Human SubjectsResearch

created April, 2009

RCR – Human SubjectsRCR – Human Subjects

• Short pre-test• Presentation Objectives

• NIH Comment• background• regulation, policy and Federal Assurance• considerations• SIT institutional processes involved in animal research • ethical considerations • available resources

• Reference Material• Faculty Presentation• Case Study and Discussion• Short post-test

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RCR – Human SubjectsRCR – Human Subjects

“Investigators must balance their interest in gathering data and answering research questions with society’s mandate to protect the rights and safeguard the welfare of research subjects.” (1)

National Institutes of Health

“Society has granted a conditional privilege to perform research on human beings……the condition is that it must be conducted in a way that puts the rights and welfare of human subjects first.” (1)

National Institute of Health

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RCR – Human SubjectsRCR – Human Subjectscreated April, 2009

• Nuremberg Code of 1947 (2)

result of medical experiments performed in German concentration camps during World War II. “…The great weight of evidence before us it to the effect that certain types of medical experiments…conform to the ethics of the medical profession generally…however…certain basic principles must be observed in order to satisfy moral, ethical and legal concepts…”

• Declaration of Helsinki adopted in 1964 (3)

adopted by World Medical Association and forms the basis of most subsequent documents addressing human subjects research. Introduced concept of oversight by an ‘independent committee’ which became a system of Institutional Review Boards • Belmont Report (4)

culmination of the work a national commission began in 1974. It was adopted by NIH in its entirety.

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Stevens’ Federal Wide Assurance with National Institutes of Health, Office for Human Research Protections (NIH OHRP) – FWA00014433

Stevens’ Institutional Policy “Human Subjects/IRB”

created April, 2009

45 CFR 46 – Protection of Human Subjects

-- http://www.hhs.gov/ohrp/documents/OHRPRegulations.pdf (5)

Stevens’ IRB Registration with NIH/OHRP – IORG0004982

RCR – Human SubjectsRCR – Human Subjectscreated April, 2009

The three most often cited concepts associated with human subjects research are:• Autonomy

• Beneficence

• Justice

RCR – Human SubjectsRCR – Human Subjectscreated April, 2009

AUTONOMY (voluntary informed consent)

> Controversy in Berlin Led to Ethical Code & Inf. Consent• Dr. Albert Neisser “treated” Berlin prostitutes without their knowledge using serum from recovering syphilis patients in the belief he was discovering a cure• Caused epidemic of syphilis among prostitutes & their customers.• Rudolf Virchow recommended code for research with humans to prevent future breaches of ethics.

> Berlin Code of 29 Dec 1900 • Required unambiguous consent• Required study be conducted or directed by the institute medical director • Excluded use of minors or incompetent subjects • Req. documentation of fulfillment of code requirements in subjects records • Did not interfere with standard diagnostics, care and prophylaxis

(Slide information taken from “Time Passages: Local Military Medical History Connections” Art Anderson MD, Office of Human

Use and Ethics, USAMRID) (6)

RCR – Human SubjectsRCR – Human Subjectscreated April, 2009

BENEFICENCE (good science & favorable benefit to risk ratio)

> 1777 Variolation* of the Troops Helped Win the Revolutionary War • George Washington's experiences during the French and Indian War convinced him that Smallpox was a bar to success of the Revolution• Washington proclaimed smallpox to be his ““most dangerous foe;””and, by 1777 he had all his soldiers variolated• He also ordered all new recruits to be variolated as soon as they enlisted• Fortunately, in this case, the ends of these actions did justify the means

(Slide information taken from “Time Passages: Local Military Medical History Connections” Art Anderson MD, Office of Human Use and

Ethics, USAMRID) (6)

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JUSTICE (7)

(equal opportunity to participate and to not participate)

> “Tuskegee Study of Untreated Syphilis in the Negro Male”

• study conducted by the Public Health Service between 1932-1972• human subjects were 399 poor, mostly illiterate, African American sharecroppers • study for research related to the natural progression of the disease if left untreated• researchers failed to treat patients appropriately after 1940s validation of penicillin as effective cure for syphilis• participants were prevented from accessing syphilis treatment programs available to other people in the area• a leak to the press in 1972 resulted in its termination

RCR – Human SubjectsRCR – Human Subjects

Often, human subjects research is done in conjunction with a sponsored research project. Proposals for sponsored projects should be submitted to the Faculty Support Center

Protocols for human subjects research as part of a sponsored project are separate activities. Human subjects protocols should be submitted to the IRB

Investigator must initiate and submit the human subjects research protocol to the IRB – understanding sponsor requirements for approvals and proposal deadlines

Funding for sponsored projects involving the use of human subjects WILL NOT be enabled until IRB approval is received and verified in OSR

