Evidence Based Medicine (EBM) – an Introduction

“Evidence-based medicine (EBM) is the integration of best research evidence with clinical expertise and patient values.” (Sackett D., 2001)

What is EBM?
“…the enhancement of a clinician’s traditional skills in diagnosis, treatment, prevention and related areas through the framing of answerable questions and the use of mathematical estimates of probability and risk.”
- Greenhalgh, 2001

What does evidence-based mean?
1/ A comprehensive, systematic, open minded review of all the evidence
2/ The evidence determines the conclusion, not vice versa
3/ Not, the citation of  papers supporting a preformed conclusion (and trashing of those that don’t)
4/ Not, the use of evidence when it is ‘positive’ but judgement when it isn’t

Why Did Evidence-Based Medicine Develop?
1/ Wide variations in clinical practice
- Example: Cesarean section rates
- Some practices must be better than others
2/ Concerns about cost and quality
3/ Gap between research and practice
4/ Up to 40% of clinical decisions are not supported by evidence from research

Information Needs and the Research-Practice Gap
1/ Effective treatments are not readily adopted
- Too many articles, no one can keep up
- Contradictory results (false +/false -)
- Most reviews are not systematic; instead are subjective
2/ Ineffective treatments adopted/maintained
- Over-reliance on clinical experience
- Uncritical acceptance of results of studies
- Over-reliance on expert opinion
- Pharmaceutical company influences

Two Different Approaches to Evidence-Based Practice
1/ Clinical practice guidelines
- “Top-down” approach
- Tell clinicians how to practice
- Favored by health care systems
2/Evidence-based medicine
- “Bottom-up” approach
- Teach clinicians how to find answers
- Favored by medical educators

Brief history
Archie Cochrane        
"It is surely a great criticism of our profession that we have not organised a critical summary, by specialty or subspecialty, adapted periodically, of all relevant randomised controlled trials.”
(Cochrane AL. 1931-1971: a critical review, with particular reference to the medical profession. In: Medicines for the year 2000. London: Office of Health Economics, 1979, 1-11)
- Cochrane Collaboration
- Cochrane database of systematic reviews

Quotation
„All medical care that is effective should be free to all”
A.L. Cochrane, Effectiveness and Efficiency:  Random Reflections on Health Services, 1972
Is this possible in 2006?

Clinical Judgment
NOT “We do it this way because we’ve always done it this way.”
Instead: “We do it this way because we know it works!” How do we know?
- Common sense (don’t drop a patient)
- Observation (try something – it works, use it again)
- Experience

Why evidence based practice?
1647 – first experiment demonstrates that lime juice can prevent scurvy
1690s – experiment repeated
1795 – becomes Royal Navy policy
147 year gap between knowledge and practice
Evidence-based practice aims to link what is known with what doctors do

Development of EBM
1990: Dept. of Medicine at McMaster Univ. (Canada) develops new philosophy of  medical education -- MDs will rely heavily on research literature rather than textbooks or opinion in approaching patient problems
1992: JAMA article on new approach
1993-2000: Evidence-Based Medicine Working Group publishes 25-part series on Users' Guides to the Medical Literature in JAMA

Lag time from time of “knowing” to time of implementation
13 yrs for thrombolytic therapy.
10 yrs for corticosteroids to speed fetal lung maturity.

The essence of evidence based practice
All evidence is sought and examined systematically
Evidence is wherever possible quantified
Evidence is considered in All decisions in healthcare
Evidence doesn’t make decisions: human beings do

Who are the players
Physician (and its clinical expertise)
and
best evidence (EB databases)
and
patient (holistic approach, with his/her values and preferences)

Physician “clinical expertise”
EBM does not eliminate the need for:
Noting signs during history taking and symptoms
Taking a good history
Interpreting results of tests
Thinking analytically

“Best research evidence”
What does “best” mean?
Why only the “best”?
Can the best be the enemy of the good?
What kind of evidence is excluded by the adjective “research”?

“Patient values”
Risk aversion
Time preference
Living arrangements
Working arrangements
Medical care vs. other goods and services
Income?

