introduction to evidenced based medicine

Introduction toEvidenced Based Medicine

Presented By

Dr.N.P.Singh

Objectives:• Define "Evidence Based Medicine"• Describe the need for EBM• List 3 components of Evidence-based decisions• Explain the concept of "hierarchy of evidence"• List reasons why the hierarchy of evidence is not

absolute• Describe the 4 steps of the "EBM process"• Explain the rationale behind the 3 "broad

questions" that can be used to evaluate any source of evidence.

Intro to EBM

Definitions:• "The integration of best research evidence with clinical

expertise and patient values” (David Sackett, et al. Evidence-based Medicine. How to Practice and Teach EBM, 2000)

• "The conscientious, explicit, and judicious use of current best evidence in making decisions about the care of individual patients..." (Gordon Guyatt, M.D., et al. Users' Guides to the Medical Literature, 2002)

What is EBM?

Key components:• "The integration of best research evidence with clinical



What is EBM?

What is EBM?

Philosophy ("conscientious, explicit, judicious..."):• "enlightened skepticism." Don't believe all you're told.• "Printed word bias. This occurs when a study is overrated

because of undue confidence in published data." (Alejandro Jadad, Randomized Controlled Trials: A Users' Guide, 1998)

• q.v. "prestigious journal bias," "non-prestigious journal bias," "prominent author bias," "famous institution bias" ...

• Rigorous, intellectually exacting approach: "intuition, unsystematic clinical experience, and pathophysiologic rationale are [of themselves] insufficient grounds for clinical decision making." (Users' Guide p. 4)

• "A formal set of rules must complement medical training and common sense..." (p. 4)

• "EBM places a lower value on authority than the traditional medical paradigm does." (p. 4)

What is EBM?




What is EBM?

What is the need?• Cost• Delay of "bench-to-bedside" research• Managing the primary literature• Counter misleading marketing• Dealing with conflicting results

Why EBM?


Why EBM?

increasing pressure to

• demonstrate effectiveness of interventions

• utilize the most cost effective measures

How do you know what really works or is the most effective?


Why EBM?

Delay of "bench-to-bedside" research:

Primary literature. Original research that generates new data.

Secondary literature. Material published based on primary literature.

Why EBM?

• No new data is generated• Existing data is made more accessible• "Four "Ss":

• pre-Selected studies: particularly relevant studies are culled from the body of primary literature.

• Systematic Reviews: Particularly relevant studies are summarized (in a systematic way to avoid bias).

• Synopses: Primary findings are re-organized and interpreted for pedagogical reasons (e.g., textbooks).

• Systems: Primary findings are re-organized and interpreted to practical reasons (e.g. decision support, practice guidelines)


Why EBM?

Secondary Research

Routine Clinical Practice

Primary Literature

Years-to-Decades


Why EBM?

Secondary Research


Primary Literature

Thrombolytic Drugs for acute MI:

6 years from the first Systematic Reviews of RCTs until most review articles and textbooks recommended their use.

(Antman, Lau, et al. JAMA 1992)


Why EBM?

Secondary Research


Primary Literature

Aspirin after acute MI:

Not recommended by expert opinion until 6 years after the first systematic review.

(Antman, Lau, et al. JAMA 1992)


Why EBM?

Secondary Research


Primary LiteratureBed rest after back injury or

surgery:

• Studies in the 1940's showed no advantages for complete bed rest after surgery

• Instead, DVT, bedsores. osteoporosis, and pneumonia identified as problems.

• Ideas about bed rest remain entrenched...

• e.g., 80% of neurological units in UK still insist on bed rest, despite 17 years of evidence showing no value

(Allen C, Glasziou P, Del Mar C. Bed rest: a potentially harmful treatment needing more careful evaluation. Lancet 1999.)


Why EBM?

Secondary Research


Primary Literature Use of albumin in fluid resuscitation:

• Based on physiologic reasoning. Used for >50 years for hypovolemia, shock, burns...

• Later RCTs suggested increased mortality in some conditions

• Modern, large Systematic Reviews showed possible biphasic effect based on dose. (Wilkes, Navickis. Ann Int Med 2001)


Why EBM?

Secondary Research


Primary Literature "Life Cycle of Translational Research"

Median time from "initial discovery of a medical intervention" to a "highly cited article" was 24 years.

(Contopoulos-loannidis, Alexiou, et al. Science 2008)

Median time from "initial discovery" to a "highly cited article" was 24 years.(Contopoulos-loannidis, Alexiou, et al. Life-cycle of translational research for medical interventions,

Science 2008)

Why EBM?Folate for prevention of neural tube defects (ca. 1963-1991)

AZT for prevention of perinatal HIV infection (ca. 1989-1994)


Why EBM?

• Early, judicious use of the primary literature may help save lives.

• How to decide what constitutes "Judicious" will to be explained more as the course progresses.


Why EBM?

Managing the primary literature

Why EBM?


Why EBM?

15 K

35 K

100 K


Why EBM?

• MEDLINE adds 4500 records daily.

