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Evidence based medicine

        Professor Janko Kersnik, MD, MSc, PhD
  Family doctor in a branch office Kranjska Gora, Slovenia
Head of Family Medicine Department, Medical School Maribor
       Head of Research Department, Department of
         Family Medicine, Medical School Ljubljana
      President of Slovenian Family Medicine Society
                   President of EURACT
Structure of the presentation

1.     Principles of EBM
2.     Demonstration in searching evidence
3.     Assessment of the evidence (paper)
4.     Information for group work: Exercise in
       assessment of evidence



7. 5. 2012             EBM                   2
Variation to the theme
s   Evidence based medicine
s   Scientific medicine
s   Evidence based practice
s   ...




7. 5. 2012          EBM       3
Read thread of EBM
s   Patient dilemma
s   Ask clinical question
s   Acquire (search) evidence
s   Apprise (assess) evidence
s   Apply in everyday practice
s   Act (monitor change)

7. 5. 2012           EBM         4
Aim of the first part
s   To demonstrate how by using IT we can
    get answers to clinical questions.




7. 5. 2012          EBM                 5
Literature
s   http://
    www.hsl.unc.edu/services/tutorials/ebm/w

s   http://medlib.bu.edu/tutorials/ebm/




7. 5. 2012            EBM                 6
By the end of the first part you will
s   Know how to set clinical question
s   Know key electronic databases
    (Medline, Cochrane, Clinical Evidence)
s   Know how to get them (Internet, CD,
    book)
s   Understand and value evidence for safe
    work
s   Be able to use evidence for your
    everyday practice
7. 5. 2012           EBM                 7
What do we know on EBM?
s   Buzz groups – discuss in groups of
    three




7. 5. 2012           EBM                 8
What is EBM?
s   Evidence instead experience and
    eminence
s   Use of IT in everyday practice
s   An answer to patient demands
s   “New religion” which is changing our
    practice


7. 5. 2012           EBM                   9
What is EBM practice?
s   EBM is defined as an application of best
    research evidence in everyday patient
    care.
s   EBM is defined as clinical decision
    which is based on systematic search,
    assessment and application of
    evidence.


7. 5. 2012           EBM                  10
EBM-4




7. 5. 2012   EBM   11
Four steps in searching
evidence
       1               2



             3             4



7. 5. 2012       EBM           12
1 Clinical question
s   To begin the EBM search process start
    with a well-developed and answerable
    question. A good clinical question will:
     – Save time when researching
     – Keep the focus directly on the patient's
       need
     – Suggest the appropriate form that a useful
       answer may take
s   The clinical question will impact the
    entire EBM literature searching process.
7. 5. 2012              EBM                     13
Typical questions
s Therapy
s Diagnostics

s Prognosis

s Prevention

s Health promotion

….
s What should I do for this patient?


7. 5. 2012          EBM                14
PICO




7. 5. 2012    EBM   15
Questions
s   Who is your patient?
s   What is the intervention?
s   What is the comparison?
s   What is the outcome?




7. 5. 2012            EBM       16
Your patient
s   In your 83-year old patient, who is 25
    years treated for high blood pressure, which is
    well organized with the average blood pressure
    values below 140/90 mmHg, you have found at
    a regular check up an irregular heart
    rhythm, which is on the ECG proved atrial
    fibrillation. Does not have any other diseases, he
    is in good physical and mental condition. Since
    you do not have data on the beginning of
    this disorder, you have referred him to a
    cardiologist. He returns with
    the result, from which you read, that he has
    undergone unsuccessful cardio conversion. The
    patient prefers aspirin, which does not require
    any monitoring, over proposed warfarin.
    7. 5. 2012             EBM                     17
Patient dilemma

 s   Shall we follow the guidelines or is
     there evidence that we can take into
     account patient preferences?




7. 5. 2012            EBM                   18
In small groups...

...define clinical
   question from
   your practice,
…or define clinical
   question from the
   case of our 83-
   years old patient.