Making change happen
Information alone rarely changes behavior
Change is hard to achieve
Just in time information
Improvement techniques
Small group education

How to ask the question
PICO format
- P = Patient or Population, age group, disease/condition, socioeconomic group. Stage of disease, healthcare setting, gender
- I = Intervention- what is being done
Therapy (drug, surgery, radio), level, stage and delivery of intervention
Diagnostic test
- C = Comparison intervention (if there is one), what could be done instead?
- O = Outcome (what happened to P as a result of I?),
 patient oriented (quality of life, reduction in severity of symptoms, adverse effects)
Stop the pain
Prevent a heart attack
Diagnose a disease or condition
Provider oriented (cost effectiveness)

PICO questions
 

Examples PICO questions
Treatment
P – In a child with frequent febrile seizures
I – would anticonvulsant therapy
C – compared to no treatment
O – result in seizure reduction?

Asking answerable clinical questions
Background
- who/when/where/how/why of condition

Foreground
- about likely interventions and approaches to situation, problem, population at hand; how it relates to alternatives and to target outcome

Quotation
My students are dismayed when I say to them “Half of what you are taught as medical students will in 10 years have been shown to be wrong. And the trouble is, none of your teachers knows which half.”
(Dr Sydney Burwell, Dean of Harvard Medical School)

What evidence-based medicine is:
The practice of EBM is the integration of
individual clinical expertise
with the
best available external clinical evidence from systematic research.   
and
patient’s values and expectations

What EBM is not:
EBM is not cook-book medicine
- evidence needs extrapolation to my patient’s unique biology, preferences and values
EBM is not cost-cutting medicine
- when efficacy for my patient is paramount, costs may rise, not fall
- it is about cost effectiveness by eliminating ineffective treatments
EBM is not primarily about guidelines and pathways
- these are not always evidence-based
EBM is not a “top-down” approach to changing clinician behavior
- it empowers clinicians to seek their own answers

Medical literature
Pyramid of publication
At the bottom level (most of articles published, least usefullness as evidence, lowest validity of information): ideas and opinions, case studies, laboratory testing, anmal testing, human testing – uncontrolled volunteers,  human testing – controlled volunteers (at the top of pyramid, few articles published, highest usefulness as evidence, highest validity of information).

General search strategy
Clinical problem – define important, searchable question – select most likely resource – design search strategy – summarize the evidence – apply the evidence. If summarization of the evidence lead to the poor yield – select second most likely resource and go on.

What is evidence-based medicine? 
Where there is evidence of benefit and value, do it.
Where there is evidence of no benefit, harm, or poor value, don’t do it.
When there is insufficient evidence to know for sure, be conservative.
One solution for the problem of obsolescence of professional education is “problem-based learning” or “learning by inquiry”.
That is, when confronted by a clinical question for which we are unsure of the current best answer, we need to develop the habit of looking for the current best answer as efficiently as possible.
Here, we consider finding evidence to help solve clinical problems about the treatment or prevention, diagnosis and differential diagnosis, prognosis and clinical prediction, cause, and economics of a clinical problem.

The practice of evidence based medicine has been conceptualised as a five step process:
recognising information needs and describing them in well formulated clinical questions;
efficiently finding information;
- critically appraising the information;
- applying the information to the individual patient;
and evaluating the outcomes.
- Not having enough time is one of the most consistent reasons given by doctors for not practicing evidence based medicine.
- Studies of the amount of time it takes to find evidence show that going to the primary literature, in particular, really is very time consuming—ranging from 43 minutes to 4.5 hours for skilled searchers.
However, the increasing number and quality of sources of high quality synthesised evidence are ameliorating the complaint that it takes too much time to find information.
Using predigested sources of information, many common questions can be answered very quickly.
Studies of information sources that practising clinicians actually use suggest that most do not.
- They answer their questions by reading review articles or textbooks, or consulting with colleagues.
- Medical students and residents can be trained to search for and critically appraise evidence from the medical literature, but they do not seem to carry this into clinical practice.

