The Unique Roles of IRB in Medical Device Clinical Trial

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THE UNIQUE ROLES OF IRB
IN MEDICAL DEVICE
CLINICALL TRIAL
Chiu Lin, Ph.D.
CITI, May, 2009
1
The World of Medical Device Industry




Venture Oriented
Diverse
- > 20,000 firms world wide
- Produce > 80,000 brand products
Rapidly Expanding
Becoming very innovative and hightech
2
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
3
4
4
DEVICES ARE NOT DRUGS

DRUGS ARE DISCOVERED

DEVICES ARE DESIGNED
5
Development of Products Clinical Investigations

DEVICES (IDE)
( ̴̴ ̴̴20% clinical trials)
- Effectiveness and/or
safety pivotal trial
(one phase)

DRUGS AND BIOLOGICS
(100% clinical trials) (IND)
- Dose limiting toxicity
(Phase I)
- Safety and efficacy (Phase
II & Phase III)
6
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

Devices vary greatly on type, intended use
population, and risk posed

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)

FDA does not automatically require clinical
trials as part of its approval process for all
devices (only about 20% devices require
clinical trials)
8
Premarket Submission
Requirements of Medical Devices

Premarket Notification [510(k)]
–Class I & Class II

Premarket Approval (PMA)
– Class III
9
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.
10
PREMARKET APPROVAL
(PMA)

The most stringent marketing application

PMA must contain sufficient information
to reasonably assure the safety and
effectiveness of the proposed device.

Valid scientific evidence must be provided
to demonstrate that the device is safe and
effective for its intended use.
11
Valid Scientific Evidence
(21 CFR 860.7)

Well-controlled clinical investigation

Partially controlled clinical studies

Studies and objective trials without
matched control
12
Regulation of Medical Device
Clinical Investigation

21 CFR Part 812 - Investigational Device
Exemption, IDE (IND – 21 CFR Part 312)

21 CFR Part 50 - Informed consent
– drugs, devices, and biologics

21 CFR Part 56 - Institutional Review Boards
(IRB)
– drugs, devices, and biologics
13
Clinical Investigations
Subject to IDE Regulation

To support marketing application [PMA,
or 510(k)]

Collection of safety and effectiveness
information for unapproved device

Sponsor-investigator studies
14
Clinical Investigation Under IDE




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
15
Significant Risk (SR) Investigation

A study that presents a potential for serious
risk to the health, safety, or welfare of a subject

Require FDA and IRB approval before clinical
investigation can begin
16
Examples of SR Devices







Cardiac catheters
Surgical tissue adhesives
Vascular and arterial graft
protheses
Dental endosseous implants
Cochlear implants
Implantable infusion pumps
Implantable pacemaker
17
Examples of NSR Devices
(Require only IRB approval for investigation)







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
18
Approving Clinical
Investigation of Medical
Devices by IRB
(21 CFR 812 Subpart D – IDE
Regulation)
19
IRB Review and Approval

§ 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
20
IRB Review and Approval

§ 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.
21
IRB Review and Approval

§ 812.64 – IRB’s ̴̴Continuing ̴̴Review ̴̴
- The IRB shall conduct its continuing
review of an investigation in accordance
with Part 56.
22
Determination of SR/NSR Study
(21 CFR 812.66)

Sponsor presents protocol to IRB and a
statement why investigation does not pose
significant risk (NSR study)

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).

If IRB disagrees, then, submit IDE application
to FDA for approval (SR Investigation with full
requirements)
23
Abbreviated IDE

No formal FDA IDE approval is needed

IRB is required to meet all aspects of:
- 21 CFR Part 50 (protection of human subjects) –
Informed consent
- 21 CFR Part 56 (IRB)

Labeling requirements
24
Comparison Between Device
and Drug/Biologics Trials
25
Regulatory Distinctions

Device Classification – risk based
- Class I
- Class II
- Class III

Drug and Biologics
- All high risk
- No Class I, II, and III classification
26
Regulatory Distinctions
* ̴̴ ̴̴Devices: ̴̴“Investigator ̴̴agreement” ̴̴generated ̴̴
by the sponsor [per 21 CFR 812.43(c)]
* ̴̴ ̴̴Drugs: ̴̴“Statement ̴̴of ̴̴Investigator” ̴̴- Form
1572
27
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)]
28
Regulatory Distinctions

Device – Significant vs. non-significant
risk trials

Drug – All significant risks
29
Research Distinctions

Device Studies (vs. drug trials)
- Small subject population (mostly 100s)
- One phase trial
- Blinding study is not common
- “Controls” ̴̴vary

Can not do placebo

Sham, active, historical controls are common
- CI training is critical (Human Factors)
- IRBs play critical role
30
Regulatory Similarities

21 CFR 50: Informed consent

21 CFR 54: Financial Disclosure of
clinical investigator

21 CFR 56: IRB
31
Regulatory Similarities
 FDA approval required
 IDE or IND
 FDA regulations specify sponsor and
clinical investigator responsibilities
 21 CFR 812 and 21 CFR 312
32
CONCLUSION

The role of IRB in approving medical
device clinical trial is identical to
approving drug investigation

Additional role in medical device trial is
the differentiation of SR and NSR
investigation
33
THANK YOU FOR YOUR
ATTENTION !!
Question ?
34
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