The Research Ethics Board

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The Research Ethics Board

• Raphael Saginur, M.D., FRCPC
• Chair, Ottawa Hospital Research Ethics Board

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The research ethics board

• Other names
• IRB Institutional Review Board (U.S.)
• Research Ethics Committee (U.K.)

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Overview

• Introduction composition why have REBs?
• Authority of REBs
• Accountability of REBs
• Human subjects research
• what sort of studies
• role of investigators

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Overview, cont.

• Important principles underpinning REB
  deliberations
• Regulation
• Issues that relate to REBs

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What is human subjects research?

• Routine clinical trial (old) comparison of new
  treatment with old in a group on patients. One
  investigator, one site, perhaps sponsored by
  industry
• Routine clinical trial (recent) comparison of
  new treatment with old in a group on patients.
  Multi-centre, multiple investigators and sites in
  multiple countries
• Routine clinical trial (contemporary) above plus
  insinuated genetic studies
• All of these may relate to drug/device
  regulation, to allow market entry of new products

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Other human subjects research

• Interventions
• Scientific studies, no benefit to subjects
  healthy people people with whatever
• Tissue/cells/genetic material creation of
  tissue banks use of samples
• Database review of information, typically
  collected for clinical or administrative purposes
  (secondary use)

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REB (TCPS)

• Composed of at least 5 people
• Men and women
• At least one knowledgeable in ethics
• Biomedical at least one knowledgeable in the
  relevant law
• At least one community member, no affiliation
  with institution U.S. regs no scientific
  background
• At least two members with broad expertise in
  the methods or areas of research
• Not a scientific review committee

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Research ethics boards(PHIPA)

• 15.  The following are prescribed as requirements
  that must be met by a research ethics board
• 1. The board must have at least five members,
  including,
• i. at least one member with no affiliation with
  the person or persons that established the
  research ethics board,
• ii. at least one member knowledgeable in research
  ethics, either as a result of formal training in
  research ethics, or practical or academic
  experience in research ethics,
• iii. at least two members with expertise in the
  methods or in the areas of the research being
  considered, and
• iv. at least one member knowledgeable in
  considering privacy issues.

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Research ethics boards

• Response to horror and scandal
• Reaction to inspeakable atrocities of Nazi
  scientists led to Nuremberg declaration,
  Declarations of Helsinki
• Horror across US political spectrum Tuskegee
  (left) and ketone studies (right) led to National
  Commission (1970s) Belmont report
• Canada MRC
• Preceded big science a creation of the 1970s
• I am an ethical scientist- how does this apply to
  me?

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Research ethics is about more than egregiously
unethical work

• Ethical people may do unethical acts (Beecher,
  NEJM)
• Enthusiasm zeal
• Interest financial promotion reputation, etc.
• Expediency
• Coercion
• Ignorance

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Authority of REB

• Claimed by defining compliance with regulation
  and guideline
• Private REB
• OCREB created de novo (just did it)
• Institution strikes REB(s) must have research
  ethics function to do human subjects research
• Canadian institutions receiving Tri-Council
  funding- must comply with rules
• U.S. funding Federal Wide Assurance

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Accountability

• REB reports to highest level of institution
  (OHREB to Board via VP Research)
• Administrative support at more terrestrial level
• Right of appeal

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Autonomy of REB within institution

• Tough to pull off
• Institution can prevent study from going ahead
• Institution cannot overrule negative REB decision

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What are important principles?

• autonomy of individual
• avoidance of coercion
• justice
• beneficence, non-maleficence
• confidentiality
• privacy

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Autonomy

• right to self determination
• translates into informed consent
• avoidance of coercion
• problem incompetence
• can be subtle
• can be transient (acute illness) or intermittent

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Avoidance of coercion

• Multiple facets to coercion
• Illness fear of death, urgency of
  decision-making
• Dependence on institution (impact of
  rationalization), on expert physician
• Example thrombolytics in acute MI
• Often cannot be entirely avoided, always can be
  managed

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Justice

• equitable distribution of risk
• equitable distribution of benefit
• complex change of thinking around AIDS crisis-
  research participation as burden or as benefit

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Justice II

• appropriateness of study
• future costs to health care system
• future availability of test, treatment
• not really addressed, yet

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Beneficence, non-maleficence

• do good
• avoid doing harm
• complex
• cannot entirely avoid risk attempting to do so
  fraught with danger
• risk should be appropriate to circumstance,
  include severity of condition, alternatives,
  potential benefit

