Transcript DIA 2009 Annual Meeting - FDA Attorney >> FDA Lawyer

Clinical Trial Registries:
Panacea or Pablum??
Presented by:
Michael A. Swit, Esq.
Vice President,
The Weinberg Group Inc.
[email protected]
760.633.3343
Overview of Session
Clinical Trials Registries: Evolution of Legal Requirements
Michael A. Swit, Esq.
Vice President, The Weinberg Group Inc.
Clinical Trials Registries: Critical Legal Issues
Demetrios L. Kouzoukas, Esq.
Of Counsel, Covington & Burling LLP
Clinical Trials Disclosure: Are We Meeting the Target
Audiences in The EU?
Gesine Bejeuhr, Pharm.D., Ph.D.
VFA, German Association of Research-Based Pharm. Co., Germany
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Clinical Trial Registries:
Evolution of Legal
Requirements
Presented by:
Michael A. Swit, Esq.
Vice President,
The Weinberg Group Inc.
[email protected]
760.633.3343
Disclaimer
•
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employed or affiliated, or any of the organization’s clients.
•
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the property of their respective owners.
•
These slides support an oral briefing and should not be solely relied upon
for any conclusion of law or fact.
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MY OBJECTIVES TODAY
• The Evolution of Demand for Clinical Trial
Registries, including the impact of the 2007
Food & Drug Administration Amendments
Act (FDAAA)
• Review of Key National and International
Registries
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DEFINITIONS – DISTINGUISH:
• Clinical Trials Registry – information
on clinical trials that are active or
completed, but not any substantive
information on the results of the study
vs.
• Clinical Trials Results Database – the
results of the trials – in summary or
other fashion -- are available for review
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GENERAL PURPOSES OF
REGISTRIES & DATABASES
• List & track clinical trials
• Make available design of clinical studies – Principle 16
of Helsinki Declaration -- http://www.wma.net/e/policy/b3.htm
• Facilitate patient recruitment
• Create a record of results of evidence so that balanced
and informed medical decisions may be made
• Eliminate duplicative research
• Eliminate “publication bias” – i.e., the tendency for only
positive data to be published
…. “transparency”
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THE EVOLVING DEMAND
FOR REGISTRIES
• FDAMA §113 –
– Since Feb. 2000
– All persons conducting clinical trials of experimental
treatments for “serious or life-threatening” diseases and
conditions
– Where the trial is to test “effectiveness” – i.e., Phase 2,
3 or 4 studies with efficacy endpoints
– Must register certain information with U.S. government,
within 21 days of study enrollment opening
– Done via ClinicalTrials.gov
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THE ROLE OF ELLIOTT
SPITZER
• GSK Settlement -- 2004
– Allegation – GSK failed to disclose results of
certain Paxil® studies in adolescent and
pediatric patients
– Required establishment of Clinical Trials
Register and posting of
• Summaries of Clinical Study Reports for
– all GSK studies from Dec. 27, 2000 on; and
– Any earlier study “likely to be material to a physician’s medical
judgment of the GSK drug”
• Future contracts – to avoid limitations on publication
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THE EDITORS STEP INTO
THE FRAY
• International Committee of Medical Journal
Editors (ICMJE) -- if you want to be
published, study must be registered
• Requirements
– Register at or before onset of patient enrollment
– Applies to any study beginning enrollment after
July 1, 2005
• If begun before that, you had to register by Sept. 13,
2005
– Information to be included – consistent with WHO
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THE EDITORS – ICMJE …
• “Clinical trial” – “any research project that
prospectively assigns human subjects to
intervention or concurrent control or
comparison groups to study the cause and
effect relationship between a medical
intervention and a health outcome”
– Excludes studies for other purposes such as to study
pharmacokinetics or major toxicity studies
• but studies of adverse events are covered
– Thus, includes devices or even surgical procedures
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EDITORS – ICMJE …
• Acceptable registers – must be:
– Electronically searchable and publicly
accessible at no charge
– Open to all registrants
– Not-for-profit
– Must have mechanism to ensure validity
of registration data
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BIG PHARMA “CAVES”
• January 2005 – major associations announce
plan to create a comprehensive clinical trial
registry – of “hypothesis-testing clinical trials”
(aka -- “confirmatory clinical trials” )
• Associations:
– European Federation of Pharmaceutical Industries
and Assns. (EFPIA),
– International Federation of Pharmaceutical
Manufacturers and Associations (IFPMA),
– Japanese Pharmaceutical Mfrs. Assn. (JPMA), and
– PhRMA –
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PhRMA –
ClinicalStudyResults.org
• 2002 – PhRMA publishes “Principles on the
Conduct of Clinical Trials and Communication of
Clinical Trials Results”
• Position today –
– All “hypothesis-testing” studies – regardless of
seriousness of condition – those that “serve to examine
pre-stated questions using statistically valid plans for data
