Human Subjects Research 101

Revised January 2008

Presentation Goals Discuss Human Subjects Research

– Definitions

Historical Background Identify Ethical and Legal Requirements

– Belmont Report– 45 CFR 46 – “The Common Rule”

Describe Institutional Review Board– Structure & Policies

Implications For Student Research

Why Discuss Human Subjects Research?

Federal guidelines

Messiah College policy regarding all research involving human subjects

Preparation for graduate studies

What Is Human Subjects Research? – Part I

Federal definition of research

A systematic investigation, including

research development, testing, and

evaluation designed to develop or

contribute to generalizable knowledge.

What Is Human Subjects Research? – Part II

Federal definition of human subject

A living individual about whom an investigator (professional or student) conducting research obtains

Data through intervention or interaction with the individual, or

Identifiable private information.

Intervention includes both physical procedures by which data are gathered and manipulations of subject or subject’s environment that are performed for research purposes.

Interaction includes communication or interpersonal contact between investigator and subject.

Definitions Continued

Definitions Continued

Private information includes information about behavior that occurs in a context in which an individual can reasonably expect that no observation or recording is taking place, and information which has been provided for specific purposes by an individual and which the individual can reasonably expect will not be made public.

Historical Background

The Nuremberg Trial Trial of Nazi doctors who experimented

on 300 Dachau concentration camp prisoner-subjects, of whom 30% died.

Held from December 9, 1946 to August 20, 1947.

23 defendants charged with murder, torture, and other atrocities committed in the name of medical science. 15 found guilty.

Nuremberg Code - 1947 Written as part of the judgment of the

Nazi trials.

Became the “ethical yardstick” by which the defendants had been measured and guilt determined.

Essential reading for everybody involved in human subject research.

Principles of Nuremberg Code

Voluntary informed consent is essential

Research should yield useful results

Risk must be outweighed by importance of research

Base research on prior animal experiments

Avoid physical and mental suffering

Principles of Nuremberg Code(continued)

Only qualified scientists may conduct research

Subjects may withdraw from study

Investigators must be willing to withdraw subjects

No expectation of death or disabling injury

Effect of Nuremberg Code Code largely ignored until 1964

because researchers did not see the relevancy to their own work– Hippocratic oath

Missed a lot of important aspects of research– Children and informed consent– People with diminished mental capacity and

informed consent

Declaration of Helsinki - 1964

Rules developed by researchers and physicians

Reinterpretation of Nuremberg

Became required for publication in scientific journals to state that the research abided by the Declaration of Helsinki

Public Health Service Policy

1966: All PHS supported research must undergo prior review to:– Protect the rights and welfare of subjects

– Assure appropriate informed consent

– Determine acceptable risk/benefit balance

Beginnings of the IRB(Institutional Review Board)

Era of StandardsStandards accepted by researchersStandards accepted by the mediaStandards became the accepted

principles for judgment of research– Thalidomide Trial– Jewish Chronic Disease Study– Willowbrook Hepatitis Study– Hidden Recorder Studies– Milgram Study– Tuskegee Study

The Tuskegee Study Purpose: identify the natural history of

untreated syphilis Began in 1932 Involved 300 black males with syphilis 1933 – added 300 controls Was initially supposed to last 1 year Study stopped in March of 1973 after

government investigations and public pressure

Syphilis Study Problems Lack of respect for persons

– No informed consent– Deception– Coercion

Lack of good will to subjects– Withholding effective treatment (penicillin)– No continuing review of the research

Unjust– Used an extremely vulnerable population: illiterate,

poor farmers in rural Alabama

Response to Research Abuses 1974 – Congress passes the National

Research Act– Requirements for informed consent– Necessary review of research by IRB

May 1974 – First version of 45 CFR 46 April 1979 – The Belmont Report 1981 – Revision of 45 CFR 46 1991 – Common Rule: 56 FR 28003 2001 – Latest revision of 45 CFR 46

incorporates Common Rule

The Belmont Principles: How They Came About

1974 – establishment of the National Commission by the federal government

Task– “Identify basic ethical principles that underlie the

conduct of human research.”– Develop guidelines to ensure that human research

follows these principles

1979 – The Belmont Report: current set of federal regulations

The Belmont Principles

Respect for persons

Beneficence

Justice

Respect for Persons

Treat individual as autonomous agents

Do not use people as a means to an end

Allow people to choose for themselves

Give extra protection to those with limited autonomy and have an inability to choose for themselves

Beneficence Do no harm Prevent harm Prevent evil Promote good Maximize possible benefits and

minimize risk– Benefits to individual and/or to society

– Risk: consider physical, social, legal, economic, psychological

Justice Fair sharing of burdens and benefits of

research– Selection of subjects should not systematically

draw from certain classes simply because of their easy availability

– Inclusion of diverse populations/groups

– Subjects should have a future chance of benefiting personally from the subsequent applications of research findings

Rules Derived From Principles Respect for persons

– Informed Consent– Respect for privacy

• Confidentiality• Anonymity

Beneficence– Good research design– Competent investigators– Favorable risk/benefit analysis