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NIH, the most common federal agency to which PI’s would submit research proposals that might include human subjects typically has three submission cycles each year. The timeline shown below is offered to help with planning the preparation and submission of various required materials:

EARLIEST FUNDING Cycle 1 Cycle 2 Cycle 3 Dec. April July

PROPOSAL SUBMISSIONCycle 1 Cycle 2 Cycle 3Feb. 5 June 5 Oct. 5

PROPOSAL SUBMISSIONCycle 1 Cycle2 Cycle 3Feb 5 June 5 Oct 5

PEER REVIEW Cycle 1 Cycle 2 Cycle 3 Jun-Jul Oct-Nov Feb-Mar

COUNCIL REVIEWCycle 1 Cycle 2 Cycle 3Sep-Oct Jan-Feb May-Jun

Feb. 5 Proposal

Deadline = mid January

FSC Deadline

Sep-Oct Council Review = full SIT

IRB approval submitted for JIT

Mar-Apr = protocol

submitted to SIT IRB

SIT IRB review process

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• Be aware of the need for Institutional Review Board review and approval-- ‘exempt’ is a category, it does not imply an investigator is ‘exempt’ from the application process

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(8)

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• Office of Sponsored Research• Can provide assistance and direction for investigators

contemplating animal research• 201.216.8762 – Barbara DeHaven, Executive Director

• Institutional Review Board• Duly constituted committee at Stevens charged with

the review and approval of all human subjects research done at the Institute

• 201.216.5032 – Dr. Zvi Aronson, IRB Chair

• Office of Institutional Risk, Compliance and Audit• Chuck Shaw – 3rd Floor Howe Center – 201.216.8568

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1. “Guidelines for the Conduct of Research Involving Human Subjects at the National Institute of Health” http://ohsr.od.nih.gov/guidelines/GrayBooklet82404.pdf

2. “Nuremberg Code of 1947” http://www.hhs.gov/ohrp/references/nurcode.htm

3. “The Helsinki Declaration” http://www.cirp.org/library/ethics/helsinki/

4. “The Belmont Report” http://ohrp.osophs.dhhs.gov/humansubjects/guidance/Belmont.htm

5. “45 CFR 46 http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm

6. “Time Passages: Local Military Medical History Connections” Art Anderson MD, Office of Human Use and Ethics, USAMRID)

http://www.geocities.com/artandersonmd/med_history.pdf

7. “The Tuskegee Study of Untreated Syphilis in the Negro Male”

http://en.wikipedia.org/wiki/Tuskegee_Study_of_Untreated_Syphilis_in_the_Negro_Male

8. www.cartoonstock.com

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RCR – Human SubjectsRCR – Human Subjects

Dr. Peter Dominick - Asst. Professor, Howe

School of Technology

Management

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@ P. Dominick, 2009

Academic Zvi Aronson, Ph.D. Industrial/Organizational Psychology Peter Dominick, Ph.D. Industrial/Organizational

Psychology Patricia Holahan, Ph.D.

Organizational behavior Ann Mooney, Ph.D.

Organizational behavior Medical and Mental Health

Glen Atlas, M.D. Anesthesiologist at UMDNJ Terence Hannigan, Ph.D. Clinical Psychologist Vincent Grasso M.D.

@ P. Dominick, 2009

Twelve Submissions in the past two years Ten accepted with no or minimal revisions Two were rejected each after two rounds of

review

@ P. Dominick, 2009

Any studies that will involve human subjects Medical and biomedical Social sciences

Psychology Sociology Anthropology Ethics

Management practices Computer science Some studies in biology and chemistry

@ P. Dominick, 2009

Subjects ostensibly assigned to be “learners” or “teachers”

“Teachers” must administer shocks to “learners” each time they make a mistake “Learners” and “teachers” located in

different rooms Shocks are painful but not harmful “teachers” will hear “learners” react to the

pain

@ P. Dominick, 2009

What concerns would you have? Who do you think might be harmed by

this research? What questions would you ask of the

researcher? Would you reject it? Might you seek to modify the

experiment?

@ P. Dominick, 2009

Original Studies made profound contributions to Social Psychology 68 percent of “teachers” complied with

experimenters instructions and administered 450 volt shocks repeatedly

Also considered the paradigmatic example of why psychology experiments must be reviewed by IRB’s

Many said they “would never be replicated”

@ P. Dominick, 2009

Studies were replicated in 2006 Stopped at 150 volts instead of 450 volts Immediate feedback to participants 15 volt “test shock” Two step screening process to ensure participants could handle

the experience “Of course, I also needed IRB approval. I knew from my own

participation on the IRB that the proposal would be met with concern and perhaps a little fear by the board’s members. . . . To address these concerns, I created a list of individuals who were experts on Milgram’s studies and the ethical questions surrounding this research. I offered to make this list available to the IRB. More important, Steven Breckler, a social psychologist who currently serves as the executive director for science at the American Psychological Association, graciously provided an assessment of the proposal’s ethical issues that I shared with the IRB. “ Jerry Burger

