Since the words evidence-based are so pervasively used in our present day practices of medicine in general, and
spine specifically, we thought it might be of interest to explore the roots of this
movement in greater detail. It is probably always a good idea to look for the origins
of medical developments in ancient writings on scientific methods from around the
world, particularly Greece and ancient Chinese medicine.
In more modern times, it has been 20 years or more since some of the first references
to and basic descriptions of evidence-based medicine (EBM) started appearing in the
medical literature [1], [2], [3]. Since then, the concept of EBM has gone through various interpretations and applications,
myths and misconceptions, uses and abuses. Tenets of EBM have seeped in to most aspects
of patient care in a variety of forms and have impacted areas from clinical practice
guidelines to reimbursement and health policy. The precepts of EBM and their application
continue to evolve.
Prior to the 1950s, health care decisions were based primarily on anecdotal information,
pathophysiology, and the expert opinions of leaders in the profession. In a 1992 article
in the Journal of the American Medical Association (JAMA), the author pointed to a „new paradigm for medical practice that is emerging,” and
defined this paradigm as the shift away from „intuition, unsystematic clinical experience,
and pathophysiologic rationale as sufficient grounds for clinical decision making”
[2]. This opinion-based article introduced the concept of examining evidence from clinical
research and applying the findings to clinical practice. Important to the introduction
of EBM in clinical practice was that EBM „requires new skills of the physician, including
efficient literature searching and the application of formal rules of evidence evaluating
the clinical literature.” Some of the earliest arguments in the 1990s for an „evidence-based”
approach to medical practice were in the context of systematic development of clinical
guidelines [3].
Modern „founders” of EBM, include Archie Cochrane, David Sachett and Gordon Guyatt,
and David Eddy among others. Each has contributed to unique areas of what we currently
perceive as EBM.
What EBM is and is not
EBM is not intended to replace clinical experience and judgment, nor is it „cookbook”
medicine. Rather, it is a „set of principles and methods intended to ensure that to
the greatest extent possible, medical decisions, guidelines, and other types of policies
are based on and consistent with good evidence of effectiveness and benefit” [3]. It considers the validity of, and gaps in, research. It facilitates correct, informed interpretation of the literature and how to best apply it in a given clinical situation
and in discussing options for care with patients. EBM has the potential to enhance
the overall quality of care by providing clinicians with the „best” current evidence
to support decision making without replacing the need for crucial consideration of
individual specific patient presentation, available resources as well as expertise
and combining it with the evidence to formulate a clinical judgment on how to treat
a given patient.
Evolution of study design—some perspectives
Most early medical literature consisted of case reports and case series in addition
to description of techniques and information from non-human studies. Over the past
several decades, much work has been done on developing study methods in epidemiology
and health services research to provide a more rigorous framework for study design
to reduce bias. Sophisticated statistical techniques for evaluating and combining
studies have advanced the ability to estimate study effects while controlling for
confounding and accounting for a variety of study factors.
Historically speaking, the randomized control trial (RTC) dates back to 600 BC when
Daniel of Judah compared the health effects of the vegetarian diet with those of a
royal Babylonian diet over a 10-day period. The trial had obvious deficiencies by
contemporary medical standards (allocation bias, ascertainment bias, and confounding
by divine intervention), but the report has remained influential for more than two
millennia [4].
Credit for the modern RTC is usually given to Sir Austin Bradford Hill for his clinical
trials on streptomycin for pulmonary tuberculosis and is rightly regarded as the landmark
study that ushered in a new era of medicine. Since Hill’s pioneering achievement,
the methodology of the RCT has been increasingly accepted and the number of RCTs reported
has grown exponentially [5].
