Introduction to Evidence-Based Medicine

(1)

Department of Neurology Neurosciences Centre, and Clinical Epidemiology Unit, All India Institute of Medical Sciences, New Delhi Delhi, India
 
Abstract
The term evidence-based medicine first appeared in 1990 in the information brochure for McMaster University Internal Medicine Residency Program. However, the work which led to its origin may be traced back to late 1970s, when Prof. David Sackett, the then Chairman of the Department of Clinical Epidemiology and Biostatistics McMaster University, Canada, published a series of articles in the Canadian Medical Association Journal beginning in 1981. The series was named ‘The Readers’ Guide to Medical Literature’. The series had one article devoted to each of the paper on diagnosis, treatment, prognosis, etc. The articles provided guides to critical appraisal of the various types of clinical papers. Internet did not exit at that time and information technology was in infancy. Not surprisingly, the series did not contain any section on ‘how to search for relevant papers’.

History

The term evidence-based medicine first appeared in 1990 in the information brochure for McMaster University Internal Medicine Residency Program. However, the work which led to its origin may be traced back to late 1970s, when Prof. David Sackett, the then Chairman of the Department of Clinical Epidemiology and Biostatistics McMaster University, Canada, published a series of articles in the Canadian Medical Association Journal beginning in 1981. The series was named ‘The Readers’ Guide to Medical Literature’. The series had one article devoted to each of the paper on diagnosis, treatment, prognosis, etc. The articles provided guides to critical appraisal of the various types of clinical papers. Internet did not exit at that time and information technology was in infancy. Not surprisingly, the series did not contain any section on ‘how to search for relevant papers’.
The starting point was a journal paper at hand. The emphasis was on critical appraisal of the paper. The section on application. More than a decade had passed, when in early 1990s, a need was felt to re-visit and update the guides and include the latest advances in the field of critical appraisal. To do this, an international evidence-based medicine working group was formed at McMaster University, Canada. The group felt that the focus of the guides be changed from readers to users. The group thought that emphasis should be placed on usefulness of the information in clinical practice. The starting point may be a problem faced by the clinicians, who looks for relevant literature, finds it, critically appraises it and puts to use the information in his clinical practice. As sources of information had become enormous by then, and Internet had come into being, there was a need to guide the clinicians in searching the relevant literature. To incorporate these changes, the group worked to develop a series of papers (Users’ Guides) to emphasise clinical practice and clinical decision-making based on sound evidence from clinical research [1]. During one of the retreats of the Department of Internal Medicine at McMaster University, one suggestion to name such clinical practice was to use the term ‘scientific medicine’, which was vehemently opposed by other members of the department, mainly because of its implications that the practice so far had been ‘unscientific’. Prof. Gordon Guyatt then suggested the term ‘evidence-based medicine’ which proved felicitous. He also chaired the working group and coedited the book ‘User’s Guide to Medical Literature’.
It would be unfair and plainly wrong to say that philosophical foundations of EBM originated in 1990s or even 1970s. In fact, it would be clear from the following discussions that the basic tenets had existed right from the inception of medical practice. All major civilisations may find some indications of some of its principles in their ancient texts and historical accounts.

What Is Evidence-Based Medicine?

In simple terms, it means using the current best evidence in decision-making in medicine in conjunction (together) with expertise of the decision-makers and expectations and values of the patients/people. The word medicine in EBM is often associated with doctors’ profession, to distinguish EBM from evidence-based nursing or evidence-based public health, etc. Sometimes, people take even a narrower view and take medicine to mean internal medicine to distinguish EBM from evidence-based surgery, evidence-based dentistry, etc. But I take it in a broad sense to relate it to the health profession and distinguish it from other professions like law or business. In its broad sense, EBM becomes broader than evidence-based health care and includes public health, health policymaking, etc. While defining EBM, one should be clear what he means by medicine. Oxford dictionary defines medicine as a discipline for prevention and cure of disease. It is in this broad sense in which I use the term EBM.
EBM is a new paradigm of clinical practice and a process of lifelong learning, which emphasises a systematic and rigorous assessment of evidence for use in decision-making in health care in conjunction with expertise of the decision-makers and expectations and values of the patients.

Knowing About EBM (1-2-3-4)

Knowing EBM is like knowing 1-2-3-4. EBM has one goal, two fundamental principles, three components and four steps. One goal is to improve quality of clinical care; two principles are hierarchy of evidence and insufficiency of evidence alone in decision-making; three components are evidence, expertise and expectations of patients (triple Es); and four steps are ask, acquire, assess and apply (4 As). These are elaborated further in the following paragraphs.

Goal of EBM

EBM has one goal: to improve the health of people through decisions that will maximise their health-related quality of life and life span. The decisions may be in relation to public health, health care, clinical care, nursing care or health policy.