@ P. Dominick, 2009

Instructional strategies conducted in established or commonly accepted educational settings

The use of educational tests (cognitive, diagnostic, aptitude, achievement), survey procedures, interview procedures or observation of public behavior

Collection or study of existing data, documents, records, pathological specimens, or diagnostic specimens, if sources are publicly available, or if the information is recorded with complete anonymity

Taste and food quality evaluation and consumer acceptance studies, if: wholesome foods without additives food that contains an ingredient that is found to be safe agricultural chemical or environmental contaminant at or

below the level FDA, EPA and or the Food Safety and Inspection Service of the U.S.D.A. deems to be safe

@ P. Dominick, 2009

Collection of hair and nail samples Collection of excreta and external secretions Recording of data from subject 18 years of age

or older using noninvasive procedures Collection of blood samples in minimal amounts Collection of dental plaque and calculus Voice recording Moderate exercise by health volunteers Study of existing data Research on an individual or group behavior

that involves no manipulation of the subjects and is not stressful

@ P. Dominick, 2009

Most research that involves children, prisoners, pregnant women, fetuses and other vulnerable populations

Research that involves experimental drugs or devices

Research that involves most invasive procedures

Survey research that involves sensitive questions or is likely to be stressful for the subject

@ P. Dominick, 2009

Contact Zvi Aronson if engaging in any research that involves human subjects Confidentiality form (Anonymity) Consent Form (Justice) Rationale Form (Beneficence)

Brief descriptions of ( usually just a few paragraphs) key research question types of participants sought experimental procedures/protocol (including any

deception) procedures for ensuring confidentiality and subject

well-being Procedures for attaining consent

@ P. Dominick, 2009

Autonomy Will people have the opportunity to opt in or out of my

research? Are those involved capable of making an informed decision

about participation? Beneficence

What are the major benefits to be derived from my research? How do they compare to any risks? In what ways might people better off because of my study?

Subjects General population?

Are there other less invasive ways to learn the same things? Justice

Is this study fair to those who are involved? Will it deny them other opportunities that may be of benefit to

them? How might they be affected or changed as a result of their

experience?

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Bob is working hard to complete his Master’s degree in the Psychology Department’s program of Research and Related Ethics through the Institute for Social and Humane Ethics at Prestigious University. His thesis focuses on the residual effects of severe psychological trauma throughout a lifetime. Specifically, he’s chosen to focus on Holocaust survivors from World War II. He’s gotten into a significant time crunch as the literature review took longer than anticipated and he had an unexpected family emergency during that same time. He needs interviews with survivors in order to make his data credible but knows he needs to submit a protocol to his institutional IRB for review and approval. That will add an additional two months (minimum) to his timeline that he frankly doesn’t have. Bob is sensitive to his research population and he’ll be careful. He really needs the interview data and decides to go ahead without submitting the protocol for review. Since he’s doing the interviews without IRB approval he decides he doesn’t need to be concerned about the informed consent.

Consider the following:created April, 2009

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Q: Who will, or might be affected by Bob’s decision to forego the required IRB application, review and approval process?

A: -- The Holocaust survivors-- Bob-- The Institute for Social and Humane Ethics-- Prestigious University

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Q: What are the possible consequences of Bob’s decision not to observe the requirement for protocol application, review and approval?A: The Holocaust survivors could definitely be affected as recalling memories of such experiences could be severely distressing, cause panic, or even result in an adverse medical event for this extremely aged population

Bob will be affected if it is discovered that he has violated one of the integral tenets of human subjects research. His degree could be in jeopardy and he would be disgraced. There is a likelihood that none of his data would be accepted in support of the thesis.

Lastly, the Institute for Social and Humane Ethics would probably be embarrassed……at a minimum

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Q: Are there any laws, regulations, or institutional policies that may apply to this situation?

A: -- The Nuremberg Code-- The Helsinki Declaration-- The Belmont Report-- 45 CFR 46-- Prestigious University’s Policy on the inclusion of human

subjects in research -- Code of professional ethics of the American Psychological

Association

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Q: If Bob had submitted the protocol for review as required, what items might the IRB have been concerned with?

A: -- Informed Consent* IRB would have wanted adequate description of the

benefits and risks for this population* IRB would have wanted a warning that some of the

questions might cause distress and that subjects could stop at any time

* IRB would have wanted to ensure Bob had planned for the possibility that recalling the subject matter content for some of the subjects might even result in an adverse medical event and what were his plans if that happened

* IRB would have required Bob to include resources for subjects who might need psychological assistance as the result of

recallingrepressed memories

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created April, 2009