All study designs have limitations, even RCTs. No one study (or study design) can
definitively address all aspects (efficacy, effectiveness, safety) of a topic. RCTs,
if done well, have the greatest potential for providing the highest-quality evidence
regarding efficacy (by reducing bias and confounding). However, RTCs may not have
the statistical power to detect differences in rare adverse events and may not have
sufficient length of follow-up to describe long-term benefits and complications. (One
only need look at the recent well-publicized recall of certain pharmaceuticals to
see that RCTs do not answer all questions.) This is where well-designed and reported
nonrandomized comparative studies (cohort and case control) and even case series can
help fill gaps in understanding. Nonrandomized studies also facilitate the development
of hypotheses and next steps for adding to the overall evidence base on a topic. While
all study designs have some role in contributing to the evidence on topic, the tenets
of EBM suggest that the focus be on the highest quality of evidence, not necessarily
the whole laundry list of studies that have been done on a given topic.
The development of systematic reviews has been crucial to EBM as they focus on research
questions that synthesize all high-quality research evidence relevant on the clinical
questions. In the early 1990s, Archie Cochrane, a British physician, began advocating
the use of systematic reviews in medicine. Cochrane is best known for his influential
book, Effectiveness and Efficiency: Random Reflections on Health Services published in 1972. He suggested that because resources would always be limited they
should be used to provide equitably those forms of health care that had been shown
in properly designed evaluations to be effective. In particular, he stressed the importance
of using evidence from RCTs because these were likely to provide much more reliable
information than other sources of evidence [6]. Cochrane’s simple propositions were soon widely recognized as seminally important—by
lay people as well as by health professionals and policymakers. The Cochrane Collaboration
is named in his honor.
Well-designed and methodologically sound systematic reviews and meta-analyses have
become a mainstay in EBM. They have become the basis for clinical guideline formation,
health technology assessment and comparative effectiveness reviews, all of which are
used increasingly for health policy and reimbursement decisions.
Critical appraisal: the foundation of EBM
A cornerstone of EBM is the critical appraisal of clinical research. As mentioned
above, EBM facilitates correct, informed interpretation of the literature. The critical appraisal provides important context
around the findings and potential biases of a study (or studies) so as to help one
put the results of a study in perspective.
During the 1980s, Canadian physician, David Sackett, began to develop a system for
the critical analysis of the medical literature. Sackett organized the principles
of the systematic review into six steps: (1) decide what information is needed; (2)
formulate one’s information needs in the form of a question that a research study
could answer; (3) search the published literature to find the evidence; (4) decide
which studies are valid and applicable to the patient at hand; (5) apply the findings
to the patient; and (6) evaluate the outcomes [7]. This approach is mirrored in a series of articles describing „how to” use various
types of research articles to answer clinical questions about diagnosis, prognosis,
and treatment to make clinical judgments for a given patient based on the best evidence.
Many systems for the critical appraisal of clinical studies have been described in
the literature [8], [9]. Overall, the intent is to evaluate the potential sources of bias in studies, allowing
the astute reader to assess the extent to which such biases may influence the results.
In general, all schemes assess components of studies that may bias studies such as
the following:
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Study design (eg, prospective cohort, RCT)
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Patient selection and evaluation methods (including outcomes evaluation)
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Patient follow-up (length and completeness)
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Sample size and ability to detect differences beyond the role of chance
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Consideration of and controlling for potentially confounding factors
All these are important when considering the extent to which the results of a study
are valid and believable. EBSJ’s format for critical appraisal takes into account
the primary sources of potential bias and is described at the back of each issue.
For each of the clinical research studies published, a critical appraisal is performed.
Within EBSJ, readers will get additional detail about the importance of these and
other factors in the „Science in Spine” section which is a regular feature.
As described below, the basics of critical appraisal form the foundation for determining
the „best” evidence.
Hierarchy of evidence
Evidence is the knowledge on which we base our beliefs (and disbeliefs) and in many
instances our actions. It stands to reason that we would want to base our actions
on the „best evidence.” So how do we know what type of „evidence” gets us closest
to the „truth” and what quality of evidence do we base our actions?
René Descartes (1596–1650), philosopher, scientist, and mathematician, provided an
important basis for the scientific method. Descartes recommended that, „When it is
not in our power to follow what is true, we ought to follow what is most probable.”