7. 5. 2012              EBM   19
Clinical question in our case
s   Is treatment with aspirin (I) in the 83-
    year old patient with chronic atrial
    fibrillation (P) as effective as warfarin
    (C) in terms of prevention of
    stroke and total mortality and
    complications of treatment (O)?


7. 5. 2012             EBM                      20
Searching evidence
s   Where do you search information?




7. 5. 2012          EBM                21
Hierarchy of evidence
s   Systematic reviews
s   Meta-analyses
s   RCT
s   Prospective studies
s   Retrospective studies
s   Case reports


7. 5. 2012           EBM    22
Types of studies
                     (iz: Silagy and Haines, Evidence Based Practice in Primary Care,
                                             BMJ Books, 1998)



                       O b s e rv a tio n a l                                              E x p e r im e n ta l


D e s c r ip tiv e                A n a ly t i c a l              U n c o n t r o lle d              C o n tr o lle d


                     C o h o rt                   C a s e -c o n tro l          N o n - r a n d o m is e d         R a n d o m is e d



              7. 5. 2012                                                 EBM                                                       23
Sources
s   Medline
s   Cochrane
s   Clinical Evidence




7. 5. 2012              EBM   24
MEDLINE
s   From 1966
s   Internet based
s   Search; PubMed - http://
    www.ncbi.nlm.nih.gov/pubmed/ (http://
    www.ncbi.nlm.nih.gov/sites/entrez )
s   Usual terms
s   Option “find related data; PubMed; related
    articles”
s   Option “Also try”
s   Options to copy in a file (Send to; File) or in own
    data base (Reference manager)
    7. 5. 2012               EBM                     25
Strategy
s   Search; MeSH (Medical Subject
    Headings)
s   English terms
s   Operators (and, not, or)
s   Limits (author, title, abstract, language)
s   “Find related articles”


7. 5. 2012            EBM                    26
http://www.ncbi.nlm.nih.gov/sites/entrez




7. 5. 2012                        EBM                   27
7. 5. 2012   EBM   28
COCHRANE
s   Systematic reviews, RCT
s   Internet
s   Rigorous inclusion criteria
s   Regular update




7. 5. 2012            EBM         29
7. 5. 2012   EBM   30
7. 5. 2012   EBM   31
CLINICAL EVIDENCE
s   Book twice a year
s   Relevant clinical questions




7. 5. 2012            EBM         32
7. 5. 2012   EBM   33
Find in Internet relevant papers for
the subject you are interested!
Select one you want to apprise.




7. 5. 2012       EBM                   34
Search for our patient
s   MeSH: warfarin aspirin stroke prevention not
    dabigatran
s   Limits
     –   RCT or systematic reviews,
     –   Not older than 5 years,
     –   Human,
     –   Male, older than 80 years,
     –   English,
     –   Free papers.
7. 5. 2012                  EBM                35
Search results for our patient
s     We got 7 hits.
s     After reading titles and abstracts we were left with
      two of them:
     –       Williams JE, Chimowitz MI, Cotsonis GA, Lynn MJ, Waddy
             SP; WASID Investigators.Gender differences in outcomes
             among patients with symptomatic intracranial arterial
             stenosis. Stroke. 2007 Jul;38(7):2055-62. Epub 2007 May
             31.
     –       Rash A, Downes T, Portner R, Yeo WW, Morgan N,
             Channer KS. A randomised controlled trial of warfarin
             versus aspirin for stroke prevention in octogenarians with
             atrial fibrillation (WASPO). Age Ageing. 2007
             Mar;36(2):151-6. Epub 2006 Dec 15.


