Research Compliance: An Overview of Ethical and Regulatory Issues

1. Research Compliance: An Overview of Ethical and Regulatory Issues Presented by: Carol B. Willeke, Miami University Joanne Altieri, University of Kansas

2. Areas of Compliance • Conflict of Interest • Misconduct in Science • Animal Research • HIPAA • Human Research • RCR Initiatives Joanne Altieri, University of Kansas

3. Profile of the University of Kansas • $153M awards in Fiscal Year 2001 • NSF Ranking for 2000 – 78th • Federal expenditures increased 30% between 1996 and 2000 • Sponsored programs reorganized in 1997 Joanne Altieri, University of Kansas

4. Conflict of Interest • NSF & PHS published policies – July 1995 • Established federal standards and procedures for disclosure and management • Minimum requirements laid out for all institutions engaged in sponsored programs • FDA established regulations requiring disclosure of financial arrangements w/PIs Joanne Altieri, University of Kansas

5. TYPES OF CONFLICTS • Individual Financial Conflict of Interest • Institutional Financial Conflict of Interest • Conflict of Commitment (Time) – not federally mandated, but often part of an institutional policy Joanne Altieri, University of Kansas

6. AAU Definition of Individual Conflict of Interest • “…refers to situations in which financial situations may compromise, or have the appearance of compromising, an investigator’s professional judgment in conducting or reporting research.”* * AAU Task Force on Research Accountability, Report on Individual and Institutional Financial Conflict of Interest, Oct. 2001 Joanne Altieri, University of Kansas

7. Individual Conflicts • Collection, analysis, and interpretation of data • Personnel decisions • Purchasing • Choice of protocols • Involvement of human subjects • Statistical methods Joanne Altieri, University of Kansas

8. WHO MUST FILE? • Determined by individual university policy • PIs of NIH and NSF projects? Or • All faculty and staff? • At KU • All faculty and professional staff • Including part-time if engaged in sponsored projects • Minimum required: annual disclosures; sooner if any change in circumstances • Many institutions require disclosure with every proposal Joanne Altieri, University of Kansas

9. Examples of Individual Conflicts • Contracting with private agencies • Competing for research support (resources) • Directing the education of students • Maintaining a free marketplace of ideas • Ownership of intellectual property • Textbooks authored by individual • Members of scientific advisory boards Joanne Altieri, University of Kansas

10. More Examples • Ensuring unbiased research • Preserving our identity as a university Joanne Altieri, University of Kansas

11. Management Tools for Individual Conflicts • #1– Public Disclosure!!!! • Disqualification from participation in some portion of research/development project • Monitoring of research by independent reviewers • Modification of research plan Joanne Altieri, University of Kansas

12. Management Tools for Individual Conflicts (cont) • Severance of relationships • Prospective indicators • Divestiture of significant financial interest Joanne Altieri, University of Kansas

13. AAU Definition of Institutional Conflict of Interest • “…occur[s] when the institution, any of its senior management or trustees, or a department, school, or other sub-unit, or an affiliated foundation or organization, has an external relationship or financial interest in a company that itself has a financial interest in a faculty research project.”* * AAU Task Force on Research Accountability, Report on Individual and Institutional Financial Conflict of Interest, Oct. 2001 Joanne Altieri, University of Kansas

14. Institutional Conflicts • Also includes serving on boards of companies that have financial ties to the university/institution • Conflicts may be real or perceived • Must be disclosed and managed Joanne Altieri, University of Kansas

15. Hypothetical Situation • A university researcher invents a new cancer drug and the university (or its foundation) license it to a start-up biotechnology company (Zap-It). Instead of a license fee, the university/fdn takes 100K shares of stock in Zap-It that represent 10% of the founders’ shares. Market value of stock at this point is $0. Joanne Altieri, University of Kansas

16. Hypothetical Situation (cont) • Later the entrepreneur raises $5M for future research and development from venture capitalists at $4 per share. (Stock now worth $400K-but no market for the stock.) The venture capitalists predict their investment will result in a gain of 2000% after the drug goes through clinical trials. Joanne Altieri, University of Kansas

17. Hypothetical Situation (cont) • Current value of stock that the university holds = $8M ($80 per share X 100,000 shares). Add to this the likelihood of future royalties and you begin to understand why the University would want to see this drug become successful! Joanne Altieri, University of Kansas

