Transcript Evidence-based Medicine

Ethics and
Evidence-based Medicine (EBM)
PHL281Y Bioethics
Summer 2005
University of Toronto
www.chass.utoronto.ca/~kirstin
Overview
1.
(Olivieri case)
2.
Decision-making in Medicine
3.
What is EBM?
4.
5.
6.
Evaluating the Evidence
Hierarchy
Ethics and EBM
Ethics and Corporate Influences
on Decision-making in Medicine
Interim findings of RCTs
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Case: Dr. Nancy Olivieri
Mid 1990’s
Hospital for Sick Children (Toronto)
Apotex
Thalassemia
Hydroxypyridin-4-1 (deferiprone)
Physician/scientist roles (Hellman &
Hellman)
Individual equipoise vs. clinical equipoise
Academic freedom in clinical research
Decision-making in Medicine
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How do physicians make decisions about treatments
for particular patients?
• Intuition? Experience? Authority? Case studies?
RCT evidence?
Is it ethical of a physician to make decisions on other
grounds? Why/Why not?
• Decision based on ‘gut feeling’?
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It matters quite a lot whether these decisions are
right or wrong (life/death)
EBM Version 1.0
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Evidence-based Medicine (EBM)
Motivation
• History: textbook information + authority of superiors +
personal experience as sources of evidence
• Surveys in the 70’s and 80’s - lack of standardization
• Increase in biomedical research - overload of
information (read 19 articles/day, 365 days/year vs. 1
hour a day to read)
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Goal: Make the practice of medicine more objective
(and hopefully therefore more standardized)
The (In)famous Declaration (1.0)
EBM “de-emphasizes intuition, unsystematic clinical
experience and pathophysiologic rationale as
sufficient grounds for clinical decision-making and
stresses the examination of evidence from clinical
research”
- EBM Working Group 1992 JAMA
The Process (1.0)
1.
Formulate a question
2.
Do a literature search (MEDLINE)
3.
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Use the evidence hierarchy to ‘critically evaluate’ the
quality of evidence
Apply the recommendations of the ‘best evidence’
directly to patients
*Don’t let intuition or clinical experience interfere
The Reaction to EBM 1.0
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Medical journals flooded with articles, editorials
Concern about a ‘cook-book’ approach to
medicine (no deviation)
The art vs. science of medicine
EBM Version 2.0
“Evidence-based Medicine is the conscientious,
explicit and judicious use of current best evidence
in making decisions about the care of individual
patients”
- Sackett, JAMA 1996
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Integration model – best evidence + individual
clinical expertise (‘neither alone is enough’)
Comparing Versions 1 & 2
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EBM 1 “de-emphasizes
intuition, unsystematic
clinical experience and
pathophysiologic rationale
as sufficient grounds for
clinical decision-making
and stresses the
examination of evidence
from clinical research”
(1992)
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EBM 2 “is the
conscientious, explicit and
judicious use of current
best evidence in making
decisions about the care of
individual patients” (1996)
The Process (2.0)
1.
Formulate a question
2.
Do a literature search (MEDLINE)
3.
4.
Use the evidence hierarchy to ‘critically evaluate’ the
quality of evidence
Integrate ‘best evidence’ with clinical experience to
produce a decision regarding treatment
Simplified Evidence Hierarchy
Meta-analyses
Randomized Controlled Trials
Non-randomized / Observational Research
Case-series, Case Studies, Qualitative Research, Anecdotal Evidence
Assumptions Underlying the Hierarchy
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Why is the hierarchy ordered the way it is?
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Best evidence is identified by 3 characteristics:
1. Simple
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The simplest explanation is often the best (Ockham’s razor)
2. Generalizable
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The results of research need to be generalizable to as many
patients as possible
3. Objective (free from bias)
Success
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EBM now widely accepted in medical schools and hospitals
across North America and much of Europe
Extended to physiotherapy, nursing, public policy,
dentistry… “Evidence-based practice”
Practice Guidelines
“One of the most influential ideas of the year” New York
Times Magazine 2001
Funding bodies, journal editors and policy makers continue
to rely on strict application of the evidence hierarchy (RCTs
and meta-analyses of RCTs)
7 Alternatives to EBM (BMJ)
1. Eminence-based medicine - the more senior the colleague,
the less importance he or she placed on the need for anything as
mundane as evidence. These colleagues have a touching faith in
clinical experience, which has been defined as “making the same
mistakes with increasing confidence over an impressive number
of years.”
