This document provides an overview of a presentation on ethics in clinical trials and the key role of informed consent. The presentation covers the historical background of informed consent, beginning with the Nuremberg Code in 1947 and the Declaration of Helsinki in 1964, both of which established the requirement of voluntary consent from subjects. It then discusses challenges with implementation of informed consent, including ensuring subjects comprehend the information and consent voluntarily without coercion. The presentation addresses debates around whether informed consent constitutes a legally enforceable contract and identifies issues that can arise with properly documenting, disclosing information, and assessing comprehension of informed consent.

1. AMERICAN CONFERENCE INSTITUTE
12th National Conference On Managing Legal Risks And
Conducting Clinical Trials
New York City
February 24, 2010
Michael A. Swit, Esq.
Vice President
Ethics in Clinical Trials –
The Key Role of Informed Consent

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Standard Disclaimers
 Views expressed here are solely mine and do not
reflect those of my firm or any of its clients.
 This presentation supports an oral briefing and
should not be relied upon solely on its own to
support any conclusion of law or fact.

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What I Will Cover on Informed Consent
 Historical Background – Quickly
 “Law” of Informed Consent
 Implementation Issues

4. 4
Historical Background of
Informed Consent

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The Nuremberg Code (1947)
 First modern ethical code requiring
 Voluntary consent
 Benefits outweigh risks
 Ability of the subject to terminate participation

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Declaration of Helsinki (1964)
 Recommendations Guiding Medical Doctors in
Biomedical Research Involving Human Subjects
 Adopted by the 18th World Medical Assembly, Helsinki,
Finland, 1964; revised in Tokyo, 1975; Venice, 1983;
Hong Kong, 1989; South Africa, 1996;Edinburgh 2000;
Note of clarification on paragraph 29; Washington 2002

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Helsinki Declaration …
 “Concern for the interests of the subject must
always prevail over the interests of science and
society”
http://www.wma.net/e/policy/b3.htm

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Beecher Article (1966)
 “Ethics and clinical research” — Henry K.
Beecher, New England Journal of Medicine 274
(1966):1354-60
 22 published medical studies presenting risk to subjects
without their knowledge or approval
 Published in some of the most prestigious journals and
conducted at some of the most acclaimed institutions by some
of the most highly regarded researchers

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Where the Burden Lies
 “The duty and responsibility for ascertaining the
quality of the consent rests upon each individual
who initiates, directs or engages in the
experiment.”
 Principle 1, The Nuremberg Code

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Where the Burden Lies …
 “When obtaining informed consent for a research
project, the doctor should be particularly cautious
if the subject is in a dependent relationship to him
or her, or under duress.”
 The Declaration of Helsinki
 “In that case, the informed consent should be obtained
by a doctor who is not engaged in the investigation and
who is completely independent of this relationship.”

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Beecher’s Paradox
 The Voluntary Consent of the Human Subject is
Paramount
 Nuremberg
 True Informed Consent Is Probably An Unattainable
Goal
 Beecher

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The Belmont Report
 1974 – The National Commission for the Protection
of Human Subjects of Biomedical and Behavioral
Research
 1979 – Commission Report – “Belmont”
 Validates IRB role as a key aspect of subject protection
 1981 – Federal Regulations Revised
 “Common Rule” – basically across whole fed. govt.
 FDA – some exceptions, minor in nature

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Where the Regulations Lie
 HHS – if supported by federal funding – 45 CFR
116.
 FDA – 21 CFR Part 50
 Differences
 Emergency Situations:
 FDA --an exception from the informed consent requirements in
emergency situations.
 Based on the Medical Device Amendments of 1976, but may be used in
investigations involving drugs, devices, and other FDA regulated
products in situations described in § 50.23.
 HHS – no exception

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Differences – FDA vs. HHS
 Waivers or altering informed consent elements:
 HHS – can waive or alter elements of informed consent
under certain conditions.
 FDA -- no such provision because the types of studies
which would qualify for such waivers are either not
regulated by FDA or are covered by the emergency
treatment provisions (§ 50.23)
 Inspection of records –
 FDA -- explicitly requires that subjects be informed that
FDA may inspect the records of the study because FDA
may occasionally examine a subject's medical records
when they pertain to the study.
 HHS – while has right to inspect records of studies it
funds, it does not impose that same informed consent
requirement.

