1. Title Place Date

2. Centre for Evidence-Based Medicine What I’ve done / do/don’t do l Done: I’ve gotten out of date and retrained in Internal Medicine twice l Do: I run an in-patient General Medicine service (all comers) at a UK DGH: »208 admissions last month »strive to use evidence at the bedside l Don’t: I’ve cancelled my journal subscriptions (and give away the JCI and BMJ)

3. Centre for Evidence-Based Medicine The Problems: l We need evidence (about the accuracy of diagnostic tests, the power of prognostic markers, the comparative efficacy and safety of interventions, etc.) about 5 times for every in-patient (and twice for every 3 out-patients). l We get less than a third of it

4. Centre for Evidence-Based Medicine The Problems: l To keep up to date in Internal Medicine, I need to read 17 articles a day, 365 days a year l Need to read l Don’t l Nor does anyone else

5. Centre for Evidence-Based Medicine Median minutes/week spent reading about my patients: Self-reports at 17 Grand Rounds: l Medical Students: 90 minutes l House Officers (PGY1): 0 (up to 70%=none) l SHOs (PGY2-4):20 (up to 15%=none) l Registrars:45 (up to 40%=none) l Sr. Registrars 30 (up to 15%=none) l Consultants: »Grad. Post 1975:45 (up to 30%=none) »Grad. Pre 1975:30 (up to 40%=none)

6. Centre for Evidence-Based Medicine Performance deteriorates, too Determinants of the clinical decision to treat some, but not other, hypertensives: 1 Level of blood pressure. 2 Patient’s age. 3 The physician’s year of graduation from medical school. 4 The amount of target-organ damage.

7. Centre for Evidence-Based Medicine No wonder, then, that CME is growing l Big, and getting huge. l Usually instructionally (fact) oriented. l Several randomised trials have shown that it does not improve clinical performance.

8. Centre for Evidence-Based Medicine Three solutions Clinical performance can keep up to date: 1 by learning how to practice evidence- based medicine ourselves. 2 by seeking and applying evidence- based medical summaries generated by others. 3 by applying evidence-based strategies for changing our clinical behaviour.

9. Centre for Evidence-Based Medicine When did EBM begin ? l Certainly in post-revolutionary Paris. l Arguably in B.C China. l Some late-comers named it in 1992.

10. Centre for Evidence-Based Medicine What evidence-based medicine is: The practice of EBM is the integration of l individual clinical expertise with the l best available external clinical evidence from systematic research. and l patient’s values and expectations

11. Centre for Evidence-Based Medicine I.Individual Clinical Expertise: l Clinical skills and clinical judgement l Vital for determining whether the evidence (or guideline) applies to the individual patient at all and, if so, how

12. Centre for Evidence-Based Medicine II. Best External Evidence: l From real clinical research among intact patients. l Has a short doubling-time (10 years). l Replaces currently accepted diagnostic tests and treatments with new ones that are more powerful, more accurate, more efficacious, and safer.

13. Centre for Evidence-Based Medicine III. Patients’ Values & Expectations l Have always played a central role in determining whether and which interventions take place l We’re getting better at quantifying and integrating them

14. Centre for Evidence-Based Medicine What EBM is not: l EBM is not cook-book medicine »evidence needs extrapolation to my patient’s unique biology and values l EBM is not cost-cutting medicine »when efficacy for my patient is paramount, costs may rise, not fall

15. Centre for Evidence-Based Medicine Evidence-Based Medicine: The Practice When caring for patients creates the need for information: 1 Translation to an answerable question (patient/manoeuvre/outcome). 2 Efficient track-down of the best evidence »secondary (pre-appraised) sources e.g., Cochrane; E-B Journals »primary literature

16. Centre for Evidence-Based Medicine Evidence-Based Medicine: The Practice 3 Critical appraisal of the evidence for its validity and clinical applicability è generation of a 1-page summary. 4 Integration of that critical appraisal with clinical expertise and the patient’s unique biology and beliefs è action. 5 Evaluation of one’s performance.

17. Centre for Evidence-Based Medicine We needn’t always carry out all 5 steps to provide E-B Care m Asking an answerable question. è Searching è Searching for the best evidence. appraising è Critically-appraising the evidence. m Integrating the evidence with our expertise and our patient’s unique biology and values m evaluating our performance

18. Centre for Evidence-Based Medicine We’ve identified 3 different modes of practice è “Searching & appraising” »provides E-B care, but is expensive in time and resources è “Searching only” »much, quicker, and if carried out among E- B resources, can provide E-B care è “Replicating” the practice of experts »quickest, but may not distinguish evidence- based from ego-based recommendations

19. Centre for Evidence-Based Medicine Even fully EB-trained clinicians work in all 3 modes è “Searching & appraising” mode for the problems I encounter daily. è “Searching only” mode among E-B resources for problems I encounter once a month. è “Replicating” the practice of experts mode for problems I encounter once a decade(and crossing my fingers!).

