Â Medical practice is intended to allow patients to
live longer, and feel better. The ultimate test of EBM would
therefore be a trial in which medical students would be
randomized to conventional or EBM training and followed
for a few years subsequent to graduation, with monitoring
of the outcomes of their patients. Such a trial is, for
a host of reasons, not feasible.
Â The dictates of EBM suggest that when the ideal
study is not available, one falls back on the strongest
evidence that one can access. In some cases, physiological
rationale provides the best guide to patient management.
An analogous argument addresses the issue of the evidence
Â Â EBM suggests that, to the extent possible,
clinicians should base their management decisions on findings
from systematic reviews of randomized trials. When appropriate,
these systematic reviews summarize their findings in meta-analyses
that provide single best estimates of the magnitude of treatment
impact on patient outcomes.
Â Â Figures 1 and 2, adapted from a paper by Antman
and colleagues, depict what is called cumulative meta-analyses
of the evidence concerning the impact of thrombolytic therapy
and prophylactic lidocaine on death rates in patients suffering
from myocardial infarction. The horizontal line in the
centre of the left portion of Figure 1 represents an odds
ratio of 1.0. An odds ratio of 1.0 denotes that thrombolytic
therapy neither increases or decreases the likelihood of
dying. Values to the left of the line indicate that treatment
is beneficial and reduces death rates; to the right that
treatment is harmful and increases death rates.
Â Â Â Â Â Â The first randomized
trial of thrombolytic therapy, designated A1" in the
figure, conducted in the late 1950s, enrolled 23 patients.
Results suggested that thrombolytic therapy could result
in a 50% reduction in the odds of dying (the point estimates,
the best estimate of treatment effect given the existing
data, are depicted in the figure by dots). However, the
95% confidence interval around that point estimate (in the
figure, the lines to either side of the dots) suggest that
the results were also consistent with an odds of dying with
thrombolytic therapy of almost 2.After investigators completed
the second trial of thrombolytic therapy (designated A2")
a total of 65 patients had participated in trials B 23 in
the first trial, 42 in the second. The point estimate continued
to suggest a 50% odds reduction. The confidence interval,
while narrower, was still wide.
Â As the data continued to accumulate, the point
estimate suggested smaller odds reductions, closer to 25%,
and the confidence interval began to narrow. By the early
1970s, when over 2 500 patients had been enrolled in 10
RCTs, the confidence interval no longer crossed 1.0, suggesting
a real effect of thrombolytic therapy on decreasing death
rates. Even a conservative interpretation of the results
would have suggested the answer was in by the early 1980s
when over 6 000 patients had been enrolled in 27 trials
and the confidence interval indicated that odds reductions
of less than 10% were very unlikely.
Â Did these data mean an end to RCTs of thrombolytic
therapy? No, it did not. After the answer was in, another
40 000 patients were enrolled in trials of thrombolytic
therapy. Half these patients received placebo or standard
care; they were denied the benefits of thrombolytic therapy,
and some therefore died unnecessarily. By 1990 when over
48 000 patients had been enrolled in 70 RCTs, the confidence
interval around the odds ratio was extraordinarily narrow.Why
was it necessary to enrol over 40 000 patients after the
answer was in? The right side of Figure 1 provides at least
part of the explanation. This part of the figure categorizes
experts¡¯ recommendations published in textbooks and journal
articles as these data were accumulating. Recommendations
offered at the same time varied between experts. For instance,
in the latter 1980s, recommendations ranged from suggestions
that thrombolysis be administered routinely to all myocardial
infarction patients, to categorizations of thrombolysis
as an experimental therapy, to not even mentioning thrombolysis.
The right side of Figure 1 suggests two conclusions. First,
experts often disagree, offering contradictory recommendations.
Second, recommendations may lag substantially behind the
data. It was close to a decade between the time the answer
was in, and when experts consistently recommended thrombolytic
therapy for patients with myocardial infarction.
Figure 2 depicts the history of routine administration of
prophylactic lidocaine to patients with myocardial infarction.
In this case, there was never any RCT evidence supporting
prophylactic lidocaine therapy. Did this stop the experts
from recommending routine lidocaine administration? No,
it did not. Indeed, up until 1989 when the first meta-analysis
was published, the majority of experts continued to recommend
prophylaxis as standard therapy for myocardial infarction
patients. There was, however, the same sort of substantial
variability in expert recommendations throughout the 1980s
as we observed with thrombolysis.
Evidence-based recommendations were not available at the
time these data were accumulating. Why not? The fundamental
methodology of developing such recommendations, the systematic
review, had not been applied to the data in question.
Had evidence-based recommendations been available, from
the early 1980s they would have consistently recommended
thrombolysis. Following the second key criterion for evidence-based
recommendations, that values and preferences underlying
the recommendations be made explicit, they would have been
qualified with statements that the recommendations placed
a relatively high value on preventing premature death, a
readiness to incur additional health care costs to achieve
that objective, and that patients who were extremely stroke
averse might decline thrombolysis.
