Evidence Based Medicine

It is astonishing with how little reading a doctor may practice medicine, but it is not

astonishing, how badly he may do it.

- Butler, "Equanimitas", 1901

Clinical PracticeClinical Practice

In

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How do we use the clinical evidence/How do we answer “What works?” (Berg)

A. Trust Me

• Dr. Smith: So which statin would you recommend?

• Dr. Jones: Atorvastatin is the drug of choice.

Translation: Does it work? It does if I say so.

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B. Deferral to Authority

• Dr. Smith: So which statin would you recommend?• Dr. Jones: I prefer atorvastatin, and the last time I

sent someone over to the Lipid Clinic, that was Dr. Doe’s recommendation as well.

Translation: Does it work? It does if Dr. Expert says so.

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C. In My Experience

• Dr. Smith: So which statin would you recommend?

• Dr. Jones: I don’t really like any of them. I have had good experience with diet and cholestyramine and never prescribe HMG-CoA reductase inhibitors.

Translation: Does it work? It does work ? It does seem to.

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D. Everyone Else is Doing It

• Dr. Smith: So I have this 55-year old man in for a complete physical, and he’s asking about screening for prostate cancer.

• Dr. Jones: (Medical Director): Make sure you do a digital rectal examination and get a PSA. We’ll get sued if you don’t and he develops prostate cancer, because screening is the standard in our community.

Translation: Does it work? It does work ? ? It does if everyone agrees that it does.

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Is there a better way to find and use clinical evidence?

Evidence - Based Medicine ! Evidence - Based Medicine !

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E.B.M. - HistoryEvidence-based medicine originated in McMaster University, Ontario, Canada;

in the 1980s where a group of researchers wanted to bring about a

change in approach of medical practice from one that had its

foundation in personal experience

to one based on scientific evidence.

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What is evidence-based medicine?What is evidence-based medicine?

“Evidence-based medicine is the integration of best research evidence

with clinical expertise

and patient values”

- Sackett, et al 2001

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Purposes of Evidence Based Medicine

Keeping Your Skills up to Date Saving Time Saving Lives Supplementing Clinical Judgment

Evidence Based Medicine provides us with the tools we need to find important new medical research quickly and easily,

and to work out its implications for our practice.

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Keeping Your Skills up to Date

"A well-used library is one of the few antidotes a

general practitioner has to the premature senility that is liable to

overtake him.”

- Butler, "Equanimitas", 1901

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Keeping Your Skills up to DateIn the years after you

graduate, two things will happen:

Your memory of what you learned in medical school will lose its freshness

New treatment methods will be found that they never taught you about in school because they didn't exist.

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Saving Time

The total amount of knowledge out there is far greater and often more reliable than the clinical experience of one physician or even a group of experts.

You no longer need to read through masses of journals in order to take advantage of it. It is no longer your job to know everything, even in your chosen specialty.

It IS your job to be able to find the information as and when you and your patients need it.

Journals on Ageing in 1974 : 28 Journals on Ageing in 1994 : 95

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Saving Lives

A detailed and exact knowledge of the outcomes of different treatments, derived from the research, can often save lives.

e.g. -- the problem of whether to perform an endarterectomy on a newly symptomatic patient with severe stenosis. The benefit of surgery in reducing the risk of a major stroke or fatality is summed up in that you need only treat 11 patients, on average, to prevent a major stroke or fatality

(L. Goldstein et al, 1995):

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Supplementing Clinical Judgment

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1. Formulate an answerable question

2. Track down the best evidence

3. Critically appraise the evidence

4. Integrate with clinical expertise and patient values

Elements of evidence-based medicineElements of evidence-based medicine Information “pull” Steps in EBM process

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Formulating an Answerable Clinical Question

P Patient or population

Describes patient (age, sex, race, past medical history, etc.)

A 50 year old woman with a family history of breast cancer

I Intervention What happens or is to be done; treatment, diagnostic test, exposure, screening

Hormone replacement therapy

C Comparison Compared to what? Nothing, placebo, gold standard, another intervention

Placebo

O Outcomes (preferably clinical)

What is the effect of the intervention? (Be specific: mortality after a particular time period,

hospitalizations).

