Development of Human Subject Protection Policy in the U'S'

1
Development of Human Subject Protection Policy
in the U.S.

• Melody H. Lin, Ph.D.
• Deputy Director, Office for Human Research
  Protections
• Director, International Activities
• Melody.Lin_at_hhs.gov
• Santiago, Chile
• April 2009

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Objectives

• US Regulations and Federal Policy
• Past
• Present
• Future
• ICH GCP
• EU Clinical Trial Directive
• Observation of different regions.

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US Regulations and Policy

• HHS Regulation
• FDA
• IRB Regulation
• Informed Consent Regulation
• Federal Policy

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Forms of Standards

• Statute
• Regulation
• Policy/Guidance

5
Process for Developing Regulations

• Regulation
• Notice and Comment
• NPRM
• Review Comments
• (Interim Final Rule Urgent)
• Final Rule

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PHS Policy

• 1947 Nuremberg Code
• 11-17-53 NIH Clinical Center Policy Group
  Consideration
• 1964 Declaration of Helsinki
• 2-8-66 PHS Policy (PPO 129) Clinical
  Investigations using HS
• 7-1-66 NIH Policy Group consideration and
  Informed consent in clinical research
  at NIH

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1966

• Policy for the Protection of Human Subjects
• Awardee to establish Committee (IRB) to oversee
• Risk/Benefit Assessment Informed Consent
• Institutional Relations Branch (IRB)
• NIH Division of Research Grants (DRG)
• Oversee the PHS Policy

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PHS Policy, contd

• 5-1-69 Revised PHS Policy Protection of the
  individual as a research subject
• 4-15-71 Extend PHS Policy to DHEW Policy
• 12-1-71 Institutional Guide to DHEW policy
  Elements of informed
• consent, signature documentation
  

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National Research Act

• 1973 Kennedy Hearings Quality of Health
  Care - Human Experimentation
• 1974 National Research Act
• Established the National Commission for the
  Protection of Human Subjects of Biomedical and
  Behavioral Research
• Required IRBs at institutions receiving HEW
  support for human subjects research

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• 45 CFR 46
• DHEW Protection of Human Subjects
• Raised PHS Policy to Regulation

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History of HHS Regulation

• 4-28-73 Tuskegee Syphilis Study Report
• 10-9-73 HEW NPRM, 45 CFR 46 Protection of
  Human Subjects
• 5-30-74 HEW Final Rule, 45 CFR 46
• 7-12-74 National Research Act

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HHS Regulation, contd

• 1-13-77 HEW NPRM, 45 CFR 46 Subpart B
• 4-1-77 HEW Notice Assurances (60 days)
• 1-11-78 Subpart B Final Rule Amendments

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HHS Regulation, contd

• 11-3-78 DHEW Interim Final Rule Informed
  Consent 45 CFR 46 elements amended
  to include advice in compensation
  
• 
  
• 11-16-78 DHEW Final Rule
  
  
  45 CFR 46 Subpart C
• 11-17-78 NPRM - Subpart E

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HHS Regulation, contd

• 11-30-78 IRB National Commission
  
  Report Recommendation
• 4-18-79 HEW Notice for Belmont Report
  Public Comment
• 10-9-80 DHHS Final Rule Debarment
  Suspension from eligibility for
  financial assistance

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HHS Regulation, contd
1-26-81 DHHS Final Rule Subpart A
3-22-82 DHHS NPRM Exemption from HHS
Regulations
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HHS Regulation, contd
3-4- 83 DHHS Final Rule Exemption
Categories 3-8-83 DHHS Final Rule, Subpart
D 8-4-83 Final Rule, Protection of Human
Subjects
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Federal Policy

• 11-9-78 Presidents Commission Biennial
  Report
  PL 95-622
• 12-81 1st Biennial Report Adequacy
  uniformity of federal rules
  policies their implementation

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Federal Policy, contd

• 3-29-82 CFR
• 5-82 Ad Hoc Committee for the Protection
  of Human Subject
• 6-3-86 Proposed model federal policy
  (Federal Register)

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Federal Policy, contd

• 11-10-88 NPRM, Federal Policy
• Comments end 2-8-89
• 6-18-91 Final Rule Federal Policy
• Common Rule

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Federal Regulations and Policy

• 45 CFR 46 - Basic DHHS Policy for Protection of
  Human Research Subjects - Subpart A
• Originally adopted January 13, 1981 Revised
  June 18, 1991
• The Common Rule - Federal Policy for the
  Protection of Human Subjects 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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• Presidential Commission

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• National Commission -1974
• President Commission - 1978
• National Bioethics Advisory Commission -1996

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Trigger Events
Milestone

• The Syphilis Study (Expose)
• 1966 The Beecher Article (NEJM)
• Declaration of Helsinki
• 1964
• Milgram Study
• Kefauver-Harris
• Amendments to the 1962
• Food, Drug and
• Cosmetic Act
• The Thalidomide Tragedy
• Nuremberg 1947
• Code
• Human Radiation Experiments
• The Nazi Experiments
• The Syphilis Study (Begins)

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Trigger Events
Milestone

• National Bioethics
• Advisory Commission 1995
• NM Tribune
• Common Rule 1991
• CIOMS Guidelines 1982
• Consolidated
• HHS/FDA Regulations 1981
• Belmont Report 1979

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FutureHuman Subject Protection
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Scrutiny

• Congressional
• Media
• Public Safety

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Legislation

• Required to enhance the current system of
  protections
• Safeguard safety well-being
• Enhance knowledge progress

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Greenwood/DeGette Bill

• All Research
• Single Oversight Office
• Conflict of Interest
• Monitoring Requirement
• IRB Review Oversight

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Kennedy Proposed Legislation

• Provide a comprehensive protection
• Promote effective oversight
• Prevent improper financial conflicts
• Individual
• Institution
• Provide effective oversight of international
  research

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Protection for Participants in Research Act (MAR.
2009)DeGette Bill

• H.R. 1715
• Amend PHS Act
• OHRP FDA Harmonization
• Accreditation of HRPP
• Increase nonscientist nonaffiliated members

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Independent Agency to Consolidate (FDA OHRP)

• H.S.P Activities
• Universal Protections

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ICH GCP

• What?
• Why?
• Adopted by emerging countries/regions

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Need for EU Directive

• Since 1997 ICH - GCP has been followed by
  industry, but, guidelines are not legally
  binding.
• Since 2001, EU recognizes trials are complex and
  often multinational.
• EU Directive rationalizes the requirement for
  starting and conducting the trial.

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EU Directive

• Legal mandate to
• Sponsors
• Investigators
• Regulators
• Ethics committees
• Simplify and harmonize administrative procedures
  and speed up clinical trials

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The strength of the EU Directive

• Central Database to share with member states
• Clinical trial supplies must be manufactured in
  compliance with GMP.
• Allow movement between M.S. without retesting.
• SUSARS (Suspected and Unanticipated Serious
  Adverse Reactions) share across M.S. including
  competent authority.
• Sponsor need to appoint the inspector the trial

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Global Observations

• EU
• Initial review by local EC
• Continuing review by competent authority or
  national central EC.
• Central and Eastern Europe
• Follows EU Directive and/or ICH-GCP
• Africa
• Follows ICH GCP
• Asia
• Follows ICH GCP and US Regulations
• Latin American
• Follows ICH GCP and National Regulations

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Challenges for Regulatory Approval

• Extended Approval Process due to
• Local EC
• National Regulation
• Cultural Diversity
• Political Realities
• Power Relationships

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Summary

• US Regulations and Federal Policy
• ICH GCP
• EU Clinical Trial Directive
• Observation of different regions.