Justice– Equitable selection of research subjects

Conflict in Belmont Principles Conflict is expected

– Sometimes decisions that are made utilizing the principles may yield different outcomes, depending on which principle is being considered: one decision is to approve the research, one to limit the research, one to deny the research

Remember: all 3 principles are on equal footing with equal moral force.– Consider each situation individually– Carefully review the principles– Avoid the tendency to always put one principle

above another

Code of Federal Regulations45 CFR 46

Title 45 of CFR Part 46

Codified by the government in 1991– Based on Belmont Principles, 56 FR 28003– Title 45: Public Welfare and Human Services– Part 46: Protection of Human Subjects

Last revised in November 2001

Supporting agencies– Department of Health & Human Services– National Institutes of Health– Office for Human Research Protections

Title 45 of CFR Part 46

Subpart A – Basic DHHS Policy for the Protection of Human Research Subjects

Subpart B – Pregnant Women, Human Fetuses and Neonates Involved in Research

Subpart C – Prisoners

Subpart D - Children

Institutional Review Board (IRB)

Institutional Review Board DHHS requirement for all human

subjects research sponsored by federal agencies

Regulations for IRB found in 45 CFR 46.107-123

IRB Structure Minimum of 5 members with varying

academic backgrounds

Every nondiscriminatory effort will be made to ensure diversity (e.g., race, gender, cultural)

One member who primary training is in nonscientific areas

One member whose primary training is in scientific areas

One member from the community

Primary Duties of IRB Protect human subjects from undue risk &

deprivation of human rights and dignity

Ensure confidentiality and voluntary participation of subjects

Balance potential benefits with risks

Determine appropriateness of research design & study methods

Assist researcher through peer review and institutional approval

Ensure research compliance with DHHS regulations & other funding agencies

Is Any Research Exempt From Review?

Yes, if the research involves no more

than minimal risk to subjects, no ethical

concerns, does not involve vulnerable

subjects, and meets at least one of the

exempt research categories established

by the government regulations. IRB

chair can make this determination.

Expedited Review Nine governmentally designated

research categories that allow for expedited review

Proposal distributed to all IRB members and all must agree on expedited review

Approval by one designated reviewer– Reviewer cannot disapprove research. Must go to

full IRB for rejection.

Decision reported to IRB at next meeting

Informed Consent

Informed Consent “Informed consent is a process of

information exchange that takes place between the prospective subject and the investigator, before, during, and sometimes after the study.” Dunn & Chadwick (1999), Protecting Study Volunteers in Research

Information Comprehension Voluntariness

Essential Basic Elements

Research– Purpose/Duration– Procedures– Experimental

Risks Benefits Alternatives Confidentiality

Compensation for injury

Whom to contact re:– Study, subject’s

rights, event of injury

Right to refuse or withdrawn

Additional Elements

Currently unforeseeable risks

Termination of participation

Additional costs to subjects

Consequence of withdrawal

Informing of new findings

Number of subjects

Other Considerations

There are situations where DHHS regulations allow for waiver of informed consent.

There are also situations where DHHS regulations allow for exception to providing written documentation of informed consent.

Informed Consent Process

Sufficient time to make decision

Sufficient opportunity to ask questions

Strategies to minimize coercion

Avoid overstating benefits

Ensure an understanding of risks/benefits

Be sensitive to subject’s needs

Informed Consent Process

Train individuals obtaining consent

Fully explain use of technology or innovative approaches

Make adjustments in process, as necessary

Obtain IRB approval for changes

Implications For Faculty and Student

Research

What Does This Mean For Me? MC policy applies only to research in certain cases;

determination can be made by IRB in consultation with IRB chair.

Approval must be obtained from the IRB prior to beginning research, including any research that will be disseminated beyond the classroom, including public presentations and publications.

Student projects that will not be disseminated beyond the classroom are considered course assignments and not subject to regulations.

However, all research must be done with due consideration of Messiah’s ethical and legal responsibility to protect subjects.

Research Likely Exempt From Review - #1

Educational tests (cognitive, diagnostic,

aptitude, achievement), survey

procedures, interview procedures, or

observation of public behavior, if

minimal risk, no correlation between

subjects/responses, and no vulnerable

population included. (Category #2)

Anonymous Versus Confidential

Anonymous: No way to trace responses to an individual person. Will not use any coding system or be able to trace responses to a person (e.g., ethnicity, gender, etc.)

Confidential: Can trace responses to an individual, even though this may not be revealed beyond the investigative team.

Research Likely Exempt From Review - #2

Research involving the collection or

study of existing data, documents,

records, or specimens if these sources

are publicly available or the information is

recorded in such a way that subjects

cannot be identified, indirectly or through

identifiers linked to the subjects. (Category

#4)

Research Likely Exempt From Review - #3

Taste and food quality evaluation and

consumer acceptance studies if

wholesome foods without additives are

consumed or food contains ingredients

approved by FDA, EPA, or USDA.

(Category #6)

If You Plan on Conducting a Research Study

Complete Form 100 – Request for Review of Faculty Project

If a student: Work with course professor to complete Form 050 – Request for Review of Student Project

Submit application and proposal to Provost’s Office, Box 3016.

If you have questions, contact Jenny Dose, IRB Chair (ext. 2320).