Explosion of knowledge since the 1970 s. Textbooks outdated before publication

Transcription

1 Explosion of knowledge since the 1970 s Textbooks outdated before publication 1

2 Scientific chaos Meta - analyses Systematic reviews Implementation of evidence into practice 2

3 KNOWLEDGE TRANSFER IN MEDICINE EVIDENCED-BASED CLINICAL PRACTICE The patient s values (concerns, expectations, preferences) The best clinical research evidence 3

4 LEVELS OF EVIDENCE DEFINITIONS Cochrane systematic review a review based on a peer reviewed, published protocol of primary research on a particular question that tries to identify, select, synthesize, and appraise all high quality research evidence relevant to that question in order to answer it Systematic review as above, but most often without a protocol (CAVE!!!)! Meta-analysis - a statistical analysis of a collection of results in order to integrate the results (but also used as a publication term - most often without a protocol (CAVE!!!)! 4

5 NUMBER OF PUBLICATIONS Meta-analyses Systematic reviews Number of publications Cochrane systematic reviews Year The best clinical research evidence coupled with the patient s values and the clinician s experience 5

6 HISTORIC DEVELOPMENT OF EVIDENCE-BASED MEDICINE Avicenna ( ) Stop doing experiments in horses and lions! Such experiments prove nothing about the effect in humans Medicine ought to be evaluated in two comparable cases The reproducibility ought to be evaluated JAMES LIND

7 JAMES LIND JAMES LIND ALLOCATED 2 - oranges and lemons 2 - spices and garlic 2 - vinegar 2 - elixir vitriol 2 - cider 2 - sea water 7

8 JAMES LIND OBSERVED The two on oranges and lemons regained health in a few days and could care for the remainder, that stayed ill JAMES LIND

9 GEORGE LÖHNER AND GEORGE LÖHNER AND HIS TEAM OF TRUTH LOVING MEN Clear protocol, published before launch Large number of participants (n = 50) Perfect randomisation Placebo controlled (melted ice) Blinded for all parties Account for drop outs Statistical comparison 9

10 WITHOUT RANDOMISATION INTERVENTION 1 INTERVENTION 2 10

11 WITH RANDOMISATION INTERVENTION 1 INTERVENTION 2 DANGERS IN NON-RANDOMISED TRIALS Biological mechanisms - Limited time of diseases - Cyclical progression of diseases - When do we see patients? Psychological mechanisms -The Rosenthal effect, we see what we want to see (BIAS)! -The Barnum effect, we believe what we want to believe (astrology)! 11

12 PERIODIC GROWTH OF PUBLICATIONS ON RANDOM AND CONTROLLED CLINICAL TRIALS to to to to to to to to 1981 Year period 1982 to to to to to 2007 NUMBER OF PUBLICATIONS ON RANDOMISED AND CONTROLLED CLINICAL TRIALS PUBLISHED PER MILLION INHABITANTS

13 IMPORTANT ASPECTS OF CLINICAL RESEARCH Systematic errors (bias) Random errors (play of chance) Design errors Low risk of systematic error High risk of systematic error Low risk of random error X High risk of random error X design errors may also lead to bias! 13

14 Mean number of patients per intervention arm (SEM) in 383 randomised trials published in Gastroenterology from (Kjærgard et al. 2002) RANDOM ERROR IN SMALL TRIALS False positive results (type I error) False negative results (type II error) 14

15 DESIGN ERRORS AFFECTING EXTERNAL VALIDITY OF RANDOMISED TRIALS INCLUDE Centres Participants Experimental intervention Control intervention Goal - explanatory or pragmatic Trial structure - parallel group, crossover, ect. Objective - superiority, equivalence, non-inferiority Outcome Unit of analysis 15

16 An international network of professionals, preparing, maintaining, and disseminating systematic reviews of the effects of health care It is surely a great criticism of our profession that we have not organised a critical summary, by speciality and subspeciality, adapted periodically, of all relevant randomised trials Archie Cochrane (1979) 16

17 RANDOMISED CLINICAL TRIALS in The Cochrane Library 1,5 million trials have been conducted, however, a large number has never been published. (10 years after the publication of a trial as an abstract, only about 60% are published as an article!) still only 19 years old needs at least another years to cover major parts of medicine with support from researchers and fundholders the misssion can be accomplished. 17

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19 FROM TITLE TO SYSTEMATIC REVIEW Request for title registration 19

20 FROM TITLE TO SYSTEMATIC REVIEW Information Management System (IMS) specialised software Cochrane Collaboration s electronic infrastructure RevMan (Review Manager) Archie FROM TITLE TO SYSTEMATIC REVIEW RevMan 5 (Review Manager 5) Software for preparing and maintaining Cochrane Reviews text preparation, building tables, graphical presentation of results Archie Central server titles, protocols and reviews storage Managing documents and contact details 20

21 Abstract Systematic review Background Objectives Search methods Selection criteria Data collection and analysis (risk of bias, measures of treatment effect,missing data,assessment of heterogeneity,assesment of reported biases, data synthesis, subgroup analysis, sensitivity analysis) Results Conclusions 21

22 1605 references found 1555 excluded references 50 references 18 RCTs included (4811 patients) Šimin et al., Aliment Pharm et Ther

23 Revision of meta-analisys: Comparison of pegylated interferon monotherapy with standard interferon Comparison of different dosage and therapy duration of pegylated interferon Comparison of administration of pegylated interferon in combination with different therapeutic possibilities other than ribavirin 23

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25 CURRENT ACTIVITIES OF OUR GROUP Collaboration with London Cochrane Centre- Pancreatic diseases V.Giljača Systematic reviews and update of systematic reviews EBM course Rijeka (March 2012) The Cochrane systematic review as PhD thesis FURTHER PLANS Establishment of a cooperative satellite Cochrane center of the Hepatobiliary Group in Rijeka Collaboration with Copenhagen Trial Unit HPB Cochrane Centre and London Cochrane Centre- Pancreatic diseases FP7 and FP8Program Participation Education of last years students and young doctors Application of EBM in clinical practice 25

26 THE COCHRANE COLLABORATION randomised trials Now 5000 systematic reviews 500 new reviews per year 500 updated reviews per year JIF