Prevention of Alzheimer's Disease

AMONG 50-year old women with a family history of breast cancer DOES hormone replacement therapy AS COMPARED TO placebo reduce the risk of Alzheimer's Disease?


• Example 1

In Preterm infant born < 32 weeks gestation does exogenous surfactant therapy compared to no therapy – reduce the mortality?

Formulate an answerable question

Track down the best evidence

Critically appraise the evidence

Integrate with clinical expertise and patient values

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Example 2: “the first sign of hyperkalaemia is death”

• An anxious laboratory technician phoned about a potassium of 7.3 mmol/l (Ref Range 3.5-5.0) found on a routine blood test of a 50 year old woman. • I arranged an urgent repeat of the electrolytes (to rule out a spurious elevation) and an ECG.• The latter was reassuringly normal, but left me asking: Does a normal ECG rule out a serious elevation

of potassium?





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1. The question

• Does a normal ECG rule out a serious elevation of potassium?

• Population - In suspected hyperkalemia• Indicator - does a normal ECG• Comparator - • Outcome - rule out hyperkalemia?





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Tracking the evidence JASPA*(Journal associated score of personal angst)





J: Are you ambivalent about renewing your JOURNAL subscriptions?

A: Do you feel ANGER towards prolific authors?S: Do you ever use journals to help you SLEEP?P: Are you surrounded by PILES of PERIODICALS?A: Do you feel ANXIOUS when journals arrive?

• 0 (?liar) • 1-3 (normal range) • >3 (sick; at risk for polythenia gravis and related conditions)

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Earlier

Great dearth of Information

Since 1987, when the first publication on the properties of the Lactobacillus GG was done, there have been over 200 publications in peer-reviewed scientific journals.

Trac

king

the

evid

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Tracking the evidence





• Over 2 million articles published every year in around 20,000 journals • A doctor has to refer 30 medical journals a week to keep abreast in his specialty - which is almost impossible considering the busy schedules.

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Review the World Literature Fortnightly*

0

500000

1000000

1500000

2000000

2500000

Trials MEDLINE BioMedical

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Art

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5,000?per day

1,400 per day55 per

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a) Medical Databases b) Search engines c) Medical news services d) Medical journals and

textbooks

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a) Medical Databases: 1. Best Evidence 2. Cochrane Library http://www.cochrane.org 3. Medlinehttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed

3. TRIP Databasehttp://www.update-software.com/

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b) Search engines

Google www.google.com OMNI www.omni.ac.uk Oncolink http://cancer.med.upenn.edu Altavista www.altavista.com

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Medical news services Amadeus www.amedeo.com Intelihealth www.intelihealth.com Medscape www.medscape.com Reuters Health www.reutershealth.com Biomednet www.bmn.com

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d) Medical journals and textbooks Eg.

Bandolier Clinical Evidence Cochrane Newsletters

Most medical journals and quite a few textbooks are now online

By the time textbooks reach the book stores, the information may get outdated

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Appraising Evidence

• Randomized Controlled Trials• Case Control Studies• Cohort Studies • Case Reports• Clinical Guidelines and Recommendations• Systematic Reviews• Meta-analysis





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Randomized Controlled Studies

There are two groups, one treatment group and one control group. The treatment group receives the treatment under investigation, and the control group receives either no treatment or some standard default treatment.

Patients are randomly assigned to all groups.

Standard method of answering questions about the effectiveness of different therapies.

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The Double Blind Method

A double blind study is one in which neither the patient nor the physician knows whether the patient is receiving the treatment of interest or the control treatment

• Reduces the risk of bias, • It can eliminate the placebo effect

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The Double Blind Method Ap

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Cohort Studies

A Cohort Study is a study in which patients who presently have a certain condition and/or receive a particular treatment are followed over time and compared with another group who are not affected by the condition under investigation.

