1. Clinical epidemiology
I am not an expert but I will do my best!
If you know and I don’t - speak up!
This is the basics - there is a major new literature to become familiar with and new skills to learn.
Taken from
Bradford VTS Web Pages for General Practice
ONLINE RESOURCES
Non-clinical Tutorials for GP Registrars
RESEARCH & STATISTICS

2. EVIDENCE BASED MEDICINE
EBM is an approach to practicing medicine in which the clinician is aware of the evidence in support of his / her clinical practice, and the strength of that evidence.

3. EVIDENCE BASED HEALTHCARE
Evidence based health care promotes the collection, interpretation, and integration of valid, important and applicable patient-reported, clinician-observed and research derived evidence. The best available evidence, moderated by patient circumstances and preferences, is applied to improve the quality of clinical judgements and facilitate effective healthcare.

4. EVIDENCE BASED MEDICINE
FORMULATE QUESTION
EVALUATE
PERFORMANCE
EFFICIENTLY TRACK
DOWN BEST
AVAILABLE
EVIDENCE
IMPLEMENT
CHANGES
IN CLINICAL
PRACTICE
CRITICALLY REVIEW THE
VALIDITY AND USEFULNESS
OF THE EVIDENCE

5. AN EXAMPLE OF EBM AND AN INDIVIDUAL PATIENT
THE PROBLEM
New patient. 11 year old girl. Generalised tonic clonic fits aged 5-8. On sodium valproate, no fits 3 years.
Parents disappointed with progress at school. Generally lethargic. “It’s the tablets - what would happen if we stopped them?”

6. SOLUTION 1 Do what the last consultant said. Advantage: Consistency
Disadvantages:
Getting the notes
Do the letters say what to do long term?
Is that advice now out of date?
Was it correct at the time?

7. SOLUTION 2 Get a new consultant opinion Advantages: Disadvantages:
Local secondary care contact made if needed in the future
Advice will be current if the question is asked and answered
Disadvantages:
Time till appointment.
Getting to hospital
Is the advice based on up to date knowledge or just clinical experience?
Resources

8. SOLUTION 3
CAN I FIND THE ANSWER MYSELF?

9. P EHRHARDT & WI FORSYTHE
LEEDS GENERAL INFIRMARY
DEVELOPMENTAL MEDICINE AND CHILD NEUROLOGY 31 (5) 633-9; OCT 1989
From a total group of 640 children with grand mal seizures, 187 who became seizure free for three consecutive years on monotherapy which was then discontinued have been followed for between 1 and 14 years. Relapse occured in 22 children (12%) and was related to age at presentation: only four of 89 children with primary grand mal seizures who had presented after the age of 3 years relapsed, compared with 12 of the 45 who had presented before their third birthday. Children who had had more seizures were at greater risk of relapse. EEGs were not useful in predicting prognosis, whether taken at presentation or before withdrawal of treatment.

10. BARRIERS TO IMPLIMENTING EBM FOR INDIVIDUAL PATIENTS
Cost
Time
It’s new
What will patients think
What will my colleagues think
I don’t have the skills to assess the quality of the evidence

11. WHY THE MOVE TO EBM?
RANDOMISED CONTROLLED TRIALS PRE-1960 WERE ODDITIES
REVIEWS AND META-ANALYSES ARE BECOMING AVAILABLE AS ACCESSIBLE DIGESTS OF EVIDENCE
ACCESS TO EVIDENCE VIA I.T.
METHODOLOGICAL ADVANCEMENTS E.G. NUMBERS NEEDED TO TREAT