18. Institutional Conflicts: The KU Solution • New policy developed by representatives of multi-campus sites – not yet approved • Requires disclosure and sets up responsibility for monitoring • Disclosure of financial interest • Requires the foundation to file a disclosure form to the COI Committee • Will require a management plan Joanne Altieri, University of Kansas

19. Institutional Conflicts: The KU Solution (cont) • Requires safeguards to ensure research integrity • Clinical trials/product testing of university licensed technology must be disclosed and managed by the COI Committee • Research results shall be designed to minimize researcher discretion in interpreting results Joanne Altieri, University of Kansas

20. Institutional Conflicts: The KU Solution (cont) • Equity Decisions • Prohibition of university chairs/directors/deans and significant others from acquiring an equity position in company where they would stand to benefit financially from the license • Same restriction for foundation officers where the foundation holds an equity interest in a company (annual disclosure in foundation’s audit) Joanne Altieri, University of Kansas

21. Institutional Conflicts: The KU Solution (cont) • The prohibition on the acquisition of an equity position by individuals also includes family/household members • Requires the foundation to divest its equity position as soon as feasible Joanne Altieri, University of Kansas

22. Misconduct in Science (Research Misconduct)

23. Historical Perspective • 1980 - Four major research centers disclosed scientific misconduct cases • 1981 – Al Gore held first meeting on the topic • Only 12 disclosures between 1974-1981 • Congress not happy Joanne Altieri, University of Kansas

24. Historical Perspective (cont) • 1985 - Congress passed the Health Research Extension Act • 1986 - Guidelines published in the NIH Guide to Grants • 1989 – Final Rule published, codified at 42 CFR Part 50, Subpart A Joanne Altieri, University of Kansas

25. Historical Perspective (cont) • March 1989 – Office of Scientific Integrity (OSI) established • March 1989 – Office of Scientific Integrity Review (OSIR) established • May 1992 – OSI + OSIR = ORI • 1995 ORI becomes an independent entity • Dec 6, 2000 – Federal Policy on Research Misconduct issued by OSTP Joanne Altieri, University of Kansas

26. Research MisconductDefined • Definition: “Fabrication, falsification, or plagiarism in proposing, performing or reviewing research, or in reporting research results.”* *Office of Science and Technology Policy Joanne Altieri, University of Kansas

27. Research Misconduct (cont) • KU policy also includes unethical treatment of human and animal subjects (Scientific/Scholarly Misconduct) • Allegations are processed according to University Senate Rules and Regulations, Article IX, August 1995 Joanne Altieri, University of Kansas

28. RESEARCH MISCONDUCT (cont) • Fabrication - making up data or results and recording or reporting them • Falsification – manipulation or omission of data or results • Plagiarism – appropriation of another person’s ideas, processes, results, or words without giving appropriate credit • Does NOT include honest errors or differences of opinion Joanne Altieri, University of Kansas

29. Plagiarism • Both theft or misappropriation of Intellectual Property • Substantial unattributed use of another’s work • Not authorship or credit disputes • Ownership of IP at heart of issue Joanne Altieri, University of Kansas

30. Plagiarism (cont) • Most allegations result from differences of opinion • Unauthorized use must be substantial Joanne Altieri, University of Kansas

31. What Constitutes a Good Environment? • Institutional Policy • Few allegations vs. many allegations Joanne Altieri, University of Kansas

32. NSF’s Revised Policy • Effective April 17, 2002 • Makes NSF policy in compliance with Federal Policy • Incorporates the OSTP standards for a finding of misconduct: “a significant departure from accepted practices of the relevant research community…committed intentionally, or knowingly or recklessly…and proven by a preponderance of evidence….” Joanne Altieri, University of Kansas

33. Quiz* • How are “questionable research practices,” such as conflicts of interest and authorship disputes, handled under the federal policy? *Reprinted with permission from Chris Pascal, Director, ORI

34. Quiz* • Is failure to obtain “informed consent” in research with human subjects research misconduct? • A. No, under federal policy • B. Yes, under some institutional policies • C. Falsified signature might be misconduct under federal policy • D. Violations of informed consent covered under human subjects regulations (OHRP) • E. All of the above *Reprinted with permission from Chris Pascal, Director, ORI

