Research Involving Human Subjects: Enough Rules, More Responsibilities

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Research Involving Human Subjects Enough Rules,
More Responsibilities

• Prof. Dominique Sprumont
• Institut de droit de la santé
• Université de Neuchâtel
• Switzerland

Cardiff, June 12, 2008
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Nature and scope of the regulation(s) of research
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Regulation of Biomedical ResearchMain Documents
of Reference

• Nuremberg Codex (1947)
• Geneva Conventions (1949)
• Declaration of Helsinki (1964, 1975, 1983, 1989,
  1996, 2000, 2002, 2004, 2008?)
• Art. 7 International Covenant on Civil and
  Political Rights (1966)
• International Ethical Guidelines for Biomedical
  Research Involving Human Subjects prepared by the
  CIOMS in collaboration with WHO (1982, 1993,
  2002)
• International Conference on Harmonisation of
  Technical Requirements for Registration of
  Pharmaceuticals for Human Use Good Clinical
  Practice Consolidated Guideline (ICH-GCP)
  (1996)
• European Union Directives on Clinical Trials
  (2001/2005)
• Council of Europe on Human Rights and Biomedicine
  and its additional protocol on biomedical
  research (1997) and its Additional Protocol of
  Biomedical Research (2005)
• US Regulation (FDA/NIH)
• National legislation (specific/general)

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Regulation of Biomedical ResearchAn Example of
Internormativity

• Nuremberg Codex (1947)
• Geneva Conventions (1949)
• Declaration of Helsinki (1964, 1975, 1983, 1989,
  1996, 2000, 2002, 2004, 2008?)
• Art. 7 International Covenant on Civil and
  Political Rights (1966)
• International Ethical Guidelines for Biomedical
  Research Involving Human Subjects prepared by the
  CIOMS in collaboration with WHO (1982, 1993,
  2002)
• International Conference on Harmonisation of
  Technical Requirements for Registration of
  Pharmaceuticals for Human Use Good Clinical
  Practice Consolidated Guideline (ICH-GCP)
  (1996)
• European Union Directives on Clinical Trials
  (2001/2005)
• Council of Europe on Human Rights and Biomedicine
  and its additional protocol on biomedical
  research (1997) and its Additional Protocol of
  Biomedical Research (2005)
• US Regulation (FDA/NIH)
• National legislation (specific/general)

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Regulation of Biomedical ResearchAn Example of
Internormativity
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Basic rules of research involving human subjects

• Pre-clinical data
• Proper design of the trial
• Scientific validity and medical relevance of the
  research
• Free and informed consent of the subjects
• Favorable balance benefits/risks
• Respect of confidentiality/privacy of the
  subjects
• Compensation for research induced damages
• Qualification of the investigator
• Sufficient ressources of the investigator (time,
  staff, infrastructures, material)
• Independance of the researcher / IP
• Favorable opinion of the competent Ethical Review
  Board
• Registration of the research
• Re-use of biological material, etc.

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Before the Declaration of Helsinki (1964)

• Nuremberg Codex (1947) or the original
  misunderstanding on the nature of the regulation
•  It was a good code for barbarians but an
  unecessary code for ordinary physician-scientists 
  
• Jay Katz 1992

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Declaration of Helsinki (1964)

• The medical profession self declared independance
• The World Medical Association interpreted the
  Nuremberg Code so it was responsive to the needs
  of the practice
• Robert J. Levine 2002
• US influence
• Research with prisoners (banned in the DoH 1962
  draft)
• Research with institutionalised children (banned
  in the DoH 1962 draft)

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US regulation and the DoH

• Drug Amendment Act 1962
• (Kefauver-Harris Bill Thalidomide)
• Consent for Use of Investigational New Drugs on
  Human Statement Policy 1966

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Effectiveness of the DoH

• 1966 Henry K. Beecher, Ethics and Clinical
  Research (NEJM)
• 1967 Maurice H. Pappworth, Human Guinea Pigs
  Experimentation on Man
• 1962 Human Guinea Pigs A Warning

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US Regulation in the 70s

• 1971 Institutional Guide to DHEW Policy of
  Protection of Human Subject
• 1972 Tuskegee Syphilis Study
• 1974 Federal Regulation of Human Experimentation
  (DHEW)
• Creation of the IRBs system

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US regulation and the DoH

• 1975 first revision of the DoH in Tokyo
• specially appointed independent committee
• 2000 fifth revision of the DoH in Edinburgh
• specially appointed ethical review committee
• 2008 proposed sixth revision of the DoH
• a research ethics committee