Systematic literature reviews
are systematic to remove bias in finding and reviewing the literature.
- Experts may interpret the data (and their own experience) differently.

Who is the learner?
Learners can be doctors, patients, policy makers, or managers.
Not all doctors want or need to learn how to practice all five steps of EBM (asking, acquiring, appraising,
applying, assessing).
Indeed, most doctors consider themselves users of EBM, and surveys of clinicians show that only about 5% believe that learning all these five steps is the most appropriate way of moving from opinion based medicine to evidence based medicine.

Doctors can incorporate evidence into their practice in three ways.
In a clinical situation, the extent to which each step of EBM is performed depends on the nature of the encountered condition, time constraints, and level of expertise with each of the steps.
For frequently encountered conditions (such as unstable angina) and with minimal time constraints, we operate in the “doing” mode, in which at least the first four steps are completed.
- Doctor is a DOER

For less common conditions (such as aspirin overdose) or for more rushed clinical situations, we eliminate the critical appraisal step and operate in the “using” mode, conserving our time by restricting our search to rigorously preappraised resources (such as Clinical Evidence).
- Doctor is a USER

Finally, in the “replicating” mode we trust and directly follow the recommendations of respected EBM leaders (abandoning at least the search for evidence and its detailed appraisal).
- Doctor is a REPLICATOR

Doctors may practise in any of these modes at various times, but their activity will probably fall predominantly into one category.

Quotation
“When a steamroller comes through you are either part of the roller or part of the road.”
Stuart Brand

Basic Clinical Trials Terms
1/ Informed consent - is a legal condition whereby a person can be said to have given consent based upon a full appreciation and understanding of the facts and implications of any actions, with the individual being in possession of all of his faculties (not mentally retarded or mentally ill), and his judgement not being impaired at the time of consenting (by sleepiness, intoxication by alcohol or drugs, other health problems etc).
2/ Clinical trial – in medicine, a clinical trial (synonyms: clinical studies, research protocols, medical research) is a research study.
3/ Randomized controlled trial (RCT) is a form of clinical trials, or scientific procedure used in the testing of the efficacy of medicine, used because of its record of reliability.
4/ Cohort study - is a form of longitudinal study used in medicine and social science. The most important cohort studies are those that track a group of children from their birth, and record a wide range of information about them. The value of a cohort study depends on the researchers' capacity to stay in touch with all members of the cohort. Some of these studies have continued for decades.
5/ Case control studies - are one type of epidemiological study design. While the 'gold standard' in terms of study design is the double blind prospective randomized controlled trial, in order to study very infrequent events a very large population must be tracked to see a large enough number of cases; furthermore, if the event may take a long time to develop, this large population must be tracked for many years, despite 'drop-outs' from the study. The expense involved is too large to permit this methodology to be used to investigate every suspected risk. Instead, the case-control study enables much more cost-effective study of the factors related to the effect being investigated; if the evidence found is convincing enough, then resources can be allocated to a double blind prospective study to confirm the results.
6/ Double-blind experiment - describes an especially stringent way of conducting an experiment, usually on human subjects, in such as way as to attempt to eliminate subjective bias on the part of both experimental subjects and the experimenters.
7/ Placebo - A placebo, from the Latin for "I will please", is a medical treatment (operation, therapy, chemical solution, pill, etc.), which is administered as if it were a therapy, but which has no therapeutic value other than the placebo effect.  Experimenters typically use placebos in the context of a clinical trial, in which a "test" group of patients receive the therapy being tested, and a control group receives the placebo. It can then be determined if results from the "test" group exceed those due to the placebo effect. If they do, the therapy or pill given to the "test" group is assumed to have had an effect.
8/ Placebo effect - (also known as non-specific effects) is the phenomenon that a patient's symptoms can be alleviated by an otherwise ineffective treatment, apparently because the individual expects or believes that it will work. Some people consider this to be a remarkable aspect of human physiology; others consider it to be an illusion arising from the way medical experiments were conducted.