7. 5. 2012                          EBM                              36
Conclusions for the first part

s Searching can make fun
s There are simple tools available

s Practice make expert




7. 5. 2012         EBM                 37
Appraisal (assessment/evaluation of
evidence)
Aims of the second part
s   What is medical literature?
s   What types of documents/papers do we
    know?
s   Sources of primary documents
s   Criteria for papers, guidelines, meta-
    analyses. Systematic reviews



7. 5. 2012           EBM                 39
Medical literature
s   Primary documents
     – primary (research) paper
     – diploma, masters,
       doctoral thesis
s   Secondary documents
     –   review paper
     –   meta-analysis
     –   seminar work
     –   guidelines
s   Tertiary documents
     – textbook
     – handbook
     – congress proceedings
    7. 5. 2012              EBM   40
Sources of primary documents
                    s   Specialist theses
                    s   Graduate theses
                    s   Maister theses
                    s   Doctoral tehses
                    s   Medical journals



7. 5. 2012    EBM                           41
Strengths and weaknesses of
 primary documents
Strengths                 Weaknesses
s Original,               s Large number of
  unpublished work          papers
s Source of new           s Evidence is mainly
  knowledge                 scattered over
s Basis of scientific       several journals
  development


7. 5. 2012              EBM                      42
Structure of primary document
s   Title                          s   Results
s   Abstract                           – Sample description
                                       – Key results
s Introduction                         – Additional analyses
     – “What was the
       problem?” “Why is this      s   Discussion
       problem interesting for         – On methods
       a reader?”                      – On results
s   Aims, hypothesis               s   Conclusions
s   Methods and patients           s   Acknowledgement
     –   Methods                   s   Financial disclosure
     –   Patients - sampling
     –   Study description
                                   s   “Conflict of interest”
     –   Data analysis             s   References
                                   s   Appendices
7. 5. 2012                       EBM                            43
External grading of “reliability”
of the source – medical journal
s   External reviewers
s   Indexed
s   On Medline
s   SCI: science citation
    index, SSCI: social
    science citation
    index
s   IF: impact factor

7. 5. 2012                  EBM     44
Appraisal of “usefulness” of the paper
s    Check in aims and Hypotheses,
      – If they agree with your need for information;
s    In methods check,
      –   If the paper studies same population as yours;
      –   If the study subject complies with your need
      –   If sample size and study power are given;
      –   If appropriate statistical methods were used;
s    In results check,
      – For ev. biases and flaws;
      – If the results are valid for your practice;
      – If the statistical significance has also any clinical
        meaning.                   EBM                          45
    7. 5. 2012
IMRAD

s      Introduction (why the authors decided
       to do this research),
s      Methods (how they did it, and how
       they analysed their results),
s      Results (what they found), and
s      Discussion (what the results mean).


7. 5. 2012             EBM                 46
Paper quality criteria
– introduction and methods
s   Is the purpose clear?
s   What is the measure of the study succes?
s   Is the methodology understandable?
s   Where are the patients from?
s   What is the selection of patients?
s   Methods of data collection
s   What is the percentage of responses?
s   Is the number of observations sufficient?

7. 5. 2012              EBM                     47
Paper quality criteria
– results and conclusions
s   Whether they used appropriate
    statistical methods?
s   Are the results shown appropriately or
    misleading?
s   Are there confidence intervals shown?
s   Are the conclusions based on the study
    results?
s   Are the authors aware
    of limitations and potential biases?
s   Recommendations for further study?
7. 5. 2012             EBM                   48
Methods

s   Random allocation of study participants
s   Researchers were blinded for the initial
    allocation
s   The groups did not differ at the beginning of
    the study
s   Researchers were blinded for actual
    allocation
s   Was analysis performed on all included
    participants?

7. 5. 2012               EBM                        49
Appraisal of recomendations in
 the guidelines
 (GRADE, BMJ 2004, 328: 1490-8)
s A: The opinion supports
  more quality studies - there is no
  major change in knowledge expected.
s B: Opinion supported by
  one or more major study weaker or incomplete
  study - we can expect changes in knowledge.
s C: Opinion support some studies, but not
  always quality ones - future research is likely
  to result in significant changes in knowledge.
s D: No reliable conclusion is possible.

