Informed Consent: Promise, Pledge, Contract, or Platitude? Presented by: Michael A. Swit, Esq. Vice President, The Weinberg Group Inc.

46 th Annual Meeting Washington, DC Disclaimer The views and opinions expressed in the following PowerPoint slides are those of the individual presenter and should not be attributed to Drug Information Association, Inc. (“DIA”), its directors, officers, employees, volunteers, members, chapters, councils, Special Interest Area Communities or affiliates, or any organization with which the presenter is employed or affiliated. These PowerPoint slides are the intellectual property of the individual presenter and are protected under the copyright laws of the United States of America and other countries. Used by permission. All rights reserved. Drug Information Association, DIA and DIA logo are registered trademarks or trademarks of Drug Information Association Inc. All other trademarks are the property of their respective owners. These slides support an oral briefing and may not be relied upon solely on their own to support any conclusion of law or fact. 2

3 Historical Background

46 th Annual Meeting Washington, DC The Nuremberg Code (1947) First modern ethical code requiring – Voluntary consent – Benefits outweigh risks – Ability of the subject to terminate participation

46 th Annual Meeting Washington, DC 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

46 th Annual Meeting Washington, DC Helsinki Declaration … “Concern for the interests of the subject must always prevail over the interests of science and society”

46 th Annual Meeting Washington, DC Beecher Article (1966) “Ethics and clinical research” — Henry K. Beecher, New England Journal of Medicine 274 (1966): –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

46 th Annual Meeting Washington, DC 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 “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

46 th Annual Meeting Washington, DC Where the Burden Lies … “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.”

46 th Annual Meeting Washington, DC Beecher’s Paradox The voluntary consent of the human subject is absolutely essential. –Nuremberg True informed consent is probably an unattainable goal. –Beecher

46 th Annual Meeting Washington, DC 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

46 th Annual Meeting Washington, DC Where the Regulations Lie HHS – if supported by federal funding – 45 CFR 116. FDA – 21 CFR Part 50 Differences –FDA, but not HHS, provides for an exception from the informed consent requirements in emergency situations. The provision is 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 ß

46 th Annual Meeting Washington, DC Differences – FDA vs. HHS HHS provides for waiving or altering elements of informed consent under certain conditions. FDA has 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) 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. While HHS has the right to inspect records of studies it funds, it does not impose that same informed consent requirement.

46 th Annual Meeting Washington, DC Differences – FDA v. HHS … FDA explicitly requires that consent forms be dated as well as signed by the subject or the subject's legally authorized representative. The HHS regulations do not explicitly require consent forms to be dated.

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

46 th Annual Meeting Washington, DC 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

46 th Annual Meeting Washington, DC 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

46 th Annual Meeting Washington, DC 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

46 th Annual Meeting Washington, DC 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

46 th Annual Meeting Washington, DC 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

46 th Annual Meeting Washington, DC 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

46 th Annual Meeting Washington, DC 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

46 th Annual Meeting Washington, DC 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

24 Call, , fax or write: Michael A. Swit, Esq. Vice President The Weinberg Group Inc. 336 North Coast Hwy. 101 Suite C Encinitas, CA Phone Fax Cell Questions?

46 th Annual Meeting Washington, DC 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 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.