12. THE ALTERNATIVE TO EBM
UNSYSTEMATIC CLINICAL OBSERVATIONS OVER TIME ARE A VALID WAY OF BUILDING AND MAINTAINING KNOWLEDGE ABOUT PROGNOSIS, THE VALUE OF TESTS, & THE EFFICACY OF TREATMENT
UNDERSTANDING BASIC MECHANISMS OF DISEASE AND PATHOPHYSIOLOGY ARE A SUFFICIENT GUIDE FOR CLINICAL PRACTICE
THOROUGH TRADITIONAL MEDICAL TRAINING PLUS COMMON SENSE IS SUFFICIENT TO EVALUATE NEW TESTS AND TREATMENTS
CONTENT EXPERTISE AND CLINICAL EXPERIENCE ARE SUFFICIENT FROM WHICH TO GENERATE CLINICAL GUIDELINES

13. EBM IS ABOUT ...
CLINICAL EXPERIENCE, DIAGNOSTIC SKILLS AND CLINICAL INSTINCT ARE A NECESSARY PART OF A COMPENTENT PHYSICIAN.
HOWEVER, CLINICAL PRACTICE BASED SOLELY UPON CLINICAL EXPERIENCE “BECOMES TOMORROW’S BAD JOKE”.
“RATIONAL” TREATMENT BASED SOLELY UPON BASIC PATHOLOGICAL PRINCIPLES MAY IN FACT BE INCORRECT, LEADING TO INACCURATE TREATMENT.
UNDERSTANDING CERTAIN RULESOF EVIDENCE IS NECESSARY TO CORRECTLY INTERPRET LITERATURE ON CAUSATION, PROGNOSIS, DIAGNOSTIC TESTS AND TREATMENT STRATEGY.

14. EBM SKILLS - STATISTICS
CHANCE - p = 1 in 20 (0.05).
> 1 in 20 (0.051) = not significant
< 1 in 20 (0.049) = statistically significant
CONFIDENCE INTERVALS
what is the range of values between which we could be 95% certain that this result would lie if this intervention was applied to the general population

15. EBM SKILLS - A BASIC INTRODUCTION
CHANCE, BIAS, CONFOUNDING VARIABLES

16. TYPES OF STUDY - HYPOTHESIS FORMING
CASE REPORTS / CASE SERIES
CROSS SECTIONAL / PREVALENCE STUDIES measure personal factors & disease states - hypothesis FORMING - cannot indicate cause & effect
CORRELATIONAL / ECOLOGICAL / GEOGRAPHIC STUDIES. prevalence &/or incidence measurement in one population c/w another pop.

17. TYPES OF STUDY - HYPOTHESIS TESTING
CASE CONTROL STUDIES

18. CASE CONTROL EXAMPLE -SMOKING & LUNG CANCER
DISEASE
Cases Controls
EXPOSURE Yes a b
EXPOSURE No c d
Odds Ratio = ad/bc (1 = no association, > 1 = possible association, < 1 = protective effect)
(lung cancer)
EXPOSURE Yes
(smoking) No
The odds ratio would therefore be 56 x 246 = = 8.6.
7 x

19. TYPES OF STUDY - HYPOTHESIS TESTING
COHORT STUDIES

20. This is expressed as a divided by c .
COHORT STUDIES
OUTCOME
Yes No
Exposed a b
Not exposed c d
Attributable risk (absolute risk or risk difference)
"What is the incidence of disease attributable to exposure"
Answer = a - c.
Relative risk "How many times are exposed persons more likely to develop the disease, relative to non-exposed persons?" i.e. the incidence in the exposed divided by the incidence in the non-exposed.
This is expressed as a divided by c
a+b c+d

21. Exposed ( on oral contraceptive ) 41 9996
COHORT STUDY EXAMPLE
Deep vein thromboses (DVT) in oral contraceptive users. (Hypothetical results).
OUTCOME (DVT)
Yes No
Exposed ( on oral contraceptive )
Not exposed (not on o.c.)
These results would give an attributable risk of 34 and a relative risk of 6 - significantly large enough numbers to indicate the possibility of a real association between exposure and outcome. However, the possibility of biases very often arises.

