsor [21 CFR 312.64(b)]
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Regulatory Distinctions
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Device – Significant vs. non-significant
risk trials
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Drug – All significant risks
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Research Distinctions
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Device Studies (vs. drug trials)
- Small subject population (mostly 100s)
- One phase trial
- Blinding study is not common
- “Controls” ̴̴vary
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Can not do placebo
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Sham, active, historical controls are common
- CI training is critical (Human Factors)
- IRBs play critical role
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Regulatory Similarities
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21 CFR 50: Informed consent
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21 CFR 54: Financial Disclosure of
clinical investigator
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21 CFR 56: IRB
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Regulatory Similarities
 FDA approval required
 IDE or IND
 FDA regulations specify sponsor and
clinical investigator responsibilities
 21 CFR 812 and 21 CFR 312
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CONCLUSION
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The role of IRB in approving medical
device clinical trial is identical to
approving drug investigation
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Additional role in medical device trial is
the differentiation of SR and NSR
investigation
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THANK YOU FOR YOUR
ATTENTION !!
Question ?
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