An Introduction to
Human Subjects Research
Office of Research Policies, Compliance, and Committees (ORPCC)
Updated March 2011
HISTORICAL EVENTS:
Nuremberg Code
• In 1947, the Nuremberg Tribunal condemned experiments
that 23 German physicians and administrators were
performing on concentration camp prisoners.
• They were convicted for the torture, mutilation and killing.
The physicians argued that the experiments were “medically
justified”.
• In the verdict, the judges included a section called
“Permissible Medical Experiments.” This became known as
the Nuremberg Code and formed the basis for international
ethic codes.
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HISTORICAL EVENTS:
Tuskegee
• The most notorious example in the U.S. of prolonged and knowing
violations to a vulnerable group of research participants was the
long-term study of black males conducted in Tuskegee, AL, by the
Public Health Service.
• More than 400 uneducated, poor black men were enrolled to follow
the natural course of syphilis. The men were enrolled without
informed consent and were deliberately misled about their disease
and the medical treatment they received.
• By the 1940’s, penicillin was a common, effective treatment for
syphilis. Instead of closing the study or adjusting the study to
research penicillin on its effectiveness to treat syphilis, the
researchers withheld penicillin as treatment.
• This led to the appointment of an advisory board to advise on how
to ensure the experiments of this kind would not be conducted.
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HISTORICAL EVENTS:
Willowbrook School
• The vulnerability of children – especially institutionalized
children – as research participants was demonstrated in a
series of experiments conducted from 1963 to 1966 in the
Willowbrook School.
• Willowbrook was a New York institution for “mentally
defective” children.
• In order to understand the natural history of infectious
hepatitis under controlled conditions, Willowbrook children
were deliberately infected with the hepatitis virus.
• The children were coerced into the experiment by the school,
which told parents of new patients that the only way to admit
their child was to agree to their child’s participation in the
study.
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HISTORICAL EVENTS:
The Belmont Report
• 1974: “Ethical Principles and Guidelines for the Protection of
Human Subjects of Research”, also known as the Belmont
Report, was published by the National Commission for the
Protection of Human Subjects of Biomedical and Behavioral
Research.
• The commission was charged with determining the basic
ethical principles to guide all investigators conducting human
subjects research.
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HISTORICAL EVENTS:
The Belmont Report
There were three basic principles established:
• RESPECT FOR PERSONS (autonomy) – acknowledges the
dignity and freedom of every person.
• BENEFICENCE – requires the investigator to maximize the
benefits and minimize the harms or risks.
• JUSTICE - requires equitable selection, recruitment and fair
treatment of human research subjects.
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Federal Regulations and Policy
• 45 CFR 46 – Basic DHHS Policy for Protection of Human
Research Subjects (originally adopted May 1974, revised
January 1981 and again June 1991) Also includes additional
protections for vulnerable populations in Subparts B-D
• Federal Policy for the Protection of Human Subjects
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HHS and FDA Regulations:
Differences
• Basic requirements for IRBs and for Informed Consent are the
same
• Differences center on differences in applicability
• HHS regulations based on federal funding of research
• FDA regulations based on use of FDA regulated products: drugs,
devices or biologics
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What is Research?
• RESEARCH is defined as “a systematic investigation, including
research development, testing and evaluation, designed to
develop or contribute to generalizable knowledge.”
45 CFR 46.103(d)
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What is a Human Subject?
• HUMAN SUBJECT means a living individual about whom
investigator (whether professional or student) conducting
research obtains:
• Data through intervention or interaction with the individual or
• Identifiable private information
45 CFR 46.102(f)
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What does 45 CFR 46 say?
• Sets forth the IRB Membership requirements:
• at least 5 members with professional competence necessary to
review research activities.
• must include one member whose primary concerns are in
nonscientific areas and at least one member who is not affiliated
with the institution.
• The IRB has the authority to approve, require modifications, or
disapprove research.
• The IRB can only meet with a quorum present.
• The IRB must notify investigators of its decision in writing.
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What does 45 CFR 46 say?
• In order to approve research, the IRB shall determine that all
of the following have been satisfied:
• Risk to subjects is minimized
• Risk to subjects is reasonable in relation to anticipated benefits (if
any) and the importance of the knowledge that may be expected
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What is an Institutional Review
Board (IRB)?
• UH’s IRB is called the Committee for the Protection of Human
Subjects (CPHS).
• Reviews research applications and makes a determination
based on the federal requirements.
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What does 45 CFR 46 say?
(continued)
• Required elements of informed consent
• Waiver of informed consent
• Documentation of informed consent
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What does 45 CFR 46 say?