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US Regulation from the 70s until early 90s

• 1978 Belmont Report (Founding document of
  Bioethics)
• 1981 coordinated revision of the FDA and DHEW
  regulation (informed consent, IRB, etc.)
• 1991 Federal Policy for the Protection of Human
  Subjects (Common Rule)

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Good Clinical Practice and the industrialization
of Research

• 1989 Nordic Guidelines for Good Clinical
  Practice
• 1991 First ICH meeting in Brussels
• 1996 Final step (5) in the approval of the
  ICH GCP
• 1997 Introduction of the ICH GCP in the
  regulation of the EU, USA and Japan
• ICH International Conference on Harmonisation of
  Technical Requirements for Registration of
  Pharmaceuticals for Human Use

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Regulation of Research in Europe

• Human Rights approach - CoE
• 1997 Convention on Human Rights and Biomedicine
• 2005 Additional Protocol to the Convention on
  Human Rights and Biomedicine on Biomedical
  Research
• Therapeutic products approach - EU
• Directive 2001/20/EC on Drug Trial
• Directive 2005/28/EC detailed guidelines for GCP

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European Research Regulation andthe national laws

• Members States of the EU and the Council of
  Europe remain compentent in the regulation of
• Competent authorities
• Research Ethics Committees (art. 2, 6 EU / art.
  16 CoE)
• Informed consent (3 and 5, art. 3 EU / art. 16
  CoE)
• Legal competency (3 and 5, art. 3 EU /art. 6
  CoE)
• Legal representative (3 and 5, art. 3 EU /art. 6
  CoE)
• Liability and Insurance (art. 3 EU /art. 35 CoE
  Add. Protocol)

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Nature and scope of research regulation
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Changes in the REC Environment
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Nature and scope of the Nuremberg Code
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Nature and scope of the Declaration of Helsinki
Subject
Investigator
Editor
Research Ethics Committees
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Nature and scope of the CIOMS Guidelines
Health authorities
Sponsor
Subject
Investigator
Editor
RECs
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Nature and scope of the ICH - GCP
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Present regulation a growing complexity
CRO
Controlling authorities (professional, public
health, justice)
Sponsor
Monitors
Auditors
Patients
Subject
Investigators
Editor
RECs
Public and non profit research funds
Social security
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Protection of Human Subjectswhere are we today ?

• Trovan Case (Nigeria 1996 - 2007)
• Jesse Gelsinger Case (US 1998)
• VanTx Case (Switzerland 1999)
• Vioxx Case (Worldwide 2004)
• Parexel Case (UK 2006)

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Protection of Human Subjectswhere are we today ?

• If the overall protection of human subjects has
  improved, old problems remain and new problems
  arise
• More rules may not be needed

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Protection of Human Subjects and the regulatory
inflation

• Lack of transparency
• Loss of meaning
• Growing technocracy
• Loss of motivation for researchers and RECs
  members
• Surrender/Delegation of responsibilities

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Protection of Human Subjects and the regulatory
inflation

• The complexity of the regulation reflects the
  complexity of the issues at stake in research
  involving human subjects
• Yet, this should not lead to confusion, a
  weakening of the protection of human subjects and
  unnecessary constraints of research

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Enough Rules, more responsibilities

• After moving from self-regulation to the law as a
  need to guarantee the protection of human
  subjects, the effectiveness of research
  regulation in protecting human subjects requires
  reinforcing the ethical responsibilities of all
  stake holders in the field

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Protection of Human Subjects Time to look back

• Education is a cornerstone for any meaningful
  attempt to construct a system of control of
  medical practice and experimentation. Once its
  importance is recognised, it has the virtue that
  something can be done about it. New rules and
  procedures are especially needed, but can only be
  promulgated after their purposes are clearly
  articulated. Here lessons from the past and
  present may serve as a guide to the future.
• Jay Katz 1969

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New Roads to Explore

• Drachtens naked road or shared space
  experiment
• From traffic light to roundabout
• Home Zones Challenging the future of our
  streets, Department for Transport, 2005

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Conclusion

• It is important to move away from a strict
  reliance on "rights" and laws, and recognize the
  potential for more personal responsibilities in
  protecting human subjects. This requires proper
  training and education.
• But the legal framework cannot achieve its
  objectives without an ethical commitment of every
  participant in research to respect them.