What is most probable is that the „best evidence” on a given spine-care topic may
not be the highest quality and its proximity to the „truth” may not be clear. Yet,
it is the „best” we have and we need to combine it with our clinical judgment and
act accordingly. Descartes even described a hierarchical pyramid of evidence and process
for moving toward the top (Fig [1]). So, at least as far back as the early 1600, the concept of aspiring to consider
the highest quality of evidence existed.
Fig. 1 Descartes’ hierarchical pyramid of evidence.
Readers are most likely familiar with some version of the more modern „evidence pyramid”
(Fig [2]). This too has evolved and there are a number of different versions. Study design
plays a key role in all. The intent is to focus on studies with the least potential
for bias as being the highest quality and, where possible, synthesis of high-quality
studies on a given topic. The highest-quality studies are not necessarily RCTs, as
suggested earlier. Where there is „higher-quality” evidence for efficacy, such as
RCTs or methodologically rigorous prospective studies comparing treatment, the usefulness
of case series for efficacy is questionable. This was part of Cochrane’s contention.
Lower-quality comparative studies (eg, retrospective cohort studies which do not control
for confounding) may have conflicting results versus the RCTs that may be attributable
more to bias than to at-true effect. So an evidence-based synthesis would logically
include only the highest-quality studies. For surgical specialties, the applicability
of RCTs in helping answer important clinical questions has increasingly been called
into question as even in major, well-designed RCTs lack of adherence to assigned treatment
groups may be a problem. For example, in the Spine Patient Outcomes Research Trial
(SPORT), comparing nonoperative and operative treatments for lumbar degenerative spondylolisthesis,
54 % of those assigned to nonsurgical treatment crossed over to surgical options by
4 years; while 66 % of those assigned to surgery received it by 4 years, resulting
in no statistical difference between treatments when intention-to-treat analysis was
performed. In the corresponding observational cohort, 97 % of those who chose surgery
received it and 33 % of those who chose nonoperative treatment eventually underwent
surgery [10].
The likely cause for this phenomenon lies in the increasing emancipation of patients
as part of the decision-making process in an era of increasing availability of information.
This quest for increased ‘shared-decision’ making, however, does not call into question
the validity of the evidence pyramid per se, rather it underscores the critical role
of well-conceived and thought-out studies for the future.
Fig. 2 Hierarchy of evidence: one modern perspective.
Strength of evidence—evolving application of EBM
In the past 5 years in particular, methods for describing the overall „strength of
evidence” for a topic have continued to evolve. The intention is to assess the overall
body of literature on a given topic by the quality of the studies (based on critical
appraisal components above), the quantity of studies (which takes into account the
comparisons and outcomes of primary importance with a focus on higher-quality studies)
and consistency (including constancy, magnitude, and direction of effect size). This
is used to determine how likely new studies are to change the confidence in the effects
estimated in the included studies.
All the systematic reviews included in EBSJ are assessed with respect to the overall
strength of evidence based on the GRADE system [11]. The overall Strength of Evidence (SoE) ranges from high for a body of evidence
if new studies are unlikely to change the effect estimates to very low if estimates
from the currently available body of evidence is very likely to change as new data
become available. This system and its variations are being used more frequently in
clinical guideline development and health policy. Extensive discussion of this application
of EBM is beyond the scope of this article, and the reader should consult the references.
Why is the evolution of EBM important to clinicians and clinical researchers?
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The evolution of the EBM has important implications for the practice of medicine.
It is a valuable component of clinical decision making and facilitates discussions
with patients.
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An important implication relates to the use of EBM components as the foundation of
health policy and reimbursement.
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For researchers, understanding aspects of critical appraisal and the hierarchy of
evidence can help facilitate designing, executing, and reporting higher-quality studies.
Conclusion
Evidence-based medicine is here to stay. Its various forms and applications will increasingly
impact medical practice, patient care, and health policy.
