Human Subjects Research

Mariam Davtyan, MPHUC Irvine

Department of Population Health & Disease PreventionProgram in Public Health

PhD Candidate/IRB Member & Ambassador04.29.2015

What is Research?• A systematic investigation,

including research development,

testing and evaluation, designed

to develop or contribute to

generalizable knowledge

• Definition applies to quantitative

research studies

• May need to be enhanced for

qualitative research protocols

Source: US Department of Health & Human Services, Code of Federal Regulations (45CFR 46.102)

Definition of Human Subject

• 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

Source: US Department of Health & Human Services, Code of Federal Regulations (45CFR 46.102)

Unethical Human Experimentation

• Nazi medical experiments (1939-

1945)

• Tuskegee Syphilis Study (1932-1972)

• Willowbrook Study (1963-1966)

• Milgram “electric shock” experiments

(1961)

• Stanford Prison Experiment (1971)

• U. Penn gene therapy study (1999)

Source: http://www.niehs.nih.gov/research/resources/bioethics/timeline/

• National Research Act (1974)

• Development of guidelines for human subjects research

• Regulation of human experimentation in medicine

• Title 45 Code of Federal Regulations Part 46

• Research conducted, supported, or otherwise subject to regulation by any

federal department or agency

• Policies pertaining to human subjects research for investigators and IRBs

• Declaration of Helsinki (1964)

• Medical research involving human subjects

• Protect health/welfare, sound design, respect, appropriate qualifications,

expectation of some benefit

• Nuremberg Code (1948)

"The voluntary consent of the human participant is absolutely essential"

Pertinent Laws & Regulations

Source: http://history.nih.gov/about/timelines_laws_human.html

Ethical Principles in Human Research

• Belmont Report (1979):

– Respect

• Understanding the study

• Making an autonomous decision to participate or not

• Those with diminished autonomy require special

protection

– Beneficence

• Expectation of benefit in research

• Minimizing risk

• Sound experimental design and rigorous review by IRBs

– Justice

• Equitable selection of participants

• Protecting vulnerable groups (ex. prisoners, children,

mentally ill) from coercion Source: http://videocast.nih.gov/pdf/ohrp_appendix_belmont_report_vol_2.pdf

Case #1

• An instructor wants to have

all students in a class

interview each other to

practice interviewing skills.

The results will not be written

up or distributed outside the

classroom in any way.

– Is this research?

• You will be analyzing data

from an existing dataset on

the dietary habits of elderly

individuals living in the

Southern US. The dataset

does not contain any personal

identifiers?

• Human subjects research?

• IRB approval ?

Case #2

Defining Risk & Benefit

• Risk: 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

• Benefit: A valued or desired outcome; an advantage

Sources: US Department of Health & Human Services, Code of Federal Regulations (45CFR 46.102(i)http://www.research.uci.edu/compliance/human-research-protections/irb-members/assessing-risks-and-benefits.html#assessment

Risk/Benefit Assessment

• Identify risks associated with research

• Assure that the risks will be minimized to

the extent possible

• Identify benefits to be derived from the

research

• Assure that the risks are reasonable in

relation to benefits to subjects

• Make certain that prospective subjects

will be provided with an accurate

description of study risks and benefits

during consent processSources: http://www.research.uci.edu/compliance/human-research-protections/irb-members/assessing-risks-and-benefits.html

Types of Risks & Benefits

Benefits:

• Personal

• Societal

Risks:

• Physical

• Psychological

• Invasion of Privacy

• Social & Economic

• Community

Sources: http://www.research.uci.edu/compliance/human-research-protections/irb-members/assessing-risks-and-benefits.html

Minimizing Risks

• Provide information on experimental design and the

scientific rationale

• Assemble a research team expertise and experience

• Determine if sample size is sufficient to yield useful results

• Collect data from standard-of-care procedures to avoid

unnecessary risk

• Appropriate data safety monitoring plan, trained

personnel, and procedures to protect the confidentiality

of the data (e.g. encryption, codes, and passwords).

Sources: http://www.research.uci.edu/compliance/human-research-protections/irb-members/assessing-risks-and-benefits.html

• Stigma is a significant stressor for

people living with HIV and often leads to

poor health outcomes. In your study,

you will be interviewing people living

with HIV and asking them to share their

experiences with Stigma. You will also

look at their medical charts and abstract

information about drug use and mental

health pathologies.”– Potential Risks? Benefits?

– Strategies for minimizing risks?

Case #3

• Based on concepts of Autonomy,

Beneficence, Justice

• More than a signature

• Process by which researchers inform

potential participants about all aspects of

research

• Prospective participants not subjected to

undue influence, fraud, duress, and

coercion

• Prospective participants agree to

participate voluntarily and with informed

choice

• Your duty as researchers to protect and

inform

Informed Consent

• Full Disclosure

– Inform about all study constructs

– Risks/Benefits

– Alternatives to participation

• Understanding

– Must understand what is being explained

– Lay Language

– Translated to other languages

• Voluntariness

– Voluntary

– Withdrawal at any point

• Competence: prospective participant must be competent to provide consent

• Consent: signature or verbal understanding

• Exculpatory Language:

– Consent must be free of language by which participant waives legal rights or releases

investigator from liability for negligence

Components of Appropriate Informed Consent

Case #4

• After having completed a study that

involved the collection of tissue from

the subjects, an investigator wishes

to perform additional analysis of the

archived tissue samples. This nature

of this analysis was not explicitly

stated in the original consent form.

