EBM

1. Asking the Right Questions

PICO Format Population + Intervention + Comparator + Outcome

2. Study Designs
Randomised Control Trial
Therapy / intervention Systematic Review
Randomised Control Trial
Cohort Study
Case-control study
Harm / Aetiology (Randomised control trial)
Cohort study
Case control study
Diagnosis Cross-sectional analytic
Prognosis Cohort Study
Frequency of occurrence Descriptive (survey)

Cohort Study Case
Control Study


Clinical Question Evidence Sources of bias Time
RCT Therapy/ Intervention
Harm/aetiology
(Unethical)
Strongest
Evidence
No Allocation concealment
Loss to follow up
No analysis by intention to treat
Non-blind assessment of outcome
Begins with study
factor-exposure
Randomised
Cohort Therapy/ Intervention
Harm/aetiology
Prognosis
Observational Loss to follow up
Non blind assessment of outcome factor
Confounding
Begins with study-
factor exposure
Non-Randomised
Case-
Control
Therapy/ Intervention
Harm/Aetiology
Observational Recall Bias
Confounding
Low response rates
Non-blind assessment of outcome factor
Controls not chosen from same population as
cases
Begins with outcome
factor
Cross-
Sectional
analytic
Diagnosis Best study to
assess
diagnostic
accuracy
Non-independent blind comparison with
reference standard
Verification bias
Inappropriate spectrum of disease
Compares a
diagnostic test to a
gold standard
Therapy/ Intervention
Harm/Aetiology
Association or
hypothesis
generating
Selection of participants non-random
(volunteers)
Confounding
Low response rate
Small sample size
Study and outcome
factors measured at
one point in time
3. Causality

Bias in Studies
Cohort Studies Case Control Studies Cross-sectional studies
Loss of follow up
Non-blind outcome assessment
Confounding
Poorly-defined study base
Low response rates
Recall bias
Confounding
Incidence-prevalence bias
Low response rat
Recall bias
Confounding

Confounders = prognostic factors that are unevenly distributed between groups of study subjects
Randomisation removes confounders it equally distributes factors in control and exposure groups
Need a large study group to ensure even distribution of confounders

Controls aim is to choose controls who are representative of the population from which the cases arise. Case and controls should
come from the same population (study base)
Eg hospital based case control studies are not good not representative of the general population + badly defined

Assembled study subjects
Subjects exposure measured by investigators
Exposed group Non-exposed group
Measure outcomes of interest in both groups and compare
Choose cases Choose controls
(Outcome known at beginning)
Measure past exposures in both cases and controls and compare
Assembled study subjects
Randomize subjects
Intervention group Control group
Measure outcomes of interest in both groups and compare
Causal Criteria
Strength of association
Temporality
Dose-response
Biological plausibility
Consistency across studies
Reversibility
Analogy






























4. Frequency and Prognosis

Prevalence = proportion of a population with an attribute of interest at a specified time
Prevalence = Total no. people with disease at a given time
Total population at given time

Measure with descriptive study Population of interest random sample measure health characteristic of interest
Survey Sampling
o Random (probability) sampling electoral roll, random digit dialling
o Non-probability sampling quota sampling, snow-balling, volunteers

Incidence = New occurrences in a population over time
Incidence = No. of person experiencing a new even during a time period
No. of persons at risk at beginning of time period

Measure with descriptive study population of interests representative sample
o Loss to follow up (include in analysis) good response rate >80%
o Measure health characteristic of interest

Prognostic Factors affect outcome once you have disease

Relative Risk
<1 protective
> 1 harmful
Eg RR = 0.77 means the study factor is protective against disease 23% less likely to have disease
RR/OR = 2.3 means you are over twice more likely to get disease

Confidence Intervals
If the same study were repeated 100 times, then the results of 95 of these 100 studies would like somewhere between the
95% confidence interval
You can be 95% confident that the result is within the 95% CI
Narrow confidence interval more confident of the result
If the CI crosses the null (=1) then the result is not statistically significant

P Values = probability of obtaining the study result if there really is no effect
Probability the study result is due to chance

Steps for Appraising Articles on Causality
1. Are the results valid?
Were there clearly identified comparison groups?
Were outcomes and exposures measured in the same way in the two groups
Was the follow up sufficiently long and complete
Is the temporal relationship correct
Is there a dose-response gradient?
2. What are the results?
How strong is the association between exposure and outcome
How precise is the estimate of risk
3. Will the results help me is caring for my patients
Are the results applicable to my practice
What is the magnitude of the risk
Should I attempt to stop the exposure














Prognosis Articles (Cohort Studies)
1. Are the results valid?
Representative sample of patients at a particular point in course of disease?
Was follow up sufficiently long and complete?
Were objective and unbiased outcome criteria used?
Was their adjustment for important prognostic factors?
2. What are the results?
How large is the likelihood of outcome events in a specified time?
How precise are the estimates of likelihood?
3. Can I apply study to my patients?
5. Intervention Studies

Randomisation makes the two groups on average the same, so that any change or difference in outcome can be attributable to the
intervention

Analysis by intention to treat preserves randomisation analyse patient outcomes based on into which group they were
randomised regardless of whether they actually receive the planned intervention

Event rate = number of people who experienced the outcome/total number of people
Experimental (EER) and Control event rates (CER)

Relative Risk (RR) = Event rate in treatment group / Event rate in control group or EER/CER

Relative Risk reduction (RRR) = 1 RR (expressed as a percentage)

Absolute risk reduction (ARR) = Event rate in control event rate in treatment group

Number needed to treat (NNT) = 1/ARR
Number of people that need to be treated to prevent one adverse outcome




















Analysing Intervention Studies (RCT)
1. Are the results valid?
Was the assignment of patients to treatments randomised?
Were the groups similar at the start of the trial?
Were all patients who entered the trial properly accounted for and attributed at its
conclusion?
o Was follow-up sufficiently long and complete?
o Were patients analysed in the groups to which they were randomised?
(analysis by intention to treat)
Were patients, study staff and outcome assessors blind to treatment?
Aside from the experimental intervention, were the groups treated equally?
2. What were the results?
How large was the treatment effect?
How precise was the estimate of treatment effect? (CI)
3. Are the results applicable to my patients?
6. Diagnostic Questions

Study type = cross sectional analytical study

Pre-test probability = prevalence in the general population

Post-test probability = chance of patient having disease after the test (depends on pre-test probability)

Disease No Disease
Positive TP FP TP + FP
Negative FN TN FN + TN
TP + FN FP + TN

Sensitivity = TP / TP + FN
Proportion of people with the disease who test +ve for disease
High sensitivity test is good at ruling OUT probability of disease (if ve, do not have disease)

Specificity = TN / FP + TN
Proportion of people without disease who test ve for disease
High Specificity test rules IN disease (if +ve, have disease)

Predictive values tell you the probability of a test being correct (prevalence dependent)

Positive Predictive Value = TP / TP + FP

Negative Predictive Value = TN / FN + TN

Likelihood ratio
LR = probability of test result in diseased patients
Probability of result in non-disease patients
LR can be combined with pre-test probability post-test probability

+ve LR = Sensitivity / 1- specificity
Want LR+ >1 the higher the better

-ve LR = 1 sensitivity / specificity
Want LR- <1 the lower the better


Analysing Diagnostic Studies
1. Is the study valid?
Was there an independent blind comparison to the gold standard?
Were the test and reference standard measured independently?
Was the choice of patients who were assessed by the reference standard
independent of the test result? (avoids verification bias)
Was there an appropriate spectrum of disease?
Is the test reproducible?
2. What are the results?
Likelihood ratios
3. Is the study applicable to my patient?