 7. 5. 2012            EBM                      50
Appraisal of meta-analysis
 (Cochrane)
s Described    protocol of meta-analysis
s Description systematic literature search
s Criteria for inclusion or exclusion
  of studies, research, and that all the
  reasons why they were excluded
s The homogeneity of the results shown by tests
s Appropriate statistical analysis were used
s In the case of statistically significant
  differences the possibility of biases due to
  variability of studies explained
s Conclusions shown with regard to
  treatment decisions EBM
  7. 5. 2012                                    51
Conclusions
s   Knowledge becomes quickly
    obsolete, or new replaces old dogmas.
s Physicians must follow new findings.
s Information is unlimited, our ability is
    limited.
s Reliance on the eminence does not suit
    any more.
s We urgently need to know how to find
    and use appropriate sources of new
    knowledge.
7. 5. 2012           EBM                   52
Thank you very much for your
attention!
Group work: Evaluate papers!




7. 5. 2012     EBM             54

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Evidence based medicine Riga 2012-05-07

  • 1. Evidence based medicine Professor Janko Kersnik, MD, MSc, PhD Family doctor in a branch office Kranjska Gora, Slovenia Head of Family Medicine Department, Medical School Maribor Head of Research Department, Department of Family Medicine, Medical School Ljubljana President of Slovenian Family Medicine Society President of EURACT
  • 2. Structure of the presentation 1. Principles of EBM 2. Demonstration in searching evidence 3. Assessment of the evidence (paper) 4. Information for group work: Exercise in assessment of evidence 7. 5. 2012 EBM 2
  • 3. Variation to the theme s Evidence based medicine s Scientific medicine s Evidence based practice s ... 7. 5. 2012 EBM 3
  • 4. Read thread of EBM s Patient dilemma s Ask clinical question s Acquire (search) evidence s Apprise (assess) evidence s Apply in everyday practice s Act (monitor change) 7. 5. 2012 EBM 4
  • 5. Aim of the first part s To demonstrate how by using IT we can get answers to clinical questions. 7. 5. 2012 EBM 5
  • 6. Literature s http:// www.hsl.unc.edu/services/tutorials/ebm/w s http://medlib.bu.edu/tutorials/ebm/ 7. 5. 2012 EBM 6
  • 7. By the end of the first part you will s Know how to set clinical question s Know key electronic databases (Medline, Cochrane, Clinical Evidence) s Know how to get them (Internet, CD, book) s Understand and value evidence for safe work s Be able to use evidence for your everyday practice 7. 5. 2012 EBM 7
  • 8. What do we know on EBM? s Buzz groups – discuss in groups of three 7. 5. 2012 EBM 8
  • 9. What is EBM? s Evidence instead experience and eminence s Use of IT in everyday practice s An answer to patient demands s “New religion” which is changing our practice 7. 5. 2012 EBM 9
  • 10. What is EBM practice? s EBM is defined as an application of best research evidence in everyday patient care. s EBM is defined as clinical decision which is based on systematic search, assessment and application of evidence. 7. 5. 2012 EBM 10
  • 12. Four steps in searching evidence 1 2 3 4 7. 5. 2012 EBM 12
  • 13. 1 Clinical question s To begin the EBM search process start with a well-developed and answerable question. A good clinical question will: – Save time when researching – Keep the focus directly on the patient's need – Suggest the appropriate form that a useful answer may take s The clinical question will impact the entire EBM literature searching process. 7. 5. 2012 EBM 13
  • 14. Typical questions s Therapy s Diagnostics s Prognosis s Prevention s Health promotion …. s What should I do for this patient? 7. 5. 2012 EBM 14
  • 15. PICO 7. 5. 2012 EBM 15
  • 16. Questions s Who is your patient? s What is the intervention? s What is the comparison? s What is the outcome? 7. 5. 2012 EBM 16
