Albert J. Grudzinskas, Jr., J.D. Clinical Associate Professor of Psychiatry

1. Career Development & Research Office“Who are These IRB People and Why are They Saying these Mean Things About Me? Albert J. Grudzinskas, Jr., J.D. Clinical Associate Professor of Psychiatry Department of Psychiatry University of Massachusetts Medical School Albert.GrudzinskasJr@umassmed.edu

2. Who are these people Albert J. Grudzinskas, Jr., JD • University of Massachusetts Institutional Review Board (2001-) Member & designee for the protection of special populations in research • Massachusetts, Department of Mental Health, Central Office Research Review Committee (2001-) Member & designee for the protection of special populations in research, Audit Committee (2004-) Chair •  Massachusetts, Department of Mental Health, Central Area Office Research Monitoring Committee (2007-) • National Association of State Mental Health Program Directors, National Research Institute, IRB (2007-), member & Special Populations designee

3. Special Thank you to: • Brian O’Sullivan, M.D., Chair, UMMS IRB • Judith Savageau, M.P.H., CHPR, UMMS IRB • Fred Altaffer, Ph.D., Chair, DMH CORRC • Daniel DeHainaut, Harvard Univ., DMH CORRC • Kristen Roy-Bujnowski, MA, DMH CORRC

4. Disclaimer The opinions expressed during this presentation are not necessarily the opinions of the IRB or the people expressing the opinions; nor should it be presumed or construed that they even are opinions or that the persons expressing them have any idea whatsoever of what they may or may not be talking about [see for example: Tennard v Dretke, 124 S. Ct 2562, 159 L. Ed 2d 384, 2004 U.S. Lexis 4575 (2004), Thomas, dissenting opinion]. The maker of the aforesaid opinions hereby reserve the right in perpetuity to change, modify, distinguish, overrule, or just plain deny that they ever made these or any other opinions at this or any other time since the beginning of the world and continuing to and through this presentation and its immediate aftermath.

5. Outline • Who? • What? • When? • Where? • Why? • How?

6. Power of Attorney

7. IRB at UMMS • Two committees that meet the first and third Tuesday of each month • One Chair and one research pharmacist serve on both committees • 15-20 members on each committee • Studies may be reviewed by the full committee or in an expedited fashion by a subset of members

8. DMH Central Office Research Review Committee • One Committee meets first Wednesday of the month • One Chair and one research pharmacist • Currently 15 members • Studies may be reviewed by the full committee or in an expedited fashion by a subset of members • Expediting Sub-Committee meets every Tuesday

9. UMMS Full/Expedited Reviews Per Month January 2008-December 2008

10. UMMS IRB Activity • 880 clinical trials involving humans open at UMMS • 65 new trials approved since January 1, 2009 • Fewer new studies over the last few months • Related to changes in personnel • New recruitment is expected to change this trend

11. Institutional Review Board • “The ultimate responsibility for protecting human subjects must be borne by the institutions that perform the research.” • Shalala, D. Protecting research subjects - what must be done. New Engl J Med 2000;343:808-10

12. Institutional Review Board • Purpose: review research and determine if the rights and welfare of human subjects involved in research are adequately protected • Authority to approve, require modification in, or disapprove all human subjects research activities • Research approved by the IRB may be subject to review/approval or disapproval by officials of the institution or Department

13. OHRP • Office for Human Research Protections • Overseen by Dept. of Health and Human Services • Oversees IRB function, audits institutions. • Can halt ALL HUMAN SUBJECT RESEARCH at an institution found not to be in compliance

14. Key Definitions • Research means a systematic investigation, including research development, testing and evaluation, designed to develop or contribute to generalizable knowledge.

15. Key Definitions (cont’d) • A human subject means a living individual about whom a researcher (whether professional or student), conducting research, obtains: • Data through intervention or interaction with the individual, or • Identifiable private information.

16. Key Points The Common Rule: 45 CFR 46, Subpart A 45 CFR 46.101...this policy applies to all research involving human subjects conducted, supported or otherwise subject to regulation by any federal department or agency.

