Career Development

1
Career Development Research OfficeWho 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_at_umassmed.edu

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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

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Special Thank you to

• Brian OSullivan, 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.

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Outline

• Who?
• What?
• When?
• Where?
• Why?
• How?

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Power of Attorney
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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

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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

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UMMS Full/Expedited Reviews Per Month

• January 2008-December 2008

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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

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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 2000343808-10

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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

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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

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Key Definitions

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

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Key Definitions (contd)

• 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.

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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.

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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.

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The Common Rule (contd)

• 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

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The Common Rule (contd)

• 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...

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The Common Rule (contd)

• 46.111 (contd)
• Selection of subjects is equitable...
• Informed consent will be sought from each
  prospective subject or his legally authorized
  representative...

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The Common Rule (contd)

• 46.111 (contd)
• Informed consent will be appropriately
  documented
• Data is monitored to ensure subject safety...
• Subject privacy and confidentiality are
  protected

22
The Common Rule (contd)

• 46.111 (contd)
• 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.

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The Common Rule (contd)

• 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

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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

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46.102 Definitions.

• Human subject means 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.

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46.102 (contd)

• 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.
• Interaction includes communication or
  interpersonal contact between investigator and
  subject.

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46.102 (contd)

• 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).

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46.102 (contd)

• 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.

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46.102 (contd)

• Minimal risk means 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.

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Guilty, Guilty, Guilty!
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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

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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

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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.

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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

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U.S. Supreme Court

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

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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

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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

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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

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The Belmont Report (contd)

• 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 (contd)

• Justice
• The issue of justice focuses 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.

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Informed Consent

• In order for consent to be informed, the persons
  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.

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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.

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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.

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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.

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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).

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Mirandas Warning
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Privacy

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

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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.

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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

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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.

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Privilege in Massachusetts

• Psychotherapists
• M.G.L., c.233, sec. 20B
• Includes psychiatrists, psychologists, licensed
  psychiatric nurse clinical mental health
  specialists
• Licensed social Workers
• M.G.L., c.112, sec. 135B

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Jaffe v. Redmond, 518 U.S. 1, 116 S. Ct.
1923, 135 L. Ed. 2d, 337 (1996)

• Effective psychotherapy depends upon an
  atmosphere of confidence and trust in which the
  patient is willing to make a frank and complete
  disclosure of facts, emotions, memories, and
  fears.
• Contrast
• The public ... Has a right to every mans
  evidence. The public good transcend(s) the
  normally predominate principle of utilizing all
  rational means for ascertaining the truth.

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Certificate of Confidentiality

• "Protection of privacy of individuals who are
  research subjects," states
• The Secretary may authorize persons engaged in
  biomedical, behavioral, clinical, or other
  research (including research on mental health,
  including research on the use and effect of
  alcohol and other psychoactive drugs) to protect
  the privacy of individuals who are the subject of
  such research by withholding from all persons not
  connected with the conduct of such research the
  names or other identifying characteristics of
  such individuals. Persons so authorized to
  protect the privacy of such individuals may not
  be compelled in any Federal, State, or local
  civil, criminal, administrative, legislative, or
  other proceedings to identify such individuals.
• The Public Health Service Act 301(d), 42 U.S.C.
  241(d)
• See http//grants.nih.gov/grants/policy/coc/inde
  x.htm

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Consent Forms

• Not a form, but a process
• Keep it simple
• Use current forms
• Avoid just cut paste
• Organize
• Find a naïve reader
• Read it aloud
• Listen to subjects consenting staff

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Challenges to UMMS IRB 2009

• Anticipate increasing complexity with
  translational research
• More phase I (first in human) trials
• Gene transfer trials
• RNAi
• Novel devices and biologics
• Human stem cell
• Accreditation process
• Anticipate initiation of process in 2010

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More Challenges

• Upgrade of electronic solution
• Recent review of enterprise-wide solutions for
  all compliance committees (IRB, IBC, IACUC)
• Vendor decision should be made in next few weeks
• New electronic system will
• Decrease investigator and staff paper burden
• Facilitate timely communication between IRB
  office staff and investigator
• Assist with evaluation of office metrics and
  process flow

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2009/2010 Plans

• Work with Office of Vice Provost for Research
• IRB office infrastructure
• Implementation plan for electronic IRB
• Initiate accreditation process
• Institutional Official John Sullivan, MD
• Institutional Oversight Sheila Noone, Ph.D.

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Seven Dwarfs
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Pet Peeves

• Lack of a research coordinator who knows good
  clinical/research practices identified
• Sponsor trying to dictate language
• Missing information
• Missing signatures

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Pet Peeves

• Cutting and pasting
• Wrong forms
• Page 11 of 9
• Informed consent paragraph that suddenly end in
  the middle of

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Pet Peeves

• Inconsistent information
• Tables that dont add up
• Non-serious but frequent risks death, renal
  failure
• Draft applications

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Web Sites

• UMMS IRB
• http//www.umassmed.edu/Subjects/human/index.aspx?
  linkidentifieriditemid13492
• Danielle Pichette
• [phone] or email  danielle.pichette_at_umassm
  ed.edu.

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Web Sites

• Mass Dept of Mental Health, Central Office
  Research Review Committee
• http//www.mass.gov/?pageIDeohhs2topicL3L0
• HomeL1ResearcherL2ResearchRules2cRegulation
  sandGuidelinessidEeohhs2
• Fred Altaffer
• [phone]
• Fred.Altaffer_at_state.ma.us

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Thank you

• Questions?
• Albert.GrudzinskasJr_at_umassmed.edu