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RESPONSIBLE RESEARCH CONDUCT

Human Research Education Program

FOR YESHIVA UNIVERSITY FACULTY

Federal and Institutional Requirements

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RESPONSIBLE RESEARCH CONDUCT

Presented by staff of the

Albert Einstein College of Medicine Committee on Clinical Investigations of

Yeshiva University

Chester M. Edelmann, Jr., M.D., Chair

Patricia Hopkins, Manager

Barbara Levy, Assistant Dean

for Academic Affairs

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HISTORICAL BACKGROUND

Three events that have had significant impact on federal regulations for the protection of human research subjects:

1. 1946 Nuremberg Trial.2. 1960s Thalidomide Tragedy.3. 1972 Tuskegee Syphilis Study Expose.

Started in 1932 – stopped in 19731979 BELMONT REPORT – cornerstoneStatement of ethical principles upon which the federal regulations for the protection of human subjects are based.

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NURENBERG CODE &DECLARATION OF HELSINKI

The NURENBERG CODE is the ‘ethical yardstick’ by which the defendants of the Nazi Doctors Trial were measured and guilt determined. (1947)

DECLARATION OF HELSINKI was drafted in 1952 by the World Medical Association and first issued in 1964. It expanded the Nuremberg Code requirements.

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THE BELMONT REPORT

In 1974 Congress passed the National Research Act which created the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research.

This Commission wrote the ethical principles and guidelines, known as the BELMONT REPORT which was published in the Federal Register in 1979.

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WHAT CONSTITUTES RESEARCH?

The following definition of research is found in the Code of Federal Regulations 45 CFR 46.102 (e): “Research means a systematic investigation including research development, testing and evaluation, designed to develop or contribute to generalizable knowledge.”

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BEHAVORIAL RESEARCH

Includes:

Human behavior

Social Science

Educational Practices/Tests

Epidemiology

Historical

Similar Areas

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ORAL HISTORY RESEARCH

The October 21, 2003 report from Chronicle of Higher Education states -

The Office for Human Research Protections issued the decision in a letter to representatives of the American Historical Association and the Oral History Association,

That oral-history interviews generally are not designed to contribute to generalizable knowledge and, therefore, do not require IRB review.

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BASIC ETHICAL PRINCIPLES

The Belmont Report contains the ethical principles upon which the federal regulations for protection of human subjects are based:

1. RESPECT FOR PERSONS

2. BENEFICENCE

3. JUSTICE

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RESPECT FOR PERSONS

Incorporates two ethical convictions: Individuals should be treated as autonomous agents, and Persons with diminished autonomy are entitled to

increased protections.

Includes two separate moral requirements:

To acknowledge autonomy. To protect those with diminished autonomy.

This principle is captured in the consent process.

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DIMINISHED AUTONOMY

Vulnerable populations include some individuals who have limited autonomy such that they cannot fully participate in the consent process, e.g. prisoners, children, some mentally disabled, and individuals with dementia and other cognitive disorders.

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BENEFICENCE

DO NO HARM.MAXIMIZE POSSIBLE BENEFITS AND MINIMIZE RISKS.

The obligations of beneficence affect both individuals and society.

The principle of beneficence is in the assessment of risks and benefits.

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BENEFICENCEPsychological/Social Risks

May be as harmful as any risk faced by a subject in a medical study.Temporary anxiety and distress to relapse and/or precipitation of behavioral disorders.Embarrassment, ostracism, stigmatization, etc.Job loss, decreased employability or insurability.Arrest, prosecution and civil or criminal liability.Impact on others including families, social groups, communities, etc.

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JUSTICE

The principle of justice is captured in the selection of research subjects. The selection of subjects should be drawn from all classes of the population.Justice demands that research should not unduly involve persons from groups unlikely to be among the beneficiaries of subsequent benefits of the research.A scientific justification is required when excluding men, women, pregnant women, minors and non English-speaking participants.

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RESPECT FOR PERSONS

Informed consent is a process, an information exchange, a dialogue, that takes place between the prospective subject and the investigator, before, during and sometimes after the study.

Freely given informed consent must be obtained from every volunteer before any research procedures have begun.

Only Key Personnel knowledgeable about the protocol may conduct the consent process.