22. RANDOMISED CONTROLLED TRIALS

23. RANDOMISED CONTROLLED TRIALS
OUTCOME
Yes No
Comparison intervention a b
Experimental intervention c d
Relative risk reduction: “ How many fewer patients will get the outcome measured if they get active treatment versus comparison intervention”
a /a+b c/c+d
a/a+b
Absolute risk reduction: “What is the size of this effect in the population”
a/a+b c/c+d

24. RCT EXAMPLE - 4S STUDY
STABLE ANGINA OR MYOCARDIAL INFARCTION MORE THAN 6 MONTHS PREVIOUSLY
SERUM CHOLESTEROL > 6.2mmol/l
EXCLUDED PATIENTS WITH ARYHTHMIAS AND HEART FAILURE
ALL PATIENTS GIVEN 8 WEEKS OF DIETARY THERAPY
IF CHOLESTEROL STILL RAISED (>5.5) RANDOMISED TO RECEIVE SIMVASTATIN (20mg > 40mg) OR PLACEBO
OUTCOME DEATH OR MYOCARDIAL INFARCTION (LENGTH OF TREATMENT 5.4 YEARS ) WERE THE OUTCOMES

25. 1/ARR = NUMBER NEEDED TO TREAT.
RCT EXAMPLE - 4S STUDY
OUTCOME (death)
Yes No
Comparison intervention (placebo)
Experimental intervention (simvastatin)
The ARR is (256/2223) - (182/2221) = =
The RRR is 0.033/0.115 = 0.29 or expressed as a percentage 29%.
1/ARR = NUMBER NEEDED TO TREAT.
1/0.033 = 30.
i.e. if we treat 30 patients with IHD with simvastatin as per 4S study, in 5.4 years we will have prevented 1 death.

26. NNT EXAMPLES
Intervention Outcome NNT

27. Why are RCTs the “gold standard” Breast cancer mortality in studies of screening with mammography; women aged 50 and over (55 in Malmo study, 45 in UK)

28. SCREENING - WILSON & JUNGEN (WHO, 1968)
IS THE DISORDER COMMON / IMPORTANT
ARE THERE TREATMENTS FOR THE DISORDER
IS THERE A KNOWN NATURAL HISTORY & “WINDOW OF OPPORTUNITY” WHERE SCREENING CAN DETECT DISEASE EARLY WITH IMPROVED CHANCE OF CURE
IS THE TEST ACCEPTABLE TO PATIENTS
SENSITIVE AND SPECIFIC
GENERALISABLE
CHEAP / COST EFFECTIVE
APPLY TO GROUP AT HIGH RISK

29. DISEASE PRESENT ABSENT SCREENING TEST POSITIVE A B NEGATIVE C D
Sensitivity = a/a+c; Specificity = d/b+d;
positive predicitive value = a/a+b;
negative predicitve value = d/c+d.

30. Value of exercise ECG in coronary artery stenosis
DISEASE
PRESENT ABSENT
TEST POSITIVE
NEGATIVE
Sensitivity = a/a+c = 60%; Specificity = d/b+d = 91%;
positive predicitive value = a/a+b = 93%;
negative predicitve value = d/c+d = 55%.

31. Sensitivities and Specificities for different tests Alcohol dependency or abuse (as defined by extensive investigations in medical and orthopaedic in patients)
SENS SPEC
GGT % %
MCV % %
LFTs % %
“Yes” to 1 or > of CAGE ?s 85% %
“Yes” to 3 or > of CAGE ?s 51% %

32. MAKING SENSE OF THE EVIDENCE - ARE THESE RESULTS VALID - i. e
MAKING SENSE OF THE EVIDENCE - ARE THESE RESULTS VALID - i.e. should I believe them?
Randomised (where appropriate)?
Drop outs and withdrawals?
Followup complete?
Analysed in the groups to which randomised?-
“Intention to treat”.

33. MAKING SENSE OF THE EVIDENCE- ARE THESE RESULTS USEFUL. - i. e
MAKING SENSE OF THE EVIDENCE- ARE THESE RESULTS USEFUL?- i.e. should I be impressed by them, are they relevant to my patients (GENERALISABLE)
How large was the treatment effect?
How precise was the estimate of treatment effect
Were all important clinical outcomes considered?
Do benefits outweigh risks?