8/ Single-blind experiment - in a single-blind experiment, the individual subjects do not know whether they are so-called "test" subjects or members of an experimentla control group. In such a trial there is a risk that subjects are influenced by interaction with the researchers - known as the experiment effect.
9/ Control group –
10/ Experimental control group –
http://www.biocrawler.com/encyclopedia/Randomized_controlled_trial



Orientation to evidence-based information resources
Where to find the best evidence (postgraduate study)

1. Burn your traditional textbooks
We begin with textbooks, only to dismiss all but the best of a new breed of them.
- If the pages of textbooks smelled like decomposing garbage, when they are outdated, the nonsmelly bits could be useful, because textbooks are generally well organized for clinical use and much of their content will be current at any one time.
- Unfortunately, in most texts, there’s no way to tell what is up-to-date and what is not.
So, although we may find some useful information in texts about “background questions”, such as the pathophysiology of clinical problems, it is best not to use them for seeking the answers to “foreground questions”, such as the causal (risk) factors, diagnosis, prognosis, prevention or treatment of a disorder if there is an up-to-date, evidence-based alternative.

Cancel your full-text journal subscriptions
Trying to keep up-to-date in your clinical practice by reading full-text journals is a truly hopeless task.
From an evidence-based perspective, for a broad-based discipline such as general practice, the number of articles you need to read to find one article that meets basic criteria for quality and relevance ranges from 86 to 107 for the top five full-text general journals.
At, say, 2 minutes per article, that’s about 3 hours to find one article ready for clinical action; and then the article may cover old ground or provide “me-too” evidence of yet-another statin, or not be useful to you because of the way you have specialized the scope of your practice.

Invest in evidence-based journals and online services
A growing number of periodicals summarize the best evidence in traditional journals, making their selections
according to explicit criteria for merit, providing structured abstracts of the best studies and expert commentaries about the context of the studies and the clinical applicability of their findings.
These synoptic journals include ACP Journal Club, Evidence Based Medicine, Evidence Based Mental Health, Evidence Based Nursing, Evidence Based Health Care Policy and Practice, Evidence Based Cardiovascular Medicine, and a number of others.
Synoptic journals do what traditional journals wish they could do in selecting the best studies, finding the best
articles from all relevant journals and summarizing them in one place.

Walking the walk
1. Searching for evidence to solve patient problems
As in swimming and bicycle riding, the use of evidence-based information resources is best learned by examples and practice, not by reading.
Commit yourself to paper on three matters for each of the problems below before you move on to the rest of the chapter:
1/ The key question to seek an answer for
2/ The best answer to the clinical problem that you currently have stored in your brain (being as quantitative as possible).
3/ The evidence resources (both traditional and avant garde) that you would consult to find best current answers.

2. Take a “4S” approach to evidence-based information access
Practical resources to support evidence-based health care decisions are rapidly evolving.
New and better services are being created through the combined forces of increasing numbers of clinically important studies, more robust evidence synthesis and synopsis services, and better information technology and systems.
You can help yourself to best current evidence by recognizing and using the most evolved information services for the topics that interest you.

4S approach to evidence based information access
Bottom of pyramid: Studies (original published articles in journals), Syntheses (Cochrane reviews), Synopses (evidence based journal abstracts), Systems (Computerized Decision Support System – CDSS) (top of pyramid, most valid).

Systems
The ideal.
A perfect evidence-based clinical information system would integrate and concisely summarize all relevant
and important research evidence about a clinical problem and would automatically link, through an electronic medical record, a specific patient’s circumstances to the relevant information.
We would then consult—indeed, be prompted by—the system whenever the patient’s medical record is reviewed.
Internet-based “aggregators” provide a special “4S supermarket” service in providing access to evidence-based information.
Ovid, for example, provides access to a huge collection of texts, journals, and databases, including systems
such as Clinical Evidence.
Ovid’s Evidence Based Medicine Reviews (EBMR) takes this several steps further in providing access to the Cochrane Library, ACP Journal Club, the Database of Abstracts of Reviews of Evidence (DARE), and MEDLINE, all in an integrated format that permits tracking from, for example, a full-text original article to a synopsis that describes it, a synthesis (systematic review) in which it is incorporated, and related articles on the same topic.