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INFORMED CONSENT PROCESS

The consent process can be analyzed as containing three components:

Information

Comprehension

Voluntariness

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INFORMED CONSENT

INFORMATIONResearch volunteers are to be given sufficient

information. These items include:

1. Purpose

2. Procedures

3. Risks

4. Benefits

5. Alternatives

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INFORMED CONSENT

COMPREHENSIONThe manner and context in which information is conveyed

is as important as the information.

Information should be: a. Organized.

b. In simple lay terms and at an 8th grade level. c. Provided slowly and clearly, permitting time for

questions and answers.

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INFORMED CONSENT

VOLUNTARINESS:

a. An agreement to participate in research constitutes a valid consent only if voluntarily given.

b. Consent must be free of coercion and undue influence.

c. Volunteers must be told that they are free to decline participation and to withdraw from the study at any time after it has begun.

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CONFIDENTIALITY

Federal regulations and CCI policy require that: Confidentiality be ensured. The steps taken by the researcher to ensure the confidentiality of the participant and the research data are discussed in the the consent process and included in the consent document. E.g., research records may be coded, kept in a locked file cabinet, etc.

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CONFIDENTIALITY

The Health Insurance Portability & Accountability Act (HIPAA) provides another layer of protection for protected health information(PHI).

Information is found at http://www.aecom.yu.edu/home/cci/hipaa.htm#help

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WRITTEN AND ORAL CONSENT

Behavioral Consent templates are found at http://www.aecom.yu.edu/home/cci/forms.htm#consent_behav

Oral consent is permitted provided regulatory criteria are met and all the elements of written consent are included. CCI approval of the oral script is required.

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ALTERNATE CONSENT MECHANISM

Under certain circumstances, e.g., school based research, the investigator may consider an alternate consent mechanism.

‘Opt Out’ example: Parents are informed of the study and given an opportunity to inform the school and/or the researcher that they do not want their child to participate.

Written permission from the student is required.

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WAIVER OF INFORMED CONSENT

• Waiver of informed consent, or waiver of documentation of informed consent, is permitted under the regulations in certain circumstances, and requires CCI approval.

• A ‘Waiver Form’ is included in the CCI Research Application and contains the waiver criteria defined under federal regulations and CCI policy.

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DECEPTION

Intentionally misleads subjects, or withholds full information about the nature of the research.

Interferes with the participant’s ability to give informed consent.

Permitted under federal regulations when it is arguably necessary and full knowledge would bias the study results.

REQUIRES FULL COMMITTEE REVIEW.

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RESEARCH INVOLVING MINORS

Under NY State law and federal regulations:

a. Parental permission is required to enroll minors 17 years of age and younger in research.

b. Exceptions are permitted as defined in the ‘Minor’s Policy’.

c. Permission of minors ages 7 to 17, capable of understanding, is also required.

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RESEARCH INVOLVING MINORS

Respect for young adults (13–17) requires the consent to be addressed to the minor, with permission from the parent. Both the minor and the parent sign the consent.

The ‘Minor’s’ Policy is found at http://www.aecom.yu.edu/home/cci/enrollment_of_minors_in_research.htm

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SCHOOL BASED RESEARCH

Research conducted in NYC Public Schools requires the approval of:

NYC Office of Educational Research.

The School Principal.

District Superintendent (on an ad hoc basis).

Research conducted in other NYS counties requires the approval of:

The School District Superintendent

The School Principal.

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SCHOOL BASED RESEARCH

Other approvals as required by the School Districts must be met.

Research CANNOT begin at the school until the required approvals have been obtained and provided to the CCI.

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THIRD PARTY PERMISSION & PARTICIPANTS WITH DIMINISHED

CAPACITY

Third Party Permission: Those authorized by law to act on behalf of a another may enroll a participant in research. Diminished Capacity:Participants with diminished capacity may be enrolled in research using a ‘Simplified Consent’ plus permission from the family member.

Consultation with YU legal counsel is required. John Scarfone, Esq., email: scarfone@yu.edu

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WHAT IS AN IRB?

An Institutional Review Board is a body of members appointed by institutional officials to review research and determine if the rights and welfare of human subjects involved in research are adequately protected. Institutions accepting federal support for human research operate under a federally designated IRB, requiring compliance with federal regulations.

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WHAT IS THE IRB’S AUTHORITY?

The IRB has the authority to:a. approve, b. require modifications, orc. disapprove research activities, including proposed changes in previously approved research. d. The IRB also has the authority to stop the research.