17. The Common Rule § 46.103 Each institution engaged in research which is covered by this policy, ... shall provide written assurance, satisfactory to the department or agency head, that it will comply with the requirements set forth in this policy.

18. The Common Rule (cont’d) § 46.103Departments and agencies will conduct or support research covered by this policy, only if the institution has assurance approved as provided in this section, and only if the institution has certified to the department or agency head, that the research has been reviewed and approved by an IRB provided for in the assurance, and will be subject to continuing review by the IRB

19. The Common Rule (cont’d) § 46.111 Criteria for IRB approval of research. In order to approve research...the IRB shall determine that...the following requirements are satisfied: • Risks to subjects are minimized... • Risks to subjects are reasonable in relation to anticipated benefits...and the importance of the knowledge...expected to result...

20. The Common Rule (cont’d) § 46.111 (cont’d) • Selection of subjects is equitable... • Informed consent will be sought from each prospective subject or [his] legally authorized representative...

21. The Common Rule (cont’d) § 46.111 (cont’d) • Informed consent will be appropriately documented… • Data is monitored to ensure subject safety... • Subject privacy and confidentiality are protected…

22. The Common Rule (cont’d) § 46.111 (cont’d) When some or all of the subjects are likely to be vulnerable to coercion or undue influence, such as children, prisoners, pregnant women, mentally disabled persons, or economically or educationally disadvantaged persons, additional safeguards have been included in the study to protect the rights and welfare of these subjects.

23. The Common Rule (cont’d) 45 CFR 46.101(b) Some research is exempt from the common rule: • Some educational testing where subjects can not be identified • Research, involving the collection or study of existing data...if these sources are publicly available • Some taste and food quality evaluation and consumer acceptance studies

24. Agencies in HHS • Administration for Children and Families (ACF) • Administration on Aging (AoA) • Agency for Healthcare Research and Quality (AHRQ) • Agency for Toxic Substances and Disease Registry (ATSDR) • Centers for Disease Control and Prevention (CDC) • Centers for Medicare & Medicaid Services (CMS) • Food and Drug Administration (Food and Drug Administration) • Health Resources and Services Administration (HRSA) • Indian Health Service (IHS) • National Institutes of Health (NIH) • Program Support Center (PSC) • Substance Abuse and Mental Health Services Administration (SAMHSA) & • Depts. of Agriculture & Energy

25. §46.102 Definitions. Human subjectmeans a living individual, about whom an investigator (whether professional or student) conducting research obtains: • Data through intervention or interaction with the individual, or • Identifiable private information.

26. §46.102 (cont’d) • Intervention includes both physical procedures, by which data are gathered (for example, venipuncture), and manipulations of the subject or the subject's environment that are performed for research purposes. • Interactionincludes communication or interpersonal contact between investigator and subject.

27. §46.102 (cont’d) • Private information includes information about behavior that occurs in a context, in which there is a reasonable expectation of privacy and information, which has been provided for specific purposes by an individual and which the individual can reasonably expect will not be made public (for example, a medical record).

28. §46.102 (cont’d) • Private information must be individually identifiable (i.e., the identity of the subject is or may readily be ascertained by the investigator or associated with the information), in order for obtaining the information to constitute research involving human subjects.

29. §46.102 (cont’d) • Minimal riskmeans that the probability and magnitude of harm or discomfort anticipated in the research are not greater in and of themselves than those ordinarily encountered in daily life or during the performance of routine physical or psychological examinations or tests.

30. Guilty, Guilty, Guilty!

31. Nuremberg CodeKey Points • The voluntary consent of the human subject is absolutely essential • The subject is at liberty to bring the experiment to an end • The experiment should be designed to avoid unnecessary physical and mental suffering • Risk should not exceed potential benefit [extended to mean benefit to society or to the subject]

32. Tuskegee Study of Untreated Syphilis in the Negro Male • 1932 Public Health Service, working with the Tuskegee Institute, began a study to record the natural history of syphilis in hopes of justifying treatment programs for blacks.  • 1969 CDC reaffirms need for study and gains local medical societies' support (AMA and NMA chapters officially support continuation of study). • 1972 AP story caused a public outcry - study ends

33. Tuskegee Study of Untreated Syphilis in the Negro Male • 1972 Assistant Secretary for Health and Scientific Affairs appoints a nine members Ad Hoc Advisory Panel to review the study from the fields of medicine, law, religion, labor, education, health administration, and public affairs. • 1974 A $10 mil. settlement U.S. promised to give lifetime medical benefits and burial services to all living participants.  The Tuskegee Health Benefit Program was established to provide these services.

