Human Subjects Research: Regulations and Review Issues

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Human Subjects ResearchRegulations and Review
Issues

• Florida Gulf Coast University
• October 23, 1998
• Jeffrey M. Cohen, Ph.D.
• The University at Albany, SUNY

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Topics

• Why do we have IRBs?
• Definitions
• IRB Review of Research
• Informed Consent
• Risk in Social Behavioral Research
• Vulnerable Populations
• Research on the Internet

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WHY DO WE HAVE IRBs?

• Philosophical Basis
• Historical Basis
• Regulatory Basis

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Philosophical Basis for IRBs

• Immanuel Kant (1724-1804)
• For all rational beings come under the law
  that each of them must treat itself and all
  others never merely as means, but in every case
  at the same time as ends in themselves.

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Philosophical Basis for IRBs

• The Belmont Report
• Basic Ethical Principles
• Respect for Persons
• - Individual autonomy
• - Protection of individuals with reduced
  autonomy
• Beneficence
• - Maximize benefits and minimize harms
• Justice
• - Equitable distribution of research costs
  and benefits

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Historical Basis for IRBs

• NUREMBERG
• During the Nuremberg
• War Crimes Trials, 23
• German doctors were
• charged with crimes
• against humanity for performing medical
  experiments upon
• concentration camp inmates and other living human
  subjects,
• without their consent, in the course of which
  experiments the
• defendants committed the murders, brutalities,
  cruelties, tortures,
• atrocities, and other inhuman acts.

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Historical Basis for IRBs

• The Nuremberg Code (1947)
• As part of the verdict, the Court enumerated
• some rules for Permissible Medical
• Experiments, now known as the
• Nuremberg Code. These rules include
• voluntary consent, benefits outweigh risks,
• and the ability of the subject to terminate
• participation.

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Historical Basis for IRBs

• Tuskegee Syphilis Study
• American medical research
• project conducted by the
• U.S. Public Health Service
• from 1932 to 1972, examined
• the natural course of untreated syphilis
• in black American men. The subjects, all
• impoverished sharecroppers from Macon
• County, Alabama, were unknowing participants in
  the study they were
• not told that they had syphilis, nor were they
  offered effective treatment.

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Regulatory Basis for IRBs

• 45 CFR 46 - Basic DHHS Policy for Protection of
  Human Research Subjects Revised June 18, 1991
• The Common Rule - Federal Policy for the
  Protection of Human Subjects Revised June 18,
  1991
• - Departments of Agriculture, Energy, Commerce,
  HUD, Justice, Defense, Education, Veterans
  Affairs, transportation, HHS, FDA, NSF, NASA,
  EPA, AID, and the Consumer Product Safety
  Commission.

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Regulatory Basis for IRBs

• Additional Protections Included in 45 CFR46
• Subpart B - Additional DHHS Protections
  Pertaining to Research, Development, and Related
  Activities Involving Fetuses, Pregnant Women, and
  Human In Vitro Fertilization
• Subpart C - Additional DHHS protections
  Pertaining to Biomedical and Behavioral Research
  Involving Prisoners as Subjects
• Subpart D - Additional DHHS Protections for
  Children Involved as Subjects in Research

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Definitions

• Research - a systematic investigation designed to
  develop or contribute to generalizable knowledge.
• Human Subject - a living individual about whom an
  investigator conducting research obtains data
  through
• - intervention or interaction with the
  individual, or
• - identifiable private information

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Definitions

• Minimal 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.

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IRB Review of Research
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IRB Responsibilities

• An IRB shall review and approve, require
  modification, or disapprove all covered research
• An IRB shall require that informed consent is in
  accordance with regulations
• An IRB shall require documentation of informed
  consent or may waive documentation in accordance
  with regulations
• An IRB shall notify investigators in writing of
  decisions
• An IRB shall conduct continuing review of
  research no less than once per year

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Criteria for IRB Approval

• Risks to subjects are minimized
• Risks are reasonable in relation to anticipated
  benefits
• Selection of subjects is equitable
• Informed consent is sought from each subject
• Informed consent is appropriately documented

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Criteria for IRB Approval

• When appropriate, data collection is monitored to
  ensure subject safety
• When appropriate, privacy and confidentiality of
  subjects is protected
• When appropriate, additional safeguards are
  included for vulnerable populations

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Exempt Research

• Some research is exempt from federal
• regulations, but institutions (not
• investigators) must certify that the research
• qualifies as exempt so many institutions
• review exempt research under expedited
• review.

