Albert J. Grudzinskas, Jr., J.D.
Clinical Associate Professor of Psychiatry
Department of Psychiatry
University of Massachusetts Medical School
Albert.GrudzinskasJr@umassmed.edu
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
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
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.
Outline
Who?
 What?
 When?
 Where?
 Why?
 How?

Power of Attorney
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
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
UMMS Full/Expedited Reviews
Per Month
January 2008-December 2008
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
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
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
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
Key Definitions
 Research means a systematic
investigation, including research
development, testing and evaluation,
designed to develop or contribute to
generalizable knowledge.
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.
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.
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.
The Common Rule (cont’d)
§ 46.103
Departments 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
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...
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...
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…
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.
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
Agencies
in
HHS
Administration for Children and Families (ACF)
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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
§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.
§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.
 Interaction includes communication or interpersonal
contact between investigator and subject.
§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).
§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.
§46.102 (cont’d)
 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.
Guilty, Guilty, Guilty!
Nuremberg Code
Key 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]
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
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.
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
U.S. Supreme Court
 Feres v. United States, 340 U.S. 146 (1950)
 United States v. Stanley, 483 U.S. 669 (1987)
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
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
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
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.
The Belmont Report (cont’d)
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.
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.
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.
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.
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.
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).
Miranda’s Warning
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.
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.
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
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.
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
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 man’s evidence.” The
“public good transcend(s) the normally predominate
principle of utilizing all rational means for
ascertaining the truth.”
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/index.htm
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
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
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
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Decrease investigator and staff paper burden
Facilitate timely communication between IRB office staff and
investigator
Assist with evaluation of office metrics and process flow
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.
Seven Dwarfs
Pet Peeves
 Lack of a research coordinator who knows good
clinical/research practices identified
 Sponsor trying to dictate language
 Missing information
 Missing signatures
Pet Peeves
 Cutting and pasting
 Wrong forms
 Page 11 of 9
 Informed consent paragraph that suddenly end in the
middle of…
Pet Peeves
 Inconsistent information
 Tables that don’t add up
 Non-serious but frequent risks: death, renal failure
 Draft applications
Web Sites
 UMMS IRB:
http://www.umassmed.edu/Subjects/human/index.aspx
?linkidentifier=id&itemid=13492
Danielle Pichette:
(508) 856-4261 or
email: danielle.pichette@umassmed.edu.
Web Sites
 Mass Dept of Mental Health, Central Office
Research Review Committee:
http://www.mass.gov/?pageID=eohhs2topic&L=3&L0=
Home&L1=Researcher&L2=Research+Rules%2c+Regulat
ions+and+Guidelines&sid=Eeohhs2
Fred Altaffer:
(617)626-8125
Fred.Altaffer@state.ma.us
Thank you
Questions?
Albert.GrudzinskasJr@umassmed.edu