34. READING CRITICALLY GENERAL The aims of the study are not stated
The study is not original in concept
The study is not particularly useful or relevant to general practice
There could be ethical objections to the design or reporting of the study

35. READING CRITICALLY METHOD
The design of the study is not consistent with the aims
The sample is not representative of the whole population in question
Controls are needed and not used
Controls used are not appropriate
Method(s) used for selecting cases / controls not clearly described
Other method details (e.g. numbers, time periods, statistical methods used) are not clear and consistent
Questionaires and proformas are not thoroughly tested or are not relevant.

36. READING CRITICALLY RESULTS
There is missing data. e.g. drop-out rates, non-responders
Other details e.g. numbers, percentages, p values are inaccurate / unclear
Statistical methods would be useful but are not used
Statistical testing is used but is inappropriate
The tests of significance used do not meet the conditions for the application of these tests
The sample size is so small that potentially clinically significant findings do not achieve statistical significance
The sample size is so large that statistically significant findings have little clinical significance

37. READING CRITICALLY DISCUSSION The study is not discussed critically
The results are not discussed in relation to other important literature in the field
The discussions and conclusions speculate too far beyond what has been shown in this study

38. THE COMMONEST ERRORS ARE:-
ERRORS IN SAMPLE GROUPS OR QUESTIONAIRE DESIGN
FAILURE TO DESCRIBE THE METHOD CLEARLY
PROBLEMS WITH ALTERNATIVE RISK FACTORS, EXCLUSIONS AND WITHDRAWLS
END POINTS AND DIAGNOSTIC DEFINITIONS UNCLEAR
POPULATION IS NOT TYPICAL OF MINE

39. GUIDELINES - SELECTING DISEASE OR CONDITION
HIGH MORBIDITY OR MORTALITY
VARIATION FROM LOCAL OR NATIONAL PATTERN
MAJOR SERVICE USER e.g.. stroke, arthritis, mental health
CURRENT SERVICES OF QUESTIONABLE EFFECTIVENESS OR EFFICIENCY
PRIORITIES - LOCAL OR NATIONAL “NOISE” - CLINICAL DEVELOPMENT OR RECOGNITION THAT IMPROVEMENT POSSIBLE
BE REALISTIC - e.g.. review D&Cs, not the whole of gynae services.

40. “The evidence isn’t there”
Bandolier
Evidence Based Medicine
DTB, MeReC
CRD
Effective Healthcare Bulletins
Effectiveness Matters
Database of Abstracts of Reviews of Effectiveness
Cochrane libraray

41. “GPs will never find the time to track the evidence down”
A lot has already been tracked down, critically appraised and packaged
A practice that collectively can find an hour a week can make huge strides
GPs don’t have to DO the work personally! - others (in the PHCT, at universities and at health authorities) can make a valid contribution

42. “GPs don’t have the skills and experience to critically appraise the evidence and determine its applicability to their locality.”
A great deal of evidence has already been appraised
It’s not difficult!
Critical appraisal skills have been shown to work (in randomised controlled trials!)
Who else is in a position to determine applicability other than the local PHCT!

43. “The relevant evidence cannot be recalled during the consultation when the answers are required”
COMPUTERS!
Most consultations do not require individual literature searching; for those that do a further appointment is no real hardship
Major areas of health gain can be handled with electronic reminders

44. EBM IN THE FUTURE

45. LIMITATIONS
EBM = WHAT IS BEST FOR AN INDIVIDUAL PATIENT (patient utility)
EVIDENCE BASED PURCHASING = BEST USE OF HEALTH CARE RESOURCES FOR THE LOCAL POPULATION (cost utility). i.e. knowledge of local needs, priorities and constraints
WHAT IF THESE CONFLICT?