  • 17. Your patient s In your 83-year old patient, who is 25 years treated for high blood pressure, which is well organized with the average blood pressure values below 140/90 mmHg, you have found at a regular check up an irregular heart rhythm, which is on the ECG proved atrial fibrillation. Does not have any other diseases, he is in good physical and mental condition. Since you do not have data on the beginning of this disorder, you have referred him to a cardiologist. He returns with the result, from which you read, that he has undergone unsuccessful cardio conversion. The patient prefers aspirin, which does not require any monitoring, over proposed warfarin. 7. 5. 2012 EBM 17
  • 18. Patient dilemma s Shall we follow the guidelines or is there evidence that we can take into account patient preferences? 7. 5. 2012 EBM 18
  • 19. In small groups... ...define clinical question from your practice, …or define clinical question from the case of our 83- years old patient. 7. 5. 2012 EBM 19
  • 20. Clinical question in our case s Is treatment with aspirin (I) in the 83- year old patient with chronic atrial fibrillation (P) as effective as warfarin (C) in terms of prevention of stroke and total mortality and complications of treatment (O)? 7. 5. 2012 EBM 20
  • 21. Searching evidence s Where do you search information? 7. 5. 2012 EBM 21
  • 22. Hierarchy of evidence s Systematic reviews s Meta-analyses s RCT s Prospective studies s Retrospective studies s Case reports 7. 5. 2012 EBM 22
  • 23. Types of studies (iz: Silagy and Haines, Evidence Based Practice in Primary Care, BMJ Books, 1998) O b s e rv a tio n a l E x p e r im e n ta l D e s c r ip tiv e A n a ly t i c a l U n c o n t r o lle d C o n tr o lle d C o h o rt C a s e -c o n tro l N o n - r a n d o m is e d R a n d o m is e d 7. 5. 2012 EBM 23
  • 24. Sources s Medline s Cochrane s Clinical Evidence 7. 5. 2012 EBM 24
  • 25. MEDLINE s From 1966 s Internet based s Search; PubMed - http:// www.ncbi.nlm.nih.gov/pubmed/ (http:// www.ncbi.nlm.nih.gov/sites/entrez ) s Usual terms s Option “find related data; PubMed; related articles” s Option “Also try” s Options to copy in a file (Send to; File) or in own data base (Reference manager) 7. 5. 2012 EBM 25
  • 26. Strategy s Search; MeSH (Medical Subject Headings) s English terms s Operators (and, not, or) s Limits (author, title, abstract, language) s “Find related articles” 7. 5. 2012 EBM 26
  • 28. 7. 5. 2012 EBM 28
  • 29. COCHRANE s Systematic reviews, RCT s Internet s Rigorous inclusion criteria s Regular update 7. 5. 2012 EBM 29
  • 30. 7. 5. 2012 EBM 30
  • 31. 7. 5. 2012 EBM 31
  • 32. CLINICAL EVIDENCE s Book twice a year s Relevant clinical questions 7. 5. 2012 EBM 32
  • 33. 7. 5. 2012 EBM 33
  • 34. Find in Internet relevant papers for the subject you are interested! Select one you want to apprise. 7. 5. 2012 EBM 34
  • 35. Search for our patient s MeSH: warfarin aspirin stroke prevention not dabigatran s Limits – RCT or systematic reviews, – Not older than 5 years, – Human, – Male, older than 80 years, – English, – Free papers. 7. 5. 2012 EBM 35
  • 36. Search results for our patient s We got 7 hits. s After reading titles and abstracts we were left with two of them: – Williams JE, Chimowitz MI, Cotsonis GA, Lynn MJ, Waddy SP; WASID Investigators.Gender differences in outcomes among patients with symptomatic intracranial arterial stenosis. Stroke. 2007 Jul;38(7):2055-62. Epub 2007 May 31. – Rash A, Downes T, Portner R, Yeo WW, Morgan N, Channer KS. A randomised controlled trial of warfarin versus aspirin for stroke prevention in octogenarians with atrial fibrillation (WASPO). Age Ageing. 2007 Mar;36(2):151-6. Epub 2006 Dec 15. 7. 5. 2012 EBM 36
  • 37. Conclusions for the first part s Searching can make fun s There are simple tools available s Practice make expert 7. 5. 2012 EBM 37
  • 39. Aims of the second part s What is medical literature? s What types of documents/papers do we know? s Sources of primary documents s Criteria for papers, guidelines, meta- analyses. Systematic reviews 7. 5. 2012 EBM 39
  • 40. Medical literature s Primary documents – primary (research) paper – diploma, masters, doctoral thesis s Secondary documents – review paper – meta-analysis – seminar work – guidelines s Tertiary documents – textbook – handbook – congress proceedings 7. 5. 2012 EBM 40
  • 41. Sources of primary documents s Specialist theses s Graduate theses s Maister theses s Doctoral tehses s Medical journals 7. 5. 2012 EBM 41
