INTERNATIONAL ETHICAL GUIDELINES: CIOMS

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INTERNATIONAL ETHICAL GUIDELINES CIOMS

• Robert J. Levine, MD
• Director Donaghue Initiative in Biomedical and
  Behavioral Research Ethics Professor of
  Medicine Lecturer in Pharmacology
• Yale University
• New York March 20, 2008

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PURPOSE OF THIS TALK

• To expose the process of design of international
  codes of research ethics.
• CIOMS 2002 as an example.
• The most satisfactory.
• Long-range goal to facilitate the better
  understanding of international ethical codes so
  that they may be more skillfully applied.

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OUTLINE OF TALK

• Historical note on CIOMS link to Declaration of
  Helsinki.
• The design of a satisfactory document.
• Specific applications to the design of the 2002
  (most recent) revision.
• Distribution of the Worlds resources and its
  relevance to Guidelines.

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THIS SHOULD NOT BE THE WEALTHY DICTATING ETHICS
TO THE WORLD

• CIOMS Guidelines are designed primarily to guide
  sponsors and investigators from the wealthy
  countries as they carry out research in
  developing countries.

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HELSINKI LINK

• Purpose in 1982 to advise how the principles of
  Helsinki could be effectively applied,
  particularly in developing countries.
• 1982 Minor deviations e.g., consent through
  intermediary.

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CIOMS 1993

• Substantial deviations circumlocutions.
• On phase I drug testing The requirementof
  Article III.2, subjects should be volunteers
  either healthy persons or patients for whom the
  experimental design is not related to the
  patients illness is not to be disregarded
  lightly.

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Short Duration AZT Trials 1997

• Criticism in New England Journal of Medicine.
• The most acrimonious debate on ethics of clinical
  trials since 1970s.
• WMA and CIOMS each launched document revision
  projects.
• A major objective of each organization was
  harmony.

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HELSINKI 2000

• Accomplishments
• Clarification of language.
• Removal of the language of therapeutic and
  nontherapeutic research.
• Remaining to be done
• Clarification of position on placebo controls
• Removal of remnants of therapeutic and
  nontherapeutic logic.

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CIOMS 2002

• There is more harmony with Helsinki than there
  was in 1993.
• There are no circumlocutions as regards
  differences with Helsinki.
• WMA 2001 clarification on placebos failed to
  secure consensus
• Some think it went too far.
• Some deplore loss of substantive standard.
• Some think it incomprehensible.

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DESIGN of SATISFACTORY GUIDLEINES

• Idealism vs pragmatism.
• Procedural vs substantive guidelines.
• Micromanagement.
• Paternalism.
• Unreconciled controversy.

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IDEALISM vs PRAGMATISM

• Idealism must be expressed
• Emphasized in introduction and appendices.
• Emphasized that these are long range goals, not
  todays expectations.
• Pragmatism must be reflected in Guidelines
  themselves
• This is the behavior expected today.
• Idealism in Guidelines encourages noncompliance

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ETHICS AS PRACTICAL REASONING

• Principlism the mistake of the 1960s.
• Applied ethics must not be purely theoretical.
• Ethical guidelines must be informed by a thorough
  empirical knowledge of the field.
• Anthropologists.
• It is not ethics vs science.
• Ethics cannot be dissociated from economic
  considerations.

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PROCEDURAL vs SUBSTANTIVE GUIDELINES

• Substantive guidelines actions required (or
  forbidden) because they are morally right (or
  wrong).
• Procedural guidelines
• To assure compliance with substantive guidelines.
• To determine what is morally right or wrong in
  particular circumstances.

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PROCEDURAL GUIDELINES

• Most numerous in guidelines designed to cover
  diverse projects and cultures.
• Enable decision-making that is especially suited
  to particular cultures or fields of research.
• May allow exploitation of individuals in corrupt
  regimes.

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SUBSTANTIVE GUIDELINES

• Most numerous in guidelines designed for
  homogeneous cultures or single fields of study.
• Restrict the use of judgment to adapt to
  circumstances unanticipated in the guidelines.
• Micromanagement.
• Reduce the probability of exploitation in corrupt
  regimes?

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PATERNALISM

• CIOMS 1993 designed to prevent exploitation of
  developing countries.
• UNAIDS Guidance Document attempted to correct
  this.
• Enabling low resource countries more freedom to
  be self-determining.
• Is the pendulum swinging back toward
  protectionism?

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IRRECONCILEABLE CONTROVERSY

• The goal is consensus, not unanimity.
• No consensus
• 1993 Genetics, embryo and fetal research.
• 2002 Proposed Guideline 16 on products of
  conception.
• Consensus without unanimity
• Compensation for research induced injury.
• Nonbeneficial procedures that present more than
  minimal risk in research involving children.

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GUIDELINE 11

• General requirement to provide each subject with
  established effective intervention EET.
• Replaced standards
• Best proven therapeutic (preventive or
  diagnostic) method. Helsinki
• Best current intervention. (CIOMS drafts).

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PLACEBO MAY BE USED1

• 1. No proven intervention exists.
• 2. Withholding EEI results in only temporary
  discomfort and no serious harm.
• 3. EEI as comparator would not yield
  scientifically reliable results.

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PLACEBO MAY BE USED2

• 4. Studies designed to develop an effective
  alternative to an EEI that is not locally
  available.
• Usually for economic or logistic reasons.
• Ethical justification
• Responsive to health needs.
• EEI as comparator would not yield scientifically
  reliable results.
• Reasonably available sustainable.

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DOUBLE STANDARD?

• No!
• The single standard is that the results of the
  research should be responsive to the health needs
  and priorities of the community of the subjects
  and the products developed must be made
  reasonably available.

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FIDUCIARY VIOLATION?

• Pathogenesis
• Pathophysiology
• Epidemiology

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Global injustice The distribution of
wealth among the nations of the world is
inequitable. Research did not cause this and
research cannot fix this. There is a temptation
to use international research documents as
devices to correct inequities to some extent
this is a reasonable and constructive activity.
However, we must avoid development of guidelines
that would impede the efforts of sponsors and
investigators in industrialized countries to
assist countries with lesser resources in their
efforts to develop treatments and preventions
that they can afford.
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RECOMMENDATION FOR INTERNATIONAL AGENCY

• Serves as interpreter.
• Serves as a monitor to identify needs for
  revision of Guidelines.
• Infinite malleability.
• New procedure
• Remains to be done