34. Other Cases • 1959 Thalidomide • 1963 Brooklyn Jewish Chronic Disease Hospital & Sloan-Kettering Cancer Research Institute • 1971 Willowbrook Hepatitis Study • 1973 National Research Act • 1975 Rockefeller Commission

35. U.S. Supreme Court • Feres v. United States, 340 U.S. 146 (1950) • United States v. Stanley, 483 U.S. 669 (1987)

36. Today in Massachusetts • Boston Medical School – Dept of Psychiatry (2007) • Patient switched before study submission to IRB • Resperidone “to qualify for consta study” • Neuroleptic Malignant Syndrome - 8 day coma • No Guardian notice • No Court approval (Rodgers plan) • Physician license revoked • Dept. Chair banned from DMH studies for one year

37. Reporting requirements for IRB • IRB must report promptly to institutional officials, OHRP, FDA and sponsoring agency: • Injuries to human subjects or other unanticipated problems involving risks to human subjects or others • Serious or continuing noncompliance with regulations or requirements of the IRB • Suspension or termination of IRB approval of research

38. The Belmont Report Respect: The concept of respect involves the idea that individuals are autonomous and should be treated as being free to make their own independent choices. The notion of respect implies autonomy

39. The Belmont Report (cont’d) Beneficence: The concept of beneficence requires, in addition to respecting a person's right to choose and ensuring that this choice is free of coercion, that any harmful risk is balanced against the likelihood of a benefit for the individual.

40. The Belmont Report (cont’d) Justice: The issue ofjusticefocuses on the distribution of risks and benefits associated with participating in research. In the past, prison populations because of their stability and large numbers were often seen as ideal groups for clinical research. The knowledge gained from these experiments, however, primarily benefited private patients in non-correctional settings.

41. Informed Consent: In order for consent to be informed, the person’s choice to participate must be based on the full disclosure of the facts relevant to the decision. The person must be able to understand the risks involved, the potential benefits, and the alternatives to the recommended course of action.

42. Informed Consent: Human subject participation must be voluntary and based on informed consent. In order to be informed, consent must be freely given in a competent manner. In order to be competent, consent must be knowing, intelligent, and voluntary.

43. Competency: A person may be considered competent if s/he is able to fully appreciate the risks and benefits attendant to a course of action. A factual understanding may not be sufficient in many jurisdictions to establish competency if the person is unable to appreciate the individual significance of the information as it applies to his/her situation.

44. Coercion: Coercion may take the form of force, compulsion, constraint, threat, or come in the form of a benefit so great in proportion to a person's normal situation that it causes him/her to overlook the nature of the attendant risk.

45. Confidential Communication The right to privacy “the right to be let alone - the most comprehensive of rights and the right most valued by civilized men.” Justice Brandeis, from the dissent in Olmstead v. United States, 277 U.S. 438, at 478 (1928).

46. Miranda’s Warning

47. Privacy The right not to have others (most especially the government) interfere with our lives. The right to determine the course of one’s wishes, hopes, and dreams - the right to live according to one’s own life plan.

48. Confidentiality The communication is intended only for the knowledge of a particular person. Requires a (professional) relationship and an expectation of privacy. Examples: Attorney/Client; Doctor/Patient; Confessor/Clergy; Husband/Wife.

49. Confidentiality in Massachusetts • Psychiatry • Alberts v. Devine, 395 Mass. 59 (1985) • Licensed Psychologists • M.G.L., c.112, sec. 129A • Licensed Social Workers • M.G.L., c.112, sec. 135A • Department of Mental Health • M.G.L., c.123, sec. 36

50. Privilege Statements made by one person to another which may be withheld as confidential by the person receiving the communication when he/she is a witness in court. Often referred to as testimonial privilege. There is no recognized researcher/subject privilege.