20. Centre for Evidence-Based Medicine Patients can benefit l Even if <10% of clinicians are capable of practicing in the “searching & appraising” mode (5% of GPs) l As long as most of them practice in a “searching” mode within high-quality evidence sources (70-80% of GPs): »Cochrane Library, E-B Journals, E-B Guidelines, etc

21. Centre for Evidence-Based Medicine Three solutions Clinical performance can keep up to date: 1 by learning how to practice evidence- based medicine ourselves. 2 by seeking and applying evidence- based medical summaries generated by others. 3 by applying evidence-based strategies for changing our clinical behaviour.

22. Centre for Evidence-Based Medicine Information required within seconds Systematic reviews, periodically updated, of randomised trials of the effects of health care (from all sources, and in all languages): The Cochrane Collaboration.

23. Cochrane Systematic Reviews (522; another 500 in preparation) Database of Abstracts of Reviews of Effectiveness (1895) Registry of Randomised Controlled Trials (218,355)

24. Centre for Evidence-Based Medicine Information required within seconds CD-Evidence-based journals of 2º publication: Ê screen 50-70 clinical journals per week for clinical articles that pass critical appraisal quality filters è conclusions likely to be true. Ë select the subset that are clinically relevant. Ì summarise as “more-informative” abstracts. Í add commentaries from clinical experts. Î introduce with declarative titles.

25. Centre for Evidence-Based Medicine

26. 2. Seeking and Applying EBM generated by others Evidence-Based Medicine is published in: l English l French l German l Italian l Portuguese l Spanish

27. Centre for Evidence-Based Medicine 2. Seeking and Applying EBM generated by others New Evidence-based journals of 2º publication: l E-B Cardiovascular Medicine l E-B Health Policy & Management l E-B Nursing l E-B Mental Health And as new departments in 1º journals.

28. Centre for Evidence-Based Medicine 2. Seeking and Applying EBM generated by others E-B Textbooks: è E-B Pain Relief è E-B Cardiology èincludes icons for levels of evidence è “E-B On-Call” èincludes > 1300 CATs

29. Centre for Evidence-Based Medicine Can you really practice EBM? l Is there any “E” for EBM ?

30. Centre for Evidence-Based Medicine Conventional Wisdom l “only about 15% of medical interventions are supported by solid scientific evidence” (BMJ Editorial)

31. Centre for Evidence-Based Medicine Even on the U.S. Talk-Shows: (“Health Outrage of the Week”) l “..... this would put 80 to 90 per cent of accepted medical procedures in this country under the heading of quackery!”

32. Centre for Evidence-Based Medicine Problems with Conventional Wisdom l uses clinical manoeuvres, rather than patients, as the denominator. l tends to focus on high-technology, “big ticket” items. l relies on simple literature searches that miss over half of the most rigorous types of evaluations. l conducted from armchairs.

33. Centre for Evidence-Based Medicine Performed an empirical study on a busy in-patient service l on the general medicine in-patient service of the Nuffield Department of Medicine at the Oxford-Radcliffe NHS Hospital Trust (“The John Radcliffe”) l all our admissions arise from urgent referral from local GPs or via the Emergency Room

34. Centre for Evidence-Based Medicine The Protocol At the time of discharge, death, or month’s end, each patient was reviewed and consensus reached on: ¶The primary diagnosis: l the disease, syndrome or condition most responsible for the patient’s admission to hospital

35. Centre for Evidence-Based Medicine The Protocol (cont.) ·The Primary Intervention l the treatment or other manoeuvre that constituted our most important attempt to cure, alleviate, or care for the primary diagnosis l traced into the literature to determine its basis in evidence –the Consultant’s “Instant Resource Book” –bibliographic data base searches

36. Centre for Evidence-Based Medicine Primary Interventions were Classified by Level: ¶ Evidence from Randomised Control Trials (better yet: systematic reviews of all relevant, high-quality RCTs) · Convincing non-experimental evidence (unnecessary & unethical to randomise) ¸ Interventions without substantial evidence

37. Centre for Evidence-Based Medicine Conclusions from E-B oriented General Medicine: l 82% of our patients received evidence- based care. ¶ treatments for 53% were justified by RCTs or systematic reviews of RCTs. è Of 28 relevant RCTs and SRs, 21 were accessible within seconds. · treatments for 29% were justified by convincing non-experimental evidence