(continued)
• SUBPART B – Additional Protections for Pregnant Women,
Human Fetuses, and Neonates Involved in Research
• Provides definitions and guidance on conditions that must be met
to include any of the populations in research.
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What does 45 CFR 46 say?
(continued)
• SUBPART C – Additional Protections for Biomedical and
Behavioral Research Involving Prisoners as Subjects
• Additional safeguards are required – prisoners may be under
constraints because of their incarceration which could affect their
ability to make a truly voluntary and un-coerced decision.
• Requires additional membership on the IRB to serve as an
advocate for the prisoners.
• Identifies the areas of permitted research involving prisoners.
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What does 45 CFR 46 say?
(continued)
• SUBPART D – Additional Protections for Children Involved as
Subjects in Research
• Allows for research with children if the IRB finds that no greater
than minimal risk to children is presented.
• Additional requirements for research that involves greater than
minimal risk but presents a direct benefit to the child.
• Additional requirements for research that involves greater than
minimal risk and no direct benefit but is likely to yield
generalizable knowledge about the subject’s disorder or
condition.
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Federalwide Assurance
• The Office for Human Research Protections (OHRP) defines a
human subject assurance as, “a legally binding written
document that commits a public or private entity to
compliance with applicable federal minimum standards for the
protection of human subjects prior to engagement in
department or agency conducted or supported research.”
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Ethical Considerations:
IRB Review
The following addresses each of the criteria for IRB approval, as
specified in 45 CFR 46:
• SPECIFIC AIMS & BACKGROUNDS – Are the purposes and aims
clearly specified? Is there adequate justification for this protocol?
• SCIENTIFIC DESIGN – Is the research design adequately described?
Are the objectives achievable as proposed?
• INCLUSION/EXCLUSION CRITERIA – Are the criteria clearly specified
and are they appropriate to the protocol? Is the choice of subjects
appropriate for the question asked? Is subject selection equitable?
• RECRUITMENT – Are the methods for recruitment well defined? Are
all recruiting materials included and appropriate? Are the location
and timing of recruitment acceptable?
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Ethical Considerations:
IRB Review (continued)
• PROCEDURES – Are the research procedures adequately
described? Are there plans to inform subjects about research
results if appropriate?
• DATA AND STATISTICAL ANALYSIS – Is the rationale for the
proposed number of subjects reasonable? Are there adequate
provisions for monitoring data?
• POTENTIAL RISKS, DISCOMFORTS & BENEFITS – Are risks and
benefits adequately identified, evaluated, and described? Are
the risks/benefit ratio acceptable? Have sample questions
been provided?
• COMPENSATION & COSTS – Is the amount of compensation or
remuneration reasonable? If children or adolescents are
involved, who receives the compensation?
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Ethical Considerations:
IRB Review (continued)
• PRIVACY & CONFIDENTIALITY – What are the provisions for
protecting the privacy and confidentiality of the subjects? Are they
reasonable? What are the plans for storage of data? Are identifiers
to be included?
• INFORMED CONSENT/ASSENT –
•
•
•
•
Are all required elements included in the consent form?
Are all institutional requirements included?
Is the process for obtaining consent well defined?
Have the issues of subject comprehension been adequately
considered and addressed?
• If minor subjects are included, are the children capable of providing
assent?
• Is the method for obtaining assent appropriate?
Assent: For potential participants who cannot give consent, investigators
must obtain permission from a legally authorized representative of the
potential participant. For children, this is usually the parent. For adults, it
may be someone designated as health care proxy.
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Ethical Considerations:
IRB Review (continued)
• WAIVER/MODIFICATION OF INFORMED CONSENT – Is the
investigator proposing a waiver or modification of informed
consent? Does the request meet the federal regulations?
• OTHER ISSUES – When should the next continuing review
occur?
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Confidential v. Anonymous
• When the Principal Investigator (PI) is filling out the
application and the informed consent document, he/she must
select either confidential or anonymous.
• Confidential information is not the same as anonymous
information.
• Anonymous means no identifiers are tied to any research subject
and the identity of the subject can never be traced back.
• Confidential means you will protect identifiers tied to research
subjects.
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Informed Consent
• A process – not a single event or a piece of paper.
• Informed consent is an educational process that takes place
between the investigator and the prospective subject.
• Informed consent must be presented in a manner that allows
a subject to voluntarily agree to participate.
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Informed Consent (continued)
• Documentation of consent must be in a language easily
understood by all potential subjects. It is generally
recommended that consent forms be written to a 6th grade
reading level.
• The written document must include all elements established
in the regulations as well as any institutional elements.