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Exempt Research

• Research that is exempt includes
• - Normal educational practices
• - Educational tests, surveys, interviews, or
  observation of public behavior unless identified
  and sensitive
• - Research on elected or appointed public
  officials or candidates for public office
• - Research using existing data
• - Evaluation of public benefit service programs
• - Taste and food quality evaluation and consumer
  acceptance studies

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Expedited Review

• An IRB may use expedited review for
• - Research on list in 45 CFR 46
• - Minor changes in previously approved research
• Carried out by IRB chair or one or more
  experienced IRB members
• Reviewers can exercise all of the authorities of
  the IRB except disapproval
• All IRB members must be informed of research
  approved under expedited review

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Expedited Review

• Eligible research
• - Collection of hair, nail clippings, teeth,
  excreta and external secretions, dental plaque,
  etc.
• - Use of non-invasive physical sensors on adults
  (not x-rays)
• - Blood samples from healthy adults
• - Collection of voice recordings to study speech
  defects
• - Moderate exercise by healthy adults
• - Existing data
• - Research on individual or group behavior
• - Research on drugs or devices not requiring and
  IND

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Full Review

• Convened meeting - no mail reviews
• Quorum consists of a majority of the IRB members
• At least one non-scientific member must be
  present
• In order for research to be approved it must
  receive the approval of a majority of members
  present

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Risk in Socialand BehavioralResearch
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IRB Responsibilities

• Identify Risks
• Determine that risks are minimized
• Determine the risks to subjects are reasonable
  in relation to anticipated benefits
• Determine the subjects are adequately informed
  about any reasonably foreseeable risks or
  discomforts

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Definition of Risk

• The probability of harm or injury occurring as a
  result of participation in a research study.
• Probability and magnitude may vary from minimal
  to significant
• Only minimal risk defined in regulations

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Identifying Risks

• Examples of Psychological Social Harm
• Emotional Distress
• Psychological Trauma
• Invasion of Privacy
• Embarrassment
• Los of Social Status
• Loss of Employment

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Identifying Risks

• Risks are TIME and SITUATION specific
• Psychological social risks are very subjective
• There is little or no empirical data on the
  likelihood of risk in behavioral or social
  research

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Identifying Risks

• Primary source of social risk results from a
• breach of confidentiality
• Confidentiality and anonymity are not the same
• Names are not the only identifiers
• Subjects participation in the research may need
  to be kept confidential as well as their data
• Procedures to protect confidentiality depend on
• the sensitivity of the information

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Minimizing Risk

• Three ways to minimize risk
• Precautions
• Safeguards
• Alternatives

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Risk / Benefit

• Evaluation of Risk / Benefit ratio is subjective
  judgment
• IRB must decide whether the anticipated benefit
  justifies asking subjects to undertake the risks
• Should take into account different subject
  populations and individual differences among
  subjects

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Informed Consent

• Since social risks are so subjective, adequate
  informed consent is particularly essential when
  there is a chance for social harm.
• Subjects must have a clear understanding of what
  the risks are so that they can decide for
  themselves if they want to assume that risk.

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Informed Consent
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Purpose of Informed Consent

• Informed consent is one of the primary ethical
  principles governing human subjects research it
  assures that prospective human subjects will
  understand the nature of the research and can
  knowledgeably and voluntarily decide whether or
  not to participate.

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Definition of Informed Consent

• Informed Consent means the knowing consent of
  an individual, or his/her legally authorized
  representative, who is able to exercise free
  power of choice without undue inducement or any
  form of force, fraud, deceit, duress or other
  form of constraint or coercion.

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The Consent Process

• Informed consent is not a single event or just a
  form to be signed - rather, it is an educational
  process that takes place between the investigator
  and the prospective subject.
• The basic elements of the consent process
  include
• full disclosure of the nature of the research and
  the subjects participation,
• adequate comprehension of the part of the
  potential subjects, and
• the subjects voluntary choice to participate.

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Elements of Information

• The federal regulations detail the elements of
  information which must be provided to each
  subject. These elements include
• Description of the research and subjects
  participation
• Explanation of voluntary participation
• Description of risks and benefits
• Explanation of confidentiality
• Alternatives
• Who to contact with questions
• Other information depending on the nature of the
  research

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Comprehension

• Informed consent is not valid unless the
  consentor understands the information that has
  been provided.
• It is the responsibility of the investigator to
  do what s/he can to enhance each prospective
  subjects comprehension of the information.
• The investigator must consider the nature of the
  proposed subject population, the type of
  information to be conveyed, and the circumstances
  under which the consent process will take place
  in determining the appropriate way to present the
  information.