38. Centre for Evidence-Based Medicine Evidence from RCTs (53%) l 36% had Cardiovascular diagnoses: »Ischaemic heart disease 17% »Heart failure 6% »Arrhythmia 2% »Thromboembolism 3% »Cerebrovascular 8%

39. Centre for Evidence-Based Medicine Evidence from RCTs (53%) l 7% had taken poison l 5% received chemotherapy or analgesia for cancer l 3 % had gastrointestinal disorders l 2% had obstructive airways disease

40. Centre for Evidence-Based Medicine Convincing non-experimental evidence (29%) l Infections15% l Cardiac disorders 7% l Miscellany (non-compliance, drug reactions, bowel or bladder neck obstruction, dehydration, micturition syncope) 7%

41. Centre for Evidence-Based Medicine Interventions without substantial evidence (18%) l Specific symptomatic and supportive care for mild poisoning, non-cardiac chest pain, viral (non-herpetic) meningitis, terminal CNS disease, confusion, and food poisoning.

42. Centre for Evidence-Based Medicine Better Outcomes for Patients When EBM Is Practised l E-B practise vs. Outcome in stroke (US): l When cared for by E-B neurologists, patients were 44% more likely to receive warfarin, and much more likely to be placed in a stroke care unit, l And were 22% less likely to die in the next 90 days. (Mitchell et al: stroke 1996;27:1937-43)

43. Centre for Evidence-Based Medicine Centres for Evidence-Based Surgery l E-B General/Vascular Unit in Liverpool: »95% received evidence-based Rx l 24% Level 1 l 71% Level 2 l E-B Paediatric Unit in Liverpool: »77% received evidence-based Rx l 11% Level 1 l 66% Level 2

44. Centre for Evidence-Based Medicine Worse Outcomes for Patients When EBM Is Not Practised: l In a city-wide study of E-B practise vs. Outcome in carotid stenosis: l Generated E-B indications for endarterectomy and reviewed 291 pts. l Found the surgical indications: » Appropriate in 33% »Questionable in 49% »Inappropriate in 18%

45. Centre for Evidence-Based Medicine Worse Outcomes for Patients When EBM Is Not Practised l Stroke or death within the next 30 days: l Expected (if left alone): 0.5% l Expected (if properly selected and operated): 1.5% l Observed among operated patients (2/3 operated for questionable or inappropriate reasons): >5% Wong et al. Stroke 1997;28: 891-8.

46. Centre for Evidence-Based Medicine Evidence-Based Ambulatory Paediatrics l 54% of manoeuvres were evidence- based (“experts” had predicted <20%) »77% of diagnostic manoeuvres »67% of treatments »59% of health promotion

47. Centre for Evidence-Based Medicine Centres for Evidence-Based Psychiatry l In-Patients (Oxford) »67% treated on the basis of RCTs l Out-Patient »>80% received evidence-based Rx

48. Centre for Evidence-Based Medicine Evidence-Based General Practice 122 consecutive consultations in a suburban (Leeds, UK) practice. l 81% evidence-based: »31% based on RCTs or overviews »50% based on convincing non-experimental evidence »19% without substantial evidence (Gill et al, BMJ 1996;312:819-21)

49. Centre for Evidence-Based Medicine Can we get evidence to the bedside? l Need it within seconds if it is to be incorporated into busy clinical rounds l Our initial attempts to bring the best evidence to a busy clinical team caring for 200+ admissions per month

51. Centre for Evidence-Based Medicine Searching for Evidence in the Month Before the Cart: l Expected searches = 98 l Identified searching needs = 72 l Only 19 searches (26%) carried out.

52. Centre for Evidence-Based Medicine Contents of the Cart: l Infra-red simultaneous stethoscope with 12 remote receivers. l Physical diagnosis text book and reprints (JAMA Rational Clinical Exam). l Notebook computer, computer projector, and pop-out screen. l Rapid printer.

54. Centre for Evidence-Based Medicine Contents of the Cart (cont) : Library Round-Trip = 7 min l 125 summaries (1-3 pp) of evidence previously appraised and summarised by Side A teams (in the form of “Redbook” entries or Critically-Appraised Topics : “CATs”). Access Time to the “bottom line” = 12 sec.

