Informed Consent: Why Patients Sue – A Review of Recent Litigation

1. Informed Consent: Why Patients Sue – A Review of Recent Litigation Joan A. Kavuru, J.D. Director, Office of Compliance The Brody School of Medicine

2. Overview • Informed Consent Process • Examples of Lawsuits • How to Avoid Liability

3. Overview (cont’d) • Most cases do not go to trial • Plaintiffs’ attorneys make allegations; use the “shock” factor • Terms of settlement confidential • Outcome usually does not make headlines – public perception remains tainted • Business decision to settle

4. Informed Consent Process Three General Components: • Information • Type of research, nature of risk, duration of research (i.e. required elements under law) • Comprehension • Must understand information • Voluntary Consent • Free from undue influence and coercion

5. Informed Consent Process (cont’d) Information Basic Required Elements [45 CFR 46.116(a)] • A statement that the study involves research, the purpose of the research and the expected duration of the subject's participation, a description of the procedures to be followed, and which procedures are experimental. • A description of any reasonably foreseeable risks or discomforts to the subject. • A description of any benefits to the subject or to others which may reasonably be expected from the research. • A disclosure of appropriate alternative procedures or courses of treatment, if any, that might be advantageous to the subject.

6. Informed Consent Process (cont’d) Basic Required Elements (cont’d): • A statement describing the extent, if any, to which confidentiality of records identifying the subject will be maintained. • For research involving more that minimal risk, an explanation as to whether any compensation and an explanation as to whether any medical treatments are available if injury occurs and, if so, what they consist of, or where further information may be obtained. • An explanation of whom to contact for answers to pertinent questions about the research and research subjects’ rights, and whom to contact in the event of a research-related injury to the subject.

7. Informed Consent Process (cont’d) Basic Required Elements (cont’d): • A statement that participation is voluntary, refusal to participate will involve no penalty or loss of benefits to which the subject is otherwise entitled, and the subject may discontinue participation at any time without penalty or loss of benefits.

8. Informed Consent Process (cont’d) Information Additional Elements (as necessary) [45 CFR 46.116(b)] • A statement that the particular treatment or procedure may involve risks to the subject (or to the embryo or fetus, if the subject is or may become pregnant) which are currently foreseeable. • Anticipated circumstances under which the subject’s participation may be terminated by the investigator without regard to the subject’s consent. • Any additional costs to the subject that may result from participation in the research.

9. Informed Consent Process (cont’d) Additional Elements (cont’d): • The consequences of a subject’s decision to withdraw from the research and procedures for orderly termination of participation by the subject. • A statement that significant new findings developed during the course of the research which may relate to the subject’s willingness to continue participation will be provided to the subject. • The approximate number of subjects involved in the study.

10. Informed Consent Process (cont’d) Comprehension 86% study volunteers read form • 14% did not read form1 • study perceived as only option • high trust level in research professionals 1 2002 Center Watch Survey of 1,561 Study Volunteers

11. Informed Consent Process (cont’d) Comprehension Who reviewed informed consent form with you? • 41% Study nurse • 21% PI • 19% No one • 12% Family member • 8% Other Source: 2002 Center Watch Survey of 1,561 Study Volunteers

12. Informed Consent Process (cont’d) Comprehension Issues: • Patients intimidated • Just don’t know what to ask • Language barriers • Complex terms in ICF (should be at eighth grade reading level) • All patient cares about is getting better • Retention of information, especially if sick or stressed

13. Informed Consent Process (cont’d) Comprehension Suggestions: • Take form home and think about it • Discourage those already “sold” on idea • Repeat back information to informed consent reviewer • Other ideas from the experts

14. Informed Consent Process (cont’d) Voluntary Consent Free from coercion and undue influence Conflict of Interest • PI/Sponsor financial interests • NIH and FDA disclosure requirements • UMCIRB policy disclosure requirements

15. Informed Consent Process (cont’d) Voluntary Consent FDA Disclosure Requirements [21 CFR Part 54]: Sponsor must disclose: • any financial arrangement entered into between sponsor and PI where the value of compensation to the PI for conducting study could be influenced by study results • significant payments to PI from sponsor, e.g. research grants, honoraria, consulting agreements, equipment (greater than $25,000)