Throughout the 1980s, evidence-based recommendations would
have consistently recommended against prophylactic lidocaine.
Initially, the recommendations would have been qualified
with the proviso that risk-taking patients might wish to
receive the treatment. As the data accumulated, the recommendation
against lidocaine would have become progressively stronger.
It is not difficult to offer other such examples of discrepancies
between recommendations arrived at through traditional approaches
to medical decision-making, and those developed using evidence-based
approaches. Consider Hormone-replacement therapy (HRT).
For over a decade, recommendations from a wide variety of
august bodies strongly favoured the widespread use of HRT.
These guidelines failed to acknowledge the weakness of the
evidence from observational studies suggesting a decrease
in cardiovascular risk, the resultant weakness of any recommendation
in favour of long-term ingestion of HRT, and the acknowledgement
that risk-averse women would want to stay away from the
therapy. The subsequent publication of two randomized trials
suggesting that HRT does not decrease, and may increase,
cardiovascular risk, has reversed recommendations[10,11]Such
examples highlight the limitation of traditional approaches
of arriving at health care decisions. They provide the evidence
that evidence-based approaches often yield courses of action
more in accord with patients¡¯ long-term best interests.
Evolution of EBM
In 1992, an article that one might describe as an EBM manifesto
appeared in the JAMA. The article emphasized four important
differences between EBM and traditional medical practice.
The authors suggested that 1) EBM places a higher value
on systematically collected evidence and a lower value on
unsystematic clinical observation; 2) EBM places a higher
value on experiments that focus on outcomes that are important
to patients, and a lower value on physiological rationale;
3) that interpreting the medical literature was a key skill
for clinicians, and that a formal study of rules of evidence
was necessary for a skilled interpretation; 4) finally,
that EBM places a higher value on the independent assessment
of the individual clinician and a lower value on authority.
Less than a decade later, the 25th and final instalment
of the JAMA series of Users¡¯ Guides to the medical literature
took a somewhat different approach in describing the principles
of EBM. This article described two key elements of the
EBM approach. The first was a hierarchy of evidence going
from the strongest (N of 1 randomized trials, followed by
systematic reviews of randomized trials) to the weakest
(physiological rationale and unsystematic clinical observation).
The second key element suggested that evidence itself was
insufficient for making health care decisions, and that
values and preferences must be part of every decision.
Another major step in the evolution of thinking about EBM
made the distinction between evidence-based practitioners
and evidence-users. This article acknowledged that only
a minority of clinicians would attain a high level of expertise
in interpreting the original medical literature. Most EBM
practitioners, the authors argued, will understand the fundamental
principles of differentiating strong from weak evidence,
and will be able to understand estimates of the magnitude
of risks and benefits of the management strategies they
are considering. They will be able to identify evidence-based
synopses and summaries of the literature, and evidence-based
guidelines and recommendations that follow from the evidence,
and will rely on these sources to guide their practice.
A mature presentation of the principles of EBM emphasizes
how EBM fits in to a humanistic approach to the practice
of medicine that fully acknowledges the clinicians¡¯ responsibility
to the community, the need for a compassionate and empathetic
practice, and the primacy of patient and societal values
and preferences in medical decisions. The discussion
puts great emphasis on the limitations of evidence in making
medical decisions, and the need for incorporating values
and preferences. Key passages include the following description
of the first principle of EBM, that evidence alone is never
sufficient to establish the best course of action.
APicture a patient with chronic pain resulting from terminal
cancer. She has come to terms with her condition, has resolved
her affairs and said her goodbyes, and she wishes to receive
only palliative therapy. The patient develops pneumococcal
pneumonia. Now, evidence that antibiotictherapy reduces
morbidity and mortality from pneumococcal pneumonia is strong.
Almost all clinicians would agree, however, even evidence
this convincing does not dictate that this particular patient
should receive antibiotics. Despite the fact that antibiotics
might reduce symptoms and prolong the patient's life, her
values are such that she would prefer a rapid and natural
Now envision a second patient--an 85-year-old man with severe
dementia, who is incontinent, contracted, and mute, without
family or friends, who spends his days in apparent discomfort.
This man develops pneumococcal pneumonia. Although many
clinicians would argue that those responsible for this patient's
care should not administer antibiotic therapy because of
his circumstances, others, by contrast, would suggest that
they should do so. Again, evidence of treatment effectiveness
does not automatically imply that treatment should be administered.
The management decision requires a judgment about the trade
off between risks and benefits; and because values or preferences
differ, the best course of action will vary from patient
to patient and among clinicians.
By values and preferences, we mean the underlying processes
we bring to bear in weighing what our patients and our society
will gain--or lose--when we make a management decision.
