Issues Surrounding Human Research Subject Protections

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Issues Surrounding Human Research Subject
Protections

• Freda E. Yoder, MA
• Division of Education
• Office for Human Research Protections (OHRP)
• Department of Health Human Services (HHS)
• NIH Acquisition Management
• Committee (AMC) Symposium
• Hershey, PA
• October 24, 2006

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Human Subject Protections

• Background
• Determining Applicability of the Regulations
• Protections Afforded by the Regulations
• Resources/Contacting OHRP

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Human Subject Protections
Institutions
IRB
Investigator
Subjects
Research Team
Sponsor
Advocates
Family

Government
Public
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Historical Precedents

• Nazi biomedical studies trials
• US studies e.g.,
• Tuskegee Syphilis (1932-1972)
• Willowbrook (1950s) hepatitis virus
• Milgram (1960s) obedience
• Beecher article (1966)
• PHS Policy (1966)
• National Research Act (1974)

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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

• Three Basic Ethical Principles
• Respect for Persons
• Beneficence
• Justice

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Regulation for Protection of Human Subjects

• HHS regulations Title 45 CFR part 46
• Subpart A basic HHS Policy - The Common Rule
  or Federal Policy
• - Basis IRB informed consent requirements
• - Other federal departments agencies have
  adopted FDA has its own
• Departments of Agriculture, Energy, Commerce,
  HUD, Justice, Defense, Education, Veterans
  Affairs, Transportation, HHS, Home land
  Security. NSF, NASA, EPA, AID, Social Security
  Administration, CIA, and the Consumer Product
  Safety Commission
• only in part

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Additional HHS Protections

• Subpart B - Pregnant Women, Human Fetuses, and
  Neonates
• Subpart C - Prisoners
• Subpart D - Children

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• Determining Applicability of Regulations

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Determining Applicability of Regulations

• Prerequisite
• Research involving human subjects conducted or
  supported by HHS and that is not otherwise exempt
• OR
• Non-exempt human subject research covered by
  Assurance of Compliance

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Determining Applicability

• Does activity involve Research?
• Does research involve Human Subjects?
• Is human subjects research exempt?

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Does Activity Involve Research?

• Research - a systematic investigation designed to
  develop or contribute to generalizable knowledge
• includes research development, testing, and
  evaluation
• 46.102(c)

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Does Research Involve Human Subjects?

• Human Subject - a living individual about whom an
  investigator conducting research obtains
• data through intervention or interaction with the
  individual, or
• identifiable private information
• 46.102(f)

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Identifiable Private Information

• Private information must be individually
  identifiable (i.e., identity of subject is or may
  readily be ascertained by the investigator or
  associated with the subject) in order for
  obtaining the information to constitute research
  involving human subjects.
• 46.102(f)

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Is Human Subject Research Exempt?
Research that is exempt includes

• Normal educational practices in established
  educational settings
• 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
• exception for prisoners exception for
  children

• Research using existing data, if publicly
  available or recorded without identifiers
• Evaluation of public benefit service programs
• Taste and food quality evaluation and consumer
  acceptance studies

46.101(b)
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Applicability of Regulations

• Bottom line HHS Regulations protecting human
  subjects apply to all non-exempt human subject
  research conducted or supported by HHS (or
  covered by an Assurance)
• Decision Charts http//www.hhs.gov/ohrp/humansub
  jects/guidance/decisioncharts.htm

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• Protections Afforded by the Regulations

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HHS Regulations (45 CFR part 46)

• HHS will conduct or support non-exempt
• human subject research only if
• the institution has an OHRP-approved assurance,
  and
• the institution has certified to HHS
• research was reviewed and approved by IRB, and
• the research will be subject to continuing
  review
• 46.103(b) (f)

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Basic Protections Afforded by Regulations
Institutional Assurance
IRB Review
Informed Consent
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• Institutional Assurance

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Institutional Assurance

• Each institution engaged in research which is
  covered by this policy and which is conducted or
  supported by a Federal Department or Agency shall
  provide written assurance ... that it will comply
  with the requirements set forth in this policy.
  46.103(a)
• See OHRP guidance on engagement in research
• http//www.hhs.gov/ohrp/humansubjects/assurance/en
  gage.htm

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Institutional Assurance, contd

• Negotiated and approved by OHRP
• Terms of Assurance
• Federalwide Assurance (FWA) only option
• Method of compliance oversight for OHRP
• Generally recognized by other federal departments
  agencies
• Registering IRB and filing Federalwide Assurance
  (FWA) http//www.hhs.gov/ohrp/assurances
• http//www.hhs.gov/ohrp/assurances/assurances_
  index.html

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Who is covered by an Institutions Assurance?

