Transcript Essential Requirements of the Clinical Trials Processes

Legal Issues Impacting Clinical Trials
Medical Device Clinical Trials Update
June 19, 2009
Overview
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Update on FDAAA 801 implementation: requirements for
registering and reporting results of device clinical trials
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Recent developments concerning clinical investigator
financial conflicts of interest
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Understanding last week’s criminal indictment: failure to
obtain IDE
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FDAAA Section 801: Clinical Trial
Registration and Results Reporting
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FDAAA defines “applicable device clinical trial” as
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a prospective clinical study of health outcomes comparing an
intervention with a device subject to section 510(k), 515 or
520(m) of the FDCA against a control in human subjects
(other than a small clinical trial to determine the feasibility of a
device, or a clinical trial to test prototype devices where the
primary outcome measure relates to feasibility and not to
health outcomes); and
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a pediatric postmarket surveillance required under Section
522 of the FDCA
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FDAAA 801
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Certification of compliance required since December 26,
2007: Form 3674
January 2009 Guidance defines scope of requirement:
PMAs
 PMA “panel track” supplements
 HDEs
 510(k)s if they refer, relate to or include information on or
from a clinical trial
initiation of the regulatory review (not amendments)
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Regulations on results posting required by November 2010
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Investigator Financial Conflicts of Interest
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Collection of financial disclosure information for “covered
clinical studies” is required under 21 CFR Part 54
Covered clinical studies are submitted studies that are used
to demonstrate the product’s effectiveness or any study in
which a single investigator makes a significant contribution
to the demonstration of a product’s safety
Four types of interests to disclose:
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Compensation affected by outcome of study
Significant equity interest (>$50,000 if publicly traded) during
study and for one year after completion
Proprietary interest (patent, trademark, copyright, license)
Significant payments of other sorts (>$20,000) during study
and for one year after completion
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OIG Report January 2009
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OIG review of financial disclosure information for 118
approved product applications during 2007
Found that only 1% of investigators disclosed conflicts (206
of 29,691 investigators)
42% of applications had incomplete disclosure information
28% of applications relied upon the ‘due diligence’
exemption for not having information to report (investigator
could not be located or would not return form)
31% of applications had no FDA documentation of
reviewing the submitted disclosures/certifications
No actions taken to minimize bias in 20% of cases
disclosing an investigator financial interest
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OIG Recommendations
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Creation of central clinical investigator list to track
disclosures
Use review template to document that financial
disclosure/certification information was properly submitted
Confirm submission of attachments to disclosures
Update guidance on due diligence exemption
Disclosure of investigator financial interests prior to
initiation of clinical study
http://oig.hhs.gov/oei/reports/oei-05-07-00730.pdf
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NJ Attorney General

Used state’s Consumer Fraud Act to obtain Assurance of
Voluntary Compliance (AVC) from spinal device
manufacturer for failure to disclose investigator financial
interests in clinical studies underlying two PMA approvals
AVC executed May 1, 2009
Among other terms, prohibits compensation of clinical
investigators with stock or stock options
Settlement payment of $236,000
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Actions from subpoenas to other companies still to come?
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May 5, 2009 Letter from New Jersey AG to then
Acting Commissioner Sharfstein
As a result of this investigation, the State has entered into a settlement agreement
with Company that requires the company, going forward, to fully disclose the
financial conflicts of interest of its clinical investigators to the public and to the
FDA. Pursuant to this agreement, Company will, inter alia, (1) monitor, collect and
disclose any and all payments to clinical investigators, including
investments held by the investigators in the product they are testing, on the
company’s website and to the FDA; (2) prohibit compensation of clinical
investigators tied to the outcome of the clinical trial, including company stock or
stock options; (3) pay clinical investigators “fair market value compensation” for
their clinical trial work, as well any other consulting services they provide to the
company; and (4) disclose all financial interests directly to health care
facilities serving as clinical trial sites. A copy of the agreement is attached.
I am gravely concerned about the conflicts of interest that pervade the medical device
industry – particularly with respect to high-risk devices - and their deleterious
effects upon consumers. The State of New Jersey calls upon the FDA to (1)
heighten its oversight authority in this area and to rigorously enforce the conflict of
interest disclosure rules and regulations; and (2) promulgate regulations that
require all medical device manufacturers and pharmaceutical companies to
adequately disclose the conflicts of interests of clinical investigators to the public.
It is our hope that the provisions in our Agreement with Company will
become part of best practices for the entire medical device industry.
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Looking under the lamppost
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1.
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June 15, 2009 Grand Jury indictment of Company for,
among other things, failure to submit an IDE prior to
initiating a 2002 “test market” study
“test market”
trained surgeons in an off-label use
collected safety and efficacy data for the purpose of
determining whether complication rate was too high
Management admitted that IDE would be required if data
were being collected
18 USC 371 and 1001 (conspiracy and false statements)
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Natasha Leskovsek
[email protected]
tel 202.728.7131