35. Quiz* • Is omission of data research misconduct? • Is use of author’s manuscript obtained during peer review of a journal article misconduct? *Reprinted with permission from Chris Pascla, Director, ORI

36. Animal Research

37. Animal Research • ‘Ouch’ said the doggy, • ‘Meow’ said the cat, • ‘Damn’ said the rattus, • “I’m a goner,” said the mouse. • “Where’s my consent form?”asked the rabbit. “I never agreed to this.” Joanne Altieri, University of Kansas

38. Animal Research - Purpose • Use of animals to advance medicine and science when there are no non-animal alternatives, and when done in an ethical and humane way. • Research • Classroom instruction • Work offering immediate and potential benefits to both humans and other species. Joanne Altieri, University of Kansas

39. Goals – The 3 Rs • Reduction • Appropriate species, quality, and minimum number required to obtain valid results • Refinement • Avoid or minimize discomfort, distress, and pain • Replacement • Mathematical models; computer simulation; in vitro biological systems; use of videotapes Joanne Altieri, University of Kansas

40. The Why: Regulations • IRAC - Interagency Research Animal Committee • “U.S. Government Principles for the Utilization and Care of Vertebrate Animals Used in Testing, Research and Education” • Public Health Service Act as published by OLAW – Office of Laboratory Animal Welfare • “Policy on Humane Care and Use of Laboratory Animals” • Animal Welfare Act – Public Law Joanne Altieri, University of Kansas

41. Regulations (cont) • NIH Publication No. 85-23 • THE GUIDE: “Guide for the Care and Use of Laboratory Animals” • 1993 AVMA Panel Report on Euthanasia (American Veterinary Medical Association) Joanne Altieri, University of Kansas

42. Institutional Assurance • PHS-OLAW approves written assurance that: • Applicant organization meets Public Law requirements of proper care and treatment of animals while being used in research; has an animal care committee; and has available instruction or training in humane practice of animal use for personnel • Assurance resubmitted every 5 years • No PHS funded activity involving animals permitted without approved Assurance Joanne Altieri, University of Kansas

43. AAALAC • Association for Assessment and Accreditation of Laboratory Animal Care • Private nonprofit organization promoting the humane treatment of animals in science • Voluntary accreditation for program and facilities • Part of PHS assurance Joanne Altieri, University of Kansas

44. THE WHAT: ANIMALS THAT MAKE THE LIST . . . • ANY LIVE, VERTEBRATE ANIMAL USED OR INTENDED FOR USE IN RESEARCH, RESEARCH TRAINING, EXPERIMENTATION, OR BIOLOGICAL TESTING OR FOR RELATED PURPOSES. • Does it have a backbone? • Dogs, cats, rabbits, guinea pigs, hamsters, rats, mice, frogs, turtles, snakes, birds, fish • LABORATORY USE • FIELD USE- study conducted on free-living wild animals in natural habitat Joanne Altieri, University of Kansas

45. . . .And Those That Don’t • Insects, arachnids, crustaceans, jelly fish • Animal tissue obtained off campus for which the animal was not specifically killed for the tissue or which was obtained commercially Joanne Altieri, University of Kansas

46. The Who: Responsibility • Principal Investigator • Prepares and submits Statements of Animal Use or Statements of Field Research involving live vertebrates • Before obtaining animals or beginning a study • Submits revised Statement for any major change in an approved Statement • Ensures qualification of all persons involved in care and use of animals in research or training program Joanne Altieri, University of Kansas

47. Animal Care Websites for More Information • Http://www.aaalac.org • http://grants.nih.gov/grants/olaw/olaw.htm Joanne Altieri, University of Kansas

48. Health Insurance Portability and Accountability Act of 1996 (HIPAA)

49. The Purpose of HIPAA • To protect private health information of individuals • Increase burdens for overpaid members of IRBs • Impose civil and criminal penalties for unauthorized disclosures • Test the theory that a straw can break a camel’s back • All of the above Joanne Altieri, University of Kansas

50. Some Other Purposes • Increases patient control of health information • Sets boundaries for use /release of health records • Sets high standards for safeguards of health information • Allows for some exemptions, i.e., public health care Joanne Altieri, University of Kansas