1. AMERICAN CONFERENCE INSTITUTE 12 th 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

2. 2 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.

3. 3 What I Will Cover on Informed Consent  Historical Background – Quickly  “Law” of Informed Consent  Implementation Issues

4. 4 Historical Background of Informed Consent

5. 5 The Nuremberg Code (1947)  First modern ethical code requiring  Voluntary consent  Benefits outweigh risks  Ability of the subject to terminate participation

6. 6 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

7. 7 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

8. 8 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

9. 9 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

10. 10 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.”

11. 11 Beecher’s Paradox  The Voluntary Consent of the Human Subject is Paramount  Nuremberg  True Informed Consent Is Probably An Unattainable Goal  Beecher

12. 12 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

13. 13 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

14. 14 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.

15. 15 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.

16. 16 The Law of Informed Consent – Contract, Fiduciary Duty, Promise, Pledge or Platitude?

17. 17 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

18. 18 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

19. 19 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

20. 20 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

21. 21 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

22. 22 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

23. 23 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

24. 24 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

25. 25 Informed Consent Implementation Issues

26. 26 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

27. 27  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

28. 28 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?

29. 29 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.