The explicit enumeration and balancing of benefits and risks
that is central to EBM brings the underlying value judgments
involved in making management decisions into bold relief.
The acknowledgement of the primacy of values and preferences
has profound implications for the role of the clinician
in the decision-making process. The discussion in the Users¡¯
Guides book puts it this way.
AThus, knowing the tools of evidence-based practice is necessary
but not sufficient for delivering the highest quality patient
care. In addition to clinical expertise, the clinician requires
compassion, sensitive listening skills, and broad perspectives
from the humanities and social sciences. These attributes
allow understanding of patients' illnesses in the context
of their experience, personalities, and cultures. The sensitive
understanding of the patient links to evidence-based practice
in a number of ways. For some patients, incorporation of
patient values for major decisions will mean a full enumeration
of the possible benefits, risks, and inconvenience associated
with alternative management strategies that are relevant
to the particular patient. For some of these patients and
problems, this discussion should involve the patients' family.
For other problems BB the discussion of screening with prostate-specific
antigen with older male patients, for instance BB attempts
to involve other family members might violate strong cultural
Many patients are uncomfortable with an explicit discussion
of benefits and risks, and they object to having what they
perceive as excessive responsibility for decision making
being placed on their shoulders. In such patients, who would
tell us they want the physician to make the decision on
their behalf, the physician's responsibility is to develop
insight to ensure that choices will be consistent with patients'
values and preferences. Understanding and implementing the
sort of decision-making process patients desire and effectively
communicating the information they need requires skills
in understanding the patient's narrative and the person
behind that narrative.@
This mature understanding of EBM places the patient, in
one way, at the centre of the decision-making process. After
all, only patients have a full and deep understanding of
their circumstances, and their values and preferences. In
another way, however, it places the physician at the centre
of the process. In most instances, the clinician will
be the only party with a full understanding of the direct
evidence that bears on the decision. Even with the exceptional
patient who may have read and understood the relevant literature,
the clinician will have an understanding of the medical
context of the disease process not available to the patient.
The clinician, moreover, must judge the manner in which
the patient wants to be involved in the decision-making
process. Finally, the clinician has brings an objectivity
that may be crucial in achieving a satisfactory decision-making
process, and that is often unavailable to the patient.
These considerations give rise to the model of evidence-based
practice presented in Figure 3. The patients¡¯ circumstances
define the problem. The clinician must make the diagnosis,
and must have a knowledge of all reasonable management options
that might follow from that diagnosis. The clinician must
be aware of all the direct and indirect evidence that bears
on the relative benefits, risks, inconvenience and costs
associated with the alternative management strategies. The
clinician must also ascertain the patient¡¯s desired style
of decision-making, and how the patient¡¯s particular circumstances,
and values and preferences, bear on the benefits and down
sides of the alternative management strategies.
Ultimately, for one patient, the clinician may present
the benefits and down sides of alternative course of actions
to the patient, who will make the decision. For another
patient, the clinician may present the benefits and down
sides, but also offer advice and direction regarding the
optimal choice. For a third patient, following a discussion
of preferences and values, the clinician might recommend
a specific course of action that she believes is in the
patient¡¯s best interests.
Future of EBM
Acknowledging the primacy of values and preferences, patients¡¯
differing wishes about their role in the decision-making
process, and the respective roles of the clinician and patient
highlights the tremendous gaps in our knowledge about how
best to incorporate evidence in the decision-making process.
Reaching a full understanding of benefits and down sides
of the alternative courses of action is challenging for
the expert, to say nothing of the front-line clinician.
Our knowledge of how best to ascertain the patients¡¯ desired
style of decision-making and (to the extent the patient
wishes) communicate the magnitude of the benefits and risks,
remains superficial. The more one considers both the complexity
of the process, and the limited time available in the clinical
encounter, the greater the temptation to throw up ones¡¯
hands in despair at the apparent impossibility of a satisfactory
Nevertheless, as clinicians wanting to do the best for our
patients, we cannot retreat from the challenge. As individuals,
we make dozens, if not hundreds, of management decisions
each day. Most are trivial, a minority are momentous for
our patients. Key research and conceptual questions for
evidence-based decision makers include the following. How
should we decide which decisions warrant using the traditional
short-circuit approach, and which merit additional time
and energy? How can we best tailor our decision-making style
to the patients¡¯ wishes? How do we best communicate risk
and benefit information to our patients? How do we decide
when the outcome of the decision-making process is optimal,
and when it is not?
Some may find it ironic where the focus on rigour in making
causal inferences, and the critical use of the medical literature
in clinical practice, has led us B that is, to a detailed
consideration of how to bring patient values and preferences
to bear on individual decisions. Personally, I find it fascinating,
and exciting. EBM will continue to evolve, possibly to further
date£º2003-12-04Â Â Revised date£º2003-12-14)