The Basics of Human Research Protections

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The Basics of Human Research Protections

• Office of Research Oversight (ORO)
• Veterans Health Administration
• Department of Veterans Affairs

February 27, 2004
Thanks to the Office of Human Research
Protections for providing some slide text.
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Outline

• Ethical Principles
• Federal Regulations
• Resources

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Ethical Principles
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The Belmont Report

• Ethical Principles and Guidelines for the
  Protection of Human Subjects of Research
  
• The National Commission for the Protection of
  Human Subjects of Biomedical and Behavioral
  Research
  
• April 18, 1979

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Ethical Principles Belmont Report

• Respect for Persons
• Individual autonomy
• Protection of individuals with reduced autonomy
• Beneficence
• Maximize benefits and minimize harms
• Justice
• Equitable distribution of research risks and
  benefits

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Federal Regulations
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Federal Regulations and Policy

• 45 CFR 46 Basic HHS Policy for Protection of
  Human Research Subjects
  
• Originally adopted May 1974, Revised January 13,
  1981, Revised June 18, 1991
  
• Federal Policy for the Protection of Human
  Subjects The Common Rule June 18, 1991
  
• Departments of Agriculture, Energy, Commerce,
  HUD, Justice, Defense, Education, Veterans
  Affairs, Transportation, and HHS. NSF, NASA,
  EPA, AID, Social Security Administration, CIA,
  and the Consumer Product Safety Commission.

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Federal Regulations and Policy

• Additional Protections Included in 45 CFR 46
• Subpart B Additional Protections for Pregnant
  Women, Human Fetuses and Neonates Involved in
  Research
  
• 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
  
• VA follows if waivers from ORD permit inclusion
  of these populations.

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Food and Drug Administration

• Regulations
• Institutional Review Board 21 CFR 56
• Informed Consent 21 CFR 50

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Differences in VA (38 CFR 16) FDA (21 CFR Parts
50 56) Regulations

• Basic requirements for IRBs and for Informed
  Consent are congruent
  
• Differences center on differences in
  applicability
  
• VA regulations based on VA conduct/support of the
  research
  
• FDA regulations based on use of FDA regulated
  product drugs, devices, or biologics

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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
• (FDA has different definitions)

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Exempt Research

• Some research is exempt from federal
  regulations six categories of research
  
• VHA facilities (not investigators) determine
  whether proposed research qualifies as exempt
  under VA regulations

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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 using existing data, documents, records,
  pathological specimens, or diagnostic specimens,
  if publicly available or unidentifiable
  
• continued

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Exempt Research

• Research on elected or appointed public officials
  or candidates for public office
  
• Evaluation of public benefit service programs
• Taste and food quality evaluation and consumer
  acceptance studies
  

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Basic Protections

• The regulations contain three basic protections
  for human subjects
  
• Institutional Assurances
• Institutional Review Board (IRB) Review
• Informed Consent

VA also requires Research and Development
Committee review by policy.
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Institutional Assurances
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Assurances

• Documentation of institutional commitment to
  comply with the Common Rule for
  Federally-supported research
  
• OR
• ALL human subject research
• Principal method of compliance oversight
• Federalwide Assurance

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Assurances

• Required from each VHA facility engaged in the
  research

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Engagement

• Institutions become engaged in human subject
  research whenever their employees or agents
  
• intervene or interact with living individuals for
  research purposes or
  
• obtain, release, or access individually
  identifiable private information for research
  purposes
  
• Awardee institutions are automatically considered
  to be engaged in human subject research even
  where all activities involving human subjects are
  carried out by a subcontractor or collaborator

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Institutional Review Board Review
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IRB Review

• Institutional Review Board (IRB) A committee
  charged with the review of human participants
  research to assure that the rights and welfare of
  human participants are adequately protected. VA
  IRBs are subcommittees of the RD Committee.
• Why do we need IRB review?
• No one can be objective about his/her own work
• People underestimate the risks involved in
  research interventions with which they are quite
  familiar
  
• People overestimate the benefit of things that
  are important to them

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Institutional Review Board (IRB)

• Membership
• At least five members of varying backgrounds
• Sufficiently qualified
• Not solely of one profession
• Both men and women
• At least one non-scientist
• At least one non-affiliated member
• Expertise on vulnerable populations
• Outside consultants

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IRB Responsibilities

• Review and approve, require modifications, or
  disapprove all covered research
  
• Require that informed consent is in accordance
  with regulations
  
• Require documentation of informed consent or may
  waive documentation in accordance with
  regulations
  
• Notify investigators in writing of decisions
• Conduct continuing review of research no less
  than once per year

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IRB Review

• IRB review and approval must precede initiation
  of research involving human subjects (Initial
  Review)
  
• IRB must review and approve changes to the
  research prior to initiation
  
• In VA, RD Committee must also approve all
  research before it commences.