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Differences – FDA v. HHS …
 Signatures & Dating on I.C. Forms:
 FDA -- explicitly requires that consent forms be dated as well
as signed by the subject or the subject's legally authorized
representative.
 HHS -- does not explicitly require consent forms to be dated.

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The Law of Informed Consent –
Contract, Fiduciary Duty, Promise,
Pledge or Platitude?

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Treatment vs. Research – Key Distinction
 Law of Informed Consent – must remember that what
governs medical treatment is not always same as what
governs research
 Treatment
 Doctor – arguably -- is a fiduciary – owes duty to protect patient
 Traditional view – unconsented treatment = battery
 Causation –
 Not disclosed
 Injured
 Reasonable Patient would want to know
 Reasonable Patient would have refused the treatment – HARD
PART

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How Research Differs from Treatment
 Goals – treatment vs. developing generalizable
knowledge
 How Overseen:
 Treatment – doctor supplies expertise
 Research – highly regulated by sources other than the doctor –
protocol and government regulation
 e.g., if sponsor concludes treatment is ineffective, must stop
research
 Law – state (treatment) vs. federal (research) –
some exceptions

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Battery
 Problem – any failure could be alleged to be a battery,
which is an intentional tort (technically); due to this,
courts do not favor it as a remedy
 Will occur:
 Complete lack of consent
 Procedure given differed from that consented
 “Ghost Surgery” – undisclosed replacement surgeon

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Is the I.C. a Contract Legally Enforceable
by the Subject?
 Basic contract law
 Parties in privity – i.e., two make a deal
 Legal subject
 Offer
 Acceptance
 Consideration
 Problem – lack of privity – sponsor may provide
the form, but it is obtained by P.I. from the subject
– no privity

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But, People (Alan Milstein) Still Argue Contracts
 Suthers & Abney Cases
 GNDF trials – discontinued by Amgen as showing no benefit
– thus, required under IND rules
 Plaintiffs – you owe us the drug under normal contracts
theory and the doctrine of “promissory estoppel” – also a
contracts theory
 Clear promise
 Detrimental reliance by promisee
 Damages by promisee

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Suthers and Abney Decisions
 No contract
 Amgen not a party to I.C., nor was the P.I. an agent of Amgen
that could bind Amgen via the I.C.; rather they were
“independent contractors”
 Look at control over the P.I.’s work
 Here the protocol drafted by the P.I.
 No promissory estoppel
 Unable to show Amgen promised continued access

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Fiduciary?
 Suthers & Abney – also asserted that the Amgen
was a fiduciary; not found by court
 Amgen did not set up the clinical initially; no unique duty
owed to subjects or proof that Amgen’s role was done for the
benefit on the patients
 Note: court suggested that the parties to be bound
by contract via the I.C. were the P.I. and the
universities where P.I. worked

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Problems with Fiduciary Theory
 Goal of research – generalizable knowledge
 Subject is not the prime beneficiary of research –
rather it is the public at large
 P.I. and sponsor both have less control over the
way research is done

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Informed Consent
Implementation Issues

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Execution Issues
 Documentation -- If it wasn’t written down … It
didn’t happen!
 Extent of Disclosure -- Sufficient (complete)
information to subject to understand
 Comprehension – was it understood?
 Voluntariness – free of coercion and undue
influence?
 Paper vs. Process – signature not enough, process
must be complete so that Principal Investigator has
confidence consent was informed

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 90% state they read the consent themselves
 8% did not read it and 2% had it read to them
 85% understood the number of visits yet
 63% understood that the study was blinded and neither they
nor their physician would know which medication they were
receiving
 60% understood that they could contact someone
other than their doctor regarding rights and risks
 30% did not understand that the study carried additional
risks and discomforts
Source: 2002 CenterWatch Survey of 1,561 Study Volunteers
Comprehension and Informed Consent

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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
michael.swit@weinberggroup.com
www.weinberggroup.com
Questions?

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About your speaker…
Michael A. Swit, Esq., is a Vice President at The Weinberg Group Inc., a premier science-based consulting firm
dedicated to helping life sciences firms bring highly regulated-products to the market and keep them there using
sound science and cutting-edge regulatory acumen. At The Weinberg Group, he develops and ensures the execution
of an array of regulatory and other consulting services to biomedical clients seeking to market products in the United
States and Europe. 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 top 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 (inactive) of the California, D.C. and Virginia bars.