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Comprehension

• Avoid technical terms and complex sentences, even
  for the educated layperson.
• Translation is required if English is not the
  subject populations primary language.
• For children, care must be taken to ensure that
  the language is appropriate to their age level.
  For elderly subjects, oral information may have
  to be presented slowly and loudly and forms
  printed in large type.

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Comprehension

• When the subject population is not homogeneous,
  different consent procedures may be required with
  different populations.
• Even if the IRB has approved a consent procedure,
  it is the investigators responsibility to ensure
  that each potential subject understands the
  information and to take whatever steps are
  necessary to gain that comprehension.
• Individuals may not be used as research subjects
  unless they understand the information that has
  been provided.

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Voluntary Consent

• Consent is a legal concept and only legally
  competent adults can give consent.
• In most cases, minors cannot give consent - only
  parents or legal guardians can give consent for
  minors to participate in research.
• Incompetent adults cannot give consent - this may
  include the developmentally disabled, the
  cognitively-impaired elderly, and unconscious or
  inebriated individuals.
• The evaluation of competence must be made on a
  case by case basis.

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Voluntary Consent

• Even though children and incompetent adults
  cannot give consent to participate in research,
  their assent or agreement to participate should
  be obtained whenever possible.
• Assent is to knowledgeable agreement to
  participate. Used whenever the potential subject
  has sufficient capacity to understand what is
  happening and express his/her wishes.
• The deliberate objection of a subject should be
  construed as a veto of the consent of a parent or
  guardian, whether that objection is verbal or
  non-verbal.

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Voluntary Consent

• In order to be valid, consent must be freely
  given. That means that it is free from all forms
  of coercion.
• In addition to overt coercion, the investigator
  needs to be sensitive to more subtle forms of
  coercion, such as social pressure, requests from
  authority figures, and undue incentive for
  participation.

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Consent Procedures

• An investigator shall seek consent only under the
  following circumstances
• The potential subject has the legal and mental
  capacity to give consent if not, consent must be
  obtained from his/her legally authorized
  representative
• Sufficient opportunity is provided to consider
  whether or not to participate to the prospective
  subject, or his/her representative
• The possibility of coercion or undue influence is
  minimized

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Consent Procedures

• The information that is given to the prospective
  subject, or his/her representative, in in
  language understandable to the subject or
  representative and
• The subject, or his/her representative, is not
  made to waive or appear to waive any of his/her
  legal rights, or release or appear to release the
  investigator, the sponsor, the institution or its
  agents from liability for negligence.

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Documentation of Consent

• Documentation of legally effective informed
  consent usually involves the use of a written
  consent form containing all of the information to
  be disclosed and signed by the subject or the
  subjects legal representative.
• - The consent form is merely the documentation
  of informed consent and does not, in and of
  itself, constitute informed consent. A consent
  form does not mean that s/he understood what was
  being agreed to or truly gave their voluntary
  consent.

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Documentation of Consent

• It is recommended that consent forms meet four
  criteria
• Be brief, but have complete basic information.
• Be readable and understandable to most people
• Be in a format that helps people comprehend and
  remember the information.
• Serve as a script for the face-to-face
  discussions with the potential subjects.

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Documentation of Consent

• Articles in most popular magazines are at the 8th
  grade level. Factors that improve readability
  include the following
• Technical terms should be replaced with ordinary
  language
• Use active tense rather than passive tense verbs
• Write shorter sentences in general and
• Make clear the links of logical sequences and of
  cause-and-effect, even if doing so make the
  sentence much longer.

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Documentation of Consent

• Format can help comprehend and remember complex
  material. Good format uses headings indents
  bolded type lists extra spacing between
  sub-topics repetition reasonable-size type and
  plenty of margins and empty space in general.

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Documentation of Consent

• Format can help comprehend and remember complex
  material. Good format uses
• headings
• indents
• bolded type
• lists
• extra spacing between sub-topics
• repetition
• reasonable-size type and
• plenty of margins and empty space in general

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IRB Waiver

• The IRB may approve a waiver of some or all of
  the consent requirements in research involving no
  more than minimal risk to subjects and that could
  not practicably be carried out without the
  waiver.
• Whenever appropriate, the subjects will be
  debriefed.
• The IRB may waive the requirement for written
  documentation of consent in minimal risk research
  or in research where the principle risk is breach
  of confidentiality.
• Waiver of documentation does not mean waiver of
  consent.