2. Vehemence-based medicine - the substitution of volume for
evidence.
3. Eloquence-based medicine - the year-round suntan,
carnation in the buttonhole, silk tie, Armani suit, and tongue
should be equally smooth. Sartorial elegance and verbal
eloquence are powerful substitutes for evidence.
7 Alternatives (continued)
4. Providence-based medicine – decision left in the hands of the
Almighty
5. Diffidence-based medicine - do nothing from a sense of
despair. (This may still be better than doing something merely
because it hurts the doctor’s pride to do nothing)
6. Nervousness-based medicine - fear of litigation is a powerful
stimulus. In an atmosphere of litigation phobia, the only bad test
is a test you didn’t think of ordering
7. Confidence-based medicine - this is restricted to surgeons
Evaluating the Hierarchy
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What is actually being done (almost exclusive focus
on RCTs and meta-analyses) vs. charitable reading of
what is proposed
• Example: 13 observational studies found same effect, all
trumped by 1 RCT that disagreed
Evaluating the Hierarchy
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“Because the randomized trial, and especially the
systematic review of several randomized trials, is so much
more likely to inform us and so much less likely to mislead
us, it has become the ‘gold standard’ for judging whether a
treatment does more harm than good”
• Note: the claim that observational research ‘overestimates’ effects is circular
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Do we have reason to doubt the RCT as the ‘gold standard’?
Do we have reason to value the lowest levels of evidence
more highly?
Evaluating the Hierarchy
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A weak claim: “An RCT is not always the best
choice of study design”
A stronger claim: “An RCT, even when possible,
often gives markedly worse evidence than an
observational study” (Grossman & Mackenzie, 2005)
Evaluating the Hierarchy
1. Treating the ‘Average’ Patient (vs. individualized
care)
• The RCT evaluates efficacy rather than effectiveness
• Restricted population in trials (inclusion and exclusion criteria)
• “Only 10% of patients in primary care have the sort of
isolated, uncomplicated form of hypertension that lends itself
to management by a standard evidence-based guideline.”
(Greenhalgh, 1999)
• “Clinical research, as currently envisioned, must inevitably
ignore what may be important, yet non-quantifiable,
differences between individuals. Defining medical knowledge
solely on the basis of such studies, then, would necessarily
eliminate the importance of individual variation from the
practice of medicine” (Tonelli, 1998)
Evaluating the Hierarchy
• “The empirical observation of populations in randomized trials
and cohort studies cannot be mechanistically applied to
individual patients (whose behavior is irremediably contextual
and idiosyncratic) or episodes of illness.” (Greenhalgh, 1999)
• “When transferred to clinical medicine from an origin in
agricultural research, randomized trials were not intended to
answer questions about the treatment of individual patients”
(Feinstein and Horwitz, 1997)
• Complexity of human beings
 Adverse Drug Reactions (rate 4-6th leading cause of death
in USA)
 Support from pharmacogenetics
• RCT results may be most helpful at policy level
• Need subgroup analysis (at the very least)
Evaluating the Hierarchy
2. False Sense of Objectivity
Some possible sources of bias in research:
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Broad social forces
Funding agencies
Publication bias
• Suppressing negative results, confidentiality clauses, presenting only
part of the data (ex/ Celebrex – first 6 months of year-long trial, AIDS
vaccine – only presented positive subgroup)
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Loopholes in methodology
• Study design bias - testing against placebo rather than current drug,
testing only young people (less side effects), suboptimal dosing, trials
too brief to be meaningful
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Backgrounds and goals of researchers (research what you fear)
Researcher’s values (ex/ interpreting data favourably)
Patient’s values
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Evaluating the Hierarchy
3. “Lower” Evidence is Often Ignored
• Many research questions cannot be answered with RCTs - think
especially of social, psychological and environmental diseases
and treatments
• If you treat patients on the EBM model, what happens to
information from these sources?
• How does this influence treatment?
 Overmedication (nutrition and exercise vs. drug)?
Evaluating the Hierarchy
4. The Problem of Moving Away from First Causes
• RCTs and symptom alleviation
• “Identify and treat the causes”
• You will need research in basic sciences (biochemistry, etc.) to get at
these first causes
• Pathophysiology
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Antibiotics for infection, pacemakers, blood transfusions, fluids for
dehydration…
Insulin and penicillin!