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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
• continued

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Criteria for IRB Approval

• When appropriate
• Data collection is monitored to ensure subject
  safety
  
• Privacy and confidentiality of subjects is
  protected
  
• Additional safeguards are included for vulnerable
  populations
  

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Full Review

• Convened meeting no mail reviews (telephone
  participation okay under some circumstances)
  
• Quorum
• Majority of IRB present
• At least one non-scientist present
• Approval by majority of those present
• Members with conflict of interest should be
  absent during discussion and vote
  
• Should the quorum fail during a meeting, no
  further votes can be taken unless the quorum can
  be restored

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Continuing Review

• Continuing review is to be conducted at intervals
  appropriate to the degree of risk, but not less
  than once per year
  
• Continuing review must be substantive and
  meaningful
  
• The criteria for IRB approval is the same as for
  initial review

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Expedited Review

• An IRB may use expedited review for
• Research on list of eligible categories IF
  minimal risk
  
• 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

• Research activities that (1) present no more than
  minimal risk to human subjects, AND (2)
  involve only procedures listed in one or more
  categories published in the expedited review
  list
• The categories in the list apply regardless of
  the age of subjects, except as noted
  
• May not be used where identification of the
  subjects and/or their responses would reasonably
  place them at risk
  

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Expedited Review

• May not be used for classified research involving
  human subjects
  
• The standard requirements for informed consent
  (or its waiver, alteration, or exception) apply
  regardless of the type of reviewexpedited or
  convenedutilized by the IRB.
• First seven categories pertain to both initial
  and continuing IRB review.
  

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Expedited Review

• Eligible research categories
• Clinical studies of drugs and medical devices
  where IND or IDE not required or device has been
  approved for marketing and is used as such
  
• Collection of blood samples by finger stick, heel
  stick, ear stick, or venipuncture with
  restrictions on age, weight, and amount
  
• Prospective collection of biological specimens
  for research purposes by noninvasive means
  
• Collection of data through noninvasive procedures
  routinely employed in clinical practice
  

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Expedited Review

• Eligible research categories
• Research involving materials (data, documents,
  records, or specimens) that have been collected,
  or will be collected solely for non-research
  purposes
• Collection of data from voice, video, digital, or
  image recordings made for research purposes
  
• Research on individual or group characteristics
  or behavior or research employing survey,
  interview, oral history, etc. methodologies
  

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Expedited Review

• Eligible research categories
• Continuing review of research previously approved
  by the convened IRB with no further direct
  subject participation
  
• Continuing review of research (not under IND or
  IDE) where the IRB has determined and documented
  at a convened meeting that the research involves
  no greater than minimal risk and no additional
  risks have been identified

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Informed Consent
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Informed Consent

• Beyond the
• Consent Form

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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 or enrolled subject.
Necessary elements of the consent process includ
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• Full disclosure of the nature of the research and
  the subjects participation
  
• Adequate comprehension on the part of the
  potential subjects, and
  
• The subjects voluntary choice to participate

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Basic Elements

• Research
• Purpose
• Duration
• Procedures
• Risks
• Benefits
• Alternatives
• Confidentiality
• Compensation for Injury
• Whom to Contact
• Right to Refuse or Withdraw

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Additional Elements

• Risks related to pregnancy
• Anticipated reasons for termination from the
  study
  
• Costs
• Consequences of withdrawal
• New findings
• Number of subjects

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Comprehension

• Informed consent is not valid unless the
  consenter understands the information that has
  been provided.
  
• 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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Voluntary Consent

• To be valid, consent must be freely given 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 incentives for
  participation.

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Documentation of Consent
Documentation of legally effective informed
consent usually involves the use of a written
consent form 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.
  
• The fact that a subject signed a consent form
  does not mean that s/he understood what was being
  agreed to or truly gave his/her voluntary
  consent.
• Informed consent is a process that is documented
  by a signed consent form.

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IRB Waivers
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IRB Waiver Informed Consent
The IRB may approve a waiver of some or all of
the consent requirements provided that

• The research involves no more than minimal risk
  to subjects
  
• The waiver will not adversely affect the rights
  and welfare of subjects
  
• The research could not practicably be carried out
  without the waiver and
  
• Whenever appropriate, the subjects will be
  debriefed provided with additional pertinent
  information after they have participated in the
  study.

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IRB Waiver Documentation of Consent
The IRB may waive the requirement for written
documentation of consent in cases where

• The principal risks are those associated with a
  breach of confidentiality concerning the
  subjects participation in the research and the
  consent document is the only record linking the
  subject with the research
• OR
• The research presents no more than minimal risk
  and involves procedures that do not require
  written consent when performed outside of a
  research setting.

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Vulnerable Populations
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Subpart C -- Prisoners

• HHS issued special protections in 1978
• No Exemptions allowed
• Definition of a prisoner
• Additional duties of the IRB

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Subpart D -- Children

• Definition of a child
• Permission
• Assent
• IRB duties

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VHA Handbook 1200.5 Requirements for the Protecti
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of Human Subjects in Research July 15, 2003
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Resources
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Electronic Resources

• OHRP Website http//ohrp.osophs.dhhs.gov
• IRB Registration Assurance Filing
• Quality Improvement Program
• Policy Guidance
• Compliance Oversight
• Educational Materials/Workshops
• ORO Website http//www.va.gov/oro/
• OROs Regional Office locations and contact
  information
  
• OROs Central Office contact information
• ORD Website http//www.va.gov/resdev/
• PRIDEs Website http//www.va.gov/resdev/fr/PRIDE
  

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