analysis and provide firm evidence of safety and/or efficacy
to support product claims”
• n/a to “exploratory studies” – unless result found to
be of medical significance
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PhRMA …
• “Will contain” results from all hypothesistesting clinical studies completed since
Oct. 1, 2002 for approved drug products
– Published articles
– Unpublished study summaries
• Timing – one year after completion of
studies (same as NDA annual report duty)
– Could be delayed if submitted to peer-review
journal
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PhRMA …
• Is a voluntary results registry
• Registry contains a complete summary
of trial, regardless of the outcome
• Does not apply to drugs not yet
marketed – allows protection of
confidential information and intellectual
property
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WHO – INTERNATIONAL
CLINICAL TRIALS REGISTRY
PLATFORM (ICTRP)
• ICTRP – not a registry itself, but to provide standards to
existing registries -- http://www.who.int/ictrp/en/
• All trials – including “earliest” stage and exploratory studies
• Trial Registration Data Set -- 20 key details to be disclosed
when study begun –
– http://www.who.int/ictrp/network/trds/en/index.htm
• Portal – to search among other registries
• Deduping – goal – avoid duplicative registrations (and
conflicting information)
• Results – strongly encouraged to be reported – although first
goal of WHO is registration
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WHO & ICTRP …
• “Interventional clinical trials” – all should be
registered – “any research study that
prospectively assigns people to one or more
health-related interventions (e.g., preventive
care, drugs, surgical procedures, behavioral
treatments, etc.) to evaluate the effects.”
• Primary and Associate Registers – will be the
network for registration
• Universal clinical trial number
• To search – go to Search Portal:
– http://apps.who.int/trialsearch/
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WHO & ICTRP …
• The Data Providers of the ICTRP Search
Portal currently are:
– Australian New Zealand Clinical Trials Registry
(ANZCTR)
– Chinese Clinical Trial Register (ChiCTR)
– ClinicalTrials.gov (U.S.)
– Clinical Trials Registry - India (CTRI)
– German Clinical Trials Register (DRKS)
– Iranian Registry of Clinical Trials (IRCT)
– ISRCTN.org
– Sri Lanka Clinical Trials Registry (SLCTR)
– The Netherlands National Trial Register (NTR)
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FDAAA & CLINICAL TRIAL
REGISTRIES
• Prior U.S. Law on registries – FDAMA §113 –
– Limitations:
• Only applies to
– “serious or life-threatening” diseases
– Drugs – not devices
• No mechanism to ensure compliance by all performing
clinicals
• Inconsistent information in required data fields
• Only applies to studies under INDs
• No requirement for Clinical Trials Results
• Food & Drug Administration Amendments Act of
2007 (FDAAA) – Public Law 110-85 – Sept. 27, 2007
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FDAAA & TRIAL REGISTRIES …
• Section 801 -- Expands Trial Registry System
• Much more detailed information required on the
clinical studies
• Applies to drugs and devices
– Devices – under 510k’s, PMAs or PDPs and HDEs or
Section 522 Postmarket Surveillance
– Drugs –
• “controlled clinical investigation” other than a Phase
I study
• Not pegged to serious or life threatening
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FDAAA & TRIAL REGISTRIES …
• Where “applicable clinical trial” is ongoing on date
of enactment or initiated after enactment
– 90 days after enactment if ongoing
– 21 days after first patient in if initiated
• Posting of data –
– Drug – within 30 days of submission
– Device –
• If not previously cleared, not earlier than date of
clearance or approval
• If previously cleared, not until 30 days after clinical
trial results data is to be submitted
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FDAAA & CLINICAL TRIAL
RESULTS
• Linking to FDA Data
– For clinical trials that form “the primary basis for an
efficacy claim” or are post-market trials
– Data
•
•
•
•
•
Advisory committee (if any) consideration – any summary by FDA
Posted pediatric assessments or reports
Public Health Advisories
Drugs -- FDA Action Package required under 505(l)(2)
Devices
– Detailed Summary of Safety & Effectiveness info for PMAs
– 510k summary of safety & effectiveness data
• Medline citations
• NIH Database of structured product labels
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FDAAA & TRIAL RESULTS …
• Phase-In of Data Results
– 1-Year
• Demographic and baseline characteristics of
patients
• Primary and secondary outcomes
• Point of contact
• Any agreements between sponsor and
investigator that “squelches” the investigator
– 3-Year – Rulemaking required not later than
3 years post-enactment for greater
expansion of results database
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FDAAA & TRIAL RESULTS …
• Expanded Registry and Results Database under
Rulemaking
– Would cover trials on both approved and unapproved
products
– Required
•
•
•
•
Summary in lay language
Summary in technical language
Full study protocol
Submission date – generally 1 year after completion date or estimated
completion date of study
• Public Meeting – within 18 months of FDAAA – held in
April 2009
• Adverse Events – how to incorporate into databanks?