59. Centre for Evidence-Based Medicine Contents of the Cart (cont) : Library Round-Trip = 7 min l CD of Best Evidence Access Time to the “bottom line” = 26 sec. l CD of WinSPIRS (5-year clinical subsets) Access Time to useful abstract = 90 sec. (so used for filling Educational Rx after rounds) (used for filling Educational Rx after rounds) l CD of the Cochrane Library (used for filling Educational Rx after rounds)

60. Centre for Evidence-Based Medicine Usefulness of the Cart: l 81% of searches were for evidence that could affect diagnostic and/or treatment decisions. l 90% of these searches were successful in finding useful evidence. *

61. Centre for Evidence-Based Medicine Of the successful searches (from the perspective of the most junior responsible team member): l 52% confirmed diagnostic and/or management decisions l 23% led to changes in existing decisions l 25% led to additional decisions

62. Centre for Evidence-Based Medicine Searching for Evidence in a 3- day period after the Cart: l Expected searches = 10 l Identified searching needs = 41 l Only 5 searches (12%) carried out.

63. Centre for Evidence-Based Medicine Can we get evidence to the bedside? l Yes, and it will improve patient care. l But can we provide it in a less cumbersome form?

65. Centre for Evidence-Based Medicine EBM and Purchasing In harmony: Ê When we clinicians stop doing things that are useless or harmful ËWhen we use just-as-good but less expensive treatments, carers, and sites for care.

66. Centre for Evidence-Based Medicine What we could save in Oxford by switching from: LASIX ê frusemide: £ 90,000 simvastatin ê cerivastatin: £ 500,000 TENORMIN ê atenolol: £ 700,000 diclofenac ê ibuprofen: £ 1,000,000 Total: £ 2,290,000 l how many hips would these savings purchase?

67. Centre for Evidence-Based Medicine EBM and Purchasing Still in harmony: Ì When we spend now to save later.

68. Centre for Evidence-Based Medicine EBM and Purchasing In grudging collaboration: Í Waiting lists, once we understand the opportunity costs of shortening them: »it’s not about money »it’s about what else we won’t be able to do if we shorten them

69. Centre for Evidence-Based Medicine EBM and Purchasing In conflict: Î When we identify so strongly with a dying patient’s short-term goals that we use resources that we know would “add more QALYs” if used for other patients.

70. Centre for Evidence-Based Medicine EBM and E-B Guidelines l EBM integrates evidence, expertise, and the unique biology and values of individual patients. l Local EB Provision ought to integrate evidence, expertise, and the unique biology and values of the local scene.

71. Centre for Evidence-Based Medicine EBM and E-B Guidelines l The best evidence comes from systematic reviews (such as Cochrane) and/or E-B journals of 2º publication: »Much more likely (than personal search and critical appraisal) to be true »Saves the clinician’s precious (scarce!) time l Avoids error and duplication of effort

72. Centre for Evidence-Based Medicine EBM and E-B Guidelines l But NO systematic review can (or should try to) identify the “4 B’s: »Burden »Barriers »Behaviours »Balance l They can ONLY be determined at the local (or even patient) level

73. Centre for Evidence-Based Medicine 1. Burden l The burden of illness, disability, and untimely death that would occur if the evidence were NOT applied l the consequences of doing nothing

74. Centre for Evidence-Based Medicine 2. Barriers l Patient-values & preferences l Geography l Economics l Administration/Organisation l Tradition l “Expert” opinion

75. Centre for Evidence-Based Medicine 3. Behaviours l The behaviours required from providers and patients if the evidence is applied. l All that guidelines can do is specify the former!

76. Centre for Evidence-Based Medicine 4. Balance l The opportunity cost of applying this guideline rather than some other one.

77. Centre for Evidence-Based Medicine Killer B’s l Burden: too small to warrant action. l Barriers: ultimately down to patients’ values. l Behaviours: may not be achievable. l Balance: may favour another guideline over this one.

78. Centre for Evidence-Based Medicine Two monumental wastes of time and energy l First, national/international evidence- summarising groups prescribing how patients everywhere should be treated. l Their expertise: predicting the health consequences if you do treat. l Their ignorance: the local B’s, and whether killer B’s are operating.

79. Centre for Evidence-Based Medicine Two monumental wastes of time and energy l Second, local groups attempting to systematically review the evidence. l Their expertise: identifying the local B’s and eliminating the killer B’s l Their ignorance: searching for all relevant evidence; Chinese; performing tests for heterogeneity.

80. Centre for Evidence-Based Medicine Applying a study result to my patient l Never interested in “generalising” l Am interested in a special form of extrapolation: particularising

81. Centre for Evidence-Based Medicine Extrapolating (particularising) to my individual patient: l First and foremost: Is my patient so different from those in the trial that its results can make no contribution to my treatment decision? l if no contribution, I restart my search l if it could help, I need to integrate the evidence with my clinical expertise and my patient’s unique biology and values...

