1. Evidence Based Medicine
Clinical Practice Guidelines

2. 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

3. Evidence Based Medicine...
We make decisions based on the best clinical, scientific ______________
Critical appraisal of published literature helps determine
______________ of evidence
Goal of EBM: to improve patient outcomes.

4. Internal Clinical Evidence
Individual Clinical Expertise
Training
Experience
Knowledge

5. 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
EBM takes changes occuring in medical practice relating to the use of medical literature to more effectively guide decision making. The foundation for the shift to EBM rests in the significant development in clinical research over the past 30 years, particularly the RCT. Also important in EBM is the Meta Analsis which sumarizes results of a number of different randomized controlled clinical trias.

6. 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. 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
Seven levels of evidence have been defined for the rating the literature studies to make recommendations for guidelines.
Good evidence is considered from 1-3
Fair evidence is considered from 4-6
Expert opinion is the lowest quality of evidence
Many guidelines have been developed based on weak methods, incomplete literature reviews and an over reliance on opinion. Such guidelines may be influenced by bias, conflicts of interest, and political motives. It is the responsibility of practitioners to evaluate the quality of guidelines, reject poor quality guidelines, and provde objective reasons why such guidelines should not be used.

8. 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.

9. 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.

10. 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

11. 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

12. 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.
Bias introduced– investigators did not select who received and did not receive drug– they just found some taking drug and some not taking.
Or taking risk factor (diabetes). Taking those with diabetes and those without diabetes– watching for development of disease (maybe heart failure- or MI)

13. 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

14. 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

15. 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.

16. 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
Guidelines are reccommendations for practice that involve a comprehensive search of the literature, an evaluation of the quality of individual studies, and recommendation grades that reflect the quality of the supporting evidence.

17. 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
One of the key factors leading to the increased use of practice guidelines is the rate of growth of health care costs in the U.S.
Another factor stimulating interest in guidelines have been the studies showing large variations in the rate with which specific procedures are performed in different geographical areas. There are significant variations in hospitalization rates, rates of surgeries for certain procedures like C-sections, coronary angiography, treatment modalities for diabetes, asthma, MI, hypertension.
Providing guidelines that summarize the available evidence and expert opinion would be useful in reducing the magnitude of practice variations and inappropriate care.
The 3rd factor that has stimulated interest in practice guidelines is research indicating considerable and inappropriate use of many services including lab tests, diagnostic or surgical procedures, prescription medicines, hospital admissions or length of stay (over utlization).
4th factor is the uncertainty about health outcomes expected from the use or non-use of various services or treatments.

18. Agencies involved in EBM and CPG
U.S. Dept of Health and Human Services
NIH (National Institutes of Health)
FDA (Food and Drug Agency)
CDC (Center for Disease Control)
AHCPR (Agency for Health Care Policy and Research)
HCFA (Health Care Financing Admin)
US Dept of Health and Human Services has identified improvement in quality of health care and efficiency of health care services as a priority since Divisions incliuded in this national effort include the NIH< FDA< CDC< AHCPR< and HCFA.
Clinical guidelines are devloped by a variety of groups and organizaitons including Federal and State governmental agencies, professional societties and associations, managed care organizations, third party payors, quality assurance organizations, and utilization review groups.
We, as pharmacists in our community, in the hospital, on the pharmacy and therapeutics committee make recommendations for developing guidelines for drug therapy in our patient populations based on the most current, relevant, literature and the best quality of literature available.

19. Key Goals in Developing Guidelines
Increasing access to health care
Cost Containment
Increasing quality of health care

20. 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.

21. 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
The pharmacists can assume a health care leadership role in areas of drug utilization review, Drug utilization evaluation, (DUE, DRR, MUE).
Also in the area of development and implementation of prescribing guidelines or protocols for restricted use drugs through the P&T committee in hospitals
or working with HMO’s, or the State Medicaid programs to improve the quality of health care and lower the overuse and misuse and underuse of the health system.

22. 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?

23. 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?

24. Disease-oriented Outcomes vs. Patient-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)
We feel Patient oriented outcomes are of higher quality and validity than disease oriented outcomes

25. Examples of Outcomes

26. 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

27. 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.

28. 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?

29. 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?

30. 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?

31. 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?)

32. 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?
Drop outs can be significant to a study.
Intent to treat analysis includes drop outs in their statistical results-- this gives more realistic picture of real population-- not everyone takes their drugs the way they are supposed to or for the correct amount of time.
Probability values and or confidence intervals should be indicated in a good study. You can’t determine clinnical significance without them.
External validity?? Can the results be extrapolated out into the real world? Can this study be reproduced in my population in my community, in my setting?

33. 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?

34. Evidence Based Table