16. Informed Consent Process (cont’d) • FDA Disclosure Requirements (cont’d) • Any proprietary interest • Any significant equity interest (any options, ownership interest in sponsor) (for stock held in publicly traded company, $50,000 equity held during study and for 1 year thereafter) • Steps taken to minimize bias

17. Informed Consent Process (cont’d) Voluntary Consent Undue influence/coercion • Inherent conflict when treating physician is PI • Trust in physician; patient does not want to “disappoint” physician • Bonuses for meeting enrollment targets • Vulnerable patients • no health insurance • desperate for treatment

18. Litigation • Gelsinger v. Univ. of Penn.(C.P. Phila. Co., 2000) • 18 year old boy died during a gene transfer experiment for ornithine transcarba – mylase deficiency. • PI founded company that sponsored trial – owned 30% of stock • University of Pennsylvania owned 5% of stock

19. Litigation (cont’d) Gelsinger v. Univ. of Penn. (cont'd) • Informed consent process did not disclose: • Monkey deaths • Previous adverse events • Relationship between PI and sponsor • Confidential settlement • FDA shutdown of gene therapy • Sued University trustees, PI, sponsor and hospital

20. Litigation (cont’d) • Gelsinger v. Univ. of Penn. • University’s Conflicts of Interest Committee was aware of the potential conflict of interest between the parties – allowed study to proceed • FDA violations: • Failure to tell NIH of change in delivery mechanism • Changing ICF to exclude information about death of monkeys • Patients prior to subject had suffered liver toxicity requiring study to be placed on hold • Failure to follow protocol

21. Gelsinger v. Univ. of Penn. (cont’d) One of the (many) Counts: Intentional Assault and Battery, Lack of Informed Consent • Understanding risks of toxic effects of gene therapy • Failure to inform of monkey deaths • Failure to inform of previous adverse events • Misrepresenting efficacy • Failure to adequately disclose conflict of interest

22. Litigation (cont’d) Fred Hutchinson Cancer Research Center Cases • Class action lawsuit by 82 families • Protocol 126: Ran from 1981 to 1993 • Tested a method to help prevent graft vs. host disease ( a potentially fatal complication in bone-marrow transplants) • Discovered that the experiment caused a graft failure, a rare but fatal complication • Plaintiffs argued that PIs did not tell them the study could increase graft failures or that a safer study was available at the time to prevent graft vs. host disease

23. Fred Hutchinson Cancer Research Center (Cont’d) • Doctors apparently owned shares of stock in a company whose antibodies were being tested in the study • Long, protracted trial – 8 weeks of testimony • Jury found in favor of defendant in 4 out of 5 cases that went to trial • Judge instructed jury to decide if failure to disclose a material fact would have change the patient’s decision to enroll in the study • Judge had previously dismissed the fraud count related to the financial conflict

24. Litigation (cont’d) Abney v. Amgen, Inc. 443 F.3d 540 (6th Cir. March 29, 2006) • 2003 Amgen sponsored Phase II placebo controlled study • Study involved infusion of GDNF for Parkinson’s patients • Protocol provided for a 33 week extended treatment period • Patients were doing well with drug • Allegedly the doctors “promised” continued access to GDNF as long as it was safe and effective and in their best interest

25. Abney v. Amgen, Inc. (cont’d) • Informed consent stated that the subject may be withdrawn from the study if there was undue risk, non-compliance, or the agency stops funding of the study for scientific reasons • The patent was set to expire soon after potential FDA approval, and thus allegedly little financial potential for drug • Amgen stopped study • Study subjects sued to continue to receive study drug • Plaintiffs argued “breach of contract” • Court ruled in favor of Amgen

26. Steps to Prevent Liability • Communication is key with all parties • Relationship with study subjects • Comprehension of ICF • Use of interpreters if necessary • Manage expectations of subject and family

27. Steps to Prevent Liability (cont’d) • Relationship with sponsor and IRB • Information regarding SAEs • Changes to protocol which may require revisions to ICF • Use of IRB approved ICF • Education to PIs on conflict of interest issues • Disclosure required pursuant to law and ECU policy • Employer responsibility to manage any conflict

28. Office of Compliance Joan A. Kavuru, J.D. Director 744-5200 Compliance Hotline 1-866-515-4587 Available 24/7 – You may remain confidential If it concerns you, it concerns us!