The role of the REB Raphael Saginur, M.D. Ottawa Hospital Research Ethics Board.
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Transcript of The role of the REB Raphael Saginur, M.D. Ottawa Hospital Research Ethics Board.
The role of the REB
Raphael Saginur, M.D.
Ottawa Hospital Research Ethics Board
REB roles
• protection of human subjects
• protection of investigator, institution
• protection of academic freedom
Research ethics: a huge bureaucracy
• in typical MCT, review at each of multiple sites: changing slowly
• at each site, multiple copies of application (TOH: 18)
• hard copies: slow migration to electronic– proprietary interests– lots of reading
The only independent review of protocol at site
• only opportunity for administrative vetting (resource impacts, approval of thesis committee, etc.)
• cost to sponsor, investigator• delay• questions, quibbles, disagrees, blocks• naturally antagonizes PI, sponsor• must earn respect : fair, transparent, accountable,
tough
Respect
• listen
• treat PI with respect
• demand respect
• don’t quibble about trivia
• have reasoned opinions based in rationale and/or regulation
• be consistent
Regulations
• not well known to PIs- a mystery. Almost never taught
• PIs semi-autonomous within hospitals; medical staff members, not employees
• PIs don’t like being told what to do• regulations and legislation were not
enforced in the past; it is novelty that they now are: tough adjustment
Why do I need to know regulation?
Jurisdictions:complex
• drug study at TOH/Faculty of Medicine:– GCP/HC– TCPS– FDA: maybe– U.S. Common Rule:
• study group NIH-funded
• study NIH funded
– Provincial law (PHIPA), regulation (e.g., professional codes)– Federal law (criminal; privacy)
Jurisdictions, cont.
• from PI perspective, jurisdiction mostly a matter of which form to sign (HC, FDA)
• adverse events: PI hands off rapidly to sponsor; sponsor addresses rules
• in general, jurisdiction more an REB and sponsor issue
• issue becomes relevant to PI: renewals, amendments
REB tries to base decisions in principle
• principle takes priority
• regulations follow– U.S.: mired in regs, rediscovering principle
What are important principles?
• autonomy
• avoidance of coercion
• justice
• beneficence, non-maleficence
• confidentiality
• privacy
Autonomy
• right to self determination
• translates into informed consent
• avoidance of coercion
• problem: incompetence– can be subtle– can be transient (acute illness) or intermittent
Avoidance of coercion
• multiple facets• 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
Justice
• equitable distribution of risk
• equitable distribution of benefit
• complex: change of thinking around AIDS crisis
Justice II
• appropriateness of study– future costs to health care system– future availability of test, treatment
• not really addressed
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
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
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
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-door clinic
Privacy
• 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?
Privacy: databases
• multiple big databases are held for clinical and administrative purposes are held at TOH
• divisional and departmental databases have become a cottage industry
• linkage of databases within and without institution a productive line of research
• database research is a risk to privacy; linkage adds fuel to the fire of risk
Privacy: new legislative context
• HIPAA (U.S.)• PIPEDA (Canada)• Ontario PHIPA• explicit standards• generally enhance public consciousness of privacy• we are working on standards for databases and
privacy: what is held, what is sent, how information is held; technical, policy, administative
Conflict of interest
• multiple levels
• institutional:– e.g., my recent call from CEO’s office about a
project related to a local tech company– present or future donations, collaborations
Conflict of interest
• investigator– developer of product– stockholder– grant: excessive inducement– travel, publication, consulting opportunities
Conflict of interest
• the patient subject– undue incentive– desperation: disease– prolongation of life– reduction of toxicity– relationship with doctor– payments: how to define appropriate
recompense for time
Often conflicting issues
• how to handle:– take patient perspective– except: avoid excessive inducement
Application process
• application form is condensed version of protocol plus it teases out certain issues usually missed in protocol
• cumbersome, slow, expensive
Application
• identification of investigators: responsibility– issue: students (the loose cannon phenomenon)
• approval by administrator:– patient stewardship(risk, over-involvement in
studies)– resource management– consistency with institutional
mission,principles
Application
• bad science is bad ethics
• various sections of our forms describing science
• REB not peer review committee
Application
• advertisements– avoidance of overzealous or outright false
claims– sufficient information– consistency with College of Physicians rules re
physician advertising
Application
• risks and discomforts– broadly defined– include prolongation of care; delay of care– delineation of what is attributable to study,
what is attributable to routine management going on concomitantly
Application
• DSMBs, stopping rules
• management of risk– changing regulatory demands (NIH, FDA)
• funding– excess: conflict of interest– insufficient: burden on Hospital
Application
• staffing– competence– e.g.,outbreak of hepatitis C
• resource impact– management
Genetics
• genetic testing frequently insinuated into otherwise routine clinical trial
• new science of pharmacogenomics; targeted therapy: opportunity for societal benefit by improving efficacy of therapy, reducing cost, reducing toxicity
• risk
• opportunity for new product development: Moore
Risk of genetic testing
• nothing to do with pain and bruises (‘the phlebotomy misconception’)
• relates to use of information– social, psychological risk– insurance, employment– marriageablity
Genetic testing: risk
• risk may be borne by individual, family, community
• opportunity for counseling
• decisions to be made regarding linkage of results with individuals
Consent forms
• pre-occupation with consent form and not consent process: a trap
• pretty standard elements
• grammar, spelling: rare forms of knowledge
• lucidity of language, organization of thought uncommon virtues
Consent form
• Intro:rationale• Procedure, including
randomization, blinding
• Voluntary nature; right to withdraw
• Confidentiality
• Risks• Benefits• Alternatives• Compensation clause• Signature
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
Monitoring of studies: AEs
• “more honoured in the breech than in the observance”
• REBs not equipped to monitor AEs• REBs given inadequate information• create paper trail• all interventional studies need data
monitoring plan
Expedited review
• feasible in “minimal risk” study• TCPS: “no greater than those encountered by the
subject in those aspects of his or her everyday life that relate to the research”
• FDA: collection of hair, nails, deciduous teeth; excreta and external secretions; EEG,ECG; <451 ml blood; dental”plaque” and calculus; voice recordings; moderate exercise; existing records; etc.
• consent may or may not be required
Minimal risk
• difficult application to percutaneous radiologic image-guided procedures
• what is risk of percutaneous ultrasound guided breast biopsy done by competent radiologist? How does it compare to risk of phlebotomy of 450 ml by a duffer?
Conclusions
• REB works within regulatory framework
• REB tries to base decisions on principles defined in ethics, and reflected in regulation
• forms seek to elicit information to define ethical issues, allowing reasoned decision-making
• www.ohri.ca/ohreb