• Not as reliable as randomized controlled studies, since the two groups may differ in ways other than in the variable under study • They can end up taking a very long time

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Case Control Studies

Case control studies are studies in which patients who already have a certain condition are compared with people who do not.

• Less reliable than either randomized controlled trials or cohort studies.• They can be done quickly. • Researchers don't need special methods, control groups, etc.

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Case Series and Case Reports

Case series and case reports consist either of collections of reports on the treatment of individual patients, or of reports on a single patient.

A type of descriptive study

• A search for case series / case reports may reveal information that will assist in a diagnosis. • Have no statistical validity .

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Case Series and Case Reports

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Descriptive Studies

Examine differences in disease rates among populations in relation to age, gender, race, and differences in temporal or environmental conditions.

Can only identify patterns or trends in disease occurrence over time or in different geographical locations

Cannot ascertain the causal agent or degree of exposure. Useful for generating hypotheses for further research

Eg. • Case reports or case series, • Surveillance systems, • Correlational (ecologic studies), • Cross-sectional studies • Cluster investigations

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Systematic Reviews

A systematic review is a comprehensive survey of a topic in which all of the primary studies of the highest level of evidence have been systematically identified, appraised and then summarized according to an explicit and reproducible methodology. Ap

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Gold standard in evidence based medicine

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Meta-Analyses

A meta-analysis is a survey in which the results of all of the included studies are similar enough statistically that the results are combined and analyzed as if it was one study.

• Analysis of analyses• Some kind of positive effect tend to be published more often than those

that do not. (Publication bias. )

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Easy Option : To go for EBM Resources - C.S.N.Vittal

Meta-Analyses Ap

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Evidence PyramidEvolution of the literature

App

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Evid

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As you move up the pyramid the amount of available literature decreases, but increases in relevance to the clinical setting. (McKinnell and Elliott, 1997).

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An Example if you are interested in which interventions are most

effective for smoking cessation, search the Cochrane Database of Systematic Reviews (CDSR) first.

If there are no systematic reviews on your question, move down to the next level of the pyramid (Randomized Controlled Double Blind Studies).

Look for reviews (DARE or ACP Journal Club) of single well-designed randomized controlled trials.

If appraised resources fail to provide evidence on your question then you must search a large online medical database like MEDLINE.

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Evidence (Study Design) Appropriate for Common Question Types Matched to EBM Search Filters

Type of Question

Study Design MEDLINE Search Filter Terms

Therapy Systematic Reviews and Meta-AnalysesRandomized Controlled Studies

Double-blind Method Meta-analysis Random Allocation Clinical Trial Randomized Controlled Trial Placebos Multicenter Study Random

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Levels of Evidence Level Type of Evidence

I Evidence is obtained from meta-analysis of multiple, well-designed, controlled studies. RCTs with low false-positive and low false-negative errors (high power).

II Evidence is obtained from at least one well-designed experimental study. Randomized trials with high false-positive and/or negative errors (low power).

III Evidence is obtained from well-designed, quasi-experimental studies such as non-randomized, controlled single-group, pre-post, cohort, time, or matched case-control series

IV Evidence is from well-designed, nonexperimental studies such as comparative and correlational descriptive and case studies

V Evidence from case reports and clinical examples

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Grading of Recommendation

Grade Grading of Recommendation

A There is evidence of type I or consistent findings from multiple studies of types II, III, or IV

B There is evidence of types II, III, or IV and findings are generally consistent

C There is evidence of types II, III, or IV but findings are inconsistent

D There is little or no systematic empirical evidence

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Some examples of the way evidence ratings will appear in the text of an article

• “To improve morbidity and mortality, most patients in CHF should be treated with an angiotensin-converting enzyme inhibitor.

[Evidence level A, RCT]”

• “The USPSTF recommends that clinicians routinely screen asymptomatic pregnant women 25 years and younger for chlamydial infection.

[Evidence level B, nonrandomized clinical trial]”

• “The American Diabetes Association recommends screening for diabetes every three years in all patients at high risk of the disease, including all adults 45 years and older.