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VulnerablePopulations
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Minors as Subjects

• Any subjects under the age of 18 are considered
  minors
• In every case, assent of the children and
  permission of their parents or guardians is
  required.
• The requirements for assent of the children
  and/or permission of their parents or guardians
  may be waived by the IRB as long as the criteria
  for waiving consent in the regulations are met
• Passive Consent is NOT consent and can only be
  used when the IRB waives the requirement for
  consent

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Minors as Subjects

• Assent means a childs affirmative agreement to
  participate in research. Mere failure to object
  should not be construed as assent
• Adequate provision are to be made to secure
  permission from both parents.
• For minimal risk research or risk research with
  direct benefit, the IRB may allow permission from
  on parent.
• For risk research without direct benefit,
  permission from both parents is required.

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Minors as Subjects

• Types of Research
• Minimal Risk
• Assent Parental Permission required
• Risk but with direct benefit to subjects
• Risk justified by benefits
• Risk / Benefit at least as favorable as
  alternatives
• Assent Parental permission required

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Minors as Subjects

• Types of Research
• Risk but with no direct benefit
• Minor increase over minimal risk
• Intervention or procedure reasonably commensurate
  with what they already experience
• Likely to yield generalizable knowledge about the
  subjects disorder or condition
• Assent Parental permission required

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Minors as Subjects

• Research in Schools
• Schools do not have the authority to grant
  permission for children to participate in
  research, only parents or guardians have that
  authority.
• Principals and teachers do not have the authority
  to grant permission for research to be conducted
  in a school, only school districts have that
  authority

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Minors as Subjects

• Research in Schools
• The Buckley Amendment (The Family Educational
  Rights and Privacy Act of 1979) - Schools cannot
  release personally identifiable information from
  student records without written consent.
• Family Privacy Protection Act - surveys in
  schools on certain topics require written
  parental consent.

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Cognitively Impaired Subjects

• All adults, regardless of their diagnosis or
  condition, should be presumed competent unless
  there is evidence otherwise.
• Where possible, consent should be obtained from
  legal guardians.
• Where appropriate, subject assent should be
  obtained.
• IRB has to determine if adequate procedures are
  proposed to evaluate competence.
• Consent from surrogates, other than legal
  guardians, is a waiver of consent.

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Prisoners as Subjects

• Additional regulations governing research with
  prisoners (45 CFR 46 Subpart C)
• At least one IRB member must be a prisoner or
  prisoner representative
• Only certain kinds or research may involve
  prisoners, basically studies directly relevant to
  prisoners, prisons, criminality, etc.
• Participation in research cannot be used in
  parole decisions.

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Research on the Internet
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Research on the Internet

• Types of Research on the Internet
• Recruiting Subjects over the Internet
• Observation of Internet Activity
• Collecting Data Over the Internet

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Research on the Internet

• Recruiting Subjects Over the Internet
• Similar issues as with any other recruiting tool
  IRB needs to review information presented to
  subjects
• Examples Recruiting rape victims from discussion
  groups, using diabetes Web site to recruit
  subjects.
• Need to determine that subjects are who they say
  they are, especially minors.

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Research on the Internet

• Observation of Internet Activity
• Gathering information about the use of the
  Internet, recording user information or users
  comments
• Example Participant observation of grieving
  discussion group
• IRB issues consent/disclosure

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Research on the Internet

• Gathering data over the Internet
• Having subjects submit data, e.g. survey data,
  over the Internet
• Example survey on the use of WWW by college
  students
• IRB issues confidentiality and participation by
  minors

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Research on the Internet

• E-mail Confidentiality
• All forms of e-mail include the senders e-mail
  address
• Many organizations publish or make available
  directories of e-mail addresses
• Technology can strip out identifiers

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Research on the Internet

• WWW Confidentiality
• Passive recording of transactional information
  The transactional information revealed in the
  normal course of surfing the net reveals a
  detailed profile of online activities without the
  users knowledge of consent.
• Client-side persistent information (cookies)
  Cookies allows any web site to store information
  about your visit to that site on your hard drive
  and access that information later.
• http//www.cdt.org/privacy/

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Research on the Internet

• The Internet will be used more and more in
  conducting human subjects research
• Research on the Internet presents new concerns to
  the traditional IRB issues of consent and
  confidentiality
• Investigators are going to have to provide
  technical information on how they will deal these
  issues
• IRBs need to become more familiar with the
  technical aspects of the Internet in order to ask
  the right questions.