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Beneficence, non-maleficence

• Study of cancer therapy in patients at risk of
  dying from disease, where existing therapy is
  toxic, would tolerate more risk of therapy than
  study of acne

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Confidentiality

• relates to protection of information from
  inappropriate scrutiny
• charts, laboratory results
• clinical trials right of sponsor, regulator to
  audit
• compromise data cannot leave site viewers on
  site bound by confidentiality rules/standards

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Privacy

• relates to knowledge of people and information
  related about them
• classic infringements
• investigator sends letter inviting participation-
  how the . . . do they know about me, and how do
  they know about my condition?
• shopping in the next clinic

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Privacy the sequel

• difficulties the demise of the solo doc
• doctors, nurses work in groups with
  decision-making by committee, cross-coverage
• who is privy to knowledge of patients?
• Complexities major databases, telecommunications,
  linkage

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Regulation

• Tri-Council Policy Statement (TCPS)
• Division 5, Food and Drug Regulations, Health
  Canada (September , 2001)
• Good Clinical Practice (GCP)
• Food and Drug Regulations, U.S. FDA
• Common Rule, U.S.
• all available at OHREB website www.ohri.ca/ohreb

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TCPS

• Applies to research funded by any of 3 federal
  funding councils (SSHRC, NSERC, CIHR)
• Applies to institutions which receive funds from
  any of councils
• Applies to all studies at Ottawa Hospital and
  Faculty of Medicine
• Draft update December 3, 2008

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Food and Drug Regulations, GCP

• Apply to all pre-marketing studies of
  drugs(Phases I, II, III)
• GCP is an international standard
• Canadian Food Drug Regulations were updated in
  September, 2001, to attempt to make the system
  more efficient first delineation of role of REBs
  in Canada

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FDA regs (21CFR)

• Apply to all drugs under U.S. IND
• Extra-territoriality
• Our acceptance reflects the fact that clinical
  research is an export industry

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Common rule (45 CFR 46)

• Regulations of all U.S. government except for FDA
• Includes all NIH-funded studies
• NIH can be involved in various ways grant for
  study by local PI funding MCT in which we
  participate funding study group (e.g., cancer
  groups such as SWOG, ECOG, NSABP AIDS research
  Parkinson's)

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Why do I need to know regulation?
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Legislation

• Privacy PIPEDA, PHIPA
• Contract law
• U.S. HIPAA, Patriot Act

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Issues

• Database research privacy
• Tissue banks genetic privacy, occasional need to
  feed back to patient

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Ethical issues

• Special populations children, incompetent
  (transient, permanent, intermittent)
• Highly innovative therapies (stem cells, gene
  therapy, transplant, artificial organs)
• Intellectual property, commercialization,
  academic freedom

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Conflict of interest

• Multiple levels
• institutional
• e.g., call from CEOs office about a project
  related to a local tech company
• present or future donations, collaborations
• Licensing and patents a spinoff of successful
  basic science

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Conflict of interest

• Investigator
• developer of product
• stockholder
• grant excessive inducement
• travel, publication, consulting opportunities

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Conflict of interest

• The patient subject
• undue incentive financial, promise of cure
• desperation disease
• prolongation of life
• reduction of toxicity
• relationship with doctor
• payments how to define appropriate recompense
  for time

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Often conflicting issues

• How to handle
• take patient perspective
• except avoid excessive inducement

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Consent form

• Introrationale
• Procedure, including randomization, blinding
• Voluntary nature right to withdraw
• Confidentiality

• Risks
• Benefits
• Alternatives
• Compensation clause
• Signature

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Consent form

• Language stated goal is Grade 8 level
• never happens
• not clear if feasible
• More memorandum of understanding than contract
  right to change mind (hard to remove that
  artificial heart)
• Excess length limits understanding, obscures key
  issues

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Consent

• Form is evaluable and tangible evidence of a
  consent process
• Process is more important than form
• More often nonoured in the breach than in the
  observance

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Summary

• Research ethics system is based in principle and
  articulated in guideline, regulation and
  legislation
• We must obey the rules of which there are many
• There is inherent paternalism in the system which
  attempts to manage the potential interests of
  institution, investigator and sponsor as well as
  the vulnerablity of the subject
• There is a desire to protect human subjects from
  physical harm or harm to their rights
• The REB is the core of the system