Date post: | 28-Mar-2015 |
Category: |
Documents |
Upload: | kyle-fletcher |
View: | 217 times |
Download: | 1 times |
Basic statistics
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
EBM SKILLS - A BASIC INTRODUCTION
CHANCE, BIAS, CONFOUNDING VARIABLES
COFFEE DRINKING LUNG CANCER
SMOKING
STUDY
CONFOUNDING VARIABLE
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.
TYPES OF STUDY - HYPOTHESIS TESTING
CASE CONTROL STUDIES
Controls
Population
CasesYes
No
Yes
No
Exposure to Risk Factor
TIME
STUDY
CASE CONTROL EXAMPLE -SMOKING & LUNG CANCER
DISEASECases Controls
EXPOSURE Yes a bEXPOSURE No c d
Odds Ratio = ad/bc (1 = no association, > 1 = possible association, < 1 = protective effect)
DISEASECases Controls
(lung cancer)EXPOSURE Yes 56 230(smoking) No 7 246
The odds ratio would therefore be 56 x 246 = 13776 = 8.6. 7 x 230 1610
TYPES OF STUDY - HYPOTHESIS TESTING
• COHORT STUDIES
Population
Sample
Yes
No
Yes
No
Time
Exposed
Not exposed
COHORT STUDIES OUTCOME
Yes NoExposed 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
COHORT STUDY EXAMPLE
Deep vein thromboses (DVT) in oral contraceptive users. (Hypothetical results).
OUTCOME (DVT)
Yes NoExposed ( on oral contraceptive ) 41 9996
Not exposed (not on o.c.) 7 10009
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.
RANDOMISED CONTROLLED TRIALS
Population Sample Time
Improved
Not improved
Not improved
Improved
Experimental intervention
Comparisonintervention
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
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
RCT EXAMPLE - 4S STUDY
OUTCOME (death) Yes No
Comparison intervention (placebo) 256 1967 2223
Experimental intervention (simvastatin) 182 2039 2221
The ARR is (256/2223) - (182/2221) = 0.115 - 0.082 = 0.033.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.
NNT EXAMPLES
Intervention Outcome NNTStreptokinase + asprirn v. placebo
(ISIS 2)prevent 1 deathat 5 weeks
20
tPA v. streptokinase(GUSTO trial)
save 1 life withtPA usage
100
Simvastatin v. placebo in IHD(4S study)
prevent 1event in 5y
15
Treating hypertension in the over-60s
prevent 1 eventin 5y
18
Aspirin v. placebo in healthyadults
prevent MI ordeath in 1 year
500
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)
Relative risk
0.1 0.2 0.5 1.0 2.0
Reduced RR Increased RR
Randomised Trials
Geographical study
Case control studies
HIP
Two County
Malmo
Edinburgh
Stockholm
UK
BCDDP
Nijmegen
Utrecht
Florence
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
SCREENING
DISEASE
PRESENTABSENT
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.
Value of exercise ECG in coronary artery stenosis
DISEASE
PRESENT ABSENT
TEST POSITIVE 137 11
NEGATIVE 90 112
Sensitivity = a/a+c = 60%; Specificity = d/b+d = 91%;
positive predicitive value = a/a+b = 93%; negative predicitve value = d/c+d = 55%.
Sensitivities and Specificities for different tests
Alcohol dependency or abuse(as defined by extensive investigations in
medical and orthopaedic in patients)
SENS SPEC
GGT 54% 76%
MCV 63% 64%
LFTs 37% 81%
“Yes” to 1 or > of CAGE ?s 85% 81%
“Yes” to 3 or > of CAGE ?s 51% 100%
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”.
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?