Principles of EBM

Two fundamental principles include:

(a)

Hierarchy of evidence: It says that evidence available in any clinical decision-making can be arranged in order of strength based on likelihood of freedom from error. For example, for treatment decisions, meta-analyses of well-conducted large randomised trials may be the strongest evidence, followed in sequence by large multi-centric randomised trials, meta-analyses of well-conducted small randomised trials, single-centre randomised trials, observational studies, clinical experience or basic science research.
 
(b)

Insufficiency of evidence alone: The second fundamental principle of EBM is that evidence alone is never sufficient for decision-making. It has to be integrated with clinical expertise and patients’ expectations and values. This principle gives rise to considerations of components of EBM which follows below.
 

Components of EBM

In one sense, EBM is a misnomer, because besides evidence, two other Es are required for decision-making, namely:

(a)

Expertise of the decision-makers
 
(b)

Expectations and values of the patients/people
 
To emphasise all the three components, I use the word Triple-E based medicine (TEBM).
To illustrate the importance of the two Es, other than evidence, two examples follow.
Example 1
A 28-year-old man is admitted to the intensive care unit with ascending paralysis and respiratory distress. The resident makes a diagnosis of Guillain–Barré syndrome (GBS) and starts to discuss evidence-based approaches to treat him. The consultant comes, takes history and suspects dumb rabies. It becomes clear that the patient had a dog bite 3 months ago and received only partial immunisation. Further investigation confirmed the suspicion of dumb rabies, and the patient was shifted to Infectious Diseases Hospital for further treatment. The whole discussion on GBS was irrelevant. This example illustrates the role of expertise in practising EBM. If the diagnosis is wrong, all the EBM discussion is superfluous.
Example 2
Expectations, values and circumstances of the patients/people:

(a)

The diagnosis of motor neurone disease (amyotrophic lateral sclerosis) requires certain level of expertise and experience. Once the diagnosis is made, one can look for evidence in favour of certain treatments like riluzole. It turns out that there is definitive evidence from RCTs and meta-analysis indicating that riluzole can prolong tracheostomy – free life for 3 months if taken regularly (usually for years). The cost of riluzole treatment is prohibitive. In view of the high cost and risk of hepatotoxicity (and the need to pay out of pocket in India), many neurologists and their patients do not use this. Patients do not consider it ‘worth it’; however, some patients who can easily afford to take riluzole for the treatment of this condition are prescribed with this drug.
 
(b)

There is a consistent evidence to show that alcohol in moderation is protective against heart attacks and stroke. However, in Islam, alcohol is forbidden. It would be unacceptable to discuss alcohol intake in moderation with a staunch Muslim even if he has many risk factors for heart attack and stroke.
 
Goal of EBM
Improve health of people through high-quality health care
Principles of EBM
Evidence has a hierarchy
Evidence alone is not enough
Components of EBM (3 Es)
Evidence
Expertise
Expectations
Steps of EBM (4 As)
Ask, acquire, assess, apply

Why EBM?

The above examples indicate the need to integrate expertise and patients’ values with the evidence in clinical decision-making. This is what practice of evidence-based medicine requires. You might ask – isn’t it what physicians always did and ought to do? How else did we make health-care decisions? Well, there have been a number of different bases for such decisions other than evidence. The examples below are mainly for clinical decisions, but similar examples for policy decisions can also be cited.

Physiologic Rationale

On many occasions, we make a decision on the basis of physiologic or pathophysiologic rationale. For example, ischaemic stroke is commonly due to occlusion of middle cerebral artery (MCA). It makes physiologic sense to bypass the occlusion by connecting some branch of the external carotid to a branch of MCA beyond the occlusion. Such on operation is called external carotid–internal carotid (EC–IC) bypass. Based on this rationale, thousands of EC–IC bypass surgeries were being performed in many parts of the world, until some people questioned it. An international trial sponsored by NIH (USA) compared this to medical treatment and showed that the surgery is not only ineffective but also delays recovery [2]. After this evidence was published, the number of EC–IC bypass surgeries crashed in North America and is rarely, if ever, performed for ischaemic stroke anywhere in the world.
A second example is use of streptokinase, a thrombolytic agent, in ischaemic stroke. It makes physiologic sense to use streptokinase to dissolve the clot in this condition (just as in myocardial infarction). But three clinical trials (known as MAST-E,1 MAST- I2 and ASK3) had to be stopped prematurely because more patients were dying with the use of streptokinase than without it. As a result, streptokinase is not used for ischaemic stroke, but surprisingly, tissue plasminogen activator (t-PA), another thrombolytic agent, is associated with less increase in mortality and overall better outcome, though physiologically, we do not know any good reason for this difference.
Several other examples (like increased mortality with encainide as antiarrhythmic agent) show that physiologically reasonable decisions may have unacceptable clinical risk and, therefore, clinical studies are necessary to determine the benefit–risk profile. Decisions based solely on physiologic rationale may cause more harm than good.