– Within 18 months, rulemaking needed on how to do
– If not, default provisions will go into effect
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FDAAA & TRIAL RESULTS …
• FDA Submission Certification – NDAs,
PMAs, BLAs, 510k’s and HDEs will have
to include certification that all applicable
requirements on trials information have
been submitted
– Noncompliance or false information in a
certification = “Prohibited Act” under FDCA
– Form 3674 – vehicle for compliance
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FDA Submission Certification -3674
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FDAAA & TRIAL RESULTS …
• Civil Money Penalties –
– up to $10,000 for all violations in a single
adjudication
– Failure to correct within 30 days, $10,000 per
day
• Preemption – “upon the expansion,” no
state may establish or continue in effect any
requirement on registries or results
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STATE LEGISLATION
• State laws generally apply to drug/device
manufacturers conducting business in that
state
• Maine – the frontrunner
– Applies to drug and biologics studies
– Requires drug manufacturers to register
study and disclose all results
– Violators assessed fine of $10,000/day
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STATE LEGISLATION …
• Numerous states have had pending
legislation
– California
• Requires drug manufacturers to post all results
of drug/biologics trials, including incomplete
studies within ninety days
• Allows time extension for publication
• Contains federal preemption language
• Industry opposition
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STATE LEGISLATION …
• New York
– Requires drug manufacturers who market
drugs in NY to post all information/results
within 90 days of trial completion
– Allows 6-month time extension for
publication
– No preemption language
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STATE LEGISLATION …
• Implications for drug/device
manufacturers
– Compliance with potentially 50 different
laws
– Preemption of state requirements
– Cost of registering
– Time consuming
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Questions?
Call, e-mail, fax or write:
Michael A. Swit, Esq.
Vice President
The Weinberg Group Inc.
336 North Coast Hwy. 101
Suite C
Encinitas, CA 92024
Phone 760.633.3343
Fax 760.454.2979
Cell 760.815.4762
[email protected]
www.weinberggroup.com
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About your speaker…
Michael A. Swit, Esq., is a Vice President at THE WEINBERG GROUP, where he develops and ensures the
execution of a broad array of regulatory and other services to drug and biologics clients seeking to market products in
the United States. His expertise includes FDA development strategies, compliance and enforcement initiatives, recalls
and crisis management, submissions and related traditional FDA regulatory activities, labeling and advertising, and
clinical research efforts.
Mr. Swit has been addressing critical FDA legal and regulatory issues since 1984. His multi-faceted experience
includes serving for three and a half years as corporate vice president, general counsel and secretary of Par
Pharmaceutical, a prominent, publicly-traded, generic drug company and, thus, he brings an industry and commercial
perspective to his work with FDA-regulated companies. Mr. Swit then served for over four years as CEO of
FDANews.com, a premier publisher of FDA regulatory newsletters and other specialty information products for the
FDA-regulated community. His private FDA regulatory law practice has included service as Special Counsel in the
FDA Law Practice Group in the San Diego office of Heller Ehrman White & McAuliffe and with the Food & Drug
Law practice at McKenna & Cuneo, both in the firm’s Washington office and later in San Diego. He first practiced
FDA regulatory law with the D.C. office of Burditt & Radzius.
Mr. Swit has taught and written on a wide variety of subjects relating to FDA law, regulation and related commercial
activities, including, since 1989, co-directing a three-day intensive course on the generic drug approval process and
editing a guide to the generic drug approval process, Getting Your Generic Drug Approved. A former member of the
Food & Drug Law Journal Editorial Board, he also has been a prominent speaker at numerous conferences sponsored
by such organizations as RAPS, FDLI, and DIA. A magna cum laude graduate of Bowdoin College, he received his
law degree from Emory University Law School and is a member of the California, D.C. and Virginia bars.
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