• Just within their own fields, physicians would need to read 19 articles per day, 365 days per year, to keep up with research. (Oxford Center for EBM)

• Not all (~10%) of these articles are considered high quality and clinically relevant. (Oxford)

EBM helps you find the most appropriate article for a specific clinical question.


Why EBM?

Pharmaceutical companies invest considerable resources to promote products based on skewed or selective evidence (or emotion appeals through direct-to-consumer advertising). EBM provides tools to help alert clinicians to potentially misleading marketing.

(Glasziou, Hayes. The paths from research to improved health outcomes, Evidenced Based Nursing, 2005; 8(2):36-8.)


Why EBM?

Dealing with conflicting results?

Why EBM?

"My students are dismayed when I say to them "Half of what you are taught as medical students will in ten years have been shown to be wrong. And the trouble is, none of your teachers know which half." -Sydney Burwell, M.D., Dean, Harvard Medical School (1956)

(Contopoulos-loannidis, Alexiou, et al. Science 2008)

Postmenopausal HRT

Vitamin E for CAD prevention Vitamin E for CAD prevention

Dealing with conflicting results

Why EBM?

• Back-to-Sleep: Based on physiologic reasoning, Dr. Benjamin Spock recommended that babies sleep on their stomach to prevent risk of vomiting and choking.

• Later shown to increase the risk of SIDS:


Why EBM?

• Beta-blockers initially avoided after MI due to pathophysiologic reasoning that they would decrease compensatory sympathetic mechanisms

• Later shown to decrease hospitalization & death:


Why EBM?

• Based on 16 cohort studies (and some physiologic reasoning) HRT used to be recommended for postmenopausal women to reduce the risk of CHD.

• Womens' Health Initiative show it actually increased the risk of MI, stroke, and venous thromboembolism:


Why EBM?

• Since the 1960s, lidocaine was used for V-fib & V-tach prophylaxis in patients with acute MI.

• A meta-analysis showed some reduction in V-fib & V-tach, but a probably increase in actual mortality:

Dealing with conflicting resultsWhy EBM?

Damned if you do...

...Damned if you don't

Dealing with conflicting results:

Hierarchy of Evidence:

The notion that some study designs are less susceptible to bias than others, with the effect that some study results are more likely to be valid than others.

"Study design," "bias," and "validity" will be more rigorously explained later. Casual understanding is sufficient for now.

Why EBM?

A Hierarchy of Evidence (strongest type of evidence on top):

Hierarchy of Evidence

Meta-Analysis

Randomized Controlled Trial

Cohort Study

Case-Control Study

Case Series

Single Case Reports

Anecdotal Reports

Pathophysiologic Reasoning

Ideas, opinions, etc.

(Petrie A. Statistics in orthopaedic papers. The Journal of Bone and Joint Surgery 2006; 88-B(9):1121-36)

Levels of Evidences

• (I-1) a well done systematic review of 2 or more RCTs

• (I-2) a RCT

• (II-1) a cohort study

• (II-2) a case-control study

• (II-3) a dramatic uncontrolled experiment

• (III) respected authorities, expert committees, etc..

• (IV) ...someone once told me.... – http://www.phru.org/casp/– See also AAFP

http://www.phru.org/casp/

http://www.aafp.org/x17444.xml

The EBM ProcessAn approach to clinical decision making that systematically incorporates available evidence, patient preference, and clinical expertise.

A four-step process:

1.Ask a "well-built" clinical question

2.Search for the best evidence to answer the question.

3.Critically appraise the evidence

4.Apply the evidence to a particular patient

The EBM ProcessAn approach to clinical decision making that systematically incorporates available evidence, patient preference, and clinical expertise.


1. Ask a "well-built" clinical question

2. Search for the best evidence to answer the question.

3. Critically appraise the evidence

4. Apply the evidence to a particular patient

The EBM ProcessStep 1: Ask a well-built clinical question

• Use the Mnemonic PICO:

P = Patient characteristics• age (adult, pediatric)• sex• diagnosis or condition• social situation, resources, values• setting: inpatient, outpatient, rural, tertiary care, etc.• public health issue or individual patient issue?


I = Intervention• What it is you are considering trying• Could be a medication, a diagnostic test, or some other

type of treatment• Most useful when you need to choose between

treatment options


C = Comparison• One of the options you are choosing between• Sometimes the labeling of one treatment as

"Intervention" and the other as "Comparison" is arbitrary.

• A treatment (or test) can really only be assessed in comparison to something else...

• ...Even if the "something else" is "standard treatment," "watch-and-wait," or "no treatment."


O = Outcome• The effect you want to achieve (or avoid)• Can include treatment effects as well as side effects• Usually, you are interested in one primary outcome

(even if the primary outcome is fairly global such as "quality of life," "functionality," or "hospitalizations."

• Surrogate outcomes: Measurements that are not of themselves important to patients (e.g., blood pressure, bone density, cholesterol level) but that are associated with outcomes that are important to patients (e.g., stroke, fracture, MI).

• Use caution with surrogate outcomes (e.g., Lidocaine use after AMI: decreased V-fib but increased death.)

The EBM ProcessOutcomesEfficacy: The effects of an intervention under ideal conditions (e.g., a laboratory experiment)

• Most RCT's measure efficacy.