Experts’ Advice

We often seek experts’ advice to take certain treatment decisions. Policymakers often seek experts’ advice to take a policy decision. However, experts’ advice without reference to adequate search and evaluation of evidence may be simply wrong.
Take example of treatment of eclampsia. A survey conducted in UK in 1992 showed that only 2 % of obstetricians used magnesium sulphate to control convulsions in eclampsia. The preferred drug was diazepam. I have personally seen neurologists advising use of diazepam rather than magnesium sulphate. But evidence from clinical trials showed clearly that magnesium sulphate is more effective in not only controlling convulsions but also decreasing maternal mortality in eclampsia [3]. It is reassuring to note that in England the Royal College of Obstetrics and Gynaecology recently adopted the recommendation to use magnesium sulphate, rather than diazepam in this condition.

Textbooks and Reviewers

We often look into textbooks or review articles for deciding to use an intervention. A number of examples are available to show that textbooks or review articles may recommend to use potentially harmful intervention and may not recommend to use potentially (or even established) helpful intervention. A classic example of this is streptokinase (SK) in acute myocardial infarction (AMI). Lau et al [4] have shown that had there been a periodically updated summary of emerging evidence (called ‘cumulative meta-analysis’), a strong case for recommending routine use of SK in AMI could be made in 1977 but even in 1982, 12 out of 13 articles did not mention SK for AMI (one mentioned it as an experimental drug). Recommendation became common (15 out of 24 articles) only near 1990, almost 13 years after there was enough clinical evidence.
On the other hand, most textbook/review articles in 1970 were recommending routine use of lignocaine hydrochloride in acute MI (in nine out of 11 articles), whereas evidence to date was showing a trend towards increased mortality with its use. It was only after 1989 when evidence summary in the form of meta-analysis was published that textbooks and review articles stopped recommending its use in AMI.

Manufacturers’ Claims

Many clinicians often start using an intervention based on the information from the drug companies. However, the information may not be valid and may result in more harm than good. An example is the use of hormone replacement therapy (HRT) in postmenopausal women. The companies promoted the use of HRT without adequate and high-quality evidence. Only when a large clinical trial showed that it may be dangerous that the clinicians have stopped recommending HRT widely [5].
Many clinicians are easily convinced by drug company information, though many a times it may be misleading.
The above examples show that decisions based exclusively on pathophysiologic rationale, experts’ advice, textbook/review articles or drug company information may turn out to be wrong. This is not to say that all the time they are wrong or that advice based on a clinical trial or meta-analysis cannot go wrong. But the point is that when physiologic rationale or experts’ advice is supported by clinical evidence, the likelihood of such decisions going wrong is lower than when they are not supported by the evidence. When there is discrepancy between the above sources, then there is a need to exercise caution and put more weight on valid clinical evidence than on other bases. EBM puts emphasis on this point.

What Is New in EBM?

It may be argued that physicians (or health policymakers) have always used and continue to use evidence, expertise and patients’ values in decision-making. Yes, this is largely true. All good physicians always did it and continue to do it. The new thing is the difference in emphasis, explicitness, rigour and understanding. The new tools and techniques of accessing, appraising and expressing the evidence make the process (of using evidence) more systematic and rigorous. Many notions and concepts carried by physicians before EBM era need to be changed. Some of such notices or concepts are given in Table 1.1.

Table 1.1

Concepts or notions before and after introduction of EBM
 
Pre-EBM notions/concepts
EBM notions/concepts
1. Clinical/medical education
Is sufficient to practice EBM
Necessary but not sufficient
Need lifelong, self-directed learning and reflective practice
2. Clinical experience
Sufficient to guide practice
Necessary but not sufficient Needs to be aware of research results
3. Textbooks and review (traditional) articles
Are sufficient
Useful but not sufficient Often need to refer to systematic review/original research
4. Medline
Is the resource of first resort
Medline is a resource of last resort
5. Evidence from basic and animal research
Is adequate to guide clinical practice
Necessary but not sufficient Needs clinical evidence
6. Validity of publications
All that is published (in top journals) is largely true (unless contradicted by another publication)
Most of what is published (even in top journals) is largely untrue
7. Reading conclusions of paper
Is sufficient
Necessary but not sufficient
Need to read methods and results
8. Critical appraisal ability
Comes automatically and informally with medical education and experience
Needs to be learnt actively and formally
9. Statistical significance
Statistical significance is sufficient
Necessary but not sufficient Needs to assess clinical significance

Steps in Practising EBM

The main (but not the only) objective of EBM is the application of the right and complete information

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Oct 18, 2015 | Posted by in General Dentistry | Comments Off on Introduction to Evidence-Based Medicine
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