Introduction to Critical Appraisal

CHRIS REDMAN
ALEX SANCHEZ-VIVAR
 Presentation Overview

• Introduction to critical appraisal

• Definition, differences, strengths and weaknesses of
systematic reviews and meta-analyses
• Sources of systematic reviews/meta-analyses
• Levels of Evidence
• Interpretation of basic statistics in meta-analyses –
confidence intervals, forest plots
• Critical appraisal of systematic reviews/meta-analyses
 What is critical appraisal?

• “Critical appraisal is the process of

systematically examining research evidence
to assess its validity, results, and relevance
before using it to inform a decision”

(Hill and Spittlehouse, 2001, p.1)

• Consideration of quantitative and qualitative

aspects
 Critical appraisal is not

• Negative dismissal of any piece of research

• Assessment on results alone
• Based entirely on statistical analysis
• Undertaken by experts only
 Why critically appraise?

• To find out the validity of the study

– are the methods robust?

• To find out the reliability of the study

– what are the results and are they credible?

• To find out the applicability of the study

– is it important enough to change my practice?
How do I critically appraise research?

• Be (critically) open to everything

• Believe (in principle) papers from high
quality journals
• Read & decide yourself
• Let other people read and decide for (with)
you
• Read for yourself and make a structured
appraisal
 Critical appraisal
• Advantages
– systematic way of assessing validity, results & usefulness of
research
– contributes to improving practice (quality)
– encourages objective assessment of information
– not difficult to develop skills

• Disadvantages
– time consuming
– not always any easy answers or what you hoped to find
– dispiriting if ‘good’ evidence is lacking i.e. little / poor
research done
 Critical appraisal

– BUT… you can all do it with the right tools &

guidance
What do I need to know?

• Awareness of study designs

• Levels of evidence
• Statistics!!
• CA checklists
• CA resources
Awareness of study design
Observational study design measures of disease, measures of risk, and temporality
 What is a systematic review?

• A review that has been prepared

using some kind of systematic approach
to minimising biases and random errors,
and that the components of the approach
will be documented
in a materials and methods section

Chalmers et al, 1995

What is a systematic review

Reviews

Systematic reviews
 Rationale for systematic reviews

• Information overload

• Publication bias

• Poor quality of reviews

– Vitamin C and the prevention of the common cold
(Pauling 1986)

• Missing link
– Inhalation of hexamethonium (comment by Clark et al, 2001)
 Sources of systematic reviews

• The Cochrane Library

– www.library.nhs.uk
• DARE (in Cochrane Library ‘Other reviews’)
• Health Technology Assessments (in Cochrane Library ‘Technology
Assessments’)
• Medline, Cinahl, Embase search on ‘systematic review’ in title,
abstract
• PubMed – Systematic Review in Limits > Topic
• TRIP
– www.tripdatabase.com
• Evidence Based Reviews - Journals and Databases
– https://www.library.nhs.uk/evidence
• NHS Evidence
– https://www.evidence.nhs.uk/
 Format of a systematic review

• Formulation of a review question

• Define inclusion/exclusion criteria
• Locate studies
• Select studies (inclusion/exclusion)
• Assess study quality
• Data extraction
• Analyse and present results
• Interpretation of results
Egger et al, 2001
 Formulation of review question

• Is the question focused in terms of

– Population studied
– Intervention/exposure given
– Outcomes considered

Do anticoagulants prevent strokes in

patients with atrial fibrillation?
 Define inclusion/exclusion criteria

• Were the right types of studies included to answer

the question? Depends on the question.

• Can have observational studies (cohort, case-

control), diagnostic/screening tests, prognostic, non-
randomised trials

• Studies should be defined according to their design,

participant characteristics, interventions and
outcomes
 Locate studies

• Comprehensive search
– Databases
– Conference proceedings
– Hand searching
– Grey literature (reports, research registers)
– Foreign language
– Follow-up references
– Contacting experts/authors
• Publication bias – unpublished studies
• Explicit
 Select and Assess Studies

• Eligibility criteria for study selection can be

applied

• More than one reviewer can help reduce bias

• Checklists/scoring systems
 What do the findings mean?

• Effect measures – odds ratios, relative risk,

mean difference

• P-values

• Confidence intervals
 Using statistics

• Assess the weight of the evidence that a

treatment works (or doesn’t)

• Give an estimate (and likely range) of the

treatment effect

• Test to see how likely it is that this effect

would have been seen by chance
 Odds ratio (OR)

• Expresses the odds of having an event compared

with not having an event in two different groups

OR = odds in the treated group / odds in the control group

• OR=1 treatment has identical effect to control
• OR<1 event is less likely to happen than not (i.e.
the treatment reduces the chance of having the
event)
• OR>1 event is more likely to happen than not
(increases the chances of having the event)

• Clinical trials typically look for treatments which

reduce event rates, and which have odds ratios of
less than one
 Importance of defining the
outcome
Type of outcome

Value of Adverse outcome (e.g. Beneficial outcome (e.g.

