Basic statistics

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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

STUDY
COFFEE DRINKING

LUNG CANCER

SMOKING
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
Exposure to Risk Factor
STUDY
Yes

Cases

No

Population

Yes

Controls

No
TIME

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)

DISEASE
Cases
Controls
(lung cancer)
EXPOSURE
Yes
(smoking)
No

56
7

230
246

The odds ratio would therefore be 56 x 246 = 13776 = 8.6.

7 x 230
1610

TYPES OF STUDY - HYPOTHESIS

TESTING
COHORT STUDIES

Exposed
Population
Sample

Yes
No

Time
Yes
Not exposed

No

COHORT STUDIES
OUTCOME
Exposed
Not exposed

Yes
a
c

No
b
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 nonexposed.
This is expressed as a
a+b

divided by
c
c+d

COHORT STUDY EXAMPLE

Deep vein thromboses (DVT) in oral contraceptive users.
(Hypothetical results).
OUTCOME (DVT)

Yes
Exposed ( on oral contraceptive )
Not exposed (not on o.c.)

No
41
7

9996
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
Experimental
intervention

Improved
Not improved

Population

Sample

Time
Improved
Comparison
intervention

Not improved

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
Experimental intervention (simvastatin) 182

2039

1967
2221

2223

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
Streptokinase + asprirn v. placebo
(ISIS 2)

tPA v. streptokinase
(GUSTO trial)
Simvastatin v. placebo in IHD
(4S study)
Treating hypertension in the
over-60s
Aspirin v. placebo in healthy
adults

Outcome
prevent 1 death
at 5 weeks
save 1 life with
tPA usage
prevent 1
event in 5y
prevent 1 event
in 5y
prevent MI or
death in 1 year

NNT

20
100
15
18
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)
Reduced RR

Increased RR

Randomised Trials
HIP
Two County
Malmo
Edinburgh
Stockholm
Geographical study
UK
Case control studies
BCDDP
Nijmegen
Utrecht
Florence

0.1

0.2

0.5

Relative risk

1.0

2.0

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
PRESENT
ABSENT

TEST

POSITIVE

NEGATIVE

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

NEGATIVE

90

137

11

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)

GGT
MCV
LFTs
Yes to 1 or > of CAGE ?s
Yes to 3 or > of CAGE ?s

SENS
54%
63%
37%
85%
51%

SPEC
76%
64%
81%
81%
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?