  • 42. Strengths and weaknesses of primary documents Strengths Weaknesses s Original, s Large number of unpublished work papers s Source of new s Evidence is mainly knowledge scattered over s Basis of scientific several journals development 7. 5. 2012 EBM 42
  • 43. Structure of primary document s Title s Results s Abstract – Sample description – Key results s Introduction – Additional analyses – “What was the problem?” “Why is this s Discussion problem interesting for – On methods a reader?” – On results s Aims, hypothesis s Conclusions s Methods and patients s Acknowledgement – Methods s Financial disclosure – Patients - sampling – Study description s “Conflict of interest” – Data analysis s References s Appendices 7. 5. 2012 EBM 43
  • 44. External grading of “reliability” of the source – medical journal s External reviewers s Indexed s On Medline s SCI: science citation index, SSCI: social science citation index s IF: impact factor 7. 5. 2012 EBM 44
  • 45. Appraisal of “usefulness” of the paper s Check in aims and Hypotheses, – If they agree with your need for information; s In methods check, – If the paper studies same population as yours; – If the study subject complies with your need – If sample size and study power are given; – If appropriate statistical methods were used; s In results check, – For ev. biases and flaws; – If the results are valid for your practice; – If the statistical significance has also any clinical meaning. EBM 45 7. 5. 2012
  • 46. IMRAD s Introduction (why the authors decided to do this research), s Methods (how they did it, and how they analysed their results), s Results (what they found), and s Discussion (what the results mean). 7. 5. 2012 EBM 46
  • 47. Paper quality criteria – introduction and methods s Is the purpose clear? s What is the measure of the study succes? s Is the methodology understandable? s Where are the patients from? s What is the selection of patients? s Methods of data collection s What is the percentage of responses? s Is the number of observations sufficient? 7. 5. 2012 EBM 47
  • 48. Paper quality criteria – results and conclusions s Whether they used appropriate statistical methods? s Are the results shown appropriately or misleading? s Are there confidence intervals shown? s Are the conclusions based on the study results? s Are the authors aware of limitations and potential biases? s Recommendations for further study? 7. 5. 2012 EBM 48
  • 49. Methods s Random allocation of study participants s Researchers were blinded for the initial allocation s The groups did not differ at the beginning of the study s Researchers were blinded for actual allocation s Was analysis performed on all included participants? 7. 5. 2012 EBM 49
  • 50. Appraisal of recomendations in the guidelines (GRADE, BMJ 2004, 328: 1490-8) s A: The opinion supports more quality studies - there is no major change in knowledge expected. s B: Opinion supported by one or more major study weaker or incomplete study - we can expect changes in knowledge. s C: Opinion support some studies, but not always quality ones - future research is likely to result in significant changes in knowledge. s D: No reliable conclusion is possible. 7. 5. 2012 EBM 50
  • 51. Appraisal of meta-analysis (Cochrane) s Described protocol of meta-analysis s Description systematic literature search s Criteria for inclusion or exclusion of studies, research, and that all the reasons why they were excluded s The homogeneity of the results shown by tests s Appropriate statistical analysis were used s In the case of statistically significant differences the possibility of biases due to variability of studies explained s Conclusions shown with regard to treatment decisions EBM 7. 5. 2012 51
  • 52. Conclusions s Knowledge becomes quickly obsolete, or new replaces old dogmas. s Physicians must follow new findings. s Information is unlimited, our ability is limited. s Reliance on the eminence does not suit any more. s We urgently need to know how to find and use appropriate sources of new knowledge. 7. 5. 2012 EBM 52
  • 53. Thank you very much for your attention!
  • 54. Group work: Evaluate papers! 7. 5. 2012 EBM 54