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YESHIVA UNIVERSITY IRB

The Yeshiva University IRB is known as the Committee on Clinical Investigations (CCI).

The Committee receives it authority from the FDA and the Department of Health and Human Services (HHS), and operates under a Federal Wide Assurance (FWA 00000140) through the DHHS Office for Human Research Protections under the Code of Federal Regulations 45 CFR 46, and FDA 21 CFR 50 and 56.

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CCI JURISDICTION

The Committee on Clinical Investigations (CCI) is the Institutional Review Board (IRB) of record for:

• Yeshiva University, and is responsible for the review, approval and monitoring of all human research at:

– All AECOM programs (e.g., Sound View Throggs Neck, Substance Abuse Program, Cancer Center, CERC, etc.)

– All YU Schools: Wurzweiler, Ferkauf, Stern, etc.

• The North Bronx Health Network (Jacobi Medical Center and The North Central Bronx Hospital)

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CCI MANDATE

The Primary mandate of the CCI is to ensure:

•That the rights and dignity of subjects are protected.

• That any risk entailed by the research is outweighed by the potential benefit.

• The protection of the researcher(s), the institution and the reputation of science.

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HOW TO DISCERN IF IRB REVIEW IS REQUIRED

IRB review is required when the research involves human subjects. The regulations define:

A ‘human subject’ as a living individual about whom an investigator obtains:

- either data through intervention or interaction with the individual, or

- through identifiable private information.

This includes research using surveys, data analysis, school based research, human tissue specimens, etc.

NOTE: CCI extends the definition to include decedent research.

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WHAT MUST AN IRB CONSIDER?

The IRB must consider:

The risks to subjects.

The anticipated benefits to the subjects and others.

The importance of the knowledge that may reasonably result.

The informed consent process/document.

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INITIAL APPROVAL AND ON-GOING MONITORING

The CCI is responsible for the initial review, approval and on-going monitoring of all human research until its completion. This includes:

Amendments (changes to a protocol).

Review of adverse events.

Progress Reports - Re-review is required not more than 365 days from initial and continuing review. All research must be recertified.

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WHO MAY BE PRINCIPAL INVESTIGATOR?

The Principal Investigator must have a faculty appointment to the applicable Yeshiva University School.Exceptions require approval by the Dean of the YU School and the Associate Vice President of Academic Affairs.All PIs and Key Personnel (including students) must complete the CITI Education Program. Information and registration are found at http://www.aecom.yu.edu/home/cci/citi_human_subjects_research_educational_module.htm

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YU STUDENT RESEARCH

Research conducted by YU students requires review and approval, or verification of exemption by the CCI. Student’s faculty mentor must be the Principal Investigator, and take full responsibility for the development and ongoing monitoring of the study.

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YU STUDENTS AS RESEARCH PARTICIPANTS

Considerations If course credit is given for participation, alternatives must be offered for receiving equal credit that are no more burdensome than the research participation.Policies regarding course-related research participation must be clearly understood.Incentives for participation may not be unduly influencing.Student subjects must have the ability to decline participation.Confidentiality must be maintained for self-disclosures of personal nature.

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YU STUDENT RESEARCH PROTOCOLS

For student protocols, consider the following:Is the faculty mentor (Principal Investigator) knowledgeable about the CCI human subject protection requirements to adequately guide the student, e.g., protocol elements, valid study design, inclusion and exclusion criteria, consent process, submission and monitoring requirements, etc.?

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YU STUDENT RESEARCH PROTOCOLS

Is there an adequate window of opportunity for the student to complete the following within the allotted time? develop a protocol, obtain required approval from the CCI and other

applicable collaborative sites, take the required CITI education program, complete the project.

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CONSENT TO PUBLISH STUDENT’S WRITING

Students are required to participate in the course curriculum. However, their course writings may be used for research. Generally ‘Exempt’ Research. Voluntariness must be ensured. Faculty are required

to follow the ethical guidelines of the profession. Refer to: http://www.ncte.org/about/over/positions/level/coll/107670.htm

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KEY PERSONNEL

Key Personnel is defined as any person who meaningfully contributes in a substantive way to the scientific development or execution of the project, or the informed consent process.

