This presentation provides an overview of the evolution of clinical trial registries and databases. It discusses key national and international registries like ClinicalTrials.gov and the WHO's International Clinical Trials Registry Platform. The presentation also covers challenges around registries like protecting intellectual property and premature disclosure, as well as developing legislation around registration and results reporting requirements.

1. CLINICAL TRIAL REGISTRIES
Presentation to
University of Southern California
Regulatory Affairs Masters Program
Michael A. Swit, Esq.
Vice President, Life Sciences
Friday, July 27, 2007

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Disclaimer
• This outline is intended to support an oral
briefing and should not be relied upon solely to
support any conclusion of fact or law
• The views reflected in this presentation are
solely those of the presenters and do not
necessarily reflect the position of their firms or
any of their clients.

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Our Objectives Today
• The Evolution of Demand for Clinical Trial
Registries
• Review of Key National and International
Registries
• Challenges of Registries and Databases
• Developments to Watch on Clinical Trial 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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FDAMA § 113
• Life-threatening
– (1) diseases or conditions where the likelihood of death is
high unless the course of the disease is interrupted and
– (2) diseases or conditions with potentially fatal outcomes,
where the endpoint of clinical trial analysis is survival
• Serious – For a condition to be serious, the condition
should be associated with morbidity that has substantial
impact on day-to-day functioning. Short-lived and self-
limiting morbidity will usually not be sufficient but the
morbidity need not be irreversible, providing it is
persistent or recurrent.

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ClinicalTrials.gov – Data Sets
• Unique protocol ID #
• Sponsor
• Verification Date
• Brief Title
• Brief Summary
• Study Design, Phase and
Type
• Condition or disease
• Intervention
• Study status
• Eligibility criteria,
gender, age
• Trial location
• Contact Information

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Limitations of ClinicalTrials.gov
• Only applies to “serious or life-threatening”
diseases – see Fast Track Guidance
• No mechanism to ensure compliance by all
performing clinicals
• Does not include actual results
• Inconsistent information in required data fields
• Only applies to studies under INDs

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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 hypothesis-
testing 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
• All trials – including “earliest” stage and exploratory studies
• Trial Registration Data Set -- 20 key details to be
disclosed when study begun –
www.who.int/ictrp/data_set/en/print.html
• 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
• Evolving process – see
www.who.int/ictrp/about/details/en/print.html

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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 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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Challenges of Registries
• Premature disclosure of competitive information,
including intellectual property
– “prior art”
– Clinical trial design can reveal a research agenda
prematurely
– WHO – is reviewing how to approach this; was to
announce its policy by May 19 (could not find evidence
they did this)

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Challenge of Registries …
• Device trials
– Much different from drug
– Iterative nature of device development makes early
trials potentially irrelevant to studies that support
marketing
– Patents are weaker for devices – easier to design
around – thus, premature info disclosure can be
competitively difficult

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Challenges of Registries …
• When to put it up – and will that preclude publication
by a peer review journal?
• Functionally – what information to put up
• Evaluating the data – who will interpret?
• Impact on IRBs and informed consent – need to
disclose other available trials??
• Too much data – will it place too much burden on
physicians to evaluate – leading to undermining the
“learned intermediary” doctrine?

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Challenge of Registries …
• Potential to create confusion for patients
– Too much (or too little) information
• Which site to search?
• What information is accurate?
• What about Phase 1 studies?
• Which terms to use in a search?
– Medical terminology very scientific
• Simplify language to make information readable

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Challenges of Registries …
• Conflict among state and federal requirements
– burdens on drug manufacturers
– preemption
• Health insurance industry reactions
– will plans cover if a study indicates negative
results?

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Liability Concerns
• Drug Manufacturers
– Failure to register/publish results – fraud or
negligence
• additional insurance/higher premiums
– Application of Learned Intermediary Doctrine –
maybe not?
– SEC violations – forward-looking statements

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Liability Concerns
• Providers
– Relying too much upon insufficient data in treating
patients
– Changing expectation by patients of standard of
care = increased risk of malpractice suits

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Contractual Considerations
– Secure adequate reps/warranties
– Add provision dealing with state law compliance
– Include additional indemnification language re:
sponsor/sponsor-investigator failure to comply with
requirements
– Drug manufacturers need to strengthen IP language
– Ensure audit rights to enable monitoring for
compliance

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CMS Revised Clinical Trial
Billing Policy
• Requires sponsors to publish results of a study in order
to qualify for Medicare coverage
• Studies involving Medicare enrollees must be registered
online at the NIH's clinicaltrials.gov database
• Protocol must specify publication specifics and how
the results will generalize to the Medicare population

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Coming to You Soon?
Food and Drug Administration
Revitalization Act (FDARA)
• Would require submission to a registry of all data for all
Phase II, III and IV clinical trials for drugs and devices.
• Provides for a feasibility study to determine the best
methods of publicly disseminating clinical trials results
• Contains State preemption language
• Authorizes civil monetary penalties and withholding of
federal funds for failure to register a clinical trial

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Questions?
Call, e-mail, fax or write:
Michael A. Swit, Esq.
Vice President, Life Sciences
THE WEINBERG GROUP INC.
336 North Coast Hwy. 101
Suite C
Encinitas, CA 92024
Phone 760.633.3343
Fax 760.633.3501
Cell 760.815.4762
D.C. Office 202.730.4123
michael.swit@weinberggroup.com
www.weinberggroup.com

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About the speaker …
Michael A. Swit, Esq., who is Vice President, Life Sciences at THE WEINBERG GROUP
INC., has extensive experience in all aspects of FDA regulation with a particular emphasis on
drugs and medical device regulation. In addition to his private legal and consulting
experience, Mr. Swit also served for three and a half years as vice president and general
counsel of Pharmaceutical Resources, Inc. (PRI) a prominent generic drug company and,
thus, brings an industry and commercial perspective to his representation of FDA-regulated
companies. While at PRI from 1990 to late 1993, Mr. Swit spearheaded the company’s
defense of multiple grand jury investigations, other federal and state proceedings, and
securities litigation stemming from the acts of prior management. Mr. Swit then served from
1994 to 1998 as CEO of Washington Business Information, Inc. (WBII) a premier publisher
of FDA regulatory newsletters and other specialty information products for the FDA
publishing company. Before joining THE WEINBERG GROUP, he served in the FDA
Regulatory Law Practices at both Heller Ehrman and McKenna & Cuneo, first in that firm’s
D.C. office and then in its San Diego office. He first practiced FDA regulatory law with the
D.C. office of Burditt & Radzius from 1984 to 1988. Mr. Swit has taught and written on a
wide variety of subjects relating to FDA law including, since 1989, co-directing a three-day
intensive course on the generic drug approval process, serving on the Editorial Board of the
Food & Drug Law Journal, and editing a guide to the generic drug approval process, Getting
Your Generic Drug Approved, published by WBII. Mr. Swit holds an A.B., magna cum
laude, with high honors in history, in 1979, from Bowdoin College, and earned his law
degree from Emory University in 1982. He is a member of the California, Virginia and
District of Columbia bars.