5. Lack of Significant Commitment to Shared Decision-making
• Even EBM version 2.0 downplays the patient’s role in evidence-based
decision-making with strict adherence to the evidence hierarchy
• If patient’s role is significant, ‘best evidence’ may vary
Evaluating the Hierarchy
6. Social, Political and Economic Forces Shifting Direction
of Research
• RCTs are expensive and require much infrastructural support
(gold)
• Lack of interest in investing/researching un-patentable
treatments (market demands)
• Orphan drugs vs. ‘me-too’ drugs
• Some treatments may not be researched because they cannot
be patented and the payoff isn’t high enough – yet they could
be effective treatments
• This skews the direction/content of ‘good evidence’
Evaluating the Hierarchy
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New Forms of Authority
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The Cochrane Collaboration (based in Oxford) – international
consortium of workers who construct, rank, and maintain an
ever-enlarging data base of clinical trials (based on the
evidence hierarchy of EBM)
Industrial-scale production of meta-analyses?
Potential Abuses
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Cookbook (as much as it is denied)
Management by policy-makers and hospitals:
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“These so-called ‘best practices’ are poised to become coercive
mandates imposed by government agencies and third-party
payers with political and financial incentives to ration health care
– and the power to do it…The public should be alarmed.” (Brase
2005)
Managed care and EBM
Malpractice suits?
EBM Assessment
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If physicians uncritically accept the EBM hierarchy, they
may make decisions about patient-care on inappropriate
evidence. Is this acceptable? Is this any different from what
existed before EBM?
Does the presence of EBM create new moral obligations for
physicians?
How do physicians maintain commitment to the ‘central aim
of medicine’ in light of these developments?
Persistent uncertainty in medicine
Ethics and Uncertainty
Uncertainty is unavoidable (though it may be
reduced through research)
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How should one make a decision under
uncertainty when an error might harm someone?
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Moral demand for reasons (vs. hunches, intuitions)
How should clinicians communicate this
uncertainty and risk to patients?
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Disclosure of relevant uncertainty
Share this management of uncertainty with patients in shared
decision-making
Ethics and Uncertainty
3.
How ought society respond to the problem of scientific or
clinical uncertainty, as well as to the tensions raised as
money and malpractice challenge efforts to incorporate
more evidence into daily practice?
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Reward quality, not compliance (many cases rather than
individual cases)
Fix malpractice liability problem (‘catastrophe’ in USA) – don’t
assume certainty of practice guidelines in law
Do more, better science (no hidden research) and improve
education (medical students should be taught the
probabilistic and uncertain nature of medicine and the ethical
challenges this raises)
-Goodman (2005)
Influences on Decision-making
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Corporate Influence (Global
Industry - $400 billion/year):
• Marketing as research
(examples earlier)
“I became increasingly troubled
by the possibility that much
published research is seriously
flawed, leading doctors to
believe new drugs are generally
more effective and safe than
they actually are.” (Angell,
2004)
Influences on Decision-making
• Marketing as education: retreats,
conferences, seminars, lunches,
information packages
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‘Thought leaders’ and ‘consultants’
‘Detailing’ 88,000 sales representatives
of pharmaceutical companies employed
to promote products in hospitals and
doctors offices (USA)
‘Preceptorship’ – shadowing doctors as
they see patients
Marketing off-label use of drugs
Educating patients – DTC advertising
• Should we try to draw a line between
education and marketing (education grants
vs. kickbacks) and use restrictions?
• Angell – it really is all marketing.
Pharmaceutical companies are not in the
education business
Influences on Decision-making
• ‘Free’ samples ($11 billion/year in
USA)
• Gifts – books, golf balls, tickets to
sporting events, Christmas trees,
champagne, family vacations to
Hawaii
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Some new regulations on this recently
• Financial incentives for recruiting
patients into studies
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Moral assessment?
Central aim of medicine?
Summary
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(Olivieri case)
Decision-making in Medicine
What is EBM?
Evaluating the Evidence Hierarchy
Ethics and EBM
Ethics and Corporate Influences on Decision-making
in Medicine
Looking Ahead
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Next class – last full lecture
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Justice and Health Care
Contact
Prof. Kirstin Borgerson
Room 359S Munk Centre
Office Hours: Tuesday 3-5pm and by appointment
Course Website: www.chass.utoronto.ca/~kirstin
Email: [email protected]