Evidence Based Medicine

Clinical Practice Guidelines

What is Evidence Based Medicine?

• Philosophy of medical practice to aid in the approach to decision making in the clinical care of patients.

• It is integrating individual clinical expertise (internal clinical evidence) with the best available external clinical evidence from systematic research of the literature

Evidence Based Medicine...

• We make decisions based on the best clinical, scientific ______________

• Critical appraisal of published literature helps determine– ______________ of evidence– ______________ of evidence

• Goal of EBM: to improve patient outcomes.

Internal Clinical Evidence

• Individual Clinical Expertise – Training– Experience– Knowledge

External Clinical Evidence

• Literature Research– Randomized Controlled Clinical Trials– Meta-Analysis Studies– Cohort Studies– Case Controlled Studies

• To answer clinical questions regarding:– Therapy, Diagnosis, Etiology, Prognosis,

Prevention, Quality Improvement

Literature Review Pitfalls

• Not all medical journals publish high quality studies. (We critically evaluate validity of studies)

• Authors will have inherent bias (by words they use, points they stress or don’t stress, etc.)

• Editors and reviewers are human (bias)• Negative studies frequently aren’t published

7 Levels of Evidence for Literature Evaluation

• Evidence from:– Grade l- Large RCT (gold standard)– Grade 2- Small, not as well designed RCT, Meta-

Analysis studies– Grade 3- Cohort studies (retrospective or

prospective, non randomized, observational)– Grade 4- Case-control studies (non-rand., always

retrospective, observational)– Grade 5- uncontrolled or poorly controlled studies,

case series (descriptive), cross-sectional, Review articles

– Grade 6 -Conflicting studies– Grade 7 -Expert opinion

Randomized Controlled Clinical Studies/Trials (RCT)

• True experimental study• Most useful for quantifying data• Well designed studies will infer

cause/affect relationship (good thing)• Randomization will reduce bias and

confounding variables.• Most useful study design to determine

benefits, harm, actual efficacy of drug, etc.

Randomized Controlled Trials

Parallel: two groups of patients– one give study drug, one group give control, watch both groups to observe outcomes

Crossover: one group of patients: half take study drug, then control drug; other half take control drug, then study drug.

Before and After (___________): one group of pts- take measurements before drug, give drug, then take measurements again.

Limitations of Randomized Controlled Trials

• Expensive to perform

• Many are funded by Drug companies-- big bias potential

• External factors can always influence validity of any study

• Statistical verses clinical significance

• Need trials long enough to see outcomes

Potential Areas of Bias in any Study

• Credentials of researchers

• Funding of study

• Is study blinded?

• Is study design adequate- internal validity

• Is population representative of real world population?

• Randomization of treatment groups

Observational Studies

• Cohort Study (follow-up study)– Most powerful after RCT.– Follows patients to find out who experiences the

outcomes– two groups: those who received intervention (drug), and those who didn’t.

– Cannot determine cause and effect since bias in design—

– Good for finding “associations”– Can be expensive because of time involved. – Usually done retrospectively– looking back at

records, using memory for recall, etc.

Observational Studies cont..

• Case-Control design– Start with patients who have outcome, identify

control group (those without outcome) and look backwards for risk factors potentially causing outcome. (Search for factors in the past that may explain the outcomes)

– Good for rare diseases, rare adverse events– Retrospective, bias easily introduced

Observational Studies cont…

• Cross-Sectional– All outcomes and exposure data present

during a specified period are evaluated. – Identifies variables that predict outcomes– Taking a look at one period in time– may not

be predictive of another time period.– Useful for outcome assessments, predicting

future costs, identifying severity of illness

Weakest Observational Design..

• Descriptive or Case-Series Report– No control group– Difficult to make conclusions or associations– Most bias, cheapest to perform– Reporting on a circumstance, event, program

and trying to make some inferences– Example: Reporting on changes in outcomes

before and after an intervention program was implemented.

Clinical Practice Guidelines

• One of the tools used in Evidence Based Medicine.

• Purpose of CPG: to increase quality and value of care.

• Provides valid information which can improve decision making, reduce errors, help correct over-use and under-use of health care system, and reduce errors

Factors Causing the Implementation of CPG

• Increased rate of growth of health care costs• Large variations of health care practice in

different geographical areas of the U.S.• Inappropriate use of health care services, ie.

Lab tests, diagnostic & surgical procedures, Rx meds, hosp. Admissions, length of stay.