Effectiveness: The effects of an intervention under the usual conditions (e.g., in the field)

• RCT's may overestimate effectiveness• Observational studies may give a better estimate of actual

effectiveness.

Efficiency: The relative ease (or lack of waste) in producing an effect.

• Related to the idea of potency• Not really an EBM concept, but included here since it is another

"eff-" word that is commonly confused with efficacy and effectiveness.

Centre for EBM: http://163.1.212.5/docs/focusquest.html

Questions: PICO

The EBM ProcessAn approach to clinical decision making that systematically

incorporates available evidence, patient preference, and clinical expertise.






The EBM ProcessStep 2: Search for the EvidenceSearching techniques can be involved and take a lot of experience and trial & error to discover what works well.

These will be covered in more detail in a later module.

In searching, you should consider:• What databases are available & relevant to my question?

• How does each database work? How do you enter searches? How can you refine or narrow searches?

• Use your PICO question to choose key words

• What type of article (treatment, harm, diagnosis, prognosis, etc.) is most relevant to my question?

• Which articles are of the highest level of evidence?

The EBM ProcessStep 2: Search for the Evidence

In general, the highest level of evidence is preferred. Emphasize additional criteria when:

• You find >1 article at the highest available level of evidence

• Results are inconsistent from article to article

• The patients studied, the clinical setting, or the outcome measured are significantly different from your PICO question

In these cases you should especially consider:• Which articles have a clinical setting, patient population, or

outcome most similar to my PICO question?

• Which studies are the most recent?

• How large are the sample sizes?

• How well done are the studies? (Step 3 of the EBM process)

The EBM ProcessStep 3: Critically appraise the evidence

"Critically appraise" refers to determining the appropriateness of a some evidence (usually a journal article) for a particular clinical situation.

Internal validity: Refers to the soundness of the research methodology• Does the study measure what it says it is measuring?• Related to efficacy: performance under ideal (or laboratory)

conditions.

External validity: Refers to generalizability of the results.• Related to effectiveness: How meaningful are the results in real

life?

Three broad questions are use to critically appraise an article:

1. Are the results valid?2. What are the results?3. How can I apply these results to my patient?

Critical AppraisalAre the results valid?

• Traditional wording of this question is misleading; it's not really about the results.

• It's about the methodology (internal validity)

• Is the methodology sufficiently sound that the results can be trusted?

• There are specific criteria than can be used to determine the soundness of the methodology.

• Different article types (harm, therapy, diagnosis, prognosis) have different criteria that are used to determine the soundness of the methodology

• Despite the wording, it is not a yes or no answer.

• How likely is it that the results are valid?

Critical AppraisalWhat are the results?

• This question is largely statistically based

• Involves knowing what the various numerical results mean.

• Knowing how to interpret results

• These will also be covered in future modules.

How can I apply these results to my patient?

• This question is about external validity (generalizability) and effectiveness: results with real patients in real world settings

• Patients recruited for studies may not be characteristic of all patients

• Study subjects are often more motivated or better educated than average...

• ...or have fewer comorbidities, or more "classic" or less ambiguous diagnoses.








This step is redundant. Same as the 3rd "critical appraisal" question.








5. Some authors add a fifth step: Evaluate your own performance.

This step is redundant. Same as the 3rd "critical appraisal" question.

Conclusion: What EBM is NOTThese are some of the criticisms you will sometimes hear about evidenced based medicine.

NOT... But it is...• "Cookbook" medicine• Rigid adherence to

clinical guidelines

A rigorously systematic way to:• Evaluate the strength of available evidence• Evaluate the appropriateness of available

evidence for a particular clinical situation• Make your own choices based on an

informed, deliberate balance of patient values, clinical expertise, and available evidence.

• Managed care companies will sometimes require rigid adherence to clinical guidelines under the guise of "EBM," but this is contrary to the principles of EBM.

Conclusion: What EBM is NOTNOT... But it is...• Managed care• Cost-cutting measures

A way to avoid waste by considering both the efficacy and effectiveness of a particular intervention in a particular clinical setting.

Limited to Randomized Controlled Trials

Recognition that:• Some study designs (esp. RCTs) are less

susceptible to bias than others, and therefore less likely to mislead.

• RCTs are not always available (or are of poor quality) but other evidence can (and should) be used in clinical decision making as long as you understand its limitations.

• Observational studies can give useful information when effect is large, consistent over time, or when external validity is especially important.

Conclusion: What EBM is NOT

NOT... But it does...The same thing as• clinical epidemiology• biostatistics• study design

Build on these concepts so you can better understand the strength of inferences from available evidence.

• No greater opportunity, responsibility, or obligation can fall to the lot of a human being than to become a physician. In the care of the suffering, [the physician] needs technical skill, scientific knowledge, and human understanding. . . . Tact, sympathy, and understanding are expected of the physician, for the patient is no mere collection of symptoms, signs, disordered functions, damaged organs, and disturbed emotions. [The patient] is human, fearful, and hopeful, seeking relief, help, and reassurance.

• –Harrison's Principles of Internal Medicine, 1950

introduction to evidenced based medicine

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