Information overload problems
Minimum reading to keep up-to-date with pediatrics
Pediatrics – 40 articles  x 12 months
New England Journal of Medicine – 5 articles x 52 weeks
Lancet - 6 articles x 52 weeks
Journal of Pediatrics – 18 articles x 12 months
Pediatric Infectious Disease Journal - 15 articles x 12 months
JAMA 8 articles x 12 months
BMJ 10 articles x 52 months
Archives of Pediatric and Adolescent Medicine – 10 articles x 12 months
1694 article per year= 5 articles per day

To keep up to date in Internal Medicine, I need to read 17 articles a day, 365 days a year
Need to read
Don’t
Nor does anyone else

Places to look for evidence
PubMed espec. Clinical Queries
Ovid Web Gateway
Cochrane Database of Systemic Reviews
ACP Journal Club
Database of Abstracts of Review and Effects
Cochrane Central Register of Controlled Trials
ClinicalTrials.gov

Evidence Based Medicíne Tool Kit
Therapy/prevention
Diagnostic test
Prognosis
Harm
Systematic review
Economic analysis
Outcomes research

Problems with
Conventional Wisdom
- uses clinical manoeuvres, rather than patients, as the denominator.
- tends to focus on high-technology, “big ticket” items.
- relies on simple literature searches that miss over half of the most rigorous types of evaluations.
- conducted from armchairs.
- Clinicians are trained to think mechanistically and to draw conclusions using pathophysiologic rationale and deductive reasoning. The biomedical literature reflects this orientation, and we are therefore most familiar with deductive, quantitative research.
- Quantitative studies (such as epidemiologic investigations and clinical trials) aim to test well-specified hypotheses concerning some predetermined variables.
- These studies suitably answer questions such as whether? (e.g., whether an intervention did more good than harm), or how much? (e.g., how strongly a risk factor predisposes to a disease).
- However, medicine is not only a mechanistic and quantitative science, but also an interpretive art.
- Interpretive research asks questions about social interactions that can be addressed systematically through qualitative methods.
- Qualitative research offers insight into social, emotional and experiential phenomena in health care.
- Examples include inquiry about the meaning of illness to individuals and families, or the attitudes and behavior of patients and clinicians.
- Qualitative research questions tend not to ask "whether" or "how much" but rather to explore " what," "how," and "why."

Problems with EBM in daily practice
We need evidence (about the accuracy of diagnostic tests, the power of prognostic markers, the comparative efficacy and safety of interventions, etc.) about 5 times for every in-patient (and twice for every 3 out-patients). We get less than a third of it.

Steps in Practicing EBM
1/ Convert information needs into answerable questions
2/ Track down best evidence with which to answer questions
3/ Critically appraise evidence for validity and importance
4/ Integrate appraisal with clinical expertise and patient values to apply results in clinical practice
5/ Evaluate performance

Basic 5-Step Process of Evidence-Based Medicine
Formulate the question
Search for answers
Appraise the evidence
Apply the results
Assess the outcome

There are identified 3 different modes of practice
“Searching & appraising”
- provides E-B care, but is expensive in time and resources
“Searching only”
- much, quicker, and if carried out among E-B resources, can provide E-B care
“Replicating” the practice of experts
- quickest, but may not distinguish evidence-based from ego-based recommendations

Three solutions
Clinical performance can keep up to date:
1/ by learning how to practice evidence-based medicine ourselves.
2/ by seeking and applying evidence-based medical summaries generated by others.
3/ by applying evidence-based strategies for changing our clinical behaviour.

