Albert J. Grudzinskas, Jr., J.D.

Clinical Associate Professor of PsychiatryDepartment of Psychiatry

University of Massachusetts Medical SchoolAlbert.GrudzinskasJr@umassmed.edu

Who are these peopleAlbert J. Grudzinskas, Jr., JDUniversity 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 IRBJudith Savageau, M.P.H., CHPR, UMMS IRBFred Altaffer, Ph.D., Chair, DMH CORRCDaniel DeHainaut, Harvard Univ., DMH

CORRCKristen Roy-Bujnowski, MA, DMH CORRC

DisclaimerThe 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.

OutlineWho?What?When? Where?Why?How?

Power of Attorney

IRB at UMMSTwo committees that meet the first and

third Tuesday of each monthOne Chair and one research pharmacist

serve on both committees15-20 members on each committeeStudies may be reviewed by the full

committee or in an expedited fashion by a subset of members

DMH Central Office Research Review CommitteeOne Committee meets first Wednesday of the

monthOne Chair and one research pharmacistCurrently 15 membersStudies 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 Activity880 clinical trials involving humans open at

UMMS 65 new trials approved since January 1, 2009Fewer new studies over the last few months

Related to changes in personnelNew 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

OHRPOffice 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 DefinitionsResearch 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 PointsThe 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 providewritten assurance, satisfactory to thedepartment or agency head, that it willcomply with the requirements set forth in

thispolicy.

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 identifiedResearch, 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 HHSAdministration 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

§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 CodeKey PointsThe voluntary consent of the human subject

is absolutely essentialThe subject is at liberty to bring the

experiment to an endThe experiment should be designed to avoid

unnecessary physical and mental sufferingRisk should not exceed potential benefit

[extended to mean benefit to society or to the subject]

Tuskegee Study of Untreated Syphilis in the Negro Male1932 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 Male1972 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 Cases1959 Thalidomide1963 Brooklyn Jewish Chronic Disease

Hospital & Sloan-Kettering Cancer Research Institute

1971 Willowbrook Hepatitis Study1973 National Research Act1975 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 MassachusettsBoston Medical School – Dept of Psychiatry (2007)Patient switched before study submission to IRBResperidone “to qualify for consta study”Neuroleptic Malignant Syndrome - 8 day comaNo Guardian notice No Court approval (Rodgers plan)Physician license revokedDept. 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 CommunicationThe 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.

ConfidentialityThe 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 MassachusettsPsychiatry

Alberts v. Devine, 395 Mass. 59 (1985)Licensed Psychologists

M.G.L., c.112, sec. 129ALicensed Social Workers

M.G.L., c.112, sec. 135ADepartment of Mental Health

M.G.L., c.123, sec. 36

PrivilegeStatements 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 MassachusettsPsychotherapists

M.G.L., c.233, sec. 20BIncludes: psychiatrists, psychologists, licensed

psychiatric nurse clinical mental health specialists

Licensed social WorkersM.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 FormsNot a form, but a processKeep it simpleUse current formsAvoid just “cut & paste”OrganizeFind a naïve readerRead it aloudListen to subjects & consenting staff

Challenges to UMMS IRB 2009Anticipate increasing complexity with

translational researchMore phase I (first in human) trialsGene transfer trialsRNAi Novel devices and biologicsHuman 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 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 IRBInitiate accreditation process

Institutional Official : John Sullivan, MDInstitutional Oversight: Sheila Noone, Ph.D.

Seven Dwarfs

Pet PeevesLack of a research coordinator who knows

good clinical/research practices identified

Sponsor trying to dictate language

Missing information

Missing signatures

Pet PeevesCutting and pasting

Wrong forms

Page 11 of 9

Informed consent paragraph that suddenly end in the middle of…

Pet PeevesInconsistent information

Tables that don’t add up

Non-serious but frequent risks: death, renal failure

Draft applications

Web SitesUMMS 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 SitesMass 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+Regulations+and+Guidelines&sid=Eeohhs2

Fred Altaffer:(617)626-8125Fred.Altaffer@state.ma.us

Thank you

Questions?

Albert.GrudzinskasJr@umassmed.edu