OR/RR death) stopped smoking)

<1 New intervention New intervention worse

better

1 New intervention no New intervention no

better/no worse better/no worse

>1 New intervention New intervention better

worse
 P-values – significance test

• A p-value is a measure of statistical

significance which tells us the probability of
an event occurring due to chance alone

• P-value results range from 0 to 1

• The closer the p-value is to zero, the less

chance there is that the effects of two
interventions are the same
 Statistical significance
• In general, p-values of either 0.05 or 0.01 are used
as a cut-off value, although this value is arbitrary

• P-value of <0.05 indicates the result is unlikely

to be due to chance

• P-value of >0.05 indicates the result might have

occurred by chance.
 Be careful…

• A p-value in the non-significant range tells you that

either there is no difference between the groups or
there were too few subjects to demonstrate such a
difference (ideally need to report confidence
intervals)

• There is not much difference between p=0.049 and

p=0.051

• P-values do not indicate the magnitude of the

observed difference between treatments that is
needed to determine the clinical significance
 Interpretation of
Confidence Intervals
• Confidence interval is the range within which we
have a measure of certainty that the true population
value lies
OR
• The confidence interval around a result obtained
from a study sample (point estimate) indicates the
range of values within which there is a specific
certainty (usually 95%) that the true population
value for that result lies.
(MeReC Briefing 2005)
What can a CI tell us?
• Tells us whether the result is significant or not

• The width of the interval indicates precision. Wider

intervals suggest less precision

• Shows whether the strength of the evidence is strong or

weak.

• The general confidence level is 95%. Therefore, the 95%

CI is the range within which we are 95% certain that the
true population value lies
 Confidence Intervals reported on
Ratios (odds ratio, etc)

• The ‘line of no effect’ centres around 1

• If a CI for an RR or OR includes 1
(the line of no effect)
then we are unable to demonstrate statistically
significant difference between the two groups
 What is a meta-analysis?

• A statistical analysis of the results

from independent studies,
which generally aims to produce
a single estimate of the treatment effect

Egger et al, 2001

 Interpretation of forest plots
Effect of probiotics on the risk of antibiotic associated diarrhoea

D'Souza, A. L et al. BMJ 2002;324:1361

 Interpretation of forest plots
• Look at the title of the forest plot, the intervention, outcome
effect measure of the investigation and the scale
• The names on the left are the authors of the primary studies
included in the MA
• The small squares represent the results of the individual trial
results
• The size of each square represents the weight given to each
study in the meta-analysis
• The horizontal lines associated with each square represent the
confidence interval associated with each result
• The vertical line represents the line of no effect, i.e. where there
is no statistically significant difference between the
treatment/intervention group and the control group
• The pooled analysis is given a diamond shape. The horizontal
width of the diamond is the confidence interval
 Advantages of a systematic
review/meta-analysis

• Limits bias in identifying and excluding studies

• Objective
• Good quality evidence, more reliable and
accurate conclusions
• Added power by synthesising individual study
results
• Control over the volume of literature
 Drawbacks to systematic
reviews/meta-analyses

• Can be done badly

– 2 systematic reviews on same topic can have different
conclusions
• Inappropriate aggregation of studies
• A meta-analysis is only as good as the papers
included
• Tend to look at ‘broad questions’ that may not be
immediately applicable to individual patients
 Conclusion

• Critical appraisal of systematic reviews and

other research is well within your capabilities
• Use a recognised checklist (i.e. SIGN)
• Update your literature searching skills
regularly (contact your library skills trainer)
D'Souza, A. L et al. BMJ 2002;324:1361
 (Other) Critical appraisal checklists
• CASP (Critical Skills Appraisal Programme)
– http://www.phru.nhs.uk/casp/critical_appraisal_tools.htm

• JAMA Users’ Guides to the Medical Literature

– http://www.cche.net/usersguides/main.asp

• Crombie I (1996) The Pocket Guide to Critical Appraisal, BMJ

Books, London

• Greenhalgh T (2001) How to Read a Paper, BMJ Books, London

• BestBETs CA database
– http://www.bestbets.org/cgi-bin/browse.pl?~show=appraisal
 References

• Systematic reviews in health care [electronic resource] : meta-

analysis in context / edited by Matthias Egger, George Davey
Smith, and Douglas G. Altman. BMJ Books 2001 (ebook)

• What is a systematic review?, What is a meta-analysis?, What

are confidence intervals?
– http://www.evidence-based-
medicine.co.uk/what_is_series.html

• Understanding systematic reviews and meta-analysis. Akonberg

AK. Archives of Disease in Childhood 2005;90:845-848.
 References
• Cochrane Open Learning Material: Systematic Reviews and
Meta-analyses (useful Forest Plot interpretation PDF)
– http://www.cochrane-net.org/openlearning/HTML/mod3-2.htm

• Funnel plots
– Bias in meta-analysis detected by a simple, graphical test.
Egger M, et al BMJ 1997 (315):629-634
– The case of the misleading funnel plot. Lau J, et al. BMJ
2006 (333):597-600

• Heterogeneity
– What is heterogeneity and is it important? Fletcher J BMJ
2007;334:94-6
The label tells you what the comparison and
outcome of interest are

Effect of probiotics on the risk of antibiotic associated diarrhoea

Scale measuring treatment effect.
Take care when reading labels!

Effect of probiotics on the risk of antibiotic associated diarrhoea

Each study has an ID (author)

Effect of probiotics on the risk of antibiotic associated diarrhoea

Treatment effect sizes for each study
(plus 95% CI)

Effect of probiotics on the risk of antibiotic associated diarrhoea

Horizontal lines are confidence intervals
Diamond shape is pooled effect
Horizontal width of diamond is confidence interval

Effect of probiotics on the risk of antibiotic associated diarrhoea

The vertical line in middle is the line of no effect
For ratios this is 1, for means this is 0

Effect of probiotics on the risk of antibiotic associated diarrhoea

Rationale for meta-analysis

Conventional
and cumulative
meta-analysis of
33 trials of
intravenous
streptokinase
for acute
myocardial
infarction.

Mulrow, C D BMJ 1994;309:597-599