Patients can benefit
Even if <10 % of clinicians are capable of practicing in the “searching & appraising” mode (5 % of GPs)
As long as most of them practice in a “searching” mode within high-quality evidence sources (70-80 % of GPs): Cochrane Library, E-B Journals, E-B Guidelines, etc

The best evidence
Reflects patients’ concerns
- By addressing health outcomes patients, their caregivers, and families care about
- By using simple measures of benefit and risk
Help you feel similar to other people
Help you feel less lonely and removed from others
Help you feel more hopeful and happy
Allow you to think and express yourself more clearly

The Promises of EBM
More effective, safer medical interventions resulting in better health outcomes for patients
Greater uniformity in the quality of care
A slower rate of growth of expenditures for medical care

Conclusions
Information on its own doesn’t change practice
We must learn more about how we move from evidence to change, but we know it’s hard
EBM is a great advance over informal, non-quantitative approaches to clinical decisions.
The complexity and high cost of modern medicine make EBM necessary. Innovations outside of medicine make it feasible.
EBM should result in more effective, more uniform, and more efficient medical care.
EBM is an adjunct, not a substitute for physicians who can diagnose accurately, access evidence efficiently, and think analytically.
The integration of EBM with cost-benefit analysis poses a major challenge for health policy.

Literature

1. Greenhalgh T. Jak pracovat s vědeckou publikací. Praha, Grada – Avicenum 2003, 208 s.
2. McAlister FA, Straus SE, Guyatt GH, Haynes RB for the Evidence Based Medicine Working Group
Integrating Research Evidence with the Care of the Individual Patient Based on the Users' Guides to Evidence-based Medicine and reproduced with permission from JAMA 2000; 283(21): 2829-2836.
3. Giacomini M, Cook DJ, for the Evidence Based Medicine Working Group - A User's Guide to Qualitative Research in Health Care Based on the Users' Guides to Evidence-based Medicine and reproduced with permission from JAMA 2000; 284(4): 478-482.
4. Guyatt GH, Sinclair J, Cook DJ, Glasziou P, for the Evidence Based Medicine Working Group - How to Use A Treatment Recommendation Based on the Users' Guides to Evidence-based Medicine and reproduced with permission from JAMA 1999; 281(19): 1836-1843.
5. Sharon E Straus, Michael L Green, Douglas S Bell. Evaluating the teaching of evidence based medicine: conceptual framework BMJ 2004; 329: 1029-1032.
6. Saarni SI, Gylling HA. Evidence based medicine guidelines: a solution to rationing or politics disguised as science? J Med Ethics 2004; 30: 171-175.
7. Guyatt G. Evidence based medicine has come a long way. BMJ 2004; 329: 990-991.
8. Dickenson D, Vineis P. Evidence based medicine and quality of care. Health Care Anal 2002; 10: 243–244.
9. National Institute of Clinical Excellence. Guideline development methods. London: NICE, 2004, ch 7. http://www.nice.org.uk/pdf/
10. Strauss S, McAlister F. Evidence based medicine: a commentary on common criticisms. CMAJ 2000; 163: 837–841.
11. Meulen R, Dickenson D. Into the hidden world behind evidence based medicine. Health Care Anal 2002; 10: 232–233.
12. Parker M. Whither our art? Clinical wisdom and evidence based medicine. Med Health Care Philos 2002; 5: 275–276.
13. Sackett DL, Rosenberg WMC, Muir Gray JA, et al. Evidence based medicine: what it is and what it isn’t. BMJ 1996; 312: 71–72.
14. Carney S. Competences for the foundation programe, part 3: Evidence based medicine. BMJ 2005, 231-232.
15. Haynes RB, Devereaux PJ, Guyatt GH. Clinical expertise in the era of evidence-based medicine and patient choice Evid Based Med 2002; 7: 36-38.
16. Haynes RB. Of studies, syntheses, synopses, and systems: the evidence "4S" evolution of services for finding current best. Evid Based Med 2001; 6: 36-38.
17. Bartkowiak BA. Searching for Evidence-Based Medicine in the Literature. Part 2: Resources Clinical Medicine & Research 2005; 3(1): 39-40.
18. Giacomini MK. The rocky road: qualitative research as evidence. Evid Based Med 2001; 6: 4-6.
19. Haynes RB, Glasziou P, Straus S. Advances in evidence-based information resources for clinical practice
Evid Based Med 2000; 5: 4-6.