Current IRB Challenges and
Practical Solutions
Institutional Review Board
Educational Conference
Columbia University
New York City
April 1, 2011
The Limits of Research with Human
Beings: Definition or Boundaries?
Alexander Morgan Capron
University Professor
Scott H. Bice Chair in Healthcare Law, Policy and Ethics
University of Southern California
Los Angeles, CA 90089-0071
Topic Addressed
The fundamental issue for IRBs
“Should we be reviewing this activity?”
• Partly determined by institutional policy
(such as “only federally funded” or “all
research with human subjects”)
• Basically determined by Common Rule
My central contention: Answering the
question is not just technical
The answer arises from the core
concept of research ethics
My Four Starting Premises
• Research – the attempt to add to our understanding of
the safety and efficacy of healthcare interventions – is a
good (indeed, laudable & essential) activity
• Special requirements* exist for research because of
history of violations of basic human rights and of
physical and other harms
• Application of these requirements to all research is
appropriate, for several reasons
1. Obtaining consent from all able to give it is basic right
2. Need IRB to determine completeness/comprehensibility
3. Need IRB to scrutinize investigator’s conclusion that risks have
been minimized & are outweighed by potential benefits
• Requirements apply to wide range of activities not just
clinical trials
* Requirements =the Common Rule, or “twin pillars” of voluntary
informed consent & prior review and approval by an IRB]
Origins of the Problem
• To regulate ethical review of human subjects research
need first to decide what constitutes “research”
• When regulation began in 1970s, major concern was
undue interference with ordinary medical practice
• Criteria such as “novelty,” “uncertainty” & “experiment”
didn’t help
• As to each individual patient, beginning treatment is a novel
intervention with uncertain consequences (“an experiment”)
• Choice made to take a taxonomic approach: identify
the features of the activity that distinguish it from
ordinary treatment
The Five Features of “Research”
Research means
“a systematic
investigation, . . .,
designed
to develop or contribute to
generalizable knowledge”
–- 45 CFR 46.102(d)
Some Problems with the Regulation
Regarding the definition of research, Dr.Baily has written:
“You know you are in the presence of dysfunctional
regulations when people can’t easily tell what they
are supposed to do.”
Some problems are immediately apparent:
1. Circularity (“research” means “investigation”)
2. Adjectives need elaboration (what is “systematic” or
what would make knowledge “generalizable”?)
EXPANDED: “a planned and organized scientific
activity designed to develop or contribution to
knowledge that is applicable to persons and
situations other than those studied”
Solves One Problem, Leaves Others
• Physician treating individual patient is not engaged in
a planned and organized scientific activity nor are
results likely to be applicable beyond the patient
• Does not address other situations that weren’t central
to debates 40 years ago as definition of research
arose
• QI activities, carried out by clinical managers, that
are planned and organized to develop knowledge
about how health care can be organized and
delivered more safely and effectively
• Activities, such as surveillance for new diseases,
carried out by public health authorities
Large numbers = statistically sound results
• Generalizable and, indeed, perhaps publishable
How to Respond?
1. Put through regular IRB review & obtain consent
•
Widely viewed as “overkill” that will prevent the activity
2. Add explicit exemption for these activities (existing:
types of educational and government benefit studies)
•
Possible, but lacks history and, at least for QI, basic rationale
3. Rely on another portion of regulations
--example: Pronovost-MHA QI activity (3/04 to 9/05)
•
•
•
No “human subjects” because data was aggregated by unit
Is research (studying hypothesis about effects of prospective
alteration of environment of care) but IRB-expedited and no
need for consent on grounds “could not have increased the
risk of hospital-acquired infection” Miller & Emanuel, NEJM
Problem = entirely ad hoc & sometimes wrong
Alternative: Borderlands
• Try a topographic, rather than a taxonomic, approach
• Don’t pretend that the ethically correct answer
emerges from an ever-more elaborate description
•
•
•
•
•
•
Similarity to existing “practice”
Degree of uncertainty
Extent and probability of harm
Amount of information gathered
Manner in which information will be held, stored & analyzed
How and to whom analysis will be disseminated – particularly,
whether it will be published
• Who will use the results
• Useful “definition” will not emerge from this process
Alternative: Borderlands
• “Definition” is in service of goal = to bring appropriate
subset of activities under IRB review and explicit
process of subject’s explicit choice to participate
• That subset reflects potential “conflict of interest” that
arises in research between interests of investigator and
interests of subject
• Principal difference between treatment and research is
that the former is undertaken to benefit a particular
patient and the latter is carried out to produce new
scientific knowledge
• Subject may or may not benefit
• Following the protocol may or may not increase risk/ decrease
benefit to particular subject – as an ethical matter, if the likely
result is any significant detriment to the subject, the investigator
should withdraw that subject or even end the experiment
Alternative: Borderlands
• Investigators can have wide range of intents
• Purpose (or intention) is notoriously slippery
concept, difficult to apply (esp. retrospectively)
• People hold multiple intents
• People’s view of what facts are relevant to a decision is
shaped subconsciously –we adjust facts to fit outcome
• Healthcare professionals are particularly sensitive to any
suggestion of a “conflicting interest”
• Nonetheless, the change from serving-the-individual to
serving-knowledge is the fundamental ethical concept
• Explains why “outsiders” (IRB) must review research plans
• Needs to be made clear to subjects (especially if they are also
patients)–but hard because of “therapeutic misconception”
• Does not provide sharp definition but justifies a
search for boundaries in contested territory
Apply to QI Activity
Question of “Research?” arises at three levels of QI
Implementation in Individual Hospital
•Practices supported by evidence (AHRQ)
•Record-keeping re: safety & effectiveness
•Adjust practices in light of experience
•Consent is to practice, not to QI activity
Development of QI
Intervention
Implementation in Multiple
Hospitals
•Right thing to do may be
known, but not how to get it
reliably adopted
•Record-keeping re: results
•Adjust practices in light of
experience
•Practices supported by
evidence (AHRQ) Practices
supported by evidence
(AHRQ)
•Records: internally & shared
•Adjust recommendations
Apply to Public Health
• Difficulty for public health is that the individual is not
the unit of “benefit”
• In ordinary public health data-gathering activity (such as
surveillance), intention is not to benefit individuals
• Data-analysis may produce new “generalizable knowledge”
• Individual consent may not be required
• In effect, permission provided by public health legislation &
regulation, subject to popularly elected representatives
• Same shift of focus can occur when public health
officials move beyond routine activities to research for
the purpose of producing new knowledge
• Appropriate oversight – may be IRB or may be another
body with specialized expertise in public health ethics
• Common problem: observational research
Apply to Therapeutic Innovation
• Close to starting point of the definition of research that
determines whether activity needs IRB review
• When innovation (for example, off-label use) involves
single patient, physician is acting for patient’s benefit
• Keeping observations on outcomes
• Making variations in light of experience
• What about a “series” of patients?
• Observations in one influences “knowledge” applied to others
• Complicating factor = FDA regulations and interest of
pharmaceutical companies in encouraging additional
uses and publication of data
Thank You
acapron@law.usc.edu