[Evidence level C, expert opinion]”

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1. The patient's situation 2. The patient's desires and values 3. Your values 4. Your experience 5. Evidence from research





Elements That Help Form Your Clinical Decision

EBM helps supply you with 5 i.e. evidence from research. It is up to you to judge how applicable that information is to your

patient and to decide on a course of action.

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What is What is not not evidence-based evidence-based medicine?medicine?

Evidence-based medicine is not "cook-book" medicine.

External clinical evidence can inform, but can never replace, individual clinical expertise, and it is this

expertise that decides whether the external evidence applies to the individual patient at all and,

if so, how it should be integrated into a clinical decision.

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What is What is not not evidence-based evidence-based medicine?medicine?

Evidence-based medicine is not restricted to randomized trials and meta-analyses.

It involves tracking down the best external evidence with which to answer our clinical

questions.....if no randomized trial has been carried out for our

patient’s predicament, we follow the trail to the next best external evidence and work from there .

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EBM Resources

Cochrane CollaborationPubMed Central

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1. The question

Does a normal ECG rule out a serious elevation of potassium? Population – hyperkal* Indicator – ECG OR EKG Comparator - Outcome – hyperkal*

Underline keywords; think of synonyms

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Diagnosisbutton

* Means any letters

“OR” synonyms

PubMed via Google

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Diagnosisbutton

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Sensitivity of 62% or 55%

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Treating hyperkalemia

She refused to go to hospital Resonium A, but it is around $100, which

she could not afford. My search had mentioned albuterol as a

treatment.

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http://images.google.com/imgres?imgurl=www.divernet.com/medical/pics/0802qna2.jpg&imgrefurl=http://www.divernet.com/medical/0802qanda.htm&h=223&w=200&prev=/images%3Fq%3Dventolin%26start%3D20%26svnum%3D10%26hl%3Den%26lr%3D%26ie%3DUTF-8%26oe%3DUTF-8%26sa%3DN

Grade A recommendation (level 1A evidence) •Treatment of acute infectious diarrhoea in children.•Prevention of antibiotic associated diarrhoea.•Prevention of nosocomial and community acquired diarrhoea in

children.•Treatment of lactose malabsorption.

Grade A recommendation (level 1B evidence) •Prevention of pouchitis and maintenance of remission.•Prevention of postoperative infections.•Prevention and management of paediatric atopic diseases.

Grade B recommendation (level 2 evidence) •Prevention of travelers’ diarrhoea.•Prevention of sepsis associated with severe acute pancreatitis.•Maintenance of remission of ulcerative colitis.•Lowering of blood cholesterol.

PROBIOTICS IN PROBIOTICS IN EVIDENCE BASED GASTROENTEROLOGYEVIDENCE BASED GASTROENTEROLOGY

Probiotics and human health: a clinical perspective H S Gill and F Guarner Postgraduate Medical Journal 2004;80:516-526 © 2004

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Systematic review of bed rest after medical procedures

Allen, Glasziou, Del Mar. Lancet, 1999

10 trials of bed rest after spinal puncture no change in headache with bed rest Increase in back pain

Protocols in UK neurology units - 80% still recommend bed rest after LP

Serpell M, BMJ 1998;316:1709–10

…evidence of harm available for 17 years preceding...

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What is evidence-based medicine?What is evidence-based medicine?

It is the process of systematically finding, apprising and using contemporaneous research

findings as the basis for clinical decisions.

Thus, EBM goes beyond reading an article and accepting the information as written.

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The Barriers to EBP

1. Attitude of question & inquiry2. Know-how in finding, appraising,

and applying evidence3. Information Resources on tap4. Lack of Time5. Cost Factor

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Conclusion

“Evidence can enhance clinical judgment but can’t replace it.”

Evidence derived from critical appraisal needs to be integrated with clinical experience so that

the patient is benefited.

Such an approach can make clinical decision-making easy

and improve the quality of care.- C.S.N.Vittal

"Kill as Few Patients as Possible" - Oscar London

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Evidence Based Medicine

Health & Medicine

Transcript of Evidence Based Medicine