82. Centre for Evidence-Based Medicine To add Clinical Expertise and Patient’s Biology & Values : l What is my patient’s RISK ? »of the event the treatment strives to prevent? »of the side-effect of treatment? l What is my pt’s RESPONSIVENESS? l What is the treatment’s FEASIBILITY in my practice/setting? l What are my patient’s VALUES ?

83. Centre for Evidence-Based Medicine To add Clinical Expertise and Patient’s Biology & Values : l I begin by considering Risk and Responsiveness for the event I hope to prevent with the treatment: l The report gives me (or I can calculate) an Absolute Risk Reduction [ARR] for the average patient in the trial. l ARR = probability that Rx will help the average patient.

84. Centre for Evidence-Based Medicine For example, Warfarin in nonvalvular atrial fibrillation: After 1.8 years of follow-up in an RCT: l Control Event Rate (placebo) = 4.3% l Exper. Event Rate (warfarin) = 0.9% l so, for the average patient in the trial, the probability of being helped, or Absolute Risk Reduction = (CER - EER) = 3.4% ACPJC 1993;118:42

85. Centre for Evidence-Based Medicine How can I adjust that ARR for my pt’s Risk and Responsiveness? l Could try to do this in absolute terms: »my Patient’s Expected Event Rate: PEER »and multiply that by the RRR »and factor in my Patient’s expected responsiveness l Clinicians are not very accurate at estimating absolute Risk and Responsiveness

86. Centre for Evidence-Based Medicine How can I adjust that ARR for my pt’s Risk and Responsiveness? l Clinicians are pretty good at estimating their patient’s relative Risk and Responsiveness l So, I express them as decimal fractions: »f~risk (if at three times the risk, f~risk = 3) »f~resp (if only half as responsive [e.g., low compliance], f~resp = 0.5)

87. Centre for Evidence-Based Medicine How can I adjust that ARR for my pt’s Risk and Responsiveness? l probability that Rx will help my patient = ARR x f~risk x f~resp l If ARR is 3.4% l and I judge that their f~risk is 3 l and that their f~resp is 0.5 l then the probability that warfarin will help my patient = 3.4% x 3 x 0.5 = 5.1%

88. Centre for Evidence-Based Medicine Must also consider the probability that I will do harm: l In the case of warfarin: serious bleeding (requiring transfusion) from the g-i tract, or into the urine, soft tissues or oropharynx. l Absolute Risk Increase = 3% at 1 yr, so ARI estimated to be 5% in 1.8 years ACPJC 1994;120:52

89. Centre for Evidence-Based Medicine …and adjust the probability of harm for my patient l Again, can express my clinical judgement in relative terms:f~harm l Given my patient’s age, I judge their f~harm to be doubled: 2 l then the probability that Rx will harm my patient = ARI x f~harm = 5% x 2 = 10%

90. Centre for Evidence-Based Medicine Can now begin to estimate the Likelihood of Help vs. Harm l Probability of help: ARR (embolus) x f~risk x f~resp = 5.1% l Probability of harm: ARI (haemorrhage) x f~harm = 10% l My patient’s Likelihood of Being Helped vs. Harmed [LHH] is: (5.1% to 10%) or 2 to 1 against warfarin! l …or is it ?

91. Centre for Evidence-Based Medicine The LHH has to include my patient’s values l I need to take into account my patient’s views (“preferences,” “utilities”) about the relative severity: »of the bleed I might cause »to the embolus I hope to prevent l Expressed in relative terms = s~ »if the bleed is half as bad as the embolus, then s~ = 0.5

92. Centre for Evidence-Based Medicine On in-patient services in Oxford and Toronto: l When Dr. Sharon Straus has described a typical embolic stroke (with its residual disability) and typical moderate bleed (brief hospitalisation and transfusion but no permanent disability): l for most of her patients, a bleed is only 1/5th as bad as a stroke l so the s~ is 0.2

93. Centre for Evidence-Based Medicine So the LHH becomes: l {ARR for embolus} x {f~risk} x {f~resp} vs. {ARI for bleed} x {f-harm} x {s~} l 3.4% x 3 x 0.5 = 5.1% vs. 5% x 2 x 0.2 = 2% l LHH = 5.1 to 2 or 2.5 to1 »(I am more than twice as likely to help than harm my patient if they accept my offer of Rx)

94. Centre for Evidence-Based Medicine We can work out the LHH for most patients <6 minutes l To be feasible on our service: has to be “do-able” in 3 minutes.

95. Centre for Evidence-Based Medicine Reactions from our patients l All are grateful that their values/opinions are being sought  1/3 want to see the calculations, perhaps change their value for s~, and make up their own minds.  1/3 adopt the LHH as presented.  1/3 say “Whatever you tell me, doctor!”