• Uncertainty of health outcomes from use or non-use of various services or treatments

Agencies involved in EBM and CPG

• U.S. Dept of Health and Human Services• NIH (National Institutes of Health)• FDA (Food and Drug Agency)

– http://www.guideline.gov

• CDC (Center for Disease Control)• AHCPR (Agency for Health Care Policy

and Research) http://www.ahcpr.gov

– HCFA (Health Care Financing Admin)

Key Goals in Developing Guidelines

• Increasing access to health care

• Cost Containment

• Increasing quality of health care

EBM Steps and Decision Process

• Do systematic search

• Gather evidence (literature, experience, opinion, etc)

• Critically evaluate evidence– If evidence of benefit and value, proceed– If evidence of no value or no benefit, or harm,

do not recommend or proceed.

• Weigh benefits, risks, costs and develop recommendations, or guidelines.

Role of Pharmacists

• Evaluating guidelines to recommend for practice

• Drug utilization review and evaluation• Development and implementation of

prescribing guidelines or protocols for restricted use drugs via P&T committee.

• Work with HMO’s, State Medicaid programs developing therapeutic guidelines for drug use and management

Examples• Do we need to use the latest quinolone

antibiotic on the market for our formulary, or can we use an existing, less expensive one to cover our typical bacteria seen in our setting/institution/community?What literature evidence is there for better therapeutic effect or better patient outcomes?

Another Example

• Vitamin E is found in some case-controlled studies to have benefit for cardiac protection in preventing an MI? Is this enough evidence for us to recommend and promote the use of Vitamin E in our population/community/setting? Or to put it into our cardiac rehab guidelines for high risk patients?

Disease-oriented Outcomes vs. Patient-oriented Outcomes

• Disease-oriented outcomes– physiologic, intermediate, surrogate endpoints

(blood sugar, blood pressure, flow rate, coronary plaque thickness) that may or may not reflect improvement in patient outcomes

• Patient-oriented outcomes– outcomes that matter to patients and help

them live longer or better (reducing mortality, morbidity, lower cost, reduce symptoms)

Examples of Outcomes

Therapy Disease-OrientedOutcome

Patient-OrientedOutcome

Doxazosin for bloodpressure

Reduces bloodpressure

Increases mortality inAfrican Americans

Lidocain followingacute myocardialinfarction

Suppressesarrhythmias

Increases mortality

Sleeping infants ontheir stomach or side

Physiology andanatomy say this willdecrease risk ofaspiration

Increases risk of suddeninfant death syndrome

How Do We Evaluate Guidelines?

• A. Recommendation based on consistent and good quality patient-oriented evidence– RCT’s, meta-analysis, good cohort studies

• B. Recommendation based on inconsistent or limited quality patient-oriented evidence– Un-controlled trials, trials with inconsistent

findings, lower quality cohort or meta-analysis or systematic reviews, case-controlled studies

How Do We Evaluate? Cont...

• C. Recommendation based on consensus, usual practice, disease-oriented evidence, case series for studies of treatment or screening, and/or opinion.

Evaluating Studies used in making

Guidelines/Recommendations

• Introduction– Is study objective clearly stated?– Is study objective reasonable?– Is study objective specific enough to be

measurable?– Is the study setting appropriate for this type of

study?

Evaluating Studies….

• Methods Section:– Is study observational or experimental?– What is the study design?– Is study randomized?– Is study prospective?– Is study blinded?– Is study controlled?

Evaluating Studies….

• Study Groups– Are they randomly selected into study?– Are they equal in ages, diseases, other factors?– Is the blinding procedure adequate?– Are the inclusion/exclusion criteria appropriate

and sufficient to describe the target population?– Are the endpoints measurable with the study

population?

Evaluating Studies...

• Methods…– Are statistical tests used for analyzing results

appropriate for the type of data collected?– Is there internal validity? (Is study design

appropriate for study population, setting, methods?)

Evaluating Studies...

• Results– Are drop-outs accounted for?– Are drop-outs included in statistical analysis?– Are the correct endpoints measured?– Are endpoints measured correctly?– Are descriptive statistics provided for all indices

of measurement stated in the methods section?– Are P-values and/or CI given?– Is there external validity?

Evaluating Studies...

• Discussion– Are author’s comments justified by the

results?– Are conclusions consistent with the study

objectives?– Is there statistical importance to this study?– Is there clinical importance to this study?

Evidence Based Table

Title/Author

StudyDesign

Level ofEvidence(1-7)

StudySize

OutcomesMeasured/(Disease/Patient-Oriented)

Statistic-allysignificant?

Comments

Moore B.et al.Therapyof StatinsIn post MIpatients

RCT 1 450 Survival(P)

Yes,survivalP=0.001Trig p=0.04

Funded byDrugcompany