• The consent document should be revised when deficiencies
are noted or when additional information will improve the
consent process.
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Tips on Informed Consent
• Use layman’s language.
• Describe the overall experience that will be encountered.
• Describe the benefits that subjects can reasonably expect to
encounter.
• Describe any alternatives to participation.
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Tips on Informed Consent
(continued)
• Confidentiality. The regulations insist that subjects be told the
extent to which their personally identifiable information will
be held in confidence. The IRB will determine the adequate
requirements for confidentiality.
• If research-related injury is possible in research that is greater
than minimal risk, an explanation must be given of whatever
voluntary compensation and treatment will be provided. Note
that the regulations do not limit injury to “physical” injury.
• The regulations prohibit waiving or appearing to waive any
legal rights of subjects.
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Tips on Informed Consent
(continued)
• The regulations provide for identification of contact persons
who would be knowledgeable to answer questions of subjects
about the research, rights as research subjects, and researchrelated injuries.
• It is important not to overlook the need to point out that no
penalty or loss of benefits will occur as a result of both not
participating or withdrawing at any time.
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Waiver of Informed Consent
• Waiver of Informed Consent
• The research involves no more than minimal risk to the subjects.
• The waiver will not adversely affect the rights and welfare of the
subjects.
• The research could not practicably be carried out without the
waiver.
• Whenever appropriate, the subjects will be provided with
additional pertinent information after participation.
• CPHS requires you submit Appendix B “Waiver of Informed
Consent” found on the Division of Research website.
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Waiver of Documentation of
Informed Consent
• Waiver of Documentation of Informed Consent
• The only record linking the subject and the research would be
the consent form document and the principal risk would be
potential harm resulting from a breach of confidentiality.
• The research presents no more than minimal risk of harm to
subjects and involves no procedures for with written consent
is required.
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Human Subject Research
Training Requirements
• All investigators submitting a grant application to the National
Institutes of Health are required to show evidence of human
subject’s education if the project includes the use of humans.
• All other investigators submitting a CPHS application are
advised to complete the training program.
• The course recommended by CPHS is the web-based Course in
the Protection of Human Research Subjects through the
Collaborative IRB Training Initiative (CITI).
• The CPHS will also accept NIH Human Subject Research
certificates.
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Tips for Interactions with the
IRB
• CPHS must review all research activities covered by the HHS
regulations, including proposed changes in previously
approved human subjects research, and have the authority to
approve, require modifications to secure approval, or
disapprove any research activity.
• CPHS must conduct continuing review of approved research at
intervals appropriate to the degree of risk, but not less than
once per year. *Exempt reviews are good for 5 years.
• CPHS has the authority to suspend or terminate approved
research that is not being conducted in accordance with the
committee’s requirements, or that has been associated with
unexpected serious harm to subjects.
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Tips for Interactions with the
IRB
• Any suspension or termination of approval must include a
statement of the reason for CPHS action and must be reported
promptly to the investigator, appropriate institutional officials,
and HHS.
• Research approved by CPHS may be subject to further review
and approval or disapproval by institutional officials. However,
institutional officials may not approve the conduct of human
subjects research covered by HHS regulations that has not
been approved by CPHS.
• Human subject research conducted by UH faculty and
students must be reviewed in a CPHS Full Committee,
Expedited Committee or under Exempt Status.
• UH faculty and students may not begin human subject
research before getting approval from the CPHS.
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Tips for Interactions with the
IRB
• Investigators have the primary responsibility of protecting the
rights and welfare of human research subjects and complying
with all rules set by CPHS.
• Investigators must pay close attention to deadlines outlined by
CPHS for review of applications. The deadline dates can be
found on the Division of Research website.
• Investigators should submit research applications at least 2
months before anticipated start of the research. This will
allow for due processing and review by the CPHS.
• If you plan on conducting human subject research at UH,
please talk with your faculty sponsor prior to designing a
research project.
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Tips for Interactions with the
IRB
• The first item the PI will complete is the CPHS application. The
application is in electronic form on the Division of Research website
under Human Subjects. PI application must be typed and submitted
in paper format to the CPHS office located at 316 E Cullen Building.
• The application must be filled out completely and signed by the
faculty sponsor and the Chair/Dean of the Department.
• The second item the PI must complete and submit along with the
application is the Informed Consent document. The Division of
Research website has a template to follow. The PI may also request
a Waiver of Consent or Waiver of Documentation of Consent if
applicable.
• The third item is to submit all documents that will be used when
conducting the research. This includes subject questionnaires,
interview questions, educational documents backing up the
research, recruiting scripts, recruiting flyers, etc.
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