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REQUIRED EDUCATION

The Principal Investigator and Key Personnel are required to complete the web-based tutorial: “Collaborative IRB Training Initiative (CITI) Human Subjects Research Module” found at http://www.aecom.yu.edu/home/cci/citi_human_subjects_research_educational_module.htm

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ANCILLARY EDUCATION

CCI Fall 2004 Administrative Education Seminar Series held at AECOM. The schedule is found at http://www.aecom.yu.edu/home/cci/seminars.htm

The Wurzweiler Fall 2004 Education Power Point Presentation is found at http://www.aecom.yu.edu/home/cci/education/background_wurz.pps

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CATEGORIES OF REVIEW AND SUBMISSION REQUIREMENTS

CATEGORY OF REVIEW

CCI FORMSUBMISSION

DATE

Exempt Exempt Form Submit at any time

ExpeditedCCI Research Application

Submit at any time

FullCCI Research

Application

Must be submitted by required

deadline

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WURZWEILER ADMINISTRATIVE APPROVAL REQUIREMENTS

The CCI Research Application including all applicable documents, e.g., detailed protocol, informed consent, measures, recruitment letters, advertisements, etc. must be reviewed and approved in the following order by:

1. Principal Investigator (Faculty Mentor)

2. Doctoral Program Director

3. Dean

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IRB/ADMINISTRATIVE APPROVALFROM COLLABORATING SITES

Collaborating institution IRB approval is required.

In instances where there is no IRB, e.g., private clinics, private schools, etc., written approval from the senior administrator is required on institution letterhead.

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CCI WEB PAGE

• www.aecom.yu.edu/home/cci/

• New CCI Research Applications with Help Text

• CCI Policies and Procedures

• Informed Consent Templates with Help Text

• All Monitoring Forms, e.g., Amendment, Progress Report, Adverse Event Report

• Educational Materials and web link

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PROTOCOL APPLICATION AND TRACKING SYSTEM (PATS)

New computerized system for the electronic submission and tracking of protocols from any internet compatible computer worldwide.

Error checking and consent form development/dating are electronically maintained by the system and are available to researchers at all time.

Conversion and education is underway.

The system requires Internet Explorer version 6.0 (or higher). Software requirements are not capable with Macintosh machines.

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URL LINKS

Belmont Report: http://ohrp.osophs.dhhs.gov/humansubjects/guidance/belmont.htm.

HHS Code of Federal Regulations 45 CFR 46: http://www.med.umich.edu/irbmed/FederalDocuments/hhs/HHS45CFR46.html.

Ethical Guidelines of the Profession: http://www.ncte.org/about/over/positions/level/coll/107670.htm.

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BEHAVIORAL RESEARCH and the RISK/BENEFIT RATIO

Evaluation of risks is less clear than in biomedical research.

What is emotional discomfort? How reversible is it? What are long-term consequences?

Usually there is no individual benefit for participants.

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PSYCHOLOGICAL and SOCIAL RISKS

DepressionAltered self-conceptIncreased anxietyDecreased confidence in othersGuilt, shame, fear, embarrassmentBoredom, frustration, inconvenienceReceiving information about oneself that is unpleasant

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CONFIDENTIALITY

When data requested is sensitive, assurance of confidentiality may actually decrease willingness to participate.

The effect of privacy and confidentiality concerns differs among various racial and ethnic groups.

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EMOTIONAL DISTRESS

Recall and discussion of a traumatic event may result in re-traumatization of the individual.

It is difficult to assess frequency and magnitude of this effect.

Nevertheless, studies on violence and trauma may provide benefit to participants.

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SOCIAL RISKS

An HIV vaccine trial led to some uninfected individuals becoming positive on HIV testing, with adverse social consequences.

Identifying the prevalence of drug abuse or child abuse in a given population can stigmatize the entire population, not just those with drug abuse.

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OTHER RISKS

There may be embarrassment when others are made privy to personal information, such as in group data collection.

There are no data on the potential long-term consequences for individual participants who may be sensitive to social evaluation.

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RISK/BENEFIT EVALUATION

Provide all available information on potential risks and benefits.

Analyze the probability, magnitude, and harm associated with each risk.

Consider alternative procedures with less risk.

Ensure risks are clear to potential participants.

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RISK/BENEFIT EVALUATION

Don’t overestimate benefits.

Evaluate risk against potential benefits.

Consider potential long-term effects of the information gained from the research.

Be aware of the difficulties in estimating risks.