1. 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.

2. 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

3. 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

4. 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

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

6. 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!

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

8. 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.

9. 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.

10. 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.

11. 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

12. 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...

13. 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 ?

14. 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.

15. 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

16. 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

17. 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)

18. 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%

19. 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

20. 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%

21. 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 ?

22. 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

23. 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

24. 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)

25. 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.

26. 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!”