• Employees and agents, including students,
  involved in the conduct of research covered by
  the FWA.
• May be extended to collaborating individual
  investigators in limited circumstances

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Assurance Applications Extending FWA

• Individual Investigator Agreement (IIA)
• independent investigators
• investigators at another institution
• Assured institution responsible for oversight of
  research
• Individual investigator must adhere to Terms of
  the IIA
• Guidance available at http//www.hhs.gov/ohrp/hum
  ansubjects/assurance/guidanceonalternativetofwa.ht
  m
• Sample Agreement http//www.hhs.gov/ohrp/humansu
  bjects/assurance/unaflsup.rtf

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Assurance Applications Relying on External
IRB

• Institution responsibility
• Written agreement
• IRB Authorization Agreement
• http//www.hhs.gov/ohrp/humansubjects/assurance/i
  protsup.rtf
• Designate IRB in FWA
• Ensure research conducted per IRB approved plan
• Procedures for reporting to OHRP

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Institutional Responsibilities

• Institutions bear full responsibility for all
  research involving human subjects covered by
  their Assurance
• All requirements of 45 CFR 46 must be met for all
  HHS-conducted or supported research
• OHRP strongly encourages institutions to embrace
  the HHS regulations regardless of sponsorship,
  and to commit to this standard in their Assurance.

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• IRB Review and Approval

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IRB Review

• Institutional Review Board (IRB)
• A committee charged with the review of human
  subject research to ensure that the rights and
  welfare of research subjects are adequately
  protected.
• Why do we need IRB review?

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IRB Review

• Ensure rights welfare of subjects are protected
  
• Review by IRB designated in assurance
• Must be substantive
• Sufficient information to make required findings
  at 46.111 and relevant subpart(s)
• Members with conflicting interest may not
  participate

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• Informed Consent

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Informed Consent

• Legally effective informed consent
• Each prospective subject or legally authorized
  representative
• In accordance with and to extent required by
  46.116
• Waiver/alteration consistent with 46.116(c) or
  (d), 46.408(c), or 46.101(i)

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Informed Consent Process

• Key principles of the informed consent
• process
• Full disclosure of the nature of the research and
  the subject's participation,
• Adequate comprehension on the part of the
  potential subjects
• The subject's voluntary choice to participate

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IRB Decision Matrix
Subject selection Inclusion/exclusion Recruitment
Risk/Benefit Analysis Experimental
Design Qualifications of PI
J. Cooper, Albany Medical Center
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• OHRP Resources Guidance

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New Guidance

• Reporting Adverse Events Unanticipated Problems
  (draft of Oct. 13, 2005 under revision)
• Procedures for Reporting Incident to OHRP
• Use of Coded Private Information or Biological
  Specimens
• Conflict of Interest
• 407 Review Process

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New Guidance, contd

• IRB Review of Clinical Trial Websites
• OHRPs Compliance Oversight Procedures for
  Evaluating Institutions
• Human Subject Regulations Decision Charts
• International Compilation of Human Subject
  Research Protections

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Guidance in the Pipeline

• Engagement of Institutions in Research (revision)
• Informed Consent for Subjects Who Do Not
  Understand English
• What Is Research?
• Definition of Human Subject
• Exempt Human Subject Research

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New Web Resource Frequently Asked Questions

• 45 CFR 46
• IRB Registration
• Federalwide Assurance
• Subpart D
• Informed Consent
• Investigator Responsibilities

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Contact Information

• OHRP Web page http//www.hhs.gov/ohrp
• Main Phone Number 240-453-6900
• Toll Free 1-866-447-47771-866-HHS-HRPP
• New Staff Phone Numbers http//www.hhs.gov/ohrp/
  about/staff.html
• IRB Registration Assurance Staff
  http//www.hhs.gov/ohrp/daqi-staff.html
• E-mail ohrp_at_hhs.gov
• Join Listserv http//www.hhs.gov/ohrp/news/index.
  html

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