• Should the investigator be required to

obtain explicit consent for the new

research?

Source: https://depts.washington.edu/bioethx/topics/resrchc3.html

• Privacy:

– About people

– A sense of being in control of access that others

have to ourselves

– A right to be protected

– Is in the eye of the participant, not the researcher

or the IRB

• Confidentiality:

– Is about identifiable data

– Is an extension of privacy

– Is an agreement about maintenance and who has

access to identifiable data

– In regards to HIPAA, protects patients from

inappropriate disclosures of "Protected Health

Information" (PHI)

Privacy & Confidentiality

Source: http://www.research.uci.edu/compliance/human-research-protections/researchers/privacy-and-confidentiality.html

Ethics Committees & IRBs

• Appropriately constituted group designated to review

and monitor research involving human subjects

• IRB has the authority to:

– approve

– require modifications in (to secure approval)

– disapprove research.

• Group review serves an important role in the protection

of the rights and welfare of human research subjects

• Assure (in advance and periodically) that appropriate

steps are taken to protect human subjects

• Group process to review research protocols and

materials to ensure protection of human subjects

Source: http://www.fda.gov/RegulatoryInformation/Guidances/ucm126420.htm

Levels of Review

• Exempt:

– Anonymous surveys or interviews

– Passive observation of public behavior without collection of identifiers

– Analyses of discarded pathological specimens without patient identifiers

• Expedited:

– Studies involving collection of hair, saliva or dental plaque samples

– Studies of blood samples from healthy volunteers

– Analyses of voice recordings

– Studies of existing pathological specimens with patient identifiers

• Full Committee:

– Proposed human subject research which does not fall into either the

exempt or expedited review categories must be submitted for full

committee review

Level of Risk Generally Determines Level of Review

ExemptChair or Administrator

ExpeditedSubcommittee

Convened IRB MeetingFull Committee

Minimal Risk

RISK

Virtually No Risk

> Minimal Risk

Source: Valerie Sanchez & Beverley Williams, UCI Office of Research

Case #5

A patient with a rare form of

incurable cancer is offered a clinical

trial opportunity at the

Comprehensive Cancer Center by

his treating physician. The clinical

trial is testing whether two

medications that are FDA-approved

for other forms of cancer, are

effective in this rare form of cancer.

– Level of review? (e.g. exempt,

expedited, full committee)

Designing Ethical Research Studies

• Participant Protection

• Rights & Interests

• Health & Welfare

• Risks & Benefits

• Participants & Society

• Maximizing benefits

• Non-maleficence

• Informed Consent

• Written

• Verbal

• Protection of Privacy & Confidentiality

• Privacy involves individual

• Confidentiality involves data

Research Misconduct

• Fabrication, falsification, plagiarism in

proposing, performing, reviewing research, or

reporting research results

• Pressure to “publish or perish”, the desire to

“get ahead”, personal issues or character

issues, and other reason

• Impact:

– Retraction of published work

– Restitution of funds to the granting agency

– Ineligibility to apply for federal grants/contracts

– Tarnished science

– Ruined ReputationSource: http://www.research.vt.edu/research-integrity-office/brochure/misconduct-brochure.pdf

Hints & Suggestions

UCI IRB Application: Protocol Narrative

• Applications & Forms

• Human Research

Protections

• Click on “Other Forms”

http://www.research.uci.edu/

Protocol Narrative

•Purpose & Background

•Role & Expertise of Study Team

•Study Methods & Procedures

•Description of Participants

•Recruitment Methods & Process

•Informed Consent Process

•Risks & Benefits

•Reporting Adverse Events

•Compensation & Reimbursement

•Confidentiality of Data

•Etc. etc. etc.

Complete Protocol Narrative First !!!!!

Informed Consent Forms

Complete Informed Consent Documents 2nd !

• Applications & Forms

• Human Research

Protections

• Click on “Consent

Forms”

Tips for IRB Approval

• Research staff CITI Training & Certification

• Navigate the UCI Office of Research website

• Use brief and concise language in narratives and consent forms

• Address risks & benefits adequately

• Address privacy & confidentiality adequately

• Don’t forget to submit supplemental documents

• Recruitment Materials (ex. fliers, scripts)

• Instruments

– Surveys

– Interview questions

• My office hours (Mondays, 12:30-1:30, AIRB 2020B)

• When in doubt ask the IRB!

Source: http://www.xkcd.com/1390/

Thank you!Questions? Comments?

References1. Cassell, E. J. (2000). The principles of the Belmont report revisited: How have respect for persons, beneficence, and justice been applied to clinical medicine?. Hastings Center Report, 30(4), 12-21.2. World Medical Association. (2001). World Medical Association Declaration of Helsinki. Ethical principles for medical research involving human subjects. Bulletin of the World Health Organization, 79(4), 373.3. Shuster, E. (1997). Fifty years later: the significance of the Nuremberg Code. New England Journal of Medicine, 337(20), 1436-1440.4. US Department of Health and Human Services. (2009). Code of federal regulations: title 45 public welfare; Department of Health and Human Services: part 46 protection of human subjects.5. Sieber, J. E. (2007). Privacy and Confidentiality: As Related to Human Research in Social and Behavioral Science (Research Involving Human Participants V2). Online Ethics Center for Engineering, 5(25), 2007.6. Adams,R. (2013). Research Ethics. Retrieved on January 